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by Dr. Geoffrey Sher on December 1, 2015

You are not alone. Dr. Sher is here to answer your questions and support you.

If you would like to schedule a one on one Skype, telephone, or in person consultation with Dr. Sher, please fill out the form on the right and our team will get you scheduled right away.

Dear Patients,

I created this forum to welcome any questions you have on the topic of infertility, IVF, conception, testing, evaluation, or any related topics. I do my best to answer all questions in less than 24 hours. I know your question is important and, in many cases, I will answer within just a few hours. Thank you for taking the time to trust me with your concern.

– Geoffrey Sher, MD

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  • Drew - February 9, 2018 reply

    I wanted to ask how late an embryo can possibly implant after FET. We transferred a 6day hatching AA blast, I had spotting on day 3, 4, and 7dpt. My home tests were negative on day 7 and I paid for a beta with a result less than 1. My home tests became positive at 10dpt and have continued to darken since. My beta on 12dpt was 12, and 14dpt was 36.8 Is there a possibility this could be a viable pregnancy? Everything I’ve read tells me that it’s either biochemical or possible ectopic but my clinic remains optimistic and we repeat beta on Monday. Any advice on late implantation would be helpful. Thank you so much

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 9, 2018 reply

    No Drew…It is possible that this could be a slow implantation. If it is…it will keep doubling for the next few weeks. If not, it could be a chemical pregnancy or even a developing tubal (ectopic) pregnancy. Discuss with your RE.

    Good luck!

    Geoff Sher

  • Jeff - February 8, 2018 reply

    Hi Dr.,

    My wife (38yrs) had her first u/s today from a euploid embryo transferred on January 10. The u/s measured at 6 weeks 5 days with a crl at 7.95mm and fetal heart beat at 117bpm. Our doctor said this is slightly below normal and asked us to come back for a repeat u/s in ten days. Is this any cause for concern or does this look promising?

    Thank you for your time.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 9, 2018 reply

    I would need much more information to comment with authority, but these findings are not incompatible with a viable pregnancy in the make.

    Good luck!

    Geoff Sher

  • Jen - February 8, 2018 reply

    Hi Dr Sher-

    I am hoping you can offer some insight on my current situation. We are diagnosed as unexplained/endometriosis. We were lucky to conceive our son with a FET- he was the only of 4 embryos from that cycle.

    We were delighted to get pregnant naturally at 18 months postpartum with a second son. We unfortunately found out that he had an abnormality and chose to end the pregnancy at 24 weeks. His chromosome testing, both before and after birth, was normal.

    We cycled again and were lucky to get pregnant on our fresh cycle. A third son was growing well and all of the testing was normal. We found out at our 20 weeks that he had an extreme case of IUGR, and his heart stopped beating days later.

    We have since done testing for clotting disorders and both of us parents have done karyotyping. Both have come back normal.

    We have four frozen embryos and are ready to go ahead on another transfer. Our RE believes that this had been bad luck. Baby aspirin and maybe an injectable blood thinners have been mentioned for my upcoming cycle. I cant help but wonder if there is something else going on, but am not sure what else we can test for. Is it possible to be treated proactively for autoimmune issues without having the testing?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 9, 2018 reply

    If you have endometriosis, you might well have an underlying immunologic implantation dysfunction that could impact placentation adversely. It could even explain the IUGR.

    More than half of women who have endometriosis harbor antiphospholipid antibodies (APA) that can compromise development of the embryo’s root system (trophoblast). In addition and far more serious, is the fact that in about one third of cases endometriosis, regardless of its severity is associated with NKa and cytotoxic uterine lymphocytes (CTL) which can seriously jeopardize implantation. This immunologic implantation dysfunction (IID) is diagnosed by testing the woman’s blood for APA, for NKa (using the K-562 target cell test or by endometrial biopsy for cytokine activity) and, for CTL (by a blood immunophenotype). Activated NK cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.
    Women who harbor APA’s often experience improved IVF birth rates when heparinoids (Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. NKa is treated with a combination of Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa.
    The therapeutic effect of IL/steroid therapy is likely due to an ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. IL/steroids down-regulates NKa within 2-3 weeks of treatment the vast majority of women experiencing immunologic implantation dysfunction. In this regard IL is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.
    The toxic pelvic environment caused by endometriosis, profoundly reduces natural fertilization potential. As a result normally ovulating infertile women with endometriosis and patent Fallopian tubes are much less likely to conceive naturally, or by using fertility agents alone (with or without intrauterine (IUI) insemination. The only effective way to bypass this adverse pelvic environment is through IVF. I am not suggesting here that all women who have endometriosis require IVF! Rather, I am saying that in cases where the condition is further compromised by an IID associated with NKa and/or for older women(over 35y) who have diminished ovarian reserve (DOR) where time is of the essence, it is my opinion that IVF is the treatment of choice.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
    • Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
    • Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
    • Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus IVF
    • Treating Ovarian Endometriomas with Sclerotherapy.
    • Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
    • Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
    • Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
    • Induction of Ovulation With Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
    • Clomiphene Induction of Ovulation: Its Use and Misuse!

    If you are interested in my advice or medical services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
    Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Connie - February 8, 2018 reply

    Do these numbers look like DOR?
    FSH 8.68, LH 4.31, Estradiol 197.
    AMH is still outstanding.
    I’m 39 years old
    Baseline ultrasound was 14 follicles today. However AFC has fluctuated from 5-14. There was a follicle that was already 10 at day 3 today.
    What stim protocol would be best? Last was antagonist/agonist that resulted in 2 eggs and 2 embryos. However there were about 10 follicles and they weren’t able to aspirate them out. Empty follicle syndrome?
    Have done 3 retrievals all with the same protocol. However the first 2 were with gonal f max dose of 375 and menopur 75. This 3rd retrieval they wanted to stim shorter so they came out with 450 of gonal f and 150 of menopur. Triggered with hcg and it worked. Beta 257 the next day after trigger. Again for this cycle my follicle sizes were great but we got only 2 eggs. I think I need to try something different.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 9, 2018 reply

    I need to msede your AMH to d]be confident in commenting on your ovarian reserve. Notwithstanding this, here is the protocol I advise for women, <40Y who have adequate ovarian reserve.

    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Tanner - February 8, 2018 reply

    Dr. Sher –
    My wife had a frozen embryo transplant 10 days prior. On day 8, we got beta level back of 17…which we thought was good. Now day 10, it is 23…which isn’t good growth. We go back in 5 days for another blood test. Shoot me straight.

    Appreciate your knowledge.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    Regrettably, this looks like a failing implantation (chemical pregnancy)

    So Sorry.

    Geoff Sher

  • veena - February 8, 2018 reply

    Hello Dr. Sher,
    In what instances would you transfer a mosaic embryo?
    This is what we have, can you tell me which ones are transferable with minimal risk? I understand this may or may not work, but I would like to give it my best.
    Embryo 1 : High Mosaic Partial Trisomy 11q 14.3-qter
    Embryo 2: High Mosaic Partial Monosomy 10q 21.1-qter
    Embryo 3: High Mosaic Partial Trisomy 12q 23.3-qter

    If we try another cycle, it would be the 3rd cycle, would I get similar results? Should I move on to donor eggs and sperm?
    please advise

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    I really think we should talk..see below!

    Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or preimplantation embryo development, and represents a major cause of early pregnancy loss. About a decade ago, I and an associate, Levent Keskintepe PhD were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3 fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.
    Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly , summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.
    Thus by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.
    The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.” As stated, some mosaic embryos will In the process of subsequent cell replication convert to the normal euploid state (i.e. autocorrect)
    It is against this background, that an ever increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
    1. Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
    2. “Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically euploid early embryo mutate and become aneuploid. This is referred to as mosaicism. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will be “competent” and capable of propagating a normal conceptus.
    Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to differentiate between these two varieties of aneuploidy would be of considerable clinical value. And would provide a strong argument in favor of preserving certain aneuploid embryos for future dispensation.
    Aneuploidy, involves the addition (trisomy) or subtraction (monosomy) of one chromosome in a given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve more than a single pair (i.e. complex aneuploidy). Aside from monosomy involving absence of the y-sex chromosome (i.e. XO) which can resulting in a live birth (Turner syndrome) all monosomies involving autosomes (non-sex chromosomes) are lethal and will not result in viable offspring). Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can progress to viable, but severely chromosomally defective babies. All other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while mitotic aneuploidy (“mosaicism) often autocorrects in the uterus. Most complex aneuploidies are meiotic in origin and will almost invariably fail to propagate viable pregnancies.
    There is presently no practical test that can reliable differentiate between meiotic and mitotic aneuploidy. Notwithstanding this, the fact that some “mosaic” embryos can autocorrect in the uterus, makes a strong argument in favor of transferring aneuploid of embryos in the hope that the one(s) transferred might be “mosaic” and might propagate viable healthy pregnancies. On the other hand, it is the fear that embryo aneuploidy might result in a chromosomally abnormal baby that has led many IVF physicians to strongly oppose the transfer of aneuploid embryos to the uterus.
    Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, unless the woman/couple receiving such embryos is willing to commit to terminating a resulting pregnancy found through amniocentesis or chorionic villus sampling (CVS) to be so affected, she/they are probably best advised not to transfer such embryos. Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated in any such cases, it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing (amniocentesis/CVS) aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.

    Geoff Sher
    800-780-7437

  • Katie - February 8, 2018 reply

    Hey Dr. Sher, how much merit do you give to embryo grading? (assuming no PGS testing). I’ve heard it matters– I’ve heard it doesn’t matter and “low graded” embryos implant all the time. Is there any actual research in this to suggest a significant difference in viable pregnancies in A, B, and C graded embryos?

    On a more personal not, our clinic *says* they grade very stringent. It’s also frustrating because they seem to use a different embryo grading scale. Rather than have a number, they just use letters (A-D).

    Our embryo that took was a Day 5 BBB. We then tried a Day 6 BBB and it was unsuccessful. We have a 5-day BCC left and I’m just trying to set realistic expectations.

    I’m 30 (28 at egg retrieval); my husband was 26 at egg retrieval. Both healthy, I just don’t ovulate on my own. Used the long down reg protocol you recommend to most women for IVF. With that said, can you give me a ballpark estimate of what you think our chances of success are?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    Embryo grading is helpful but now that most opt for blastocyst transfer, it supersedes morphological grading of the cleaved embryo…so we do not do trhis any longer.

    The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.
    After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).

    One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.
    Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).

    Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.

    The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
    The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.

    It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.

    The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).
    While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.
    During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.
    However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.

    It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

    In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH

    It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.

    Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.

    Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.

    Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.
    The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases (see below) can obviate this effect.

    Severe Ovarian Hyperstimulation Syndrome (OHSS): Women with certain types of absent or dysfunctional ovulation as well as those who have polycystic ovarian syndrome (PCOS) are highly sensitive to gonadotropins and are at risk of developing OHSS. Such women are also more likely than others to produce poor quality eggs/embryos which, they are often led to believe is attributable to an intrinsic egg defect that is characteristic of their PCOS condition. This is not necessarily so. The most likely reason as to why many women with PCOS develop an excessive number of follicles and then go on to produce poor quality eggs/embryos has to do with the fact that, in an attempt to contain reduce the risk of OHSS they are often administered hCG prematurely – prior to the attainment of optimal egg maturation.

    “Prolonged Coasting”: In the early nineties, we introduced “Prolonged Coasting”, a procedure which eliminates the risk of OHSS while allowing the hCG trigger to be deferred for long enough as to allow for optimal follicle/egg maturation to take place. Coasting involves withholding gonadotropin therapy while the administration of GnRH agonist/antagonist is continued. The daily measurement of blood estradiol is continued until the concentration drops below a safe threshold level, at which time HCG is administered (regardless of the number of follicles). When appropriately implemented “coasting” results in the production of good quality eggs/embryos, in circumstances where this might otherwise not have been possible.

    Call 800-780-7437 and set up a Skype consultation with me to discuss.

    Geoff Sher

    Katie - February 9, 2018 reply

    Thanks for the reply! Just so I’m clear “morphological grading of the cleaved embryo”– is that PGS testing?

    So from what I think I hear if we have two blastocysts (Day 5)– a BBB and a BCC — you’re saying you wouldn’t put much merit in one being “better” than the other unless they were PGS tested? (i.e.- the B vs. C embryo grading is trivial?)

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 9, 2018 reply

    No I am saying that a morphologic day 2-3 microscopic grading is superseded by blastocyst grading and even more so if PGS was done.

    Geoff Sher

    Katie - February 10, 2018

    Thanks for clarifying Dr. Sher. I’m a little bummed because that wasn’t even offered when we did our egg retrieval in 2016… not sure if it’s relatively new but I’ll be sure and ask my clinic about it. Thanks again for your time.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 10, 2018

    You are welcome.

    Geoff Sher

  • Shalee - February 8, 2018 reply

    Hi Dr Sher, do you also recommend halving dose of lupron (to 5u) on CD1 of period with a lupron day 21 start? Or is it only for lupron cycles with BCP?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    Same for both!

    Geoff Sher

  • rose - February 8, 2018 reply

    Hi Doc,

    I have large fibroids, i dont want to have them surgically removed. I am currently ttc. Please i want to know if i can take fertil aid and ova boost . Or will they make the fibroids grow?.

    Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    It depends on their size and especially whether they are protruding into the uterine cavity.

    Fibroids or leiomyomas are non-malignant muscle tumors that grow in the uterine wall. They can be found in about one out of every five (1:5) women >30Y of age. Fibroids are far more prevalent in African Americans and women and less frequent in other ethnic groups (i.e. Caucasians and Asians).
    Fibroids, enlarge and/or distort uterine configuration. They can produce symptoms such as heavy, painful and prolonged menstrual periods. Other symptoms include pain with intercourse, backache, severe abdominal pain when large fibroids run out of blood supply or when superficial fibroids on a stem (pedunculated) undergo twisting (torsion). Sometimes fibroids will protrude into the uterine cavity, cause severe cramping and bleeding and so irritate the uterine lining as to compromise embryo attachment (anatomical implantation dysfunction). Women with fibroids are also at greater risk of miscarriage, premature delivery, malposition of the baby (mandating cesarean delivery) and an increased risk of bleeding after birth (post-partum hemorrhage)
    Diagnosis can be made by one or more of the following symptoms/presentations: Symptomatology, pelvic examination pelvic ultrasound, hysterosalpingogram (HSG), sonohysterogram (HSN), CT-scan or MRI..
    Fibroids are classified as:
    • Submucosal: Here the fibroid grows just under the lining of the uterine cavity (mucosa) or protrudes into the uterine cavity. They might mold into the underlying uterine muscle (sessile) or be on a stalk (pedunculated). Submucosal fibroids can change the shape of the uterine cavity, irritate the lining and prevent implantation, cause miscarriage. These lesions must be removed in their entirety prior to undertaking embryo transfer, usually hysteroscopically. (see below)
    • Subserosal: – Here the tumors grow under the outer layer (serosa) of the uterus. These fibroids will not compromise implantation, but if they are large, causing severe pain, and especially if they are multiple, pedunculated and thus at risk of undergoing torsion (twisting) the3y should be removed, usually laparoscopically. (See below).
    • Intramural: – when the fibroids develop within the muscular wall of the uterus. This is the commonest presentation. Unless they are large and multiple and do not encroach on the uterine cavity, they can be left alone Surgical removal is usually by laparoscopy or laparotomy/abdominal open incision (See below)
    The uterus is composed of a thick layer of smooth muscle (myometrium) surrounding the endometrial lining into which the embryo implants and which serves to protect and nourish a growing pregnancy. These tumors are rarely malignant (see below). Fibroid tumors, even large ones, can occur without producing any symptoms at all.
    For the most part, only those fibroids that impinge upon the uterine (endometrial) cavity (submucosal) affect fertility. Exceptions include large fibroids in the muscle wall of the uterus (intramural) that can block the openings of the fallopian tubes as they enter the uterus, and where multiple fibroids cause abnormal uterine contraction patterns.
    In some cases multiple uterine fibroids may so deprive the uterine lining (endometrium) of blood flow, that the delivery of estrogen to the endometrium is curtailed to the point that the lining cannot thicken sufficient to support a pregnancy. This can result in early 1st trimester (prior to the 13th week of pregnancy) miscarriages. Large or multiple fibroids, by curtailing the ability of the uterus to stretch in order to accommodate the spatial needs of a rapidly growing pregnancy, may precipitate 2nd trimester (beyond the 13th week) miscarriages and/or trigger the onset of premature labor.
    Sizable fibroid tumors are usually easily identified by simple vaginal examination. However, even the smallest fibroid can be identified by transvaginal ultrasound. Sometimes it is difficult to tell if the fibroid is impinging on the uterine cavity. In such cases, a hysteroscopy (where a telescope like instrument, inserted via the vagina into the uterine cavity) or a sonohysterogram where injected fluid, distends the uterine cavity allowing for examination of its inner configuration can help distinguish between intramural and submucosal fibroids. CT scan and MRI can also be used to distinguish between fibroid tumors and another condition that also involves affects the uterine muscular wall, known as adenomyosis. This condition is characterized by endometrial tissue growing deeply into the uterine wall.. Given the often-diffuse nature of adenomyosis, it can be very difficult to remove surgically. This contrasts with fibroid tumors, which are well defined and are usually easily removed.
    Surgical Treatment: The mainstay for the treatment of fibroid tumors is surgical removal (myomectomy). Small, asymptomatic fibroids that do not impinge upon the endometrial cavity will usually not require treatment other than observation and vigilance. Large fibroids and submucosal fibroids should be removed prior to starting fertility treatments such as In Vitro Fertilization (IVF) in order to decrease the chance of implantation failure, miscarriage, pregnancy complications and premature labor. Intramural and subserosal fibroids are readily removable by laparoscopic resection or via an abdominal incision. The former allows for a more rapid convalescence and is ideal for the removal of small and accessible superficial fibroid tumors, while the latter approach is preferred for treating larger and less accessible fibroids.
    Myomectomy can affect fertility in several ways. If the endometrial cavity is entered during the surgery, there is a possibility of post adhesions forming within the uterine cavity. This should always be checked by the performance of a hysteroscopy or through a \sonohysterogram, prior to beginning fertility treatment. Because myomectomy can be bloody, there is a high likelihood of post-operative abdominal adhesion formation, which could bind down or encase the ovaries, preventing the release of the eggs, or block the ends of the fallopian tubes. For this reason, it is important that myomectomies be formed only by accomplished surgeons, who are familiar with techniques to limit blood loss and prevent adhesion formation.
    Regardless of whether the laparoscopic or abdominal approach is employed, adequate closure of the uterine wall is essential in order to reduce the subsequent risk of uterine rupture during pregnancy or labor. This is one of the main arguments used against the use of laparoscopic removal of large, multiple or remotely situated fibroids. While laparoscopic myomectomy requires but a few days (at most) for post-operative convalescence, abdominal myomectomy usually requires 6-8 weeks of recovery time. When myomectomy necessitates or results in the uterine cavity being entered (purposefully or inadvertently), it should always be followed up with a “2nd look” hysteroscopy to rule out scar tissue formation, which occurs frequently in the presence of submucosal fibroids.
    Uterine polyps (and in some cases, also submucosal fibroids), can usually be removed hysteroscopically (through the vagina). This eliminates the need for abdominal surgery and greatly reduces the recovery time. Hysteroscopic surgery is only useful if the majority of the fibroid protrudes into the endometrial cavity, ensuring that the tumor defect will not be too large. This surgery is often done under laparoscopic guidance, to reduce the risk of uterine perforation. After hysteroscopic surgery it is often advisable to prescribe cyclical hormonal therapy for a few months to encourage regeneration of the endometrial lining over the area of tumor defect and healing of the uterine muscle. A 2nd look hysteroscopy should be performed a few months later in all cases, to rule out scar tissue formation even if it means delaying or deferring the initiation of definitive fertility treatment.
    Medical Treatment: The growth of fibroid tumors is estrogen-dependent. Thus when a woman enters menopause and stops making female hormones, fibroids tend to shrink in size on their own. Conditions that mimic menopause can also reduce the size of fibroid tumors. The most common of theses treatment is with a medication such as leuprolide acetate (Lupron), which shuts off the communication of the brain with the ovaries, preventing hormone production. However, this type of medication can only be taken for a limited period (usually 6 months) and once the medication is stopped the fibroids will usually regain their original size within a few months. The medication is therefore only a “temporary fix,” used mostly to decrease the size of large fibroids in order to make their ultimate surgical removal easier, or to help a woman bridge the gap until spontaneous menopause sets in. For the majority of women there is no major benefit from Lupron therapy prior to surgery.
    Embolization of Fibroid Tumors: Myomectomy always carries the small (although infrequent) risk that severe, uncontrollable intra-operative bleeding could require the performance of a hysterectomy (complete removal of the uterus) as a life saving measure. Moreover, some women are poor candidates for surgery. This is where a new procedure known as embolization comes in. Embolization is a procedure in which small particles are injected into the arteries of the uterus under radiological guidance to shut off the blood supply to the fibroids, in the hope that they will “shrink” and perhaps, even disappear.
    Embolization is relatively new to the field of gynecology and little is known about its potential effects on future fertility. We are concerned that in the process of shutting off the blood supply to the uterus, it will permanently so reduce endometrial blood flow, as to compromise embryo implantation. For this reason, I do not currently recommend this therapy for women who still wish to conceive and carry a baby in their uterus. At present, it seems best suited for symptomatic women who are finished with their childbearing or who are planning to use a gestational surrogate.
    Malignant Change in Fibroid Tumors: Fibroids rarely undergo malignant change. The reported incidence is less than 1 in 2000 cases. Fibroids usually grow very slowly (over a number of years). However, when growth occurs rapidly over a month or two, especially in older women who have large fibroids, it should raise the suspicion of this very rare but extremely serious complication.

    Geoff Sher

  • Erika - February 8, 2018 reply

    Dear Dr Sher ,
    Wanted to make sure with you , my fet protocol is to do intralipid 10 days prior transfer and than with the positive pregnant blood test and than 4 weeks later . Also 2 mg estrace twice a day , 1 aspirin 81 mg , 1 Multivitamin , 1 Medrol 4 mg nightly start 3 days before transfer until heart beat of the baby And 2cc progesterone injection.
    Do you think the Medrol could be dangerous for the baby when you take it in pregnancy?
    Maybe I should stop using Medrol after the transfer and just continue with the rest of the protocol ?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    The treatment with IL sounds reasonable. The steroid can also be used as suggested. I prefer to start tailing it down from the 8th week of pregnancy, stopping by the 10th wek.

    Geoff Sher

    Erika - February 12, 2018 reply

    Thank you , and how much mg daily do you recommend to take daily oral of dexamethasone or of Medrol please ? Also want tell you I did the Fet with 5 days embryo on 02/05 and checked today afternoon with home pregnancy test that showed positive results .
    Wanted to tell you the last time I took Medrol 4 mg was on Thursday 02/08 , if I will continue now with Medrol is it too late ? Or it’s better to continue now than stop completely?
    Thank you sooo much , for taking your time to answer me

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 12, 2018 reply

    Sounds encouraging….Good luck. I personally would resuime the steroid but for dosage of steroid you should confirm with your RE. I prescribe dexamethasone 0.75mg daily!

    Geoff Sher

  • Lauren Manning - February 8, 2018 reply

    QUESTION :Is it time to move on to donor eggs? We just had our second failed IVF cycle. My husband 43 years old has lower sperm count usually 10-15 million/ml on hcg injections. Before trying to conceive he was on testosterone replacement therapy and sperm was only 1-2 million. We thought this was our problem until now because I just turned 30 last month & have a 9 year old ( from another partner) and a two year old (which we convinced naturally while he was on hcg injections). All my preliminary testing came back normal. I have a high AMH 11.2 I’m a good responder to stimulation medications and started out on 125 of follistim and 75 menopur each day . My dose was decreased twice on follistim and ended at 75 units. They used the antagonist protocol with ganirelix. Prior to starting my cycle I was on birth control pills for 20 days and was started on metformin. My stimulation was 9.5 days and my e2 got up to 4600. 43 eggs retrieved and the lab said mixed egg quality. 29 mature eggs ICSI’ed, and 19 fertilized. 11 embryos on day 3 had between 8-11 cells but fragmenting I guess and by day 5 there was only 3 early blastocysts that were bad quality. They let them culture another day to see and ended with 1 arresting and the remaining 2 quit progressin. (I triggered a hcg and lupron for fear of OHSS) My first cycle at a different clinic & failed as well. It was the lupron agonist protocol and we had lots of eggs but ended with 10 blastocysts which 5 were Pgd normal. All failed to implant but best quality was like BB the rest were CB, CC. The current clinic now thinks our problem is poor egg quality due to lots of eggs resulting in no blastocysts. It seems their recommendation now is donor eggs? Any suggestions if we tried another cycle?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    I do not believe that you should at this point be considering egg donation. Rather the protocol used for ovarian stimulation needs in my opinion, to be thoroughly reviewed and revised.The male factor is a separate issue. Granted, high responders have a tendency to produce poorer quality eggs .In some cases it is due to an underlying condition such as polycystic ovarian syndrome (PCOS) but iin many cases it is a result of a subtomal protocol for ovarian stimulation and its implementation.

    The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.
    After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).

    One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.
    Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).

    Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.

    The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
    The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.

    It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.

    The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).
    While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.
    During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.
    However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.

    It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

    In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH

    It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.

    Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.

    Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.

    Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.
    The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases (see below) can obviate this effect.

    Severe Ovarian Hyperstimulation Syndrome (OHSS): Women with certain types of absent or dysfunctional ovulation as well as those who have polycystic ovarian syndrome (PCOS) are highly sensitive to gonadotropins and are at risk of developing OHSS. Such women are also more likely than others to produce poor quality eggs/embryos which, they are often led to believe is attributable to an intrinsic egg defect that is characteristic of their PCOS condition. This is not necessarily so. The most likely reason as to why many women with PCOS develop an excessive number of follicles and then go on to produce poor quality eggs/embryos has to do with the fact that, in an attempt to contain reduce the risk of OHSS they are often administered hCG prematurely – prior to the attainment of optimal egg maturation.

    “Prolonged Coasting”: In the early nineties, we introduced “Prolonged Coasting”, a procedure which eliminates the risk of OHSS while allowing the hCG trigger to be deferred for long enough as to allow for optimal follicle/egg maturation to take place. Coasting involves withholding gonadotropin therapy while the administration of GnRH agonist/antagonist is continued. The daily measurement of blood estradiol is continued until the concentration drops below a safe threshold level, at which time HCG is administered (regardless of the number of follicles). When appropriately implemented “coasting” results in the production of good quality eggs/embryos, in circumstances where this might otherwise not have been possible.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
    • Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
    • Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
    • IVF Outcome in Patients with Polycystic Ovarian Syndrome (PCOS): Minimizing the Risk of Severe Ovarian Hyperstimulation Syndrome (OHSS) and optimizing Egg/Embryo Quality.
    • Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
    • IVF & Polycystic Ovarian Syndrome (PCOS): Reducing the Risk of Severe Ovarian Hyperstimulation Syndrome (OHSS), Improving Egg Quality and Optimizing Outcome.
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    • The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?

    If you are interested in my advice or medical services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
    Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    Lauren Manning - February 8, 2018 reply

    I will bring up some of these points at my regroup appointment. I follow your blog and was apprehensive about the lupron trigger when suggested. Im just shocked they seem so hopeless with my own eggs when I conceived naturally with my youngest that just turned two. I wonder if without the COS I still make a sufficient egg every few months that make it possible to conceive again? Do you think the lupron trigger could have a lot to do with poor egg quality? I just don’t know if I could do donor eggs 🙁

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    Yes I do think it can be a factor. We should talk!

    Ideal egg development sets the scene for optimal egg maturation that occurs 36-42h prior to ovulation or egg retrieval. Without prior optimal egg development (ovogenesis), egg maturation will be dysfunctional and most eggs will be rendered “incompetent” and unable upon fertilization to propagate viable embryos. In IVF, optimal ovogenesis requires the selection and implementation of an individualized approach to controlled ovaria stimulation (COS). Thereupon, at the ideal time, maturational division of the egg’s chromosomes (i.e. meiosis) is “triggered” through the administration of hCG or an GnRH-agonist such as Lupron/Decapeptyl/Superfact, which induces an LH surge. The, dosage and timing of the “trigger shot” profoundly affects the efficiency of meiosis, the potential to yield “competent (euploid) mature (M2) eggs, and as such represents a rate limiting step in the IVF process .

    “Triggering meiosis with Urine-derived hCG (Pregnyl/Profasi/Novarel) versus recombinant hCG (Ovidrel): Until quite recently, the standard method used to “trigger” egg maturation was through the administration of 10,000 units of hCGu. Subsequently,, a DNA recombinant form of hCGr (Ovidrel)was introduced and marketed in 250 mcg doses. But clinical experience strongly suggests that 250 mcg of Ovidrel is most likely not equivalent in biological potency to 10,000 units of hCG. It probably only has 50%-70%of the potency of a 10,000U dose of hCGu and as such might not be sufficient to fully promote meiosis, especially in cases where the woman has numerous follicles. For this reason, I firmly believe that when hCGr is selected as the “trigger shot” the dosage should best be doubled to 500 mcg at which dosage it will probably have an equivalent effect on promoting meiosis as would 10,000 units of hCGu. Failure to “trigger” with 10,000U hCGu or 500mcg hCGr, will in my opinion increase the likelihood of disorderly meiosis, “incompetent (aneuploid) eggs” and the risk of follicles not yielding eggs at egg retrieval (“empty follicles”). Having said this, it is my personal opinion that it is unnecessary to supplant hCGu with hCGr since the latter is considerably more expensive and is probably no more biopotent than the latter.

    Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the dosage of hCG administered as a trigger in the hope that by doing so the risk of critical OHSS developing will be lowered. It is my opinion, that such an approach is not optimal because a low dose of hCG (e.g., 5000 units, hCGu or 25omcg hCGr) is likely inadequate to optimize the efficiency of meiosis particularly when it comes to cases such as this where there are numerous follicles. It has been suggested that the preferential use of an “agonist (Lupron/Decapeptyl/Superfact) trigger” in women at risk of developing severe ovarian hyperstimulation syndrome could potentially reduce the risk of the condition becoming critical and thereby placing the woman at risk of developing life-endangering complications. It is with this in mind that many RE’s prefer to trigger meiosis by way of an “agonist trigger” rather than through the use of hCG. The agonist promptly causes the woman’s pituitary gland to expunge a large amount of LH over a short period of time and it is this LH “surge” that triggers meiosis. The problem with using this approach, in my opinion, is that it is hard to predict how much LH will be released in by the pituitary gland. For this reason, I personally prefer to use hCGu for the trigger, even in cases of ovarian hyperstimulation hyperstimulated, with one important proviso…that being that is she underwent “prolonged coasting” in order to reduce the risk of critical OHSS, prior to the 10,000 unit hCGu “ trigger”.

    The timing of the “trigger shot “to initiate meiosis: This should coincide with the majority of ovarian follicles being >15 mm in mean diameter with several follicles having reached 18-22 mm. Follicles of larger than 22 mm will usually harbor overdeveloped eggs which in turn will usually fail to produce good quality eggs. Conversely, follicles less than 15 mm will usually harbor underdeveloped eggs that are more likely to be aneuploid and incompetent following the “trigger”.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
    • Why did my IVF Fail
    • Staggered IVF
    • IVF: Selecting the Best Quality Embryos to Transfer
    • Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
    • PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • Avoiding High Order Multiple Pregnancies (Triplets or Greater) with IVF
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in my advice or medical services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
    Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoff Sher

  • Karenlynn - February 8, 2018 reply

    Hello, I am 40 (41 in April) I have had 5 failed IVF from oct 2016- Jan 2018. Three were patch-FSH-antagonist and two were patch-clomid with gonal F. I had a range of eggs retrieved. I averaged about 10 eggs retrieved. Three times I had an early blast on day 5 that was transferred. Once I had a day 6 blast frozen for a FET. Once I had nothing to transfer or freeze. All my transfers failed. My FSH was 10 when last tested. AMH has varied. It was 2.75 in May 2017 but 1.33 in Sept. my LH rises early causing me to ovulate early. I am sensitive to BCP and am unable to take them. Therefore, my estrogen priming has to be the patch. The last two cycles are the only ones I know LH numbers for. It rises early causing the nurse to call in a panic for me to start ganarelix. They have said it isn’t common to see that and they always start ganarelix on cd 6/7. After this most recent failure I requested an appt. my dr feels I cannot get pregnant with my eggs. when I requested to try again with a new protocol, he stated that they only use one of three protocols with DOR poor responders, and will only consider changing me to patch, gonal f, and ganarelix when needed (removing the clomid) Or do donor eggs. I am very frustrated. I believe that the early LH rise is damaging my eggs. His feeling is that LH doesn’t effect eggs, only the lining by starting to release progesterone. He is inflexible on altering my protocol. I am stuck. Do you have any advice on how to alter my protocol for getting better quality eggs? I forgot to mention, my first dr had me take dhea. I asked this dr to check testosterone because my hair was falling out in clumps and I had cystic acne. My testosterone was raised. But he said not high. (Free testosterone was .6) i stopped the dhea. I am looking for a way to change my protocol. I hope to meet with my dr again and ask about a new protocol again. Any advice is welcome!! This 6th try is my last. Thank you so much.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    I respectfully disagree with your RE. In my opinion, excessive LH increases ovarian testosterone and when too much of the latter is produced it compromises egg quality. Premature luteinization can damage eggs/embryos.

    In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
    Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

    While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

    Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
    • A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
    • Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
    • Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
    • Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
    • Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
    • Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
    • PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • Traveling for IVF from Out of State/Country–
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
    • IVF Egg Donation: A Comprehensive Overview

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • vivienne - February 7, 2018 reply

    Thank you so much Dr Sher on your expertise and advice! I wanted to ask do you recommend PGS or NGS when it comes to embryo screening? Also I have two frozen embryos from a previous IVF cycle.. since I am older do you recommend thawing those two and having them tested also alongside the ones I will hopefully get in another fresh cycle? or is is to much risk to the embyros?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    NGS is the form of PGS we do.

    Although pregnancies are reported from secondary thawing and testing, I think it is too traumatic on the embryos and do not recommend this to my patients.

    Geoff Sher

  • Sarah - February 7, 2018 reply

    I have had 2 6 week miscarriages. The first- no heartbeat, a d and c, subsequent ashermans ,one surgery to fix scarring and one surgery to fix recurrent scarring (stent was used). We were told we could try again a couple months later as all the scarring had been removed and the uterine cavity was clear with 8 mm endometrium returning monthly. I miscarried again (2nd miscarriage at 6 weeks) and luckily had no horrible sequelae. A corpus luteum was visualized but no pregnancy on ultra sound in the uterus. All labs have been normal with the exception of amh 5.3 (I’m 34), a tsh 3.1 (t3, t4 normal). Immune related blood work came back negative but NK cells not tested. We have decided to do ivf. I have an in office hysteroscopy scheduled during the stim to make sure the uterine cavity is in good shape after the second miscarriAge. I’m not sure if I should request immune marker biopsies/ era/ bcl6. We have chosen to do pgs but not icsi as there is no male factor. I have 32 day cycles and ovulate on day 21 but have recently been ovulating on day 17-18 after initiating ubiquinol for 2 months. I want to have 2 children but not twins/triplets so I think at least freezing embryos may be beneficial to grow our family in the future. Is there anything that is concerning or something you would suggest for us to do/ test before proceeding with ivf.

    Sarah - February 7, 2018 reply

    Sorry forgot to add we get pregnant easily. I have not been on fertility medication but it has been suggested to try letrozole. I did not want to waste time with it and was worried given two early miscarriages it may have been chromosomal. I think it’s unusual though that I have regular cycles regular ovulation and very normal fsh and lh levels and still cannot keep a pregnancy.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    It sounds like a possible implantation dysfunction.

    When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
    Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
    • Early pregnancy loss (first trimester)
    • Late pregnancy loss (after the first trimester)
    • Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
    • Early pregnancy losses usually occur sporadically (are not repetitive).
    In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
    Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
    There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
    Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
    Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
    1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
    • Inadequate thickening of the uterine lining
    • Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
    • Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
    • Deficient blood flow to the uterine lining (thin uterine lining).
    • Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
    • Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
    2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

    IMMUNOLOGIC IMPLANTATION DYSFUNCTION
    Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
    But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
    Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
    Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

    Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
    However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
    DIAGNOSING THE CAUSE OF RPL
    In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
    Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

    • Karyotyping (chromosome analysis) both prospective parents
    • Assessment of the karyotype of products of conception derived from previous miscarriage specimens
    • Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
    • Hysterosalpingogram (dye X-ray test)
    • Hysteroscopic evaluation of the uterine cavity
    • Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
    • Immunologic testing to include:
    a) Antiphospholipid antibody (APA) panel
    b) Antinuclear antibody (ANA) panel
    c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
    d) Reproductive immunophenotype
    e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
    f) Alloimmune testing of both the male and female partners
    TREATMENT OF RPL
    Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
    Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
    Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

    Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
    Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
    The Use of IVF in the Treatment of RPL
    In the following circumstances, IVF is the preferred option:
    1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
    2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
    The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
    Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
    There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
    The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers Should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 7, 2018 reply

    When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
    Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
    • Early pregnancy loss (first trimester)
    • Late pregnancy loss (after the first trimester)
    • Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
    • Early pregnancy losses usually occur sporadically (are not repetitive).
    In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
    Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
    There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
    Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
    Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
    1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
    • Inadequate thickening of the uterine lining
    • Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
    • Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
    • Deficient blood flow to the uterine lining (thin uterine lining).
    • Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
    • Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
    2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

    IMMUNOLOGIC IMPLANTATION DYSFUNCTION
    Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
    But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
    Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
    Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

    Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
    However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
    DIAGNOSING THE CAUSE OF RPL
    In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
    Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

    • Karyotyping (chromosome analysis) both prospective parents
    • Assessment of the karyotype of products of conception derived from previous miscarriage specimens
    • Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
    • Hysterosalpingogram (dye X-ray test)
    • Hysteroscopic evaluation of the uterine cavity
    • Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
    • Immunologic testing to include:
    a) Antiphospholipid antibody (APA) panel
    b) Antinuclear antibody (ANA) panel
    c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
    d) Reproductive immunophenotype
    e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
    f) Alloimmune testing of both the male and female partners
    TREATMENT OF RPL
    Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
    Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
    Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

    Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
    Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
    The Use of IVF in the Treatment of RPL
    In the following circumstances, IVF is the preferred option:
    1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
    2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
    The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
    Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
    There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
    The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers Should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    Sarah - February 7, 2018 reply

    Thank you so much for your detailed response. Our karyotypes are normal but unfortunately the results of the testing from the first fetus was inconclusive. So we didn’t get any answers from the d and c.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    Copy!

    Geoff Sher

  • recklace - February 7, 2018 reply

    Hi Dr. Sher,

    I’ve posted previously regarding my previous miscarriages and ATA testing. My question is, (and forgive me if it has been answered before): do the Sher Institute clinics across the country use the same protocols that you do in your own practice? I have my first appointment on Monday and feel strongly that ATA/NK may be my issue. I’m just wanting to ensure that the clinic I visit is knowledgable of your work and opinions in this ATA/NK realm. Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 7, 2018 reply

    Unfortunately…not necessarily!

    Geoff Sher

  • Priya - February 7, 2018 reply

    Hello Dr. Sher,
    I am 36 years old, with AMH levels around 0.8 and diminished ovarian reserves. I was diagnosed with endometriosis about 8 yrs back and my left ovary had to be removed along with the tube. I have tried ivf several times, with no success.
    Recently, I went to get a second opinion from another fertility specialist. US was done during the visit at which time the doctor saw endometrium growth on my right ovary of about 3cm. The doctor is recommending that Sclerotherapy be performed to drain the cyst.
    My concern is that I have not heard about the procedure and don’t know how effective it is. Also, I don’t know how long the cyst has been there and should it be monitored for a few months (to see if it goes away on it own) or go ahead with the procedure?
    Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    The precise mechanism by which ovarian endometrioma causes infertility is unknown. In women with ovarian endometriomas, infertility is potentially associated with a decreased oocyte retrieval rate, reduced oocyte quality and reduced embryo quality. I personally believe that it is local irritation caused by the cystic space occupying lesion within the ovary that irritates surrounding connective tissue increasing ovarian testosterone production which in turn permeates ovarian follicles resulting in compromised follicle and egg development in the affected ovary (ies)

    Traditional surgical treatment of endometriomas involves gaining access to the ovary (ies) through an abdominal incision, or via laparoscopy, for drainage of the cyst contents and subsequent removal or ablation of the cyst wall. Unfortunately, in many cases, normal ovarian tissue is inadvertently removed along with the cyst wall, which may decrease the number of available oocytes for subsequent fertility treatment. A large percentage of such women have advanced stage disease and have had multiple previous surgeries. In the presence of pelvic adhesions, visualization of anatomic structures may be inadequate, leading to a higher incidence of cyst recurrence. This may further diminish the potential response to ovarian stimulation with gonadotropins. Additionally, women with advanced endometriosis are more likely to develop pelvic adhesions as well as an increased risk of surgical complications.

    About 15 years ago I introduced sclerotherapy to treat women who had endometriomas and were preparing for IVF treatment. Sclerotherapy is an effective non-surgical treatment for endometriosis of the ovary. Ovarian sclerotherapy involves ultrasound-guided aspiration of endometrioma content followed by the introduction into the cyst cavity of a sclerosing agent such as 5% tetracycline hydrochloride (my preference), 95% ethanol or methotrexate either under local anesthesia or with the patient receiving conscious sedation. The sclerosing agent destroys the endometrium lining the inside of the endometrioma and prevents cyst recurrence. Sclerotherapy is much less invasive than laparoscopic surgery and takes approximately 20–30 min to perform. Unlike other treatment options, it will not damage healthy surrounding ovarian tissue and is thus also less likely to reduce ovarian reserve. Risks of sclerotherapy treatment are uncommon but they include infection, pain (due to leaking of the sclerosing agent into the pelvic cavity, internal bleeding, and recurrence in about 10% of cases. To prevent this, I infuse about 250cc of sterile normal saline solution into the pelvic cavity before performing sclerotherapy so that any leakage of the sclerosing agent into the pelvis will be diluted. Thereupon at the conclusion of the procedure, I aspirate the solution from the pelvis and with it , most of the potentially irritating sclerosing agent. In more than 70% of cases, treatment will result in disappearance of the lesion within 6 to 8 weeks. In 20% of cases, residual seroma develops within 6 weeks. Simple transvaginal drainage of the residual cyst will in most cases lead to permanent dissolution.
    Ovarian sclerotherapy can be performed under local anesthesia or under general anesthesia. It has the advantage of being an ambulatory office-based procedure at a low cost, with a low incidence of significant post-procedural pain or complications, and the avoidance of the need for surgery.
    Sclerotherapy is a safe and effective alternative to surgery. It is a definitive treatment, even for recurrent ovarian endometriomas, in properly selected patients planning to undergo IVF. Since the procedure is associated with a small, but realistic possibility of adhesion formation, it should only be used in cases where IVF is the only fertility treatment appropriate for a patient. Women who intend to try and conceive through natural conception or intrauterine insemination will be better off undergoing standard laparotomy or laparoscopy to treat their endometriomas.

    Geoff Sher

    Priya - February 8, 2018 reply

    Thanks you Dr. Sher
    Is there any possibility of the cyst disappearing on its own? Or once it is there it will have to taken care of using either one of the procedure (traditional procedure or Sclerotherapy)?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    It should disappear completely after sclerotherapy.

    Geoff Sher

  • SC - February 7, 2018 reply

    I have had five unsuccessful rounds of Clomid and timed intercourse due to unexplained infertility. This cycle with clomid I did an ultrasound and have one 21 follicle and was prescribed and HCG injection. When is the optimal time for intercourse. If this is unsuccessful, do you recommend FSH injectibles?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 7, 2018 reply

    In my opinion, it is necessary to fully reevaluate you for a cause relating to your infertility before going any further.

    For about 10% of all infertile couples, the cause of the infertility cannot be readily determined using conventional diagnostic methods. Such cases are often referred to as “unexplained infertility.” The truth however is that in most such cases, the diagnosis of “unexplained infertility is in fact “presumptive because a more in-depth evaluation would have revealed a cause. This having been said, people diagnosed with so called “unexplained infertility” fall into two broad groups: a)those couples who don’t have any biological problems interfering with pregnancy and, b) those who do but the reason cannot be found due to insufficient medical information or technology. It is in this latter group that improved testing techniques have made infertility easier to diagnose and treat.
    In order to make even a presumptive diagnosis of “unexplained infertility” the answers to the following questions must be in the affirmative.
     Is the woman ovulating normally?
     Is the couple having intercourse regularly in the periovulatory phase of the cycle?
     Are the fallopian tubes normal and open?
     Can endometriosis be excluded?
     Does the male partner have normal semen parameters (most specifically with regard to sperm count and motility?
     Is the post coital (Huhner) test (periovulatory examination of cervical mucous, done 6-18 hours after intercourse) normal?
    The definitive diagnosis of “unexplained infertility” has a lot to do with the thoroughness of the health care provider in excluding all possible causes. The fewer tests performed, the more likely a presumptive diagnosis
    For Example:
     Abnormalities of the fallopian tubes (adhesions or developmental defects) of the finger-like “petals” at their outer ends of the tubes that help sweep eggs inside (i.e. fimbriae). can prevent eggs from being collected and transported to the awaiting sperm
     Chromosomal abnormalities of eggs or embryos: Eggs must be euploid (contain the right number of chromosomes) to be successfully fertilized and embryos must also be euploid in order to implant successfully in the uterine lining. Until recently there was no reliable method for determining whether eggs and embryos were euploid. The recent introduction of genetic tests such as comparative genomic hybridization (CGH) now allows for identification of all chromosomes in the egg and embryo. As such CGH represents an important addition to the “infertility” diagnostic armamentarium.
     Luteinized Unruptured Follicle (LUF)Syndrome: Here, the eggs can become trapped in the follicle and not be released (trapped ovulation) In such cases routine tests done to detect ovulation ((temperature charting, Urine LH testing, Blood progesterone levels) may be normal resulting in false interpretation that ovulation is actually occurring.
     Ovulation (hormonal) Dysfunction: Abnormalities in ovarian hormone production in the preovulatory phase of the cycle (follicular phase defect) and/or in the postovulatory phase (luteal phase defect) can negatively affect preparation of the uterine lining (endometrium), thus thwarting normal implantation.
     Immunologic implantation dysfunction (IID): Sometimes, the woman’s or the man’s own immune system can attack sperm cells, killing them or causing them to become immobilized. Also, immunologic dysfunction involving the uterine lining can cause the implanting embryo to be rejected so early that the woman does not even recognize that she in fact had conceived.
     Cervical infection; Ureaplasma urealyticum infection of the cervical glands can prevent sperm from migrating through the cervix and uterus to reach the egg(s) in the fallopian tube(s). Such infection will usually not be detectable through routine examination and/or cervical culturing methods.
     Mild or Moderate Endometriosis: Endometriosis is in 100% of cases associated with the production of “pelvic toxins” that reduce the fertilization potential of otherwise normal eggs by a factor of 3-5. In addition, about 1/3 of woman with endometriosis (regardless of its severity) have immunologic implantation dysfunction (IID). Furthermore mild and often even moderately severe endometriosis can only be accurately diagnosed by direct visualization of the lesions through laparoscopy or laparotomy and, the detection of IID requires highly sophisticated tests that can only be adequately performed by a handful of Reproductive Immunology Reference Laboratories in the United States. Finally, a condition called nonpigmented endometriosis, in which the endometrium may be growing inside the pelvic cavity with many of the same deleterious effects as overt endometriosis, cannot be detected even by direct vision (at laparoscopy/laparotomy). The fertility of these patients may be every bit as compromised as if they had detectable endometriosis.
     Psychological Factors: The entire reproductive process is governed by the brain. Thus it should come as no surprise that stress and negativity can interfere with hormonal balance and decrease the ability to conceive.
     Mild Male Factor
     Antisperm antibodies in the man or woman.
    Management:
    Successful management of “Unexplained Infertility” requires that a very individualized approach be taken. Wherever possible the underlying cause should first be identified. Problems that involve ovulation dysfunction (hormonal imbalance) require ovulation induction with oral or injectible fertility drugs. Cervical mucous hostility due to infection with ureaplasma (which is transferred back and forth sexually to both partners) requires specific and concurrent antibiotic therapy. In other cases involving younger women (under 39 years) where there is a problem with sperm migration via the cervix and uterus to the fallopian tube(s) intrauterine insemination (IUI) with or without ovulation induction, is indicated. When these treatments fail, in cases, women over the age of 39 years, in women with IID, in men or women who harbor antisperm antibodies in significant concentrations and in cases associated with tubal abnormalities, in vitro fertilization (IVF) is needed. All cases of intractable, moderate or severe male infertility call for injecting sperm directly into the egg to achieve forced fertilization (intracytoplasmic sperm injection-ICSI).
    It is an indisputable fact that most causes of infertility can be diagnosed and it is a great pity that the diagnosis of “unexplained infertility” is often used as an excuse for not having performed a full and detailed evaluation of the problem. Couples should not simply accept a diagnosis of “unexplained infertility” at face value since treatment is most likely to be successful when the specific cause of the problem can be fully identified

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.”
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
    • Staggered IVF
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • A Thin Uterine Lining: Vaginal Viagra is Often the Answer (update)
    • Cervical Ureaplasma Urealyticum Infection: How can it Affect IUI/IVF Outcome?
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Basic Infertility Work-Up
    • Defining and Addressing an Abnormal Luteal Phase
    • Endometriosis and Infertily
    • Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus
    • Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
    • Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!IUI-Reflecting upon its Use and Misuse: Time for a Serious “Reality Check
    • Micro-IVF: Often Preferable to Ovarian Stimulation with or Without IUI
    • Induction of Ovulation With Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
    • Clomiphene Induction of Ovulation: Its Use and Misuse!

    If you are interested in my advice or medical services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
    Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • JT - February 7, 2018 reply

    I listened to your webinar in Youtube, where you talk about empty follicles (which actually have an egg inside, but are so abnormal that don’t come out). How common is it that some follicles are “empty” in egg retrieval? For example if 20 follicles are empty from a total of 40 follicles, is this a normal result or an indication that something went really wrong? Could it explain why the other 20 were also bad quality?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 7, 2018 reply

    In my opinion, most follicles of >15mm will should produce eggs at retrieval. There are many factors that can affect egg “competency”. Age, genetics ovarian reserve and the protocol used for ovarian stimulation are important one’s. However, when there is a low yield in a woman with many ovarian follicles, it is in my experience relatively often due to the protocol used for ovarian stimulation and/or its implementation. This includes the type/timing and dosage of the trigger.

    Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.
    This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”
    Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
    Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
    Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
    Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
    The developing eggs of women who have increased LH activity (older women, women with diminished ovarian reserve, and those with PCOS) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
    The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
    There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • Staggered IVF
    • Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
    • Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
    • Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
    • Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
    • IVF: Selecting the Best Quality Embryos to Transfer
    • Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
    • PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • Premature Luteinization
    . How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Joelle - February 7, 2018 reply

    Dear Dr. Sher ,
    On 01/29 right before I started my progesterone injections the lining was 9.9 and than yesterday on 02/05 on the day of my fet went down to 8.5 .
    Do you think It Reduce my chances to succeed? And why do you think it’s reduce ,is it normal after progesterone to happened?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 7, 2018 reply

    When it comes to outcome, it is the thickness of the lining prior to hCG trigger or progesterone administration that is relevant.

    Geoff Sher

  • Mr. V - February 7, 2018 reply

    Hello, Dr. Sher.

    I am interested in whether mini-IVF/IVF may be a viable option for us. Here is our situation:
    Me (36) – no health problems, sperm analysis 3% morphology, otherwise normal.
    My wife (35) – no health problems, diagnosed with DOR yesterday (02/05/18).
    Follicles seen on ultrasound (01/29​, CD3​): one 11mm​ (left)​ and one 17mm​ (right)
    AFC: 1 (left)
    AMH: 0.25

    She had two viable pregnancies at age 20, both terminated. She is 4’11″ and 115lbs.
    We have had insemination by natural intercourse every other day (or more frequently) for the past 6 months. She has had periodic anovulatory cycles but regular periods for an unknown amount of time.

    Her OB prescribed 50mg of Clomid CD5-CD9, her last two cycles. Her BBT showed now thermal shift indicating ovulation either cycle.

    1. How many women fit all of the following criteria:
    -were treated at 35 years of age
    -used their own eggs
    -have diminished ovarian reserve (at 0.25 AMH or less)
    -had previous viable pregnancies
    -have no other health problems and normal partner
    -safely underwent IVF at max level (3 embryos per attempt?)

    2. How many of the above women subsequently had live births?

    3. What is the data set you are using to provide these statistics? (Total in the history of the world, total in the United States last year, number of women you’ve personally treated, etc.)

    We are trying to remain optimistic, but we need hard facts. Any insight would be greatly appreciated as we decide how best to move forward.

    Thank you,
    Mr. V

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 7, 2018 reply

    Mini-IVF is a procedure that involves ovarian stimulation using low dosage medications (often oral drugs like clomiphene and letrozole) under the premise that it is a “safer” and less expensive than conventional gonadotropin stimulation regimes while yielding comparable success. …….. Nothing could be further from the truth. The fact is that success rates per fresh mini-IVF cycle ranges between 10% and 12%s (i.e., about one third of that which reported national average for conventional IVF performed on women under 39y of age) ). And when it comes to older women and those with diminished ovarian reserve (DOR), the success rate with mini-IVF is usually much lower still.
    There can be little doubt that aside from a woman’s age, the method used for ovarian stimulation represents the most important determinant of egg/embryo quality and thus of IVF outcome. There is no single stimulation protocol that is suitable for all IVF patients. It must be individualized…. especially when it comes to women who, regardless of their age have diminished ovarian reserve (DOR) and for women over >40y of age. The reason for this is that in such cases, the pituitary gland often over-produces LH which in turn causes the ovarian stroma/theca (connective tissue) to thicken (stromal hyperplasia/hyperthecosis) and over-produce male hormones (mainly testosterone). This in turn adversely influences egg and follicle growth, resulting in poor egg/embryo “competency” and compromised IVF outcome.
    So let us examine the validity of the claims made in support of mini-IVF:

    1. Milder stimulation using oral agents such as clomiphene, letrozole (alone or in combination with low dosage gonadotropins (Follistim/Gonal-F/Puregon/Menopur) reduces stress on the ovaries and overall risk associated with IVF. This argument while perhaps having some merit when applied to mini-IVF conducted in younger women who also have normal ovarian reserve, does not hold water for older women and those with DOR who (s stated above) often already have excessive LH-induced ovarian testosterone production. Furthermore, addition of clomiphene and letrozole by further increasing pituitary LH (and thus ovarian testosterone) only serves to add “fuel to the fire” in such cases and Menopur which contains both LH and hCG ( that both have similar effects on ovarian testosterone production), if administered in large amounts (>75U per day) can also do harm in my opionion.

    2. Women with DOR will respond better to “milder stimulation” and egg quality will so be enhanced. This assertion borders on the ridiculous. It is like saying that applying less force to a heavier object will increase the likelihood of moving it”. That is simply not how FSH stimulates follicle development. You see…the cell membranes that envelop the follicular granulosa cells that line the inside surface of ovarian follicles have on their surfaces, a finite number of FSH receptors. FSH molecules attach to these receptors and mediate intracellular events that lead to granulosa cell proliferation with production of estradiol and the concurrent development of the egg (oogenesis) that is attached to the inner wall of the follicle. Once all the FSH receptors on the cell membranes are saturated, any residual FSH is discarded. This is why, when it comes to older women and women with DOR whose granulose cell membranes harbor fewer FSH receptors, it is virtually impossible to overstimulate them. Excessive FSH will simply be rejected and discarded.

    3. Use of fewer drugs translates into lower cost. This would be true, were it not for the fact that success rates with mini-IVF across the board are much lower than with conventional ovarian stimulation. More important is the fact that the cost of IVF should be expressed in terms of “the cost of having a baby” rather than “cost per cycle of treatment”. When this is taken into account the cost associated with mini-IVF will b be significantly higher than conventional IVF. Then there is the additional emotional cost associated with a much higher IVF failure rate with mini-IVF.
    4. Mini-IVF is less technology driven, less stressful and easier to execute. This assertion is in my opinion also without merit. Aside from reduced cost of medications, the same monitoring and laboratory procedures are needed for mini-IVF as with conventional treatment.

    What is the best approach? When it comes to older women and those with DOR, it is in my opinion preferable to use a long pituitary down-regulation protocol with conversion from an I.M agonist (e.g. Lupron or Buserelin) to an antagonist such as Cetrotide/Orgalutron or Ganirelix (the agonist/antagonist conversion protocol) augmented with human growth hormone (HGH) and/or estrogen priming and combing this “embryo banking” over several cycles. In such cases preimplantation genetic screening (PGS) can be incorporated to help select the most “competent” embryos for transfer.

    What about younger women with normal or increased ovarian reserve? If mini-IVF has any role at all, it could be in young women who have normal or increased ovarian reserve. I do not o not advocate aggressively stimulating the ovaries of younger women who have normal or increased ovarian reserve (as assessed by basal FSH, AMH and estradiol) simply to try and access more eggs. In fact, such an approach is neither safe nor acceptable. In such women it is often wiser to use lower dosage stimulation to try and prevent the development of severe ovarian hyperstimulation syndrome (OHSS) which aside from putting the woman at severe risk of (sometimes) life-endangering complications, can also compromise egg/embryo quality. However, it is my fervent belief that in such women, the preferred approach to ovarian stimulation is through the use of low dosage FSHr-dominant gonadotropins (rather than oral agents such as clomiphene or letrozole and/or high dosage Menopur). This approach is referred to as Micro-IVF.

    Here is the protocol I advise for women, <40Y who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • SriRam - February 7, 2018 reply

    Good evening. I did my ivf transfer exactly 4 weeks back. It was 5 day embryo transfer. My first, second and third HCG beta were 199, 357 and 1253. I started bleeding today sometime back – its bright red with thread like clots with light cramping but no abdomen pain. Is anything i need to worry about and take action or is it common to have?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 7, 2018 reply

    Vaginal bleeding occurs in about 25% of all pregnancies. When it happens, it almost invariably raises the concern of pregnancy loss (miscarriage). Bleeding can also be a sign of a tubal (ectopic) pregnancy, and in cases where the distended Fallopian tube ruptures it can precipitate a life-threatening crises. However, a small amount of painless vaginal bleeding can also be the result of normal embryo implantation (i.e. implantation bleeding) or it can result a local erosion of the vagina or cervix and/or trauma during intercourse.
    Notwithstanding, in virtually all cases the occurrence of early pregnancy vaginal bleeding congers concerns or even alarm regarding the possibility of miscarriage. And when this happens to women who conceived following infertility treatment, the alarm often turns into panic. However, the truth is that in most such cases the bleeding soon stops and the pregnancy proceeds unabated to the birth of a healthy baby. However, because some do progress and end in miscarriage, and in most cases, only time will tell how things will ultimately turn out, we use the term “threatened miscarriage” to describe such early bleeding. The term “inevitable miscarriage” is used once symptoms and signs confirm a miscarriage is in progress. The term “complete miscarriage” is used if all products of conception are passed, leaving the uterus “empty”. An “incomplete miscarriage” refers to cases where some products remain retained in the uterus.

    Geoff Sher

    SriRam - February 7, 2018 reply

    Thanks Doctor for the brief explanation. So do i need to wait and see before coming to conclusion? Obviously i was panic since i didnt bleed post transfer. Today is my 4th week day 1 post transfer and was worried due to bleeding.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 7, 2018 reply

    Copy and good luck!

    Geoff Sher

  • Sanaa - February 6, 2018 reply

    I am a case of multiple abdominal sugeries. Not a single laproscopy but all wide open cuts. First was done when i was 14 to take out Appendix. In the same month i had another surgery to remove congential Jacsonian Membrane around my large intestine filled with fluid. At the age of 28 years i was trying for pregnancy but wasnt successful. Got myself checked and was told i have the same membrance appeared back and filled with fluid. They removed it. The surgeon did manage to rightly position my tubes and ovaries which were burried under adhesions and scar tissues. After 9 years of trying naturally with combination of IVF i get to know that my tubes are filled with fluid and are hampering embryo transplant. The same became base of my latest surgery where 1 tube was cut and other was tied as that was not in a position to be cut( burried under adhesions).My recovery was slow and i developed anxiety and gut issues. As a routine ultrasound today i was told that my tied tube is all filled with fluid again and is pretty swollen. I am devastated. I cant afford any surgery whether laproscopy(due to tons of adhesions its impossible) or wide cut open. I have pain in my lower pelvic area on one side(not constantly). For the past 4 months my periods are extremly heavy for 1st 3 days and then just spotting for 2 days and cycle ends. I get really heavy blood clots too during first 3 days. Never missed my periods date though. Is this all due to post tubal ligation?. I am too tensed and worried. Have developed stomach acidity issues due to all this. Can i take some oral drugs for this swollen tube which is tied and is presumably not leaking into uterus(is this due to post tubal ligation)?. I did all this to attempt IVF but cant as this new development has happened. I am 37 at the moment.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    Hi Sanaa, Obviously the hydrosalpinx involves the ligated tube. Thus since that tube is blocked as it leaves the uterus, the fluid from the hydrosalpinx cannot drain back into the uterus. Thus it is of no consequence and will not impede your ability to conceive with IVF.

    Good luck!

    Geoff Sher

  • Veena Bhatia - February 6, 2018 reply

    We went through 2nd egg retrieval using donor sperm per the doctors recommendations per our results and failed outcome in the previous ivf round.

    1st Egg Retrival
    16 eggs received
    Total : 4 embroyos with 1 normal after PGS (grade 5AA normal male)
    Miscarried at 7 weeks

    2nd egg retrieval (using donor sperm)
    16 eggs retrieved
    day 1 : 14 fertilized ICSI
    day 3 , 11 hatched
    day 5 : 7 embroyos for pgs .
    PGS results : 3 mosiac, 4 abnormal

    What advice would you give us by these results? Doctor is ok to transfer the mosiac embroyos but there are risks involved as of genetic diseases and higher risk of miscarriage.
    Should we transfer the mosiac embroyos as this is our only transferable embroyo?
    Is this an egg or sperm issue?

    I can send my detailed PGS report as well

    Please advise.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    I would recommend you do the transfer.

    Geoff Sher

    Veena Bhatia - February 6, 2018 reply

    Transfer how many, we have 3 usable? Would you recommend a genetic test for me just to see if I carry a disease such as Down syndrome? I did not get these kind of results from my last pgs using my husbands sperm.
    Please Advise

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    No Veena, you cannot be tested to see if your embryo is affected by trisomy 21 (Down syndrome). That requires embryo biopsy and PGS.

    I would transfer no more than 2 embryos.

    Good luck!

    Geoff Sher

  • Angela - February 6, 2018 reply

    Hi Dr. Sher, I was wondering if going in a hot tub or steam room is harmful in any way before starting an IVF cycle (ovarian stimulation) and/or during an IVF cycle?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    I do not think so as long as you drink lots of water and keep well hydrated.

    Geoff Sher

  • Katie - February 6, 2018 reply

    Dr. Sher, I’m on birth control while waiting for our next FET attempt. I’m on a low dose (Alesse) pill, one that I’ve been on before. But I’m a week in now and starting spotting last night, now much moreso.

    This SAME thing happened in prep for our last (unsuccessful) FET. I spotted/bled for about 2-3 weeks on the pill.

    What could this be? Or is it just my body adjusting to the pill/hormones?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    It is likely your body adjusting and in my opinion is not any cause for alarm.

    Geoff Sher

  • Valerie - February 6, 2018 reply

    Dr. Sher, currently starting my 3rd IVF protocol. First two failed win nothing to freeze. My RE has me on Microdose Lupron 10 units once a day, but following the long lupron calendar so I won’t start stims for another week. I can’t find anything that suggests the use of Microdose Lupron in this manner. I’ve voiced my concern to them and their response is I’m on a long lupron protocol with Microdose Lupron to prevent too much suppression, but I don’t feel confident in this approach.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    Hi Valerie,

    Frankly I agree with your RE to use this dosage of Lupron in a long protocol arrangement, provided the dosage and type of gonadotropin is optimal and the timing and dosage of the hCG trigger is ideal.

    Here is the protocol I advise for women who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • JT - February 6, 2018 reply

    Hi,

    I had 0,2 mg of gonapeptyl as trigger shot in our IVF, because I have PCOS, plenty of follicles and a risk of OHSS. I don’t think gonapeptyl is an hCG trigger, but GnRH agonist .. What’s your opinion using that as a trigger shot? I had very poor result in IVF.. 🙁

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the dosage of hCG administered as a trigger in the hope that by doing so the risk of critical OHSS developing will be lowered. It is my opinion, that such an approach is not optimal because a low dose of hCG (e.g., 5000 units, hCGu or 250mcg hCGr) is likely inadequate to optimize the efficiency of meiosis particularly when it comes to cases such as this where there are numerous follicles. It has been suggested that the preferential use of an “agonist (Lupron/Gonapeptyl/Buserelin/Aminopeptidyl etc.) trigger” in women at risk of developing severe ovarian hyperstimulation syndrome could potentially reduce the risk of the condition becoming critical and thereby placing the woman at risk of developing life-endangering complications. It is with this in mind that many RE’s prefer to trigger meiosis by way of an “agonist (Lupron) trigger rather than through the use of hCG. The agonist promptly causes the woman’s pituitary gland to expunge a large amount of LH over a short period of time and it is this LH “surge” that triggers meiosis. The problem with using this approach, in my opinion, is that it is hard to predict how much LH will be released in by the pituitary gland. For this reason, I personally prefer to use hCG for the trigger, even in cases of ovarian hyperstimulation hyperstimulated, with one important proviso…that being that is she underwent “prolonged coasting” in order to reduce the risk of critical OHSS, prior to the 10,000 unit hCGu “ trigger”.

    Geoff Sher

  • Blossom U. - February 6, 2018 reply

    Dear Dr Sher, I ‘m 46, in the process of preparing for FET. 1st attempt failed, and was cancelled by RE; Endo lining was 8mm after 5-7 days of estradiol, but US on the day before scheduled transfer after progesterone therapy showed the lining had degenerated. RE thinks inadequate estrogen support. What do you think is responsible for this and what is your advise or what protocol will you use for next cycle to maximize/improve outcome? Do you recommend herbals?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    There are different protocols used by different doctors.This is something you need to discuss with your RE.

    I do not believe Herbals will help.

    Geoff Sher

  • Ann - February 6, 2018 reply

    I just finished off my 1st (failed) IVF. I am 37 and have 2 previous children and have gone through 5 years of unexplained infertility. I was on 450 of Follistim daily after a cold start, ending with 4 days of cetrotide with the stims. I had 10 follicles >18mm and was triggered with hcg 10000. There were only 3 were retrieved, rest were empty, and only one fertilized. RE has never checked AMH. FSH and LH have always been normal. She thinks we need to go straight to donor egg after this one shot. Would there be a better protocol?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *The 4th edition of my book,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Michela - February 5, 2018 reply

    Hi Dr. Sher,

    How long can 250mcg of Ovidrel stay in your system? I’m seeing anywhere from 10-14 days. I would prefer to do an HPT prior to my bloodtest, but I know the risk of a false positive. I know the HPT is discouraged, but clinically speaking, how many days post trigger would I be without great risk of a false positive?

    I appreciate your time and expertise! Thank you so much.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 6, 2018 reply

    About 12-14 days. You can do a HPT after 16 days.

    God luck!

    Geoff Sher

  • Samantha - February 5, 2018 reply

    Hi Dr. Sher:

    I’m 37 with no children and have been trying to conceive for a year. I went to a specialist and was told I have premature DOR, with no genetic relation. The plan of action was go with IUI, with 75iu after 3 days blood work showed: Progesterone 0.89 E2 <25.0 Endo: 4.88
    I was then upped the dose of Menopur to 150 iu with results 3 days later of: Progesterone: 1.05 E2 28.7 Endo 7.60 followed by 3 more days of Menopur at 150 iu with results of Progesterone 0.76 E2 74.0 LF 11 Endo 5.93 and the last dose of Menopur 150 iu for an additional 3 more days showing results of: Progesterone: 0.52 E2 168.7 LF 14 Endo 8.21 before my final Ovidrel 250 trigger shot 2 days later. I produced one follicle and was wondering if you would have recommended this course of action and what you recommend I do moving forward if IVF is not an option because of cost? I'm feeling hopeless and trying my best to stay positive. Thank you Dr. Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2018 reply

    Samantha,

    I can understand and empathize with you regarding IVF, cost-related issues, but alas, IUI is in my opinion not the right way to go,. given your DOR. You simply do not have the latitude of time. You need IVF.

    Here is the protocol I advise for women, <40Y who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Ayesha - February 5, 2018 reply

    Hi Dr,
    I posted yesterday about the spotting i was facing. I consulted my gynaecologist and she gave duphaston 10mg a week before and now she is asking me to take transamine 500 mg twice a day. Is it safe to have these both at the same time ?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2018 reply

    Respectfully, I have no idea why you would be prescribed an antifibrinolytic agent such as Transamine. I have never heard of it being used in this setting.

    Geoff Sher

    Geoff Sher

  • Lena - February 5, 2018 reply

    Hi Dr Sher
    We had 5 blastocysts and all tested PGS abnormal chromosomes. We have none for FET. Doctor is telling us they were so bad that she ethically won’t try IVF again with us. She said problem is with both of us. We are in our late 20s with egg/sperm problems. We did ICSI and were able to fertilize 12 with 5 blastocysts. Doctor said even a donor egg wouldn’t work. Doctor said, both my husband and I are not genetically made to have biological children. Is there any hope for us?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2018 reply

    Very respectfully Lena, if that is what you were told, I cannot agree. At age 20y, you should not respond with uniformly abnormal embryos. This sounds very much like an ovarian stimulation issue, in my opinion.

    Here is the protocol I advise for women, <40Y who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Stefanie - February 5, 2018 reply

    Hi, Dr. Scher. I have had six IVF transfers, two resulting in BO, two chemicals, two negatives. Just this month I conceived naturally after my second excision lap that also resulted in Chemical. I am under the care of a reproductive immunologist, and we seem to have gotten my immune system under control. If my immune system is not causing these recent chemicals, do you think I have an egg quality issue? Will I continue to have chemicals or will I eventually find an egg that’ll stick/ With this many early losses and never reaching a heart beat, does this sound like a chromosone issue? What would be your advise for me?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2018 reply

    When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
    Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
    • Early pregnancy loss (first trimester)
    • Late pregnancy loss (after the first trimester)
    • Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
    • Early pregnancy losses usually occur sporadically (are not repetitive).
    In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
    Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
    There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
    Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
    Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
    1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
    • Inadequate thickening of the uterine lining
    • Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
    • Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
    • Deficient blood flow to the uterine lining (thin uterine lining).
    • Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
    • Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
    2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

    IMMUNOLOGIC IMPLANTATION DYSFUNCTION
    Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
    But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
    Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
    Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

    Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
    However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
    DIAGNOSING THE CAUSE OF RPL
    In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
    Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

    • Karyotyping (chromosome analysis) both prospective parents
    • Assessment of the karyotype of products of conception derived from previous miscarriage specimens
    • Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
    • Hysterosalpingogram (dye X-ray test)
    • Hysteroscopic evaluation of the uterine cavity
    • Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
    • Immunologic testing to include:
    a) Antiphospholipid antibody (APA) panel
    b) Antinuclear antibody (ANA) panel
    c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
    d) Reproductive immunophenotype
    e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
    f) Alloimmune testing of both the male and female partners
    TREATMENT OF RPL
    Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
    Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
    Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

    Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
    Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
    The Use of IVF in the Treatment of RPL
    In the following circumstances, IVF is the preferred option:
    1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
    2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
    The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
    Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
    There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
    The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers Should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Rholand - February 4, 2018 reply

    What are your thoughts on luteal-phase stimulation? I’m doing FET so the timing of my uterine lining doesn’t matter anyway, so perhaps this can save time (by getting started quickly) and even allow for back-to-back stim in the follicular phase?

    Articles for reference:
    https://www.ncbi.nlm.nih.gov/pubmed/25154677
    http://journals.sagepub.com/doi/pdf/10.1177/0300060516669898
    https://www.sciencedirect.com/science/article/pii/S1028455915002910

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2018 reply

    Here is the protocol I advise for women, <40Y who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Megan - February 4, 2018 reply

    Good Morning Doctor! I need some hope! I had my hcg levels tested 13 dpo (3 days before my period) and they came back at 70. Two days later (exactly 48 hrs later) they were at 112. I heard in early pregnancy they can take 72 hrs to double so I wasn’t extremely concerned. I went back for more blood draw 3 days later and they had only gone from 112 to 136. This was very upsetting. Two days later they went from 136 to 216. I go back tomorrow for more blood draw. My doctor said to hold out hope. I had an ectopic pregnancy a year ago so this is my fear again. I have no cramping or bleeding yet. I am only 5 Weeks 3 days today. My question is do I have hope? Is there anything that could cause my levels to barely go up over 72 hrs but still have a healthy pregnancy? This was my first round of Clomid 100mg. Thank you for hearing my case. Megan

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2018 reply

    This is troubling. It could be a chemical prfegnancy, an ectopic or a slowly implanting pregnancy. Only tgime will tell.

    Needless to say, if you start experiencing pain or light headedness go straight to the ER.

    Good luck!

    Geoff Sher

  • Ayesha - February 4, 2018 reply

    Dear Dr,
    First i’d like to thank you for having this website and always replying. I consulted you before as well. I had brighht red spotting one week ago but that was due to intercourse , im assuming. Now im in my 5th week and 2 days and experiencing some light pink to brownish red spotting since yesterday with one to two hour breaks and it only comes out when i go to pee and wipe a tissue. I have no cramping or whatsoever. I did beta hcg last week and the results were 176.6 and then after 2 days they were 455.5. Im extremely confused and worried . Kindly help.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    Without cramping and heavy bleeding, I do not think this is significant.

    Keep me in the loop please.

    Good luck!

    Geoff Sher

  • M - February 4, 2018 reply

    Dear Dr.
    I am 35 yrs my husband is 40 yrs, he has 100% teratozoospermia, I am normal just i have common migriane.
    Ihad 1 abortion after spontenous pregnancy in 4 wks. We had ICSI and fresh ET on D5, last Dec failed after 11 D. Then I had my menses(it was heavy 8 D bleeding) we started preparation for FTI in Jan 20 , us showed functional overian cyst 4cm whuch regressed in subsequent us to 2.5cm , Iwas started on climen on D 3 of period 2mg bid for 10 D , in us the thickness of endometrium was 5.5mm so dose increased to tid plan for 4 days but Ihad vaginal bleeding 2 days after increasing the dose it less than period bleeding but its significant.
    Ihave called the clinic and they told me to stop climen and come next month when I have another period.
    I am warried why Ihave this bleeding & when could i start next FET cycle? Should they use same protocol with me or no.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    With such a thin lining, you are very likely having break through bleeding. In my opinion, your protocol needs to be reviewed and consideration should be given to changing it and adding vaginal Viagra.

    It was as far back as 1989, when I first published a study that examined the correlation between the thickness of a woman’s uterine lining (the endometrium), and the subsequent successful implantation of embryos in IVF patients. This study revealed that when the uterine lining measured <8mm in thickness by the day of the “hCG trigger” (in fresh IVF cycles), or at the time of initiating progesterone therapy (in embryo recipient cycles, e.g. frozen embryo transfers-FET, egg donation-IVF etc.) , pregnancy and birth rates were substantially improved. Currently, it is my opinion, that an ideal estrogen-promoted endometrial lining should ideally measure at least 9mm in thickness and that an endometrial lining measuring 8-9mm is “intermediate”. An estrogenic lining of <8mm is in most cases unlikely to yield a viable pregnancy.

    A “poor” uterine lining is usually the result of the innermost layer of endometrium (the basal or germinal endometrium from which endometrium grows) ) not being able to respond to estrogen by propagating an outer, “functional” layer thick enough to support optimal embryo implantation and development of a healthy placenta (placentation). The “functional” layer ultimately comprises 2/3 of the full endometrial thickness and is the layer that sheds with menstruation in the event that no pregnancy occurs.

    The main causes of a “poor” uterine lining are:

    1. Damage to the basal endometrium as a result of:
    a. Inflammation of the endometrium (endometritis) most commonly resulting from infected products left over following abortion, miscarriage or birth
    b. Surgical trauma due to traumatic uterine scraping, (i.e. due to an over-aggressive D & C)
    2. Insensitivity of the basal endometrium to estrogen due to:
    a. Prolonged , over-use/misuse of clomiphene citrate
    b. Prenatal exposure to diethylstilbestrol (DES). This is a drug that was given to pregnant women in the 1960’s to help prevent miscarriage
    3. Over-exposure of the uterine lining to ovarian male hormones (mainly testosterone): Older women, women with diminished ovarian reserve (poor responders) and women with polycystic ovarian syndrome -PCOS tend to have raised LH biological activity.. This causes the connective tissue in the ovary (stroma/theca) to overproduce testosterone. The effect can be further exaggerated when certain methods for ovarian stimulation such as agonist (Lupron/Buserelin) “flare” protocols and high dosages of menotropins such as Menopur are used in such cases.
    4. Reduced blood flow to the basal endometrium:
    Examples include;
    a. Multiple uterine fibroids - especially when these are present under the endometrium (submucosal)
    b. Uterine adenomyosis (excessive, abnormal invasion of the uterine muscle by endometrial glands).

    “The Viagra Connection”

    Eighteen years ago years ago, after reporting on the benefit of vaginal Sildenafil (Viagra) for to women who had implantation dysfunction due to thin endometrial linings I was proud to announce the birth of the world’s first “Viagra baby.” Since the introduction of this form of treatment, thousands of women with thin uterine linings have been reported treated and many have gone on to have babies after repeated prior IVF failure.

    For those of you who aren’t familiar with the use of Viagra in IVF, allow me to provide some context. It was in the 90’s that Sildenafil (brand named Viagra) started gaining popularity as a treatment for erectile dysfunction. The mechanism by which it acted was through increasing penile blood flow through increasing nitric oxide activity. This prompted me to investigate whether Viagra administered vaginally, might similarly improve uterine blood flow and in the process cause more estrogen to be delivered to the basal endometrium and thereby increase endometrial thickening. We found that when Viagra was administered vaginally it did just that! However oral administration was without any significant benefit in this regard. We enlisted the services of a compound pharmacy to produce vaginal Viagra suppositories. Initially, four (4) women with chronic histories of poor endometrial development and failure to conceive following several advanced fertility treatments were evaluated for a period of 4-6 weeks and then underwent IVF with concomitant Viagra therapy. Viagra suppositories were administered four times daily for 8-11 days and were discontinued 5-7 days prior to embryo transfer in all cases.

    Our findings clearly demonstrated that vaginal Viagra produced a rapid and profound improvement in uterine blood flow and that was followed by enhanced endometrial development in all four cases. Three (3) of the four women subsequently conceived. I expanded the trial in 2002 and became the first to report on the administration of vaginal Viagra to 105 women with repeated IVF failure due to persistently thin endometrial linings. All of the women had experienced at least two (2) prior IVF failures attributed to intractably thin uterine linings. About 70% of these women responded to treatment with Viagra suppositories with a marked improvement in endometrial thickness. Forty five percent (45%) achieved live births following a single cycle of IVF treatment with Viagra The miscarriage rate was 9%. None of the women who had failed to show an improvement in endometrial thickness following Viagra treatment achieved viable pregnancies.

    Following vaginal administration, Viagra is rapidly absorbed and quickly reaches the uterine blood system in high concentrations. Thereupon it dilutes out as it is absorbed into the systemic circulation. This probably explains why treatment is virtually devoid of systemic side effects

    It is important to recognize that Viagra will NOT be effective in improving endometrial thickness in all cases. In fact, about 30%-40% of women treated fail to show any improvement. This is because in certain cases of thin uterine linings, the basal endometrium will have been permanently damaged and left unresponsive to estrogen. This happens in cases of severe endometrial damage due mainly to post-pregnancy endometritis (inflammation), chronic granulomatous inflammation due to uterine tuberculosis (hardly ever seen in the United States) and following extensive surgical injury to the basal endometrium (as sometimes occurs following over-zealous D&C’s).

    Combining vaginal Viagra Therapy with oral Terbutaline;
    In my practice I sometimes recommend combining Viagra administration with 5mg of oral terbutaline. The Viagra relaxes the muscle walls of uterine spiral arteries that feed the basal (germinal) layer of the endometrium while Terbutaline, relaxes the uterine muscle through which these spiral arteries pass. The combination of these two medications interacts synergistically to maximally enhance blood flow through the uterus, thereby improving estrogen delivery to the endometrial lining. The only drawback in using Terbutaline is that some women experience agitation, tremors and palpitations. In such cases the terbutaline should be discontinued. Terbutaline should also not be used women who have cardiac disease or in those who have an irregular heartbeat.
    About 75% of women with thin uterine linings see a positive response to treatment within 2-3 days. The ones that do not respond well to this treatment are those who have severely damaged inner (basal/germinal) endometrial linings, such that no improvement in uterine blood flow can coax an improved response. Such cases are most commonly the result of prior pregnancy-related endometrial inflammation (endometritis) that sometimes occurs post abortally or following infected vaginal and/or cesarean delivery.
    Viagra therapy has proven to be a god send to thousands of woman who because of a thin uterine lining would otherwise never have been able to successfully complete the journey “from infertility to family”.

    To be effective, Viagra must be administered vaginally. It is NOT effective when taken orally. We prescribe 20mg vaginal suppositories to be inserted four times per day. Treatment is commenced soon after menstruation ceases and is continued until the day of the “hCG trigger.” While ideally the treatment should be sustained throughout the first half of the cycle, most women will respond within 48-72 hours. For this reason, Viagra can be used to “rescue” a poor lining after the cycle has already started, provided that there is enough time remaining prior to ovulation, egg retrieval or progesterone administration.

    Good luck!

    Geoff Sher

    PH: 800-780-7437

    M - February 5, 2018 reply

    Thank you v.much Dr

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 5, 2018 reply

    You are welcome.

    Geoff Sher

    M - March 19, 2018 reply

    Dear Dr Sher
    Thank you v.much for your great effort helping us.
    I have sent you my queries around 7 weeks back.
    Last week another event occured i discovered ihave ectopic pregnancy , it was spontenous pregnancy , endometrial thickness this time was 1cm, and large overian cyst 5*7 mm (previously diagnosed as functional cyst ,it was regressing ) , laproscopic salpengectomy and cystectomy was done for me. My questions now : why this happened?
    What is my chance to have spontenous pregnancy? Should i wait for that to happen? Or should i go directly for FET as i have 4 freezed?
    Should i take contraception for few months?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 20, 2018 reply

    It is in most cases usually due a tubal factor (usually previous salpingitis which in first world countries often goes unrecognized at the initial stage). Such tubal damage is almost always bilateral (involving both tubes) , even if the tube is open. I recommend you go for FET to reduce the chance of another ectopic.

    Since the lining of the fallopian tube does not represent an optimal site for healthy implantation, a large percentage of pregnancies that gain early attachment to its inner lining will usually be absorbed before the woman even knows that she is pregnant. This is often referred to as a tubal abortion.

    The advent of advanced sonographic and hormonal monitoring technology now makes it possible to detect an ectopic pregnancy much earlier than previously, …usually well in advance of it rupturing. A decade or two ago, the diagnosis of an ectopic pregnancy, ruptured or not, was an indication for immediate laparotomy to avoid the risk of catastrophic hemorrhagic shock. This often resulted in the affected fallopian tube having to be completely removed, sometimes along with the adjacent ovary. In the late 1980’s, early conservative surgical intervention by laparoscopy began replacing laparotomy (a wide incision made in the abdominal wall) for the treatment of ectopic pregnancy, often allowing the affected fallopian tube to be preserved and shortening the period of post-surgical convalescence. In the 90’s, early detection combined with the advent of medical management with methotrexate (MTX) has all but eliminated the need for surgical intervention in the majority of patients. If administered early enough, MTX will allow spontaneous resorbtion of the pregnancy and a dramatic reduction in the incidence of catastrophic bleeding. This was especially true in ectopic pregnancies arising from In Vitro Fertilization, where the early progress of pregnancy is usually carefully monitored with hormone levels and ultrasound.

    Classically women with an ectopic pregnancy present with the following symptoms:

    • Missed menstrual period: Although some patients will have spotting or other abnormal bleeding. The pregnancy test will be positive in such cases.

    • Vaginal bleeding. When a pregnancy inadvertently implants in the fallopian tube the lining of the uterus undergoes profound hormonal changes associated with pregnancy (primarily associated with the hormone progesterone). When the embryo dies, the lining of the uterus separates. Initially, vaginal bleeding is dark and usually is quite scanty, even less than with a normal menstrual period. In some cases, of ectopic pregnancy will bleeding is more severe, similar to that experienced in association with a miscarriage. This sometimes leads to an ectopic pregnancy initially being misdiagnosed as a miscarriage and is the reason to examine the material that is passed vaginally, for evidence of products of conception.

    • Pain. In the early stages this is typically cramp-like in nature, located on one or another side of the lower abdomen. It is caused by spasm of the muscular wall of the fallopian tube(s). When a tubal pregnancy ruptures the woman will usually experience an abrupt onset of severe abdominal followed by light headedness, coldness and clamminess and will often collapse due to shock. Her pulse will become rapid and thready and her blood pressure will drop. Miscarriage. Sometimes the woman will experience pain in the right shoulder. The reason for this is that that blood which tracts along the side of the abdominal cavity finds its way to the area immediately below the diaphragm, above the liver (on the patient’s right side), irritates the endings of the phrenic nerve, which supplies that part of the diaphragm. This results in the referral of the pain to the neck and the right shoulder. The clinical picture is often so typical that making the diagnosis usually presents no difficulty at all. However, with less typical presentations the most important conditions to differentiate from an ectopic pregnancy are: a ruptured ovarian cyst, appendicitis, acute pelvic inflammatory disease (PID), or an inevitable

    • Vaginal bleeding. When a pregnancy inadvertently implants in the fallopian tube the lining of the uterus undergoes profound hormonal changes associated with pregnancy (primarily associated with the hormone progesterone). When the embryo dies, the lining of the uterus separates. Initially, vaginal bleeding is dark and usually is quite scanty, even less than with a normal menstrual period. In some cases, of ectopic pregnancy will bleeding is more severe, similar to that experienced in association with a miscarriage. This sometimes leads to ectopic pregnancy initially being misdiagnosis as a miscarriage and is the reason that we often want to examine the material that is passed vaginally, for evidence of products of conception.

    The easiest and most common method of diagnosing an ectopic pregnancy is by tracking the rate of rise in the blood levels of hCG. With a normal intrauterine pregnancy, these usually double every two days throughout the first few weeks. While a slow rate of increase in blood hCG usually suggests an impending miscarriage, it might also point to an ectopic pregnancy. Thus the hCG blood levels should be followed serially until a clear pattern emerges.

    A vaginal ultrasound examination usually will clinch the diagnosis by showing the ectopic pregnancy within a fallopian tube and if the tube has already ruptured or internal bleeding has occurred, ultrasound examination will inevitably detect the presence of free fluid into the abdominal cavity.

    If there has been a significant amount of intra-abdominal bleeding, irritation of the peritoneal membrane will cause the abdominal wall to become hard tense and, depending on the amount of internal bleeding abdominal distention will be evident. Palpation of the abdominal wall will evoke significant pain and when a vaginal examination is done, movement of the cervix will produce excruciating pain, especially on the side of the affected fallopian tube.

    Surgical Treatment: In questionable situations laparoscopy is usually performed for diagnostic purposes. If an ectopic pregnancy is in fact detected, a small longitudinal incision over the tubal pregnancy will allow its removal, without necessitating removal of the tube. (linear salpingectomy). Bleeding points on the fallopian tube can usually be accessed directly and appropriately ligated (tied) via the laparoscope. Sometimes the damage to the fallopian tube has been so extensive that the entire tube will require removal.

    On occasions where very severe intra-abdominal bleeding heralds a potential catastrophe, a laparotomy (an incision made to open the abdominal cavity) is performed to stop the bleeding post haste. In such cases a blood transfusion is usually required and may be life saving.

    Medical Treatment: The introduction of Methotrexate (MTX) therapy for the treatment of ectopic pregnancy has profoundly reduced the need for surgery in most patients. MTX is a chemotherapeutic that kills rapidly dividing cells, such as those present in the “root system” of the conceptus. Extremely low doses of MTX are used to treat ectopic pregnancy. Accordingly the side effects that are often associated with such chemotherapy used for the treatment of other conditions are seldom seen. It is important to confirm that the ectopic pregnancy has not yet ruptured prior to administering MTX.

    MTX is given by intramuscular injection. Prior to its administration, blood is drawn to get a baseline blood hCG level. After the injection of MTX the patient is allowed to return home with strict instructions that she should always have someone with her and never be alone in the ensuing week. The concern is that were the patient to be on her own and an intraabdominal bleed were to occur, she might not readily be able to access someone who could get her to the hospital immediately. Instructions are also given to look for early signs that might point towards severe intra-abdominal bleeding such as the sudden onset of severe pain, light-headedness or fainting.

    The patient returns to the doctor’s office four days later to check the blood hCG level. Three days later (7 days after MTX), the level is checked again. By this time the hCG level should have dropped at least 15% from the value on day 4. If not, a second MTX injection is given and the blood levels are tested twice weekly until hCG level is undetectable. Once this occurs, vaginal bleeding will usually ensue within a week or two.

    It is important to note, especially in cases where more than one embryo or blastocyst has been transferred to the uterine cavity or fallopian tube (as with Tubal embryo transfer –TET/ZIFT), that implantation may occur in two sites simultaneously (i.e. in the fallopian tube as well as inside the uterine cavity). This is referred to as a heterotopic pregnancy. It is therefore important that before administering MTX, which will cause the death and absorption of any early pregnancy, that the physician makes certain that he/she is not dealing with a heterotopic pregnancy. In such cases, surgery is required to treat the tubal ectopic, while every precaution is taken to protect the pregnancy growing within the uterine cavity.

    When an ectopic pregnancy occurs following infertility treatment, there is the added advantage that the physician will be on the lookout for the earliest possible signs of trouble. The performance of a vaginal ultrasound within two weeks of a positive blood pregnancy (HCG) test following IVF allows for early detection of the unruptured pregnancy and timely intervention with MTX and/or laparoscopy.

    Good luck and G-d bless!

    Geoff Sher

  • Dya - February 4, 2018 reply

    Thanks dr.Sher i am so grateful for all of your explanation, but now i am doubtful shall i proceed to another ivf trial? Does having blunted empty follicle once mean my ovaries producing such a follicle repeatedly each cycle?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    Not necessarily Dya. I would not give up.

    Geoff Sher

  • Leah - February 4, 2018 reply

    Hi Dr. Sher,
    I recently had a day 5 blast FET and I am in the TWW. About 76 hours after the transfer, I woke up to an orgasm (not normal, perhaps progesterone?).

    My clinic restricted intercourse, but did not specify orgasms. I’m terribly concerned that the uterine contractions from the orgasm compromised implantation. Are these uterine contractions significant enough to affect implantation at 76 hours post transfer?

    Thanks for this forum!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    It would not do harm! Do not worry!

    Geoff Sher

  • Miranda - February 4, 2018 reply

    Dr. Sher,

    Would a Clomid (3-7 cycle days)+Menopur (7, 9 11) cause a false positive urine LH surge? My clinic will see me on days 3, 7 and 12. Would it be possible to detect a reliable ( and not premature) surge before day 12 in order to not miss my ovulation window, if I have not been given the trigger shot thus far?
    In other words, does the fact that Menopur has LH result in a false positive OPK (urine test) if I am not ovulating?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    I doubt the LH will go high enough to produce a “false surge”.

    Geoff Sher

  • Juliet - February 3, 2018 reply

    Hi Dr,
    First thank you for dedicating time answering our questions graciously.

    I had a tranfer on Jan 12th of 1 5-day blastocyst, grade A, PGD positive
    Hcg numbers were Ok at the beginning but the last ones are scaring me :
    10dp5dt 15dpo 81
    12dp5dt 17dpo 200
    14dp5dt 19dpo 395
    18dp5dt 23dpo 929
    I must say that I have been on the lower side of normal ranges in previous pregnancies, with the sae pattern of rise, but never out of bounds like here.

    My RE scheduled an U/S in 2 weeks (at 7w 1/2), but I am very scared that this pregnancy is going wrong. The initial numbers were OK but from 19 t4 to 18dp5dt, they rose very slowly, less than doubling in 3 days, and the level for 23dpo is lower than the lower bound, and the levels were multiplied only by 10 in a week, all indicating that this pregnancy is going to end badly…

    What are your odds here ? Can ectopic be ruled out ? Will this end in miscarriage ? Should I ask for an U/S earlier, for example next week ?

    Or am I just to stressed here an the situation is not so bad as it looks ?

    Many thanks in advance for your insight.

    Juliet

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    I am optimistic that all is well, based upon the information you provided. Please keep me in the loop!

    Geoff Sher

  • Janee - February 3, 2018 reply

    Hi Dr. Sher,
    I am currently on my first FET protocal and I just completed 39 days of low estrogen birth control pills due to having mild pcos and to have a better chance of timing ovulation for upcoming FET. I was advised to stop taking the birth control pills on day 6 of my lupron shots and was told to notify my Nursing team when I stated cycle day 1 of my menstral. The concern that I have is the fact that exactly one week after starting the birth control pills i started having whats called breakthrough bleeding that was more than spotting but not quite a full flow which was continuous through my last birth control pill on Tuesday Jan. 30th. And on Thursday Feb. 1st I started to have cramping and a few medium sized blood clots through Friday Feb. 2nd. How do i differentiate the start of my actual menstral from the breakthrough bleeding and determine my cycle day 1?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    Hi Janee,

    PCOS is commonly associated with dysfunctional ovulation. Respectfully, I would do a hormone replacement FET and not do this in a natural cycle.

    Geoff Sher

  • Katie - February 3, 2018 reply

    Hey Dr. Sher, we have another roadblock in our FET transfer. My RE found a small polyp in today’s saline sonogram and even though it’s likely nothing to worry about, is recommending surgery to remove. I think I’m on board since I know I’d be agonizing over “what if” had we transferred again and not been successful, but I’m curious to hear your procedure for handling polyps. Do you recommend removing anything that can be seen (regardless of size?)– or do you have a size cut off?

    Thanks in advance.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    The polyp needs to be removed before the FEDT cycle. It can be doner with dilatation and evacuation or laparoscopically.

    Good luck!

    Geoff Sher

  • Pavani - February 3, 2018 reply

    I am 36yrs old, is it possible to increase the egg quality and endometrium thickness, if I take medicine, will it work?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    Yes it is possible in most cases.

    Call 800-780–7437 and set up a Skype consultation with me to discuss.

    Geoff Sher

  • Dya - February 3, 2018 reply

    Hi dr. Sher, i an 36 yr, i did 2 ivf cycle on 2016 first one on march and there was 3 eggs but hcg after 2 weeks was 25 then dropped down to 2 and then misscarriage, then on August 2016 did second ivf with 2 eggs but failed and hcg was 0.1. On December 2017 did 3rd cycle again hcg was 0.2, for these 3 cycles all my hormones including prolactine, LH,FSH, Estradiole, Proges and were normal before egg pickup, then in January my physician suggest to do another trial but without ovarian stimulation and there was one follicle during pick up , but without egg, unfortunately. My question is that does i have chance to concieve or i have blighted follicle and there is no hope? Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 3, 2018 reply

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Pavani - February 3, 2018 reply

    My Embryo transfer was done on 16/01/2018 and blood test was on 31/01/2018 but hcg level is 2.26mlu, I took the same test on 02/02/2018 and hcg level is .25mlu, so doctor told me that embryo’s were not implanted and I will get periods by 14/02/2018, she told me to visit her on that day..but I am feeling heavy stomach and pain/crams in stomach(@vigina) as well. I am not understanding anything about pregnancy. Can you please help me to understand this situation( urine test is also negative)

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 3, 2018 reply

    Regretfully, it does not sound as if you are pregnant. I agree with your doctor tyat a period is likely iminent.

    Geoff Sher

    Pavani - February 3, 2018 reply

    I am 36yrs old, is it possible to increase the egg quality and endometrium thickness, if I take medicine, will it work?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    Here is the protocol I advise for women, <40Y who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Sally - February 3, 2018 reply

    Hi Dr Sher, you asked me to keep you informed on my progress with the partially compacting morula on day 5.

    My HCG on 14dpo was 5, p4 was 35 but I did have a period that lasted 4 days.

    On 16dpo it was 15.7, p4 was 11 (I stopped progesterone pressaries on 14dpo but resumed again on 16dpo).

    On 18dpo it was 19 and progesterone was 28. At this point my RE told me it was not viable and to stop progesterone.

    On 22dpo my HCG was 62 and progesterone was 1.82.

    My RE doesn’t think this is a viable pregnancy on the basis that my progesterone has plummeted and if it was a viable pregnancy HCG would be causing my body to produce progesterone.

    I’ve typed these figures into a beta calculator and its doubling within 58 hours. Google says so long as its within 72 hours that’s ok?

    What do you think? Do you agree think this is not viable? Was my RE right to get me to stop progesterone on 18dpo wheh HCG was 19??

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 3, 2018 reply

    This does not look very promising , I am afraid. However repeat the hCG in about 4 days time and then if it is still rising, do an US in about 2 weeks.

    Good luck!

    Geoff Sher

    Sally - February 3, 2018 reply

    Thanks Dr Sher. Would you advise your patients to continue with their progesterone if they were in the same position as me?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 3, 2018 reply

    Yes!

    Geoff Sher

  • Mindy - February 2, 2018 reply

    Just completed first IVF with no success. Age 40.
    Here are the details: 16 eggs retrieved, 15 fertilized, 6 made it to blast. All 6 PGS tested abnormal.
    Protocol: Spontaneous Antagonist Lupron Trigger

    For my second IVF cycle in March, they will either do Antagonist Lupron Trigger with BCP or Spontaneous Antagonist Lupron Trigger protocol.

    Any thoughts on how I could improve egg quality? Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 3, 2018 reply

    Hi Mindy,

    Age plays a critical role in determining egg/embryo competency. That aside, it is the protocol used for ovarian stimulation that nust be carefully constructed and individualized.

    Here is the protocol I advise for women with adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    Mindy - February 3, 2018 reply

    Thank you Dr. Sher.
    Can you tell me why my doctor would recommend the Antagonist Lurpon Trigger protocol instead of yours? If what you are recommending will help create more normal eggs for women age 40, why aren’t more doctors advising patients to do the same. Thanks.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    I am not suggesting that my proposed protocol is the only way to go, but my approach is based upon > 3o years of personal experience.

    Geoff Sher

  • vivienne - February 1, 2018 reply

    Hello Dr Sher and thank you in advance for sharing your expertise!
    I am 40 soon to be 41, and my partner is 43 and we are in the UK. I have elevated TSH level and take thyroxine for this, but no thyroid antibodies and no other issues( other than immunes)
    We have undergone 2 IVF cycles. Both flare protocol, maximum doses, producing 11 eggs, 7 fertilised. The first cycle( no immune treatment) I had a split transfer, day 3 and 2 x BC blasts day 5 and one BC blast to freeze. HCG was 2 , BFN
    2nd cycle, immune treatment with humira & IVIG to treat elevated cytokines and NK cells. Same protocol, 11 eggs, 7 fertilise and 4 to day 5. 2 x AB blasts & 1 BC blast transferred. 1 BC frozen. BFN
    We did not have PGS testing though I asked for it on the 2nd cycle.
    We are now having further tests, Sperm DNA fragmentation, DQ Alpha Match, karyotyping and LIT, a biopsy etc. Would you suggest doing PGS on my next cycle? I am meeting with the clinics embryologist this week as the clinic are not pro PGS but they will do it if you ask for it.
    Would you also recommend to freeze the embryos ( maybe batch) and do a FET instead of a fresh where my body can be in an optimal condition for transfer or is fresh always preferable?
    and last question, do you think it is worth doing PGS on the frozen embryos we have or will the thawing/ refreezing cause undue stress on the embryos?

    Thank you so much in advance!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 2, 2018 reply

    In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
    Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
    Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
    I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
    • Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
    • Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
    • Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
    • Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
    • Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
    • PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
    • Implications of “Empty Follicle Syndrome and “Premature Luteinization”
    • Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my book,”In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

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