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Measuring and interpreting Blood hCG to Assess Pregnancy Viability Following ART Treatments

by Dr. Geoffrey Sher on December 23, 2015

I know of no medical announcement associated with the degree of emotional anticipation and anguish as that associated with a pending diagnosis/confirmation of pregnancy following infertility treatment. In fact, hardly a day goes by where I am not confronted by a patient anxiously seeking interpretation of a pregnancy test result.

Testing urine or blood for the presence of human chorionic gonadotropin (hCG) is the most effective and reliable way to confirm conception. The former, is far less expensive than the latter and is the most common method used. It is also more convenient because it can be performed in the convenience of the home setting. However, urine hCG testing for pregnancy is not nearly as reliable or as sensitive e as is blood hCG testing. Blood testing can detect implantation several days earlier than can a urine test. Modern pregnancy urine test kits can detect hCG about 16-18 days following ovulation (or 2-3 days after having missed a menstrual period), while blood tests can detect hCG, 12-13 days post-ovulation (i.e. even prior to menstruation).

The ability to detect hCG in the blood as early as possible and thereupon to track its increase, is particularly valuable in women undergoing controlled ovarian stimulation (COS) with or without intrauterine insemination (IUI) or after IVF. The earlier hCG can be detected in the blood and its concentration measured, the sooner levels can be tracked serially over time and so provide valuable information about the effectiveness of implantation, and the potential viability of the developing conceptus.

There are a few important points that should be considered when it comes to measuring interpreting blood hCG levels. These include the following:

  • All modern day blood (and urine) hCG tests are highly specific in that they measure exclusively for hCG. There is in fact no cross-reactivity with other hormones such as estrogen, progesterone or LH.
  • Post conception hCG levels, measured 10 days post ovulation or egg retrieval can vary widely (ranging from 5mIU/ml to above 400mIU/ml. The level will double every 48–72 hours up to the 6th week of gestation whereupon the doubling rate starts to slow down to about 96 hours. An hCG level of 13,000-290, 0000 mIU/ml is reached by the end of the 1st trimester (12 weeks) whereupon it slowly declines to approximately 26,000– 300,000 mIU/ml by full term. Below are the average hCG levels during the first trimester:
    • 3 weeks LMP: 5 – 50 mIU/ml
    • 4 weeks LMP: 5 – 426 mIU/ml
    • 5 weeks LMP: 18 – 7,340 mIU/ml
    • 6 weeks LMP: 1,080 – 56,500 mIU/ml
    • 7 – 8 weeks LMP: 7, 650 – 229,000 mIU/ml
    • 9 – 12 weeks LMP: 25,700 – 288,000 mIU/ml
  • A single hCG blood level is not sufficient to assess the viability of an implanting embryo. Caution should be used in making too much of an initial hCG level. This is because a normal pregnancy can start with relatively low hCG blood levels. It is the rate of the rise of the blood hCG level that is relevant.
  • In some cases the initially hCG level is within the normal range, but then fails to double in the ensuing 48-72hours. In some cases it might even plateau or decline, only to start doubling appropriately thereafter. When this happens, it could be due to:
    • A recovering implantation, destined to develop into a clinical gestation
    • A failing implantation (a chemical pregnancy)
    • A multiple pregnancy which is spontaneously reducing (i.e., one or more of the concepti is being lost) or,
    • An ectopic pregnancy which will either absorb spontaneously (a chemical-tubal gestation), or evolve into a full blown tubal pregnancy continue and declare itself through characteristic symptoms and signs of an intraperitoneal bleed.
  • The blood hCG test needs to be repeated at least once after 48h and in some cases it  will need to be repeated one or more times (at 48h intervals) thereafter, to confirm that implantation is progressing normally.
  • Ultimately the diagnosis of a viable pregnancy requires confirmation of the presence of an intrauterine gestational sac by ultrasound examination. The earliest that this can be achieved is when the beta hCG level exceeds 1,000mIU/ml (i.e., around 5-6 weeks).
  • Most physicians prefer to defer the performance of a routine US diagnosis of pregnancy until closer to the 7th week. This is because by that time, cardiac activity should be clearly detectable, allowing for more reliable assessment of pregnancy viability.
  • There are cases where the blood beta hCG level is extraordinarily high or the rate of rise is well above the normal doubling rate. The commonest explanation is that more than one pregnancy has implanted. However in some cases it can point to a molar pregnancy  
  • Finally, there on rare occasions, conditions unrelated to pregnancy can result in detectable hCG levels in blood and urine. They include ovarian tumors that produce hCG, such as certain types of cystic teratomas (dermoid cysts) and some ovarian cancers such as dysgerminomas.
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  • Lexi - May 29, 2018 reply

    Hi Doctor!
    I recently did an IVF transfer using a PGS normal frozen embryo. My first beta was 8 days post-transfer and came back at 72; the second beta was 11 days post-transfer and came back at 262. I realize those are good numbers and my levels are doubling appropriately, but my question is regarding what this means when comparing to my previous IVF fresh 5day blast transfer. Those betas were significantly higher, even with the extra days given for progress. My first beta then was 12 days post-transfer at 663, and my second (14dpt) was 2281. Both transfers were with a single embryo, so what could the difference be in how my body produces this hCG? Thank you, sir.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 29, 2018 reply

    You cannot read too much into this…except that it is a good value.

    Geoff Sher

    Brc - June 1, 2018 reply

    I had iui with 4 mature follicles and my beta hcg results are 12dpiui:48 15dpiui:364. The increase in the number is so much, why do you think this could be like that?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - June 1, 2018 reply

    It could be a multiple pregnancy!

    Good luck!

    Geoff Sher

  • Sara - May 22, 2018 reply

    Dear Dr,
    Can you please advice whether my hcg level are normal? I had my last period on 6th April (so today I should be 6w+4, but according to a scan I had yesterday, where we saw the heartbeat (110) I am exactly 6w+1. Below are my hcg level:
    2 May 32
    4 May 115
    8 May 775
    11 May 2376
    14 May 6057
    21 May 17769

    Thank you
    Sara

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 22, 2018 reply

    This looks good to me! I would not worry about the scan being a few days off! The HB is a little slow. Recheck it in 1 week.

    Geoff Sher

  • Lyndie - May 22, 2018 reply

    Dear Dr,
    My 9dp5dt (14dpo) HCG was 54 and my 14dp5dt (19dpo) HCG was 278.1 Currently, I am using 4oomg of progesterone thrice daily and estradiol. Progesterone is >135. I have had some cramping and mildly brownish discharge which I have been told can be from the pessaries. My IVF nurse has said it does not look promising. What advice would you have at this early stage. Is the pregnancy still viable?
    Thank you for your time.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 22, 2018 reply

    I am not alarmed at all by the hCG rise. It looks OK to me.

    Geoff Sher

  • Jennifer - May 8, 2018 reply

    Hi Doctor- going by my LMP I am close to 8 weeks pregnant, however, at my last ultrasound last week the fetal pole (with a heartbeat of 120) was measuring just under 6. I had a week of bleeding and cramping/back pain early on My hCG has been high all along and last I was told it was around 26,000. However, my progesterone dropped from 11.9 to 7. My doctor was preparing for a d&c based on my dropped progesterone, but then saw the heartbeat and is certain everything is on track and didn’t suggest supplements of any kind. I have a gut feeling something is wrong. What is your take on the numbers? Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 8, 2018 reply

    Jennifer. Have a repeat US in a week! Hopefully all will be well!

    Geoff Sher

    Stacey - May 13, 2018 reply

    I am currently 15dpo and pregnant. I have a history of unexplained recurrent early miscarriage (a sac has never been detectable). 3 miscarriages all with what appears to be very late implantation as I never usually get a positive test until after my period is due. This time I had a positive urine test 11dpo with a blood serum hcg result of 14 that same day. Two days later, 13dpo, my hcg was 31. My progesterone was 15 on 11dpo, but that was with 200mg of Progesterone taken daily since ovulation. I increased it to 600mg when I received the 11dpo result. On 13dpo it had increases to 19. My estrogen level was 438 on 11dpo and 568 on 13dpo. My doctor is saying my hcg is low and likely not viable, especially since the progesterone would be low without the supplement. However, I am reading that my estrogen levels suggest that this may be a viable pregnancy despite the low, but doubling numbers. I’ve been through this beta nightmare before, so I guess what I’m looking for is a gut instinct. I have another beta tomorrow and if doubling properly anything over 93 should be fine I would think. The doctor says it needs to be closer to 200?? I know when it comes down to it I have to wait to see a sac etc, but what do you think of my numbers? If you had to guess?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 13, 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

    Stacey - May 14, 2018

    I read your articles and may schedule an appointment. Question. All of my losses were very early and deemed chemical due to the facct that a sac was never visible. Does that suggest it is autoimmune rather than alloimmune? I of course am hoping so. I was on predisone (10mg) this cycle after ovulation, but the hcg is already dropping at 16dpo. I had some immune testing done at my current fertility specialist’s office including thyroid, celiac’s, lupus, and some others, and all came back normal. I also do not have endometriosis. But based on my history would u say it looks more like autoimmune or allomune?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 14, 2018

    It is hard to say without doing the testing! Sorry!!

    Geoff Sher

    Stacey - May 14, 2018

    I should also add that I have PCOS.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 14, 2018

    Copy!

    Geoff Sher

    Stacey - May 14, 2018

    Ok then I probably shouldn’t make an appointment. If it is alloimmune my husband I really wouldn’t want to know that. We r considering having me tested for the natural killer cells, but only if it sounds like it’s autoimmune based on my history.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 15, 2018

    Good luck Stacey

    Geoff Sher

    Stacey - May 15, 2018

    If I tested positive for elevated NK cells while not pregnant, wouldn’t that confirm that it’s autoimmune rather than aulloimmune. Also, doesn’t PCOS cause inflammation and elevated NK cells?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 15, 2018

    First, the risk in my opinion, has nothing o do with the concentration of NK cells. Rather it is the concentration of activated (toxic) NK cells as measured by the K562 Target cell test and/or uterine cytokines that is relevant. And no…PCOS does not predispose to NKa+.

    Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.
    Who Should Undergo IID testing?
    When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:
    • A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
    • A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
    • “Unexplained” infertility
    • Recurrent pregnancy loss (RPL)
    • A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
    • Unexplained IVF failure
    • “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby
    What Parameters should be tested?
    In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.
    The parameters that require measurement include:
    o For Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
    o For Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).
    How should results be interpreted?
    Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.
    There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.
    Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.
    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.
    • 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!

    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

    Stacey - May 15, 2018

    Ok, I can come in to one of your facilities for testing, but my husband will not participate unfortunately. So we will only be able to evaluate me alone. I assume that’s ok? We just won’t be able to know about alloimmune, but can test to see if something is wrong with me alone. Also, I’m surprised about PCOS because my current doctor (as well as many studies online) say that auto immune diseases AS WELL AS inflammatory conditons like Endometreosis and PCOS cause Natural Killer Cell problems.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 15, 2018

    Copy!

    Geoff Sher

  • Jamie - May 1, 2018 reply

    Im 5w4d Pregnant – This will be my third pregnancy since august. 1st one ended in a MMC in November and second one ended in a natural MC in January.

    My HCG Levels have been low and not doubling properly

    13DPO 27
    15Dpo 29
    17Dpo 84
    20Dpo 165
    25DPo 485

    I’m 28 Years old – I have hypothyroidism which is managed and Rheumatoid Arthritis which untreated and has been semi in remission for over 10 years with the occasional flare ups about once per month. Please let me know your opinion on the viability of this pregnancy

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 1, 2018 reply

    This is a sluggish rise in hCG. Only time will tell how this will evolve.

    Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
    The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
    It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
    Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
    The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.

    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

    Jamie - May 1, 2018 reply

    Thank you so much for your detailed reply I really appreciate it. I was tested for lupus anticoagulant as well as thrombophilia and it came back negative are these the same thing as the killer antibodies you mentioned above or are those completely different?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 1, 2018 reply

    No they are entirely different!

    Geoff Sher

  • Laura - April 30, 2018 reply

    Dear Doctor, I had ICSI 3d embryo transfer (2 embryos). My Beta HCG levels are as follows:
    12dpt 3d – 66
    14dpt 3d – 235 (26.2 doubling time)
    17dpt 3d – 1085 (32.6 doubling time)
    Progesterone levels rising as well.
    Does it look promissing? I am aware my initial # was on a low side

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 30, 2018 reply

    Looks VERY romising!

    Good luck…

    Geoff Sher

  • mg - April 28, 2018 reply

    hi
    i had a FET with 3 embryos. my hcg post 14 days of transfer came to be zero. is there any chance of late implantation? or is this a total negative? pls advise

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 28, 2018 reply

    Sadly this is not likely!

    Geoff Sher

  • Carolyn - April 27, 2018 reply

    My hCG levels started out doubling nicely, but seem to have slowed down. My nurse assures me they are fine, but I’m pretty worried about them. I’ve got:

    14 dpo: 87 (estrogen 579, progesterone 41)
    16 dpo: 213 (estrogen 778, progesterone 73)
    21 dpo: 938 (estrogen 986, progesterone 88)
    23 dpo: 1321 (estrogen 939, progesterone 76)

    What are your thoughts on this?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 27, 2018 reply

    The rise in Beta hCG does often slow down as the level rises above 1000!

    Geoff Sher

  • Cat - April 19, 2018 reply

    We’ve been trying for a second child (our daughter and all attempts since have been ivf). We’ve had two miscarriages in 6 months and are pregnant again now.

    Current situation:
    8 weeks 2 days
    Had some minor (old) blood a few days ago. Heartbeat and measurements confirmed all okay for 8 weeks. HCG taken that day was 169,000. Repeat HCG approx 36 hours later (different lab) was 174,00.

    Should I be anticipating another loss?

    Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 19, 2018 reply

    Not necessarily. Either way, all you can now do is take a wait and see approach!

    Geoff Sher

    Diane - April 19, 2018 reply

    Dr. Sher,
    I had 2 fresh embryo transfer 14 days ago. Did a blood test this morning and came back negative. I was told that there’s no trace of hcg found in the blood. What does that mean? Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 20, 2018 reply

    Sadly, this does not look promising at all!

    Geoff Sher

  • Lori - April 14, 2018 reply

    My hcg was 120 two days ago. Exactly 48 hours I went back to retest, and it came back at 295. My progesterone level was 21.31 two days ago. My dr. put me on 400 twice a day since it was a bit low and due to my history. I had 2 miscarriages and one late term. I’m 41 years old and have been trying for a long time. I’m not sure what to think since my numbers didn’t exactly double. Any thoughts you might have would be greatly appreciated.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 14, 2018 reply

    It is a slower rate of the progressive increase than ideal…but there is still reason for hope!

    Geoff Sher

    Amy - April 16, 2018 reply

    Thank you for your informative blog! I’m wondering if you can shed some light on my numbers. After taking clomid with timed intercourse, my hcg levels are the following:

    14 dpo (positive test): 131 hcg
    16 dpo: 219 hcg
    20 dpo: 350
    23 dpo: 502
    27 dpo: 1,058 (5weeks,5days pregnant)

    The rose at 67%, then the rise decreased and then went back up. I understand ectopic is a possibility, and chemical. Is there any chance it’s viable and healthy? I also heard slow rising hcg could be a sign of chromosomal defects?

    Thank you.
    Amy

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 17, 2018 reply

    This is not an optimal rise. You need to have an US in about 10 days from now. Your doctor also needs to be on the lookout for an ectopic (tubal pregnancy, in my opinion.

    Geoff Sher

  • Kelly - April 8, 2018 reply

    Hello Dr. Sher,

    We transferred 1 3aa and 1 3ab blastocysts 12 days ago. My first beta at 10dp5dt was 695 and my second beta at 12dp5dt was 981. Is there hope? I had a chemical pregnancy back in January but the lightest beta I got then was 181.

    Kelly - April 8, 2018 reply

    Apologies, my previous message should have said the highest beta I got with the previous chemical pregnancy was 181

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 8, 2018 reply

    Copy!

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 8, 2018 reply

    You need to repeat the beta in 2 days…but frankly this does not look very promising!

    Geoff Sher

  • Joan A - April 6, 2018 reply

    Hi Dr. Sher, I had my first beta yesterday (day 9 after an FET with a 5 day blastocyst) and it was positive. My HCG was 173.4. I got for my next beta on Monday. Is 173.4 a good number?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 6, 2018 reply

    Very promising!

    Good luck!

    Geoff Sher

  • Liz - April 4, 2018 reply

    I had my first Hcg done on march 20, 2018 which was 4 days after my missed period and my level was 965 I had another test done yesterday April 3, 2018 and my level is 67,000 my doctor is happy with results but I was wondering if this is a good sign.

    thank you,

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 4, 2018 reply

    Looking good….

    Good luck Liz!

    Geoff Sher

  • Emily O - March 29, 2018 reply

    Hi there,
    I did a blood Beta test yesterday at about 15 days past ovulation. When I called for my results today, the nurse told me that my beta level was 385. When I asked her what that meant she sounded as if it was really low and said that at 385, that would measure me as 1-2 weeks when according to my last period, I would be more around 4-5 weeks. When researching online, I see many people with much lower levels that 385 at the same dpo as me. I’m so confused on how to take what the nurse was saying. I’m doing another beta blood test in the morning, and I know that it really depends on if it doubles or not…but was the nurse correct in saying that I was measuring weeks off with that number? Thanks so much.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 29, 2018 reply

    I respectfully do not agree with the opinion given by your nurse. Your level could be compatible with a viable pregnancy, provided the level doubles 2 days later.

    Good luck!

    Geoff Sher

    Emily O - March 29, 2018 reply

    Thank you for the response!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 29, 2018 reply

    You are very welcome!

    Geoff Sher

    Amber - April 15, 2018 reply

    Hey
    I’m In the same situation. With the same numbers. I go back on Tuesday to recheck levels. How was your outcome ?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 15, 2018 reply

    I guess under such circumstances, my answer to you would be the same.

    Geoff Sher

  • Dee MacManus - March 21, 2018 reply

    Dear Dr Sher,

    After 2 unsuccessful IVF transfers (5 rounds of egg collection , first transfer ended in MC at 5 weeks, in my last cycle in Oct 2017 I had immune therapy and transferred 3 embryos, but they did not implant), I fell pregnant naturally and am approximately 5 weeks and 4 days. My HCG rises are as follows:
    18DPO 824
    19DPO 1293
    21DPO 3379
    23DPO 5806
    24DPO 7074 (scan showed gest and yolk sac)
    26DPO 7274
    I’m worried by HCG has slowed too much. What do you think? Another miscarriage?

    Dee - March 21, 2018 reply

    I should add I am on enoxaparin BD, aspirin and progesterone suppositories and my doctor started me on low dose dexamethasone on day 24 DPO and I had an intrapilid infusion too which appears to have coincided with the slowing in HCG rise.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 21, 2018 reply

    Copy!

    Geoff Sher

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 21, 2018 reply

    It is normal for the rise in hCG to slow down when they reach around 3,000.

    Good luck and G-d bless!

    Geoff Sher

    Dee - March 23, 2018 reply

    You were right. I just saw the heart beat on the scan. Thank you!! x

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 23, 2018 reply

    So happy for you!

    Geoff Sher

    Laken T - March 22, 2018 reply

    Hey Dr. I went to my 8 week visit ultrasound this last Tuesday on March 20th. A yolk sac was visible but no fetus. My first HCG levels was taking yesterday and the levels was 35558. I go back tomorrow for a repeat HCG levels. Could this be that I’m not as far as long as we calculated from my last period? Or is this a bad sign that a miscarry maybe possible?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 22, 2018 reply

    Hard to say!

    I would repeat the US in 1 week to determine with confidence how to proceed.

    Good luck!

    Geoff Sher

  • Nicki - March 17, 2018 reply

    Dr. Sher,

    I’m having a hard time interpreting my Beta HCG results, and hoping you can help. Here are the results:
    8dp5dt: 188
    10dp5dt: 454
    18dp5dt: 3497

    (We transferred one 4aa, 5 day embryo. It was a FET.)

    As you can see, my HCG initially doubled in under 48 hours, but now the doubling rate has slowed considerably. By my calculations, if it were to maintain the same rate, it should have been around 7300 at 18dp5dt.

    My RE said the numbers “aren’t what she’d hoped for,” and that we’ll just have to wait and see what the ultrasound shows 6 days from now. I’m obviously having a hard time waiting, and I just can’t seem to accept her response. I found a few articles online that say the HCG doubling rate slows after 1200, and then again after 6000 (which you state in this article) which gives me a little hope, but I can’t find the source of that information. What would your interpretation of my results be?

    Thank you so much for your help.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 17, 2018 reply

    Th hCG levels do not double once the level gets to around 2,00. I would do an US now. It should provide more definitive information.

    Geoff Sher

  • Keri - March 5, 2018 reply

    Hi Dr. Sher:

    My first bHCG was 44 at ~12 days past ovulation. I had a repeat bHCG 3 days later and it doubled to 88, my doctor said it is exactly where she’d expect it to be as it should double very 48-72 hours. My number is kind of low, but she said it doesn’t matter the baseline as long as it rises appropriately. What are your thoughts?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 6, 2018 reply

    The increase is a little on the slow side. At this stage it should double every 48h. Repeat in 2 days to see what happens.

    Good luck!

    Geoff Sher

    Sonya - March 8, 2018 reply

    Dear Doctor Sher
    After one ectopic pregnancy( metotryx. shot) and one chemical pregnancy . I’m again pregnant 5 w 3 day
    My betaHCG level are following: 26.02- 231 4 w
    28.02-355 4w 2d
    01.03 -438 4w 3d
    03.03-838 4 w 5d
    05.03-1606 5 w
    06.03- 2776 5 w 1d
    08.03-3652 5w 3 ( progesterone level is 18.9 – with 2 times a day 400mg pessaries )
    Please let me know whats you thoughts about my situation. I’m really scared – the beta HCG today shows really law increase . Do I still have a chance for healthy baby and positive outcome? Please advise

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 8, 2018 reply

    It will likely be fine! However, stay on the lookout for pain or bleeding and if this occurs, go straight to the emergency room.

    Good luck!

    Geoff Sher

  • Wen - March 5, 2018 reply

    Dear Doc, I had a 5d hatching blastocyst transfer. My HCG on 10th day was 41.5, on 12th day it was 68.6. Just had a 3rd beta today (15th day post transfer), level is at 242. Is it looking good at all? 🙁 thank you in advance for your reply!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 5, 2018 reply

    That is an improvement. Hopefully all will be well!

    Good luck!

    Geoff Sher

    Wen - March 5, 2018 reply

    Thank you so much for replying! It’s very very much appreciated and I have ease of mind now!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 6, 2018 reply

    You are welcome.

    Geoff Sher

  • Stacy - February 26, 2018 reply

    12 days today after transfer HCG reading of 11. Is there any hope? My Dr just said lets do another test after 2 days. Devastated

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 26, 2018 reply

    That does not look promising….So sorry!

    Geoff Sher

  • Samantha heath - February 26, 2018 reply

    Hello, I’m 14dp5dt and have been taking pregnancy tests since 10dp5ft. Have been getting faint positives. On 11dp5dt I got a clearblue 1-2 and since then it hasn’t changed still saying 1-2. It’s been 72 hours. Also the other tests I’ve taken are still faint one is 10miu and the other 25miu both are faint? My doctor has told me to test again tomorrow see if it changes. If not go for blood tests. Any advice? Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 26, 2018 reply

    You need a blood quantitative hCG test or wait 2 weeks and do an ultrasound.

    Good luck!

    Geoff Sher

    Samantha heath - February 26, 2018 reply

    In your experience should the lines be darker? Do they represent the amount of hcg? Or is a line a line? Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 26, 2018 reply

    The darker..the higher the level!

    Geoff Sher

  • Laura - February 17, 2018 reply

    Hi I had a blood hcg level drawn at 4 weeks 4 days and level was 147 and progesterone 14. They had me do a repeat beta hcg test a little less than 72 hours. Is this concerning?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 17, 2018 reply

    It all depends on what the repeat beta hCG is. It should be around 450 or better.

    Geoff Sher

  • Tara E - February 13, 2018 reply

    Hi Dr. Sher!
    Thank you for this wonderful website and for all the time that you take to insightfully answer these questions.

    I had a naturally occurring pregnancy that ended in a natural miscarriage around 8-9 weeks in 2013 and then went on to conceive via IUI with injectable meds in 2014. That pregnancy resulted in 1 healthy, full term baby and also had an empty gestational sac that was resorbed. I then conceived with Clomid in 2016, which resulted in another healthy, full term baby. Most recently, I conceived naturally late in 2017, which ended in a blighted ovum at 7 weeks (D and C was performed). I am now pregnant again (unexpectedly) immediately after the D and C procedure in January and awaiting HCG and progesterone results. Is this pregnancy likely to result in another miscarriage since it was so close to my D and C, given my history? It should be noted that I am also still nursing my youngest baby, however, in the process of weaning.

    Should I revisit my RE to look into the cause of my RPL?

    Thank you so much for your time and expertise.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 13, 2018 reply

    I think it is too late now. So give this pregnancy a chance and if you lose it…then see your RE regarding RPL.

    Geoff Sher

  • Renee - February 8, 2018 reply

    Hi Dr. Sher
    I came across your article and was curious on your thoughts about my Beta numbers so far. I transferred 2 fresh 5 day blasts (4AA and 4BB). My first beta was 10dp5dt 191.7 and then my second beta was 13dp5dt 807.1. With my numbers more than doubling could that indicate both implanted?

    Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    Looks promising!

    Good luck!

    Geoff Sher

  • Juliet - February 3, 2018 reply

    Dear Dr Sher,
    First, thank you for your informative site and your q/a support.
    I have had a 5 day transfer of 1 grade A blastocyst with PGD on Jan 12
    I am very nervous because my HCG is not rising properly.

    10dp5dt 81
    12dp5dt. 200
    14dp5dt. 400
    18dp5dt. 929 = 23 dpo

    So the numbers started fine, but over the last 4 days the rise has been very slow, below 2 times in 3 days, the last level is below the lowest bound of the norm for 23dpo, and the 1 week rise is well below the recommended 15 times as well.

    I am very scared… Do you think there is a chance for this pregnancy to have a positive outcome ?

    Thank your ofr your time and support.

    Juliet

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    Yes Juliet , I am optimistic that all will be OK. Please keep me in the loop!

    Good luck and G-d bless!

    Geoff Sher

  • mary - January 26, 2018 reply

    Hi Doctor. At 4 weeks 4 days, my hcg was 863,9. i did not take second test hcg. is it a good sign of pregnancy? thanks a lot Doctor.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 26, 2018 reply

    Yes it is …but you should measure the hCG again in 2 days to see if it at least doubles.

    Geoff Sher

  • Kelly - January 1, 2018 reply

    Hello. I had my first beta yesterday, Sunday, at 9dp5dt and my level was at 15. I go back tomorrow, Tuesday. What number should I hope to see the hcg increase to? I’m so nervous.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 1, 2018 reply

    Above 30!

    Happy New Year!

    Geoff Sher

    Jane Smith - January 11, 2018 reply

    13dpo (1 day before period was due) hcg was only 6; 16dpo hcg was 16 (so doubling between 48-72 hours; 18dpo hcg is 42…more than doubled. From 16dpo to 18dpo progesterone increases frim 7-10 and estrogen went from 456-558. Doctor is acting like it’s already over. Not viable she says because numbers are so low. But what if I implanted late? What do u think?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 11, 2018 reply

    Only time will tell but there is hope!

    Good luck!

    Geoff Sher

    Jane Smith - January 11, 2018 reply

    So you think there is actually a chance it’s viable?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 11, 2018

    Modest…but yes!

    Geoff Sher

    Jane Smith - January 11, 2018

    Ok thank you. I have had two early miscarriages already this year so perhaps that’s why my doctor is already calling this inevitable miscarriage.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 11, 2018

    Copy!

    Geoff Sher

  • Aggy - December 24, 2017 reply

    Hi Dr ,I had 3dFET on 13 dec2017 then went for beta hcg on 22 DEC which was 9dpt and my hcg was 4.85 my Dr advice me to recheck 4 days later is it possible for this no.to increase

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 24, 2017 reply

    Hi Aggy,

    Sadly this does not look promising!

    G-d bless!

    Geoff Sher

  • Karen - December 22, 2017 reply

    I had 2 fresh embryos transferred. And my HCG results are …. 14 DPO/11 dp3DT = 64, 17 DPO/ 14 dp3dt = 160, 20 DPO/ 17 dp3dt = 240, 21 DPO/ 18 dp3dt = 279. I am worried that my results were more than doubling and have now slowed down. Is this possibly due one of the embryos not taking?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 23, 2017 reply

    Hi karen,

    This does not look very promising to me. I am afraid that implantation could be failing here, unless you started with 2 and are in the process of reducing down to one implantation now. I hope I am wrong!

    G-d bless and good luck!

    Geoff Sher

    Karen - December 23, 2017 reply

    Thank you. I will stay hopeful over the Christmas period. My scan isn’t until 8th Jan. So far there’s no pain and no spotting. Although, I am on 400mg progesterone twice a day, which could be keeping anything sinister at bay.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 23, 2017 reply

    Copy and G-d bless!

    Geoff Sher

  • Tina - December 22, 2017 reply

    Hi. I took a test on the day before my period was due and had an HCG drawn the following day (period due date) that was 485. What range does that put me in? 4 or 5 weeks?

    Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 23, 2017 reply

    Hard to say, but an US done 7-10 days drom now should provide an answer.

    Good luck and G-d bless!

    Geoff Sher

  • Kaye - December 21, 2017 reply

    Hi Dr. Sher,
    Do you believe that the HCG level can indicate multiples? I had a 5-day fresh transfer on 12/11 (two embryos transferred – 4BB and 2BB). I started seeing positive home pregnancy tests Saturday, and my first beta today was at 658. This is almost triple the HCG level I had with my daughter after my first IVF cycle a few years ago (it was 213). Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 21, 2017 reply

    More important is how the level up in 2 days time. If it triples or greater, it could be a multiple.

    Good luck!

    Geoff Sher

    Kaye - December 28, 2017 reply

    Hi Dr.Sher – we had the second test today (exactly one week later) and the HcG level is now 12,965. Is that normal or could it be multiples (it was 658 last Thursday- 10dp5dt). Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 28, 2017 reply

    Could be multiples!

    Good luck kaye!

    Geoff Sher

  • Jennifer - December 21, 2017 reply

    Hi Dr.

    I had an IUI on 12/1 and got a BFP. I went in for my HCG test on 12/18 and it was at 350 and then went back 12/20 and it was only 489. They told me its concerning but doesn’t mean its necessarily a loss. I had read that for IUI a 35% increase is needed, but then other things say it needs to double. What would be your perspective on this? I’m worried I went through all of this for nothing..

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 21, 2017 reply

    There needed to ideally be a doubling in 48h. this is of concern but it could be that you started with >1 pregnancy and one is absorbing. Unfortunately only time will tell!

    Geoff Sher

  • Siu - December 15, 2017 reply

    Hello! I had a fresh transfer and yesterday 10dp5dt had my first beta which was 16. It seems really low and I am worried about it. Also, we planned a trip this upcoming weekend. Is it recommended to flight? What do you think about that low result? Thank you so much for all the info you provide!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 15, 2017 reply

    I personally would recommend that you stay put until you know which way the “pregnancy” is headed.

    Good luck!

    Geoff sher

    Siu - December 16, 2017 reply

    Thank you so much for getting back! Do you think is too low the hcg level?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 16, 2017 reply

    What is really relevant is whether it doubles every 2 days.

    Good luck!

    Geoff Sher

    Haylee Szumlinski - December 16, 2017 reply

    Hello doctor I’m wondering what your opinion would be. I had a TV ultrasound at 5 weeks 6 days that showed a gestational sac and a yolk sac. No fetal pole was seen. A SCH was also detected. Hcg was checked that same day with a level of 2717. Progesterone came back that day very low so I was started on Crinone. Two days later at 6 weeks 1 days hcg was at 3732. No bleeding or spotting but non stop cramping. Doctor was worried with the rise and said it didn’t double how they wanted it to. I go in twice next week for more blood draws. I wish they would do an Us to determine viability. Would you say that my chance of miscarrying or that I already have is high at this point? Thank you so much I just want to prepare myself.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 17, 2017 reply

    It is difficult to say with an US done so early. You need to repeat it in 1 week.

    Good luck!

    Geoff Sher

    Geoff Sher

  • Sarah Nolan - December 14, 2017 reply

    Dr Sher,

    Just got my beta back – my HCG is 7.99, (9dp5dt, FET). My nurse said to be “cautiously optimistic” but this seems way too low to be viable. Any thoughts? Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 14, 2017 reply

    The level is low…so please hope for the best and prepare for the worst!

    G-d bless!

    Geoff Sher

  • Carrie Garner - December 13, 2017 reply

    Hello Dr. I am on my 4th round of off. Resulting in a bfn, mc at 4 weeks, bfn, and lastly BPD. I had an fet Nov 30 2017. I chose to have 2 embryos transfered. My first beta was on Dec. 11, 2017 reading 1444. Second beta Dec. 13, 2017 reading 4063.2
    I won’t be back to Dr. Visit until Dec. 21, 2017 for an ultrasound. How would you view my experience. Or do you have any advice Thank you Dr.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    Sounds very promising…possibly even twins!

    Good luck!

    Geoff Sher

  • Tammy - December 13, 2017 reply

    Hello Doctor. Found out today that I am 5 weeks 6 days pregnant. I am very excited that this round of IVF worked. The did an ultrasound and said everything looks good. I returned home and now I am bleeding red blood, not brown, quite a lot and I have just passed a large clot (larger than a quarter) I am very scared that I am now miscarrying.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    My thoughts are with you Tammy! Unfortunately, aside from trying to avoid any over-activity until hopefully the bleeding stops , there is nothing you can do except wait it out.

    I wish you well!

    Please keep me updated.

    Geoff Sher

    Tammy - December 13, 2017 reply

    Update: It was a subchorionic hematoma! Phew! The ultrasound and bloodworm this morning look good to the doctor. The bleeding stopped overnight, and I am still feeling no discomfort. I have been instructed to rest for a few days and return next week for a check up. Thank you for your encouraging words.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    I am so happy for you!

    G-d bless and good luck!

    Geoff Sher

  • TMR - December 12, 2017 reply

    Me again. Just went for an ultrasound today to check on everything. Doctor said they saw the yolk sac and fetal pole, but still too early to see the heartbeat. Been having very scant brown discharge, but since I got home from the ultrasound, discharge has become more watery and lighter in colour. Could the ultrasound have caused this? Office is closed, so I can’t call to ask.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    I would not be concerned about a non-bloody discharge!

    Good luck!

    Geoff Sher

  • TMR - December 11, 2017 reply

    Hello,
    20dp5dt transferred 1 4BB hatching blastocyst as of today. Started beta tests on 14dp. Started with 576 then 1303, 2679, today 4288. Doctor wants an ultrasound tomorrow since I didn’t double in 48hrs. Do I have reason to be concerned?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 12, 2017 reply

    My bet is that all will be well!

    Good luck!

    Geoff Sher

  • Heather - December 6, 2017 reply

    Hi Dr. Sher,
    How many embryos (percentage wise) typically make it from day 3 to day 5-6 (Blast stage)?
    I had 11 embryos at day 3 and only 4 made it to day 5. What factors play into a poor outcome like this? If we need to do another cycle- is there anything I could do to help increase the amount of day 5 blasts?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    Age and the cause of the infertility both impact blastocyst conversion rates. For younger women (<35y) who have normal ovarian reserve, the conversion rate of cleaved embryos to blastocysts is about 40% and the percentage of these blastocysts that are chromosomally normal = about 50%. The older the women the lower these statistics become so that bu the mid-40's the rates would be about 15% and 10% respectively.

    The only way to optimize this conversion is to implement an optimal protocol for ovarian stimulation.

    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

  • Hanah - December 6, 2017 reply

    Hi thank you Doctor for your reply. Would you concur with my doctor also to be optimistic with my numbers? They seem to be thinking my numbers were good but to me they seem low.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    Guardedly optimistic!

    Geoff Sher

    Hannah - December 13, 2017 reply

    Thank you doctor. I’m currently 6 weeks 4 days and go in for ultra sound tomorrow. I’m pretty nervous but still no signs of miscarriage this far in. I wish my numbers were better or I had them rechecked again. The not knowing is so tough. Are things pointing more positively being 6 weeks 4 days and no signs of miscarriage?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    Good luck and G-d bless!

    Geoff Sher

    Hannah - December 14, 2017

    Hi Doctor. Good news. They found the baby measuring at 6 weeks 4 days which is one day behind with a heartbeat of 123. they said that was a good heartbeat. Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 14, 2017

    So happy for you!

    Geoff Sher

  • Hanah - December 6, 2017 reply

    Hi Doctor. I had two 3 day frozen embryos transferred and my HCG levels have been concerning.

    13 days after transfer 143
    15 days after transfer 210
    17 days after transfer 387
    20 days after transfer 1026

    The first to second tests only went up 48 percent but then the doubling rate got on track after that. Also the 1026 level seems low for 20 days after transfer. My doctor stopped ordering HCG testing and I’m going in for US in 9 days.

    Should I be worried with my HCG level?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    I concur with your RE’s decision. It will take an US to tell at this stage.

    Geoff Sher

  • Marissa - December 6, 2017 reply

    Hi Dr. Sher! I have had 2 previous ectopic Pregnancies. 1 treated with a salpingectomy and the 2nd with methotrexate. Hsg after treatment showed an open tube. I just got a positive pregnancy test and hcg is 27, progesterone 11. I am anywhere from 3 weeks 6 days to 4 weeks 1 day. Do you think this could be indicative of another ectopic?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    It is impossible to say with any confidence at this stage. You need to repeat the test in 2 days to see how the level is changing and if it doubles. Thereafter, an ultrasound in about 2-3 weeks time will confirm one way or the other.

    Good luck!

    Geoff Sher

  • Megan Joyner - December 5, 2017 reply

    Hi Dr. Sher – I’ll try to make this brief. My husband and I are both 36. We have a healthy 8 year old son, no problems conceiving or with the pregnancy and delivery. We have now been trying for 4 years for # 2 and we’ve had a chemical, a 15 weeks loss, another chemical, another 16 week loss, an 8 week loss, and a blighted ovum, in that order. 6 consecutive losses. The second tri losses and 8 week loss were tested and had normal chromosomes. I have beea on a combination of plaquenil, prednisone, lovenox, asa, estrogen, progesterone, and neupogen for several of these pregnancies. I have Sjogren’s, mildly elevated anticardiolipin IgM antibodies, positive ANA, mildly elevated NK cell activity, low uterine NK activity, and am hypothyroid. How I had a healthy child with no complications is a sheer miracle in itself, apparently.

    I recently found out I was pregnant on an immune protocol after doing a TI cycle with femara days 3-7, second month trying. I had 4 large follies ready to rupture. I did not do a trigger. I got a very faint positive at 9dpo. Here is a summary of my betas so far. They are rising erratically and have sort of slowed down. Just curious if you have seen any similar betas that ended with a take home baby. I am currently on prednisone, plaquenil, lovenox, asa, neupogen, metanx, synthroid, estradiol, and oral and vag and PIO progesterone, all before conception. I know it is up to God at this point, truly. Any feedback is appreciated.

    11/14 9dpo 7
    11/16 11dpo 29 (314% rise) DT 23 hrs
    11/18 13dpo 58 (100% rise)) DT 48 hrs
    11/20 15dpo 102 (76% rise) DT 59 hrs
    11/22 17dpo 146 (43% rise) different lab, DT 92 hrs
    11/24 19dpo 312 (113% rise) DT 44 hrs
    11/27 22dpo 698 (71% rise over 2 days) DT 62 hrs
    11/28 Gestational sac seen on US 5w0d
    11/29 24 dpo 988 (41% rise) Out of state lab DT 95 hrs
    12/1 26dpo 1540 (55.9% rise) DT 75 hrs
    12/4 29dpo 2063 (21% rise) DT 170 hrs – also had a repeat scan today and a yolk was seen in addition to the gestational sac. Measuring 5w5d and I am 5w6d.

    Thank you in advance for you time and feedback.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    I am afraid…this does not look very encouraging. You could be on yourv way to another loss…I hope I am wrong but only time will tell for certain.

    What stands out to me is that you could have an implantation issue. I am concerned about an immunologic cause, given your history of recurrent loss with chromosomally intact embryos. Also, hypothyroidism is usually autoimmune in women and if so, there is a 50:50 chance of natural killer cell activation which if present has not been fully addressed , in my opinion.

    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

  • Dasha - December 2, 2017 reply

    Hi Dr. Sher, i’ve Had 5 pregnancies and on to the 6th right now. I’ve had 2 mc’s at 5 weeks, then a healthy baby girl 4 years ago, and 2 more mc’s at 5 weeks. Pregnant right now, conceived on Nov 6, had beta drawn on nov 29- 452, I’m very concerned that that’s a McDonald’s again:( What are your thoughts on this? Thank you so much

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 2, 2017 reply

    This probably is not a repetitive issue…based on the information you gave me.

    Good luck!

    Geoff Sher

  • Preeti - December 1, 2017 reply

    Hi Dr Sher, I went had a 3 day embryo transfer on Nov 6, 2017 and my first beta on Nov 17 was 36. Since then it has been rising oddly, went to 76, 83, 126, 356 and was 574 on Nov 30th. My Re said it isn’t normal and did an ultrasound and ordered a full pelvic sonogram too. They couldn’t find an ectopic and couldn’t find a viable sac. I have been asked to stop progesterone suppositories and am in holding pattern. Have to go back for more blood work. What do you think is going on? Regards, Preeti

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 2, 2017 reply

    This does not look promising Preeti. I think this is simply a chemical pregnancy but please make sure your RE continues to watch for an ectopic.

    Geoff Sher

  • MENNA - November 30, 2017 reply

    hi Dr. i had a blood test yesterday with a 0.25 result my last period was on the 7th of November and ovulation date according to my calendar was on the 22nd of November.

    does this mean that i am not pregnant for sure?do i need to re do the test after a while?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 30, 2017 reply

    I am afraid it does not look good Menna!

    Sorry!

    Geoff Sher

  • Hannah Medina - November 23, 2017 reply

    Hi dr! I had my beta drawn 11dp5dt it was only 11 48 hours later 18.. I did transfer 2 embies… I am concerned however with my son it started at 20 12dp5dt and doubled from there… could I just be someone who starts low? Or because it didn’t double does it sound like cp?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 24, 2017 reply

    Hopefully this is a false alarm. You need another beta hCG done 2 days after the last one. If that doubles you could be OK.

    Good luck!

    Geoff Sher

    Hannah Medina - November 24, 2017 reply

    I am waiting for results now.. if it doubles how many more blood draws do you think I should have.? I’m over betas already!!! I wish one part of this journey could be normal!!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 25, 2017 reply

    It depends on the level! BUT possibly one more!

    Geoff Sher

  • Julie A Steinhofer - November 22, 2017 reply

    Hi!!! I am 4 weeks 4 days today and my HCG was 55 and progesterone was 10.6. Is this concerning?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 22, 2017 reply

    It could be a little on the low side. Repeat in 2 days to see if it doubles.

    Good luck!

    Geoff Sher

  • Fouzia Khan - November 22, 2017 reply

    I am at 11dp5dt today on 22 Nov 2017. Yesterday at 10dp5dt my beta hcg level was 110. As we had only single grade 4AA embryo for FET. Is this levl okay at Day 10 of transfer. Tomorrow, second Beta is schedules.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 22, 2017 reply

    The level is fine but it needs to double every 2 days from here on out!

    Geoff Sher

    Fouzia Khan - November 24, 2017 reply

    Dear Dr.Geoffrey Sher
    Yesterday at day 12, we conducted 2nd beta that was 264 ( First bet two days ago was 110, it is more than doubbled with in two days. Is it Okay? Our RE is satisfied with this . As it is by Single 5Day Embryo. He asked me for U/S December 07/2017. He does not think to go for ny further beta level tests.
    Kindly give your expert opinion.
    Regards, Fouzia Khan Dubai UAE

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 24, 2017 reply

    That is good news!

    Good luck!

    Geoff Sher

    Fouzia Khan - November 25, 2017

    Thank You So much Dr.
    God bless you for guidence.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 25, 2017

    You are very welcome Fouzia!

    Geoff Sher

  • Becky - November 21, 2017 reply

    Hello, just came across your article. I believe I am approx 4/5 weeks pregnant. On Friday my HCG levels were 690 and on Sunday they had only risen to 900, the doctor performed an ultrasound yesterday and could see a gestational sac and yolk (The ultrasonographer performed one on Friday but couldn’t see anything) In your experience are there any happy outcomes from a hcg rising slowly? Thanks in advance, Becky

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 21, 2017 reply

    I would repeat the hCG in 2 days (from the last). If therfe is still a slow rise, it would, I am afraid be a poor prognostic sign. If it doubles or better, it could be that you started of with a single pregnancy and one was lost.

    Good luck!

    Geoff Sher

    Becky - November 21, 2017 reply

    Thank you, the hospital have told me they don’t want to repeat the blood test they just want to perform another scan in a weeks time. Fingers crossed!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 21, 2017 reply

    Good luck!

    Geoff Sher

  • Sandy - October 24, 2017 reply

    Hi Dr. Sher, At 4 weeks 2 days my HCG was 56. At 4 weeks 4 days, it was 58, and then 5 week 1 day it was 60. I’m assuming this isn’t going to be viable. But since the levels are rising (though VERY slowly), do you have any idea what else it could mean? Could this still potentially be a viable pregnancy? I’m also feeling symptoms of pregnancy (nauseous, headache, tired, sore breasts), so I’m confused! Any help would be appreciated!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 25, 2017 reply

    Hi Sandy!

    This sounds like a failing implantation…i.e. a chemical pregnancy!

    Sorry!

    Geoff Sher

    Sandy - October 25, 2017 reply

    Thanks for writing. Today – I ended up having a little bit of bleeding, nothing heavy like I’ve read online for a CP. It’s also brown. Is that normal? Will this become heavier? Once it’s done, does that mean my HCG levels will be back at 0 and we can start trying again? Thanks again for your help!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 26, 2017 reply

    Unfortunately time is the only determinant.

    Geoff Sher

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