Progesterone-Estrogen Hormonal Supplementation in IVF: How Does it Work and What is its Value?

Ovulation occurs within 38-42 hours of initiation of the spontaneous luteinizing hormone (LH) surge (which can be detected in the blood or urine prior to this event) and/or hCG administered following controlled ovarian stimulation (COS) with gonadotropins.

One or more eggs are released with spontaneous or induced ovulation. Those follicles that ovulate and many of those emptied at egg retrieval, then undergo “luteinization”, converting to one or more a yellow bodies or corpora lutea (CL) that produces both progesterone and estrogen. The greater the original number of mature follicles, the greater the progesterone/estrogen production is likely to be. Accordingly, women on fertility drugs have higher luteal phase progesterone/estrogen levels.

The effect of the pre-ovulatory hCG injection is usually sustained for 1-2 weeks exerting a protracted influence on ovarian progesterone/estrogen production. A few days later, provided that embryo implantation takes place, the early trophoblast (root system of the conceptus) begins to produce its own progesterone/estrogen as well as hCG, in ever increasing amounts. By the 8th week of pregnancy the early placenta provides for all hormonal needs of the developing conceptus. There is compelling evidence to show that hCG augments ovarian (corpus luteum) progesterone release while also promoting growth and development of the trophoblastic “root system” of the conceptus (which eventually will develop into the placenta) as well as estrogen and progesterone production. Since, at the same time, hCG probably also promotes the production of more hCG, it might be considered to be a self-propagating hormone.

By the 8th-9th week of pregnancy, the trophoblast has replaced the ovaries as the dominant source of progesterone and estrogen production. Thereafter there is probably little or no benefit in supplementation with progesterone/estrogen It follows that a low blood progesterone blood level is much more likely to be the consequence rather than the cause of a failing pregnancy. Thus in such cases the administration of progesterone/estrogen in an attempt rescue a failing pregnancy is tantamount to “shutting the gate after the horse has left the stable.”

An obvious situation where progesterone/estrogen supplementation is required is in cases where the woman is an embryo recipient (i.e., ovum donation, embryo adoption, gestational surrogacy and frozen embryo transfers-FET).

By the 8th to 10th week of pregnancy, conversion from reliance upon the corpus luteum to sustain the pregnancy has occurred and further fetal development, supported by the hormonal production of the placental trophoblast. Thus thee is in my opinion little or no benefit in estrogen/progesterone supplementation beyond the 10th week.

While progesterone /estrogen supplementation likely has benefit in cycles involving pituitary down-regulation with GnRH agonists (e.g. Lupron, Buserelin, Superfact, Decapeptyl) or antagonist (Ganirelix, Orgalutron, Cetrotide) where luteal phase hormonal deficiency is more prevalent, there is no conclusive evidence that patients undergoing gonadotropin stimulation without the use of a GnRH agonist or an antagonist would derive benefit from such hormonal supplementation.

Hormonal supplementation usually involves the daily intramuscular administration of progesterone +/-  vaginal suppositories (comprising estradiol and micronized progesterone) until a blood pregnancy test is performed approximately eight days later (the chemical diagnosis of pregnancy). If the pregnancy test is negative or the plasma hCG levels fails to rise appropriately in the ensuing days, such hormonal support is discontinued. For those that cannot tolerate daily intramuscular progesterone, Crinone or Endometrin vaginal applications can be used instead.

107 Comments

Karen

Dr Sher,
Thank you for the wonderful information. I am 36 with repeated pregnancy failure after IVF. I had a fresh cycle 3D transfer and had a positive hcg 11dp3dt of 345. On 14dp3dt it has gone up to 1521, and my progesterone was measured as >120 ng/ml.
I was instructed that it is ok to discontinue my Crinone and estrogen patches given my serum level of progesterone.
Is there data to support continuing? Would you still recommend continuing until week 10 as I’ve read often through these posts?
I appreciate you time.
Sincelery,
Karen

reply
Dr. Geoffrey Sher

I routinely recommend continuing progesterone to the 10th week.

Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about 15y ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.

4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:

a. A“ thin uterine lining”
b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c. Immunologic implantation dysfunction (IID)
d. Endocrine/molecular endometrial receptivity issues
e. Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF?
______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Tanya

Hello- I am currently 10 weeks pregnant after a frozen embryo cycle with my only PGS normal embryo. I have premature ovarian failure and a host of autoimmune issues (high thyroid antibodies, MTHFR gene). My doctor wants me to stay on progesterone in oil until week 12 but stop the estrogen. However, when I stopped the estrogen, I have started to have severe headaches. Is this normal? I read that the headaches might be a symptom of changing estrogen, but does this mean I should go back on the estrogen? So terrified of losing this baby since it’s my only embryo, have had multiple miscarriages,, and I have zero follicles on my ovaries at this point. Many thanks

reply
Dr. Geoffrey Sher

Atvb10m weeks, the developing placenta has taken over producing adequate hormones. In my opinion there is little merit in going back on the E/P therapy beyond 12 weeks.

Good luck!

Geoff Sher

reply
Hope Trivia

Hello Dr Sher,

I am currently 11 weeks pregnant conceived via IVF 5dFET. I am taking Endometrin 1 mg vaginal insert 2 times a day and PIO shot of 0.5 ml every three days. My progesterone level came back at 20 this morning. Is this pretty low at this stage and means my body is not producing enough progesterone yet? I read everywhere that by 11 weeks the placenta should take over. Please let me know your thoughts. Thanks a lot.

reply
Dr. Geoffrey Sher

It is OK and yes! I would stop at 10 weeks because by that time the placenta would have taken over.

Geoff Sher

reply
Hope Trivia

Dr Sher,

Thanks a lot for your prompt reply. I left a comment regarding this issue with a little more details in the Open Forum..I would really appreciate if you could review that as well and leave a few words. I sincerely thank you for your support.

reply
Hope Trivia

Thanks a lot Dr Sher.

After my 5d FET, my RE put me on Endometrin 100 mg 2 times/day and PIO 1ml shot every 3 days. I did weekly blood drawn for progesterone level check . My progesterone levels were as follows:

4w: 30
5w: 12
6w: 24
7w: 26
8w: 22
9w: 21
10w: 40

After 10 week blood draw, my RE reduced my medicine to PIO 0.5 ml shot every 3 days and Endometrin 100mg 2/ day. Then my 11 week blood draw showed my progesterone level at 20. My RE said the level is lower than where they expect it to be at this point. So i am continuing my medications.

I am really worried as i read low progesterone at this stage might be a consequence not reason for a failing pregnancy. I did my Ultrasound at weeks 6, 7,8 and 10. All came normal with normal heartbeat. Please let me know if you have any comment or guidance. I sincerely appreciate your support. Thanks a lot.

Dr. Geoffrey Sher

Quite honestly Hope, I concur with the action taken by your RE. Although, no one can predict with complete confidence, I also believe that this pregnancy will progress normally.

Good luck!

Geoff Sher

Jay

Hello Dr Sher, We had a previous FET day 5 with crinone supplementation twice a day. Do you recommend to lower the estrogen dose after the transfer? Is there an ideal level for estrogen. We used patches plus estrofem due to thin lining.

reply
Dr. Geoffrey Sher

Protocols differ from center to center. Sorry!@ can’t help here. Here is the approach I use for FET:

Until less than a decade ago, most women undergoing IVF would have embryos transferred to the uterus in the same cycle that the egg retrieval was performed (“Fresh” Embryo Transfer). This was because embryo cryopreservation (freezing) was a hazardous undertaking. In fact, it resulted in about 30% not surviving the freezing process and those that did, having about one half the potential of “fresh embryos to implant and propagate a viable pregnancy. The main reason for the high attrition rate associated with embryo cryopreservation is that the “conventional” freezing” process that was done slowly and this resulted in ice forming within the embryo’s cells, damaging or destroying them. The introduction of an ultra-rapid cryopreservation process (vitrification) freezes the embryos so rapidly as to avoid ice crystals from developing. As a result, >90% survive the freeze/thaw process in as good a condition as they were prior to being frozen and thus without being compromised in their ability to propagate a viable pregnancy.
Recently, there have been several articles that have appeared in the literature suggest that an altered hormonal environment may be the reason for this effect. There have also been reports showing that when singletons (pregnancy with one baby) conceived naturally are compared to singletons conceived through a “fresh” embryo transfers they tend to have a greater chance of low birth weight/prematurity. This difference was not observed in babies born following FET. Hence, there is a suspicion that the altered hormonal environment during the fresh cycle may be the causative factor.
Available evidence suggests that FET (of pre-vitrified blastocysts) is at least as successful as is the transfer of “fresh” embryos and might even have the edge. The reason for this is certainly unlikely to have anything to do with the freezing process itself. It more than likely has to do with two factors:
a) An ever increasing percentage of FET’s involve the transfer of PGS-tested, fully karyotyped, euploid blastocysts that have a greater potential to propagate viable pregnancies, than is the case with “fresh” ET’s where the embryos have rarely undergone prior PGS selection for “competency”…and,
b) With targeted hormone replacement therapy for FET, one is far better able to better to optimally prepare the endometrium for healthy implantation than is the case where embryos are transferre3d following ovarian stimulation with fertility drugs.
There are additional factors other than method used for embryo cryopreservation that influence outcome following FET. These include
• An emerging trend towards selective transferring only advanced (day 5-6) embryos (blastocysts).
• (PGS) to allow for the selective transfer of genetic competent (euploid) embryos
• Addressing underlying causes of implantation dysfunction (anatomical and immunologic uterine factors) and
• Exclusive use of ultrasound guidance for delivery of embryos transferred to the uterus.
Against this background, the use of FET has several decided advantages:
• The ability to cryostore surplus embryos left over after fresh embryo transfer
• The ability to safely hold embryos over for subsequent transfer in a later frozen embryo transfer (FET) cycle (i.e. Staggered IVF) in cases where:
1. Additional time is needed to perform preimplantation Genetic testing for embryo competency.
2. In cases where ovarian hyperstimulation increases the risk of life-endangering complications associated with critically severe ovarian hyperstimulation syndrome (OHSS).
3. To bank (stockpile) embryos for selective transfer of karyotypically normal embryos in older women or those who are diminished ovarian reserve
4. The ability to store embryos in cases of IVF with third party parenting (Egg Donation; Gestational Surrogacy and Embryo donation) and so improve convenience for those couples seeking such services.
Preimplantation Genetic Sampling with FET:
The introduction of preimplantation genetic sampling (PGS) to karyotyping of embryos for selective transfer of the most “competent” embryos, requires in most cases that the tested blastocysts be vitribanked while awaiting test results and then transferred to the uterus at a later date. Many IVF programs have advocated the routine use of PGS in IVF purported to improve IVF outcome. But PGS should in my opinion should only be used selectively. I do not believe that it is needed for all women undergoing IVF. First there is the significant additional cost involved and second it will not benefit everyone undergoing IVF, in my opinion.
While PGS is a good approach for older women and those with diminished ovarian reserve (DOR) and also for woman who experience recurrent pregnancy loss (RPL) or “unexplained” recurrent IVF failure recent data suggests that it will not improve IVF success rates in women under 36Y who have normal ovarian reserve, who represent the majority of women seeking IVF treatment. Nor is it needed in women (regardless of their age) undergoing IVF with eggs donated by a younger donor. This is because in such women about 1:2/3 of their eggs/embryos are usually chromosomally normal, and in most cases will upon fertilization produce multiple blastocysts per IVF attempt, anyway. Thus in such cases the transfer of 2 blastocysts will likely yield the same outcome regardless of whether the embryos had been subjected to PGS or not. The routine use of
It is another matter when it comes to women who have diminished ovarian reserve and/or DOR contemplating embryo banking and for women with unexplained recurrent IVF failure, recurrent pregnancy loss and women with alloimmune implantation dysfunction who regardless of their age or ovarian reserve require PGS for diagnostic reasons.
Embryo Banking: Some IVF centers are doing embryo banking cycles with Preimplantation Genetic Screening (PGS). With Embryo Banking” several IVF cycles are performed sequentially (usually about 2 months apart), up to the egg retrieval stage. The eggs are fertilized and the resulting advanced embryos are biopsied. The biopsy specimens are held over until enough 4-8 blastocysts have been vitribanked, thus providing a reasonable likelihood that one or more will turn out to be PGS-normal. At this point the biopsy specimens (derived all banking cycles) are sent for PGS testing at one time (a significant cost-saver), the chromosomally normal blastocysts are identified and the women are scheduled for timed FET procedures….. with a good prospect of a markedly improved chance of success as well as a reduced risk of miscarriage.
Standard (proposed) Regimen for preparing the uterus for frozen embryo transfer FET) is as follows:

The recipient’s cycle is initiated with an oral contraceptive-OC (e.g. Marvelon/Lo-Estrin; Lo-Ovral etc) for at least 10 days. This is later overlapped with 0.5 mg. (10 units) Lupron/Lucrin (or Superfact/Buserelin) daily for 3 days. Thereupon the OC is withdrawn and daily 0.25 mg (5 units) of Lupron/Lucrin/Superfact injections are continued. Menstruation will usually ensue within 1 week. At this point, an ultrasound examination is performed to exclude ovarian cyst(s) and a blood estradiol measurement is taken (it needs to be <70pg/ml) until daily progesterone administration is initiated some time later. The daily Lupron/Lucrin/Superfact is continued until the initiation of progesterone therapy (see below).

Four milligram (4mg) Estradiol valerate (Delestrogen) IM is injected SC, twice weekly (on Tuesday and Friday), commencing within a few days of Lupron/Lucrin/Superfact-induced menstruation. Blood is drawn on Monday and Thursday for measurement of blood [E2]. This allows for planned adjustment of the E2V dosage scheduled for the next day. The objective is to achieve a plasma E2 concentration of 500-1,000pg/ml and an endometrial lining of >8mm, as assessed by ultrasound examination done after 10 days of estrogen exposure i.e. a day after the 3rd dosage of Delestrogen.. The twice weekly, final (adjusted) dosage of E2V is continued until pregnancy is discounted by blood testing or an ultrasound examination. Dexamethasone 0.75 mg is taken orally, daily with the start of the Lupron/Lucrin/Superfact. Oral folic acid (1 mg) is taken daily commencing with the first E2V injection and is continued throughout gestation. Patients also receive Ciprofloxin 500mg BID orally starting with the initiation of Progesterone therapy and continuing for 10 days.

Luteal support commences 6 days prior to the ET, with intramuscular progesterone in oil (PIO) at an initial dose of 50 mg (P4-Day 1). Starting on progesterone administration-Day 2, PIO is increased to 100 mg daily continuing until the 10th week of pregnancy, or until a blood pregnancy test/negative ultrasound (after the 6-7th gestational week), discounts a viable pregnancy.

Also, commencing on the day following the ET, the patient inserts one (1) vaginal progesterone suppository (100 mg) in the morning + 2mg E2V vaginal suppository (in the evening) and this is continued until the 10th week of pregnancy or until pregnancy is discounted by blood testing or by an ultrasound examination after the 6-7th gestational week. Dexamethasone o.75mg is continued to the 10th week of pregnancy (tailed off from the 8th to 10th week) or as soon as pregnancy is ruled out. With the obvious exception of the fact that embryo recipients do not receive an hCG injections, luteal phase and early pregnancy hormonal support and immuno-suppression is otherwise the same as for conventional IVF patients. Blood pregnancy tests are performed 13 days and 15 days after the first P4 injection was given.

Note: One (1) vaginal application of Crinone 8% is administered on the 1st day (referred to as luteal phase day 0 – LPO). On LP Day 1, they will commence the administration of Crinone 8% twice daily (AM and PM) until the day of embryo transfer. Withhold Crinone on the morning of the embryo transfer and resume Crinone administration in the PM. Crinone twice daily is resumed from the day after embryo transfer. Contingent upon positive blood pregnancy tests, and subsequently upon the ultrasound confirmation of a viable pregnancy, administration of Crinone twice daily are continued until the 10th week of pregnancy.

Regime for Thawing and Transferring Cryopreserved Embryos/Morulae/Blastocysts:

Patients undergoing ET with cryopreserved embryos/morulas/blastocysts will have their embryos thawed and transferred by the following regimen.

Day 2 (P4) Day 4 (P4) Day 5 (P4) Day 6 (P4)
PN Thaw ET
Day 3 Embryo Thaw ET
Blastocysts frozen on day 5 post-ER Thaw in PM
ET
Blastocysts frozen on day 6, post-ER Thaw in AM
ET in PM

______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

Patients are encouraged to share the information I provide, with their treating Physicians and/or to avail themselves of my personal hands-on services, provided through batched IVF cycles that I conduct every 3 months at Los Angeles IVF (LAIVF) Clinic, Century City, Los Angeles, CA.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Alice

Hi Dr Sher,

Fantastic article thank you.

I’m 42 years old this is my 3rd IVF protocol and I am in the middle of my Flare Cycle (Menopur 450 Day2-11; Decapeptyl 100 Day1-11, Trigger shot Day 11, follicle growth monitored, Timed intercourse agreed with the clinic Day12,13).

My question is on use of Crinone 8% gel. Would you recommend it for my current “protocol”? The nurse told me not to worry about Luteal Support with timed intercourse and 3 follicles??? This was unexpected. I thought it was necessary for a “Flare Cycle” type with the antagonist etc I’m on.

What would be your suggested Luteal Support for this circumstance?

Background:

I’m over 40, a poor responder to IVF drugs, with a history of miscarriage (we’ve had 6 miscarriages in the last 3 years) this stimulation round we grew 3-4(one not likely to mature) follicles and given the current Covid 19 situation we opted to try timed intercourse, instead of egg collection,IVF. Our risk of pregnancy is low, same with multiples.

I’ve already done 2 other “failed IVF” cycles. First one was a different protocol and drugs (we grew only 2 follicles and also did timed intercourse without Crinone) – No pregnancy. Second one was the Flare protocol, we grew 5 follicles, did IVF (5 collected, 5 mature, 5 fertilised, 1 made it to expanded expanded blastocyst, but did not implant – I did Crinone 8% twice a day until I got my negative HCG 14 days after embryo transfer).

I’m also on Baby Aspirin, that was the initial medication we were given

My partner and I already have 1 child together (almost 3yo), and we also had 5 other natural pregnancies apart from my son/all miscarried before we tried IVF. We’ve been trying for almost 5 years. Very lucky to have one baby. We’d love another or more if we can. So I really don’t want to mess up the cycle by not taking Crinone gel. Especially since I’ve been advised to take it in the past.

Thoughts?

reply
Dr. Geoffrey Sher

Frankly, in my opinion, the use of progesterone supplementation in non-IVF stimulation cycles is probably redundant. The bigger issue is your repeatd IVF failures and recurrent pregnancy loss (RPL)

Why did IVF fail:

Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about 15y ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.

4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:

a. A“ thin uterine lining”
b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c. Immunologic implantation dysfunction (IID)
d. Endocrine/molecular endometrial receptivity issues
e. Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).

Recurrent Pregnancy Loss (RPL)

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.SherIVF.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

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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Alice

Thank you for your detailed response. I really appreciate it. I’ll need some time to go over all the info provided.

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Anonymous

I have no fertility issues but underwent Frozen Embryo transfer to have a boy (after having 3 beautiful daughters). I am now 6 weeks pregnant. When I told my doctor I was going to run out of Estradiol in a few days, hoping confirm how much I should get in refill, he replied that I could reduce my dose from 8mg daily to 6mg and then discontinue when I run out. This would mean I stop taking them before the 7 week mark. He assured me that the estradiol has already fulfilled its purpose in the endometrial lining and that it is safe. I am continuing to use progesterone pessaries until 12 wks. According to what I read everywhere else it seems uncommon to discontinue estradiol before the 10 week mark. How important is estradiol in supporting the pregnancy at this point and until what point should I be taking it?

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Dr. Geoffrey Sher

Respectfully,

The conversion from dependency on outside hormone support (in regular pregnancies from the ovaries and in Embryo recipient cycles through administered estrogen and progesterone) is believed to take place towards completion of the 8th week. Accordingly, to be on the safe side, I advise my patients to continue hormone therapy for a few additional weeks…. until the 10th week. While you might be OK stopping so early, I personally would not recommend this.

Geoff Sher

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Monique

Hi Dr Geoff,
I was diagnosed with PTSD a few months ago after suffering g for the last 2 years. I knew that something was not quite right with my cycle as I was and still am getting mid cycle bleeding around day 14/15. My fiancé had been trying to fall pregnant, but k ew there was an underlying issues and suspected my hormones levels. After testing recently I have very high cortisol levels throughout the night and when I wake, but somewhat normal after lunch till about dinner time. My Estrogen is very high the entire cycle and progesterone low the whole cycle with out too many dips or rises. If I test for ovulation using a home kit I sometime a get a LH surge around day 10. So the spotting/bleeding would be approx 2 days after ovulation ( but dr very doubts I have ovulated in that 2 years) . I have been prescribed 100mg of progesterone and of course doing everything I can to help minimise stress . I have been doing this for about 3 weeks now. Other tests have shown ultrasound no fibroids etc everything normal, FSH is 2, thyroid function is normal , Pap smear clear!
Up until this trauma I have had 3 children naturally, never a hormone problem, never a miscarriage, no issues at all.
So my questions are , would you recommend anything else to help balance my hormones and would this hormone imbalance affect me if I was thinking about IVF? Would it be a waste of time until my progesterone increased
Thanks
Monique

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Dr. Geoffrey Sher

Hi Monique,

Thank you for thge inquiry. Unfortunately, I would need to have much more detailed and specific information to be able to advise authoritatively.

Feel free to contact Patti (my assistant() at 702-533-2691 to set up an online consultation with me to discuss in detail.

In the interim…Please STAY SAFE!!

Geoff Sher

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Megan

I am in very early pregnancy and my progesterone right off the bat was at 15.5 my doctor has me taking extra progesterone 2 200mg in the am and 2 200mg in the pm. The second test my progesterone was at 21 now I am on my 3rd and it dropped to 13.5 with taking that extra progesterone it worries me. I had one miscarriage before this pregnancy and I am so worried about having another with this progesterone dropping like that. He told me to start taking One in the morning one in the afternoon and 2 in the evening so I get it throughout the day. Well I had already taken my two this morning and he would rather I take the 2 at night than 1. My a question is should I just do 1 extra one in the afternoon today or wait to start what he recommended tomorrow? I am just so nervous about this drop. Thank you

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Dr. Geoffrey Sher

Hi Megan,

In my opinion, a dropping progesterone is usueally the consequence rathe3r than the cause of a failing pregnancy. I personally do not believe that pushing the progesterone will help much, if at all. You just have to wait this through , I am afraid! Hopefully all will turn out OK!

Good luck!

Geoff Sher

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Alexandra Garcia

Good afternoon Dr. Sher and thank you for responding to our questions…

I had a successful IVF, however I’m always thinking if I did any significant harm to my body after taking all the hormones, I was on 8mg of oral estrogen and progesterone via injection daily for about 10-11 weeks. Is this the usual amount prescribed… and are there any serious side effects I should be concerned about? Thank you in advance.

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Dr. Geoffrey Sher

I would completely dispel this concern as it has no validity whatsoever, in my opinion.
Good luck and G-d bless!

Geoff Sher

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rabia rashid

Hello I am 8 weeks pregnant (from my last period date which was feb 8 2020 but my FET was 3/4/2020) can I discontinue my progesterone and estrace safely? we have confirmed blood tests and ultrasound. Both meds make me feel so sick. Normal protocol for my clinic is 10 weeks but is it harmful to discontinue before then?

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Dr. Geoffrey Sher

You probably would be OK stopping at the end of the 8th week but my advice is to continue hormone support until the 10th week!

Good luck!

Geoff Sher

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Autumn

Great article!
I am currently 8 weeks, 5 days pregnant (conceived naturally). During my 6 week bloodwork my progesterone was 16.3. At 8 weeks and 3 days pregnant it was tested again and had gone up to 18.9. My doctor wants to put me on Endometrin progesterone suppositories (twice a day). She said although my progesterone had improved, it was not at the level that she would like. I will say that my sister had 3 miscarriages and she also had low progesterone, so I am not sure if that is why she is doing this as a precaution. This is my first pregnancy and I am 35 years old. I will take it if it will help maintain the pregnancy; however, I am concerned about birth defects as all of the main organs are developing during this time. I do not want to do anything that could create more harm if it isn’t needed in the first place. Would you prescribe progesterone for someone in my position? Are there any known birth defects?
Thank you so much for any advice!

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Dr. Geoffrey Sher

I concur with your RE’s advice. It will not cause birth defects in my opinion.

Geoff Sher

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Lee

Thank you for this wonderful article! My clinic have asked me to stay on estradiol 6mg and PIO until week 14, as it’s normal protocol for them. Are there any adverse effects staying on the hormones that long, even though it may not be necessary? Many thanks!

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Lee

I should day that mine was a frozen embryo cycle, and I am now 12 weeks pregnant. I began day 2 of my cycle with 8mg estradiol, and PIO about 5 or 6 days before my transfer. We are so happy with our result, but can’t wait to come off the medication, as nerve wracking as that will be!

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Dr. Geoffrey Sher

I do not believe there are serious down-sides. Not certain as to why they so recommend. however.

Geoff Sher

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Kyle Koepp

Thank you for your time! Is that 10 weeks gestation or 10 weeks from the transfer date? Thank you for your help it’s has been difficult getting some clarity on this!

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Kyle Koepp

Dr. Sher

Do you feel there is any issue with continuing PIO for an additional week (after 10 weeks) without oral estradiol? Could we possibly taper down the PIO for another week without estrogen supplementation. I didn’t know if there are problems with supplementing one without the other.

Thanks again!

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Worried

What should my E2 level be in early pregnancy? My doctor has me taking 6 pills of Estrace daily, which seems high. Is there danger in taking too much? Could my actual E2 level be higher than the blood draws indicate, because the blood monitoring always happened first thing in the morning, prior to my morning (3 pill) dose? I take the meds every 12 hours but the first dose of the day was always 30 to 60 min after the blood draws. The last time my blood was checked, I was 2 weeks post 5 day frozen transfer, and E2 was in the 300s. They have not checked since because ultrasound 1.5 weeks later showed fetal sac. I wonder if I should get blood tested again or if high Estrace dose is not concerning.

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Dr. Geoffrey Sher

I do not believe retesting with have any benefit!

Geoff Sher

Maggie S

Taking PIO (1ml) now as taking crinone (8%, twice a day) did not curb luteal phase bleeding for me (I spot/bleed consistently about ten days prior to menstruation). Does PIO seem more effective than crinone? Despite delivering a lower dose of the hormone?

Also my E2 level seem okay/high – the day before my IUI I was at 694 (I had surged (LH 34) on my own). My RE and nurses have never mentioned supplementing my progesterone with EE pills… is there a benefit to do so even if E2 levels seem okay?

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Dr. Geoffrey Sher

Crinone 8% twice daily offers excellent P$ support. I honestly do not believe you need estrogen supplementation.

Geoff Sher

Liz

Hi Dr Sher,

I had a FET on 10/14, artificial cycle. After transfer I am taking prometrium 100mg x2 daily, progesterone pessaries 220mg x2
daily, and 20mcg ethinyl oestradiol daily( I had thin lining, dr put me on high dose ee) On 11/8, 6w2d I had a blood test of HCG Progesterone and E2, HCG is 35000, progesterone level is 64 nmol/L and E2 is 1200 pmol/L. The nurses told me to keep progesterone but drop EE pills completely without any weaning, do you think it’s ok to stop the estrogen so early at 6 weeks? (Also my morning sickness seems to be disappearing after stopping the EE tablets. I am really worried as I had a missed miscarriage back in March at 6 weeks (fresh transfer)) Thank you!

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Dr. Geoffrey Sher

Respectfully, while it probably will do no harm, I prefer to continue both E2 and progesterone to 10 weeks and then stop.

Geoff Sher

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Dana

I just did a FET cycle and was alternating with IM injections every other day and 3 x day endometrium every day. 2 days before my FET Progesterone levels were over 12 and on the day of FET were 3.7. They mentioned their lab sometimes gives low levels and I went back 2 days after FET and their lab was 4.7 and outside lab was 7.2. I was then told sometimes taking vaginal inserts the levels drop, but they increased the IM injections to 1.5ml every day and no more pessaries. Is it normal for levels to drop and can pessaries not be detected in blood? Is it possible to still get a BFP with such low levels as the embryo may not be able to implant?

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Dr. Geoffrey Sher

I personally prefer PIO shots than vaginal…but blood levels are commonly much lower after vaginal steroid administration than with IM shots….I would not be overly concerned.

Geoff Sher

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Sona

In April 2019, my pregnancy was terminated due to cervical ecptopic at 6th week.
I had second frozen embryo transfer on 28th Nov. Doctor made changes this time by supplementing more estrogen (2-2-2 tabs daily)which is continued till now and progesterone gel twice a day, pessaries once a day and drydogesteron twice a day.
Also daily injection to slow down uterine convulsions, Do you think this will prevent cervical ecptopic this time ? I am slightly worried as my home pregnancy test shows light pink line. Thanks in advance.

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Dr. Geoffrey Sher

Cervbical ectopics are VERY, VERY rare and it is unlikely that b”lightening will strike” at the same spot again.

Geoff Sher

reply
Jo

Dear Dr. Sher,

Thank you for this incredibly interesting article! I’m 30, have extremely low early follicular (day 1 of cycle) estrogen levels (17-beta estradiol) at 0.09 nmol/L (24.5 pg/mL), and have three failed IVF cycles (two fresh, one frozen) behind me. What sort of estrogen supplementation regimen (patch versus oral or injected, and dosage) would you recommend for patients like me? Should I be taking estrogen supplementation during fresh cycles as well as frozen ones?

Thank you incredibly much for any insight you can provide!

Kind regards 🙂

reply
Dr. Geoffrey Sher

With the exception of post-menopaual women with chronically hypoestrogenic and are unable to develop an ideal endometrium, I would only use estrogen? progesterone supplementation durinG embryo replacement cycles.

The recipient’s cycle is initiated with an oral contraceptive-OC (e.g. Marvelon/Lo-Estrin; Lo-Ovral etc) for at least 10 days. This is later overlapped with 0.5 mg. (10 units) Lupron/Lucrin (or Superfact/Buserelin) daily for 3 days. Thereupon the OC is withdrawn and daily 0.25 mg (5 units) of Lupron/Lucrin/Superfact injections are continued. Menstruation will usually ensue within 1 week. At this point, an ultrasound examination is performed to exclude ovarian cyst(s) and a blood estradiol measurement is taken (it needs to be <70pg/ml) until daily progesterone administration is initiated some time later. The daily Lupron/Lucrin/Superfact is continued until the initiation of progesterone therapy (see below).

Four milligram (4mg) Estradiol valerate (Delestrogen) IM is injected SC, twice weekly (on Tuesday and Friday), commencing within a few days of Lupron/Lucrin/Superfact-induced menstruation. Blood is drawn on Monday and Thursday for measurement of blood [E2]. This allows for planned adjustment of the E2V dosage scheduled for the next day. The objective is to achieve a plasma E2 concentration of 500-1,000pg/ml and an endometrial lining (≥8mm) as assessed by ultrasound examination following the 4th dose of E2V. The twice weekly, final (adjusted) dosage of E2V is continued until pregnancy is discounted by blood testing or an ultrasound examination. Dexamethasone 0.75 mg is taken orally, daily with the start of the Lupron/Lucrin/Superfact. Oral folic acid (1 mg) is taken daily commencing with the first E2V injection and is continued throughout gestation. Patients also receive Ciprofloxin 500mg BID orally starting with the initiation of Progesterone therapy and continuing for 10 days. Luteal support commences 6 days prior to the ET, with intramuscular progesterone in oil (PIO) at an initial dose of 50 mg (P4-Day 1). Starting on progesterone administration-Day 2, PIO is increased to 100 mg daily continuing until the 10th week of pregnancy, or until a blood pregnancy test/negative ultrasound (after the 6-7th gestational week), discounts a viable pregnancy.

Geoff Sher

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Nayab

Hello Dr,Sher I am on 7dpt and my question is I was taking estradiol patch before the fet the dose was increased from 1 to 4 patch every 3 days but after the transfer my RE decreases it to 2 patch is it ok? My second question is I’m having abdominal cramp and diarrhea after 3dpt is that a sign of problem? Thanks!

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Dr. Geoffrey Sher

I do not use estrogen patches on my patients. My preference is to use injectible estradiol valerate twice weekly. Accordingly, I suggest that you discuss this with your treating8 RE.

Geoff Sher

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Chrissy

Hi Dr Sher, I am currently day 5 after donor egg FET (5 day early blasto) and on Progynova and progesterone pessaries 100mg*3 after a failed fresh transfer last month. I started bleeding day 2 with cramps and stopped overnight dull cramps continuing for the day. Two days later (yesterday) bleeding started again pm and continuing today (clear mainly watery bright red). My clinic says could be the cervix rather than uterus bleed? Is there any chance at this point of a positive result and when do you think I can do first home test? are the oestrogen and progesterone supposed to stop period so this is maybe something else? Thank you for your time.

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Dr. Geoffrey Sher

It could well be bleeding from a friable cervix. If so, all should be OK!

Good luck!

Geoff Sher

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Lisa Wilson

Hi Dr Sher,
I’m 7.5 weeks pregnant with twins after donor embryo transfer. I’m taking 600mg Utrogestan (vaginally)and 6mg Progynova (orally) daily. At two weeks post transfer, my HCG readings were 1440 (Wed), 5300 (sat) and 14500 (tues) respectively, so doubling well.
Recent scan at 6w5d revealed two heartbeats and all going well. I’m interested to read your article about continuing medicating until 10weeks. After 10 weeks should I be reducing the dose gradually or can I just stop? I’m concerned of the effect of a significant drop in hormone levels on the pregnancy.
Thanks

reply
Dr. Geoffrey Sher

In my opinion, you could just stop at 10 weeks, but first pass this by your own RE…your treating doctor.

Geoff Sher

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Horlicks

Thankyou so much for this article! I am currently 10weeks pregnant from a medicated FET cycle. Had a scan last week at 9 weeks baby growing on target with a heartbeat of 184. I’ve been instructed to come off meds at 10 weeks. Is it normal to come of progesterone ( IM ) and estradiol at exactly 10 weeks even with a medicated FET ? The placenta is producing what is needed for the pregnancy ? Thanks!

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Sam

So my question Dr, in some parts of Asia progesterone suppository meds are hard to get. Is 3x10mg duphaston for the first 10 weeks sufficient? I have read studies that injected progesterone results in better live birth rates. Regards,

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Elle

Hello Dr. Sher,
I’m 41 and had a FET on 7/8 with a 4AA PGS blastocyst that had fully hatched after thawing. Went in for my beta on 7/17 hcg was 143, then again on 7/15 hcg was 417. I was then handed off to my OB. I went in on 8/2 for my first ultrasound at which I was 6wks 2 days. The baby measured exactly at 6wks 2 days and had a heartbeat of 119. The doc tested my estrogen and progesterone levels – they came back this morning as estrogen = 343 and progesterone = 18.5. My question is do you feel that my progesterone level is high enough? I’m currently on 1ml PIO nightly. I’ve read on certain sites that over 25 is ideal. Also, he started me on a baby aspirin – what are your thoughts about taking that as well? Thank you SO much for your help & guidance!! Elle

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Fab

My doctor has increased my dsily progynova frm 8mg daily to 12mg after embryo transfer 3 weeks ago. I had beta hcg done 2 weeks after transfer positiv 745 and on 3rd week today 4800. Is it safe for me and the fetus, to be takin tat dose of progynova? Doctor may keep it until week 10. My lining was 9.3mm the day before transfer. Also taking 75mg aspirin, 60mg duphaston and crinone twice a dah.

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Dr. Geoffrey Sher

I am not sure why this increase?. However it should not adversely affect the conceptus or the pregnancy…in my opinion.

Geoff Sher

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Izabela Kaczynska

Dear Doctor Sher,

I am two and a half weeks after FET. The pregnancy have been confirmed and I am waiting for my 8 week scan. I am on high doses of Progynova tablets (10mg a day) and 400mg Cyclogest pessaries twice a day and I was told to continue with this dosage. The infertility comes from male factor and I have never had any issues with building of the lining. I asked for a blood test to check my hormones levels because I was worried that the dose is to high but my clinic says it’s a standard protocol.
Does too much estrogen can affect in any way the development of the fetus?

Thank you,
Izabela

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Dr. Geoffrey Sher

I do not think there is anything for you to be concerned about at this point!

Geoff Sher

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Izabela Kaczynska

Dear Dr. Sher
Thank you very much for your comment. It put my mind at ease.
Izabela

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Tera

I am currently in my 8th week of pregnancy from an FET. I’m on 800mg of progesterone (prometrium) and 8mg of estrace daily. The last two weeks I’ve had a problem with thrombosis in a hemangioma in my hand. It’s very painful, swollen and a little scary. I’ve read estrogen can agitate this. Is it safe to cut back my estrogen dose at this time to 4mg daily?

Thanks for any information.

Dr. Geoffrey Sher

Hi Tara,,

From my personal point of view, you could lower the dosage of estradiol but that decision is one that needs to be discussed with your personal treating physician.

Geoff Sher

MZ

Hello, in your experience have you seen any cases of estrogen induced pancreatitis in ivf patients? I am 3 days post transfer and my pregnancy test is not for another few days. My upper left abdomen has been hurting constantly. Also how many weeks after a positive pregnancy test does the estrogen intake usually continue?

Dr. Geoffrey Sher

I could be wrong but I am not aware of a link to pancreatitis.

Geoff Sher

Ange

Hi Dr Sher
Can you please clarify, when you say “8th week of pregnancy” do you mean gestational age, fetal age, or weeks after ET?
Thanks for the very helpful article!

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Dr. Geoffrey Sher

No,it refers to 8 weeks following the last menstrual period…

Geoff Sher

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Shannon Kimsey

Hi Dr. Sher. I was scheduled for fet today but one last scan before showed signs of degeneration in lining so transfer was canceled. For this cycle, I was started on 4mg po and 4 mg vaginally and at first scan was 7mm and second scan had dipped to 5.5. My dose of estrace was raised to 6 mg po and 6mg vaginally at which I got back up to 8.2. However that extra week on estrace I felt was detrimental to my lining. Was a total of 24 days. Why the dip in lining earlier on? Would a step dosage of estrace have prevented this ? The plan is to restart lupron tonight and once period begins, start estrogen again. They are giving me a choice of form of estrogen bc I voiced concern in absorption vaginally etc. She said she would be ok doing either Patches or IM but was trying to talk me into patches. What should I do??

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Dr. Geoffrey Sher

I think this was bad luck! Respectfully however, I do not advocate oral estrogen. My preference is to prescribe the protocol below or to use E2 skin patches. The absorbtion is in my opinion far better.

Standard (proposed) Regimen for preparing the uterus for frozen embryo transfer (FET):

The recipient’s cycle is initiated with an oral contraceptive-OC (e.g. Marvelon/Lo-Estrin; Lo-Ovral etc) for at least 10 days. This is later overlapped with 0.5 mg. (10 units) Lupron/Lucrin (or Superfact/Buserelin) daily for 3 days. Thereupon the OC is withdrawn and daily 0.25 mg (5 units) of Lupron/Lucrin/Superfact injections are continued. Menstruation will usually ensue within 1 week. At this point, an ultrasound examination is performed to exclude ovarian cyst(s) and a blood estradiol measurement is taken (it needs to be <70pg/ml) until daily progesterone administration is initiated some time later. The daily Lupron/Lucrin/Superfact is continued until the initiation of progesterone therapy (see below).
Four milligram (4mg) Estradiol valerate (Delestrogen) IM is injected SC, twice weekly (on Tuesday and Friday), commencing within a few days of Lupron/Lucrin/Superfact-induced menstruation. Blood is drawn on Monday and Thursday for measurement of blood [E2]. This allows for planned adjustment of the E2V dosage scheduled for the next day. The objective is to achieve a plasma E2 concentration of 500-1,000pg/ml and an endometrial lining (≥8mm) as assessed by ultrasound examination following the 4th dose of E2V. The twice weekly, final (adjusted) dosage of E2V is continued until pregnancy is discounted by blood testing or an ultrasound examination. Dexamethasone 0.75 mg is taken orally, daily with the start of the Lupron/Lucrin/Superfact. Oral folic acid (1 mg) is taken daily commencing with the first E2V injection and is continued throughout gestation. Patients also receive Ciprofloxin 500mg BID orally starting with the initiation of Progesterone therapy and continuing for 10 days. Luteal support commences 6 days prior to the ET, with intramuscular progesterone in oil (PIO) at an initial dose of 50 mg (P4-Day 1). Starting on progesterone administration-Day 2, PIO is increased to 100 mg daily continuing until the 10th week of pregnancy, or until a blood pregnancy test/negative ultrasound (after the 6-7th gestational week), discounts a viable pregnancy.
Also, commencing on the day following the ET, the patient inserts one (1) vaginal progesterone suppository (100 mg)in the morning + 2mg E2V vaginal suppository (in the evening) and this is continued until the 10th week of pregnancy or until pregnancy is discounted by blood testing or by an ultrasound examination after the 6-7th gestational week. Dexamethasone o.75mg is continued to the 10th week of pregnancy (tailed off from the 8th to 10th week) or as soon as pregnancy is ruled out. With the obvious exception of the fact that embryo recipients do not receive an hCG injections, luteal phase and early pregnancy hormonal support and immuno-suppression is otherwise the same as for conventional IVF patients. Blood pregnancy tests are performed 13 days and 15 days after the first P4 injection was given.
Note: One (1) vaginal application of Crinone 8% is administered on the 1st day (referred to as luteal phase day 0 - LPO). On LP Day 1, they will commence the administration of Crinone 8% twice daily (AM and PM) until the day of embryo transfer. Withhold Crinone on the morning of the embryo transfer and resume Crinone administration in the PM. Crinone twice daily is resumed from the day after embryo transfer. Contingent upon positive blood pregnancy tests, and subsequently upon the ultrasound confirmation of a viable pregnancy, administration of Crinone twice daily are continued until the 10th week of pregnancy.
Regime for Thawing and Transferring Cryopreserved Embryos/Morulae/Blastocysts:
Patients undergoing ET with cryopreserved embryos/morulae/blastocysts will have their embryos thawed and transferred by the following regimen.

Geoff Sher (800-780-7437)

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Sharon

Dr. Sher.

Thank you for the helpful information!

It appears that different fertility centers stop Estrace/Progesterone at different time points. Is there any harm in taking Estrace/Progesterone past 10 weeks gestation? Do you typically stop Estrace/Progesterone at the same time or sequentially (for example stopping Estrace at 8 weeks and Progesterone at 10 weeks).

Thank you

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Dr. Geoffrey Sher

I do not believe there is a need to go beyond 10 weeks, but doing so should not be harmful…in my opinion.

Geoff Sher

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Angela Mcgee

What is your preference? Oral estradiol vs intravaginal vs Delestrogen injections? And Why?

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Dr. Geoffrey Sher

Oral estrogen is first absorbed via the gastrontestinal system into the portal blood system to reach the liver. and from there it passes via the liver before reaching the systemic circulation and the uterus. In the process it is altered. This is avoided when vaginal or parenteral (injections) are used. Vaginal absorbtion is somewhat erratic. Parenteral estrogen (injections) estradiol valerate (Delestrogen) is the best way to go because absorption can be controlled allowing the estrogen to directly access the systemic circulation and thereby reach the uterus, unaltered. Furthermore, a significant amount of oral estradiol or Estrace (the oral estrogen compound used most commonly) converts to estrone before reaching the uterus and this is this is far less beneficial than estradiol.

Geoff Sher
Geoff Sher

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Dr. Geoffrey Sher

I do not prescribe Estrace. discuss with your personal RE please!

Geoff sher

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Resh

Hello doc.
I had done fet blastocyst on 22nd jan and underwent blood test yesterday. The readings of prog is 25 and e2 is 615. Pls advise if this reading is good enough. I am 41 years old and this is my 2nd ivf cycle. Had 5 good blastocyst which they have inserted 2 of yhem in this cycle.

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Dr. Geoffrey Sher

I would need to know the hCG level rather than E2 and progesterone to tell if you are implanting and likely to be pregnant.

Geoff Sher

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Resh

Thanks for ur revertal. The doc has asked me to do bhcg on 5th feb. I am sure tat will show the actual results. I was quiet surprised why this blood test was done wen it doesnt give an idea of positive or negitve results. Wl revert bak as soon as i hv my reports. Tks n hv a great day ahed.

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Nadine

Hi Dr. Sher,
I am 8.5 weeks pregnant with twins following a Clomiphene cycle. I took Prometrium 200mg and oral Estrace 2mg daily as a ‘safety net’ due to my severe DOR and LPD. Doc said after 8 weeks it is fine to stop both cold turkey. Thoughts?

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Dr. Geoffrey Sher

It would likely be OK but I personally recommend stopping a little later….. at 10 weeks!

Geoff Sher

Jamie

This was a great article Dr. Sher. Many thanks! I love the level of detail you use. It’s really helpful.

I have been looking and looking, but I can’t find an answer to this question so maybe you can enlighten me. I am 31 years old with no known issues (our infertility is male factor). We are gearing up for our first frozen cycle and my doctor has me on Estrace and Progesterone (vaginally) for 7 days until the end of my cycle, then I after stopping those I should get my period. Then I’ll call in my Day 1 and we’ll start prepping for a FET that cycle. My question is…why am I on anything at all this cycle when technically we’re taking a “break” between our egg retrieval (which was in December) and our FET (which will be in February). What is the purpose of taking both these meds if we’re not doing anything this month? Please help….this feels like such a technical question but I can’t find an answer!

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Jamie

I should add that originally we were going to head straight into a FET in January so they had me take Estrogen starting on my Day 1. But we changed out minds around about Day 8 and said that we would prefer to have a month off. Could having started Estrace on Day 1 be the reason they feel we must keep up the protocol this month, even if we’re not having a FET until the following month? (Thought I’d provide that info in case it’s relevant.)

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Dr. Geoffrey Sher

As I see it the likely reason is to be able to launch and precisely time the treatment for your FET.

Geoff Sher

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Grace

Hi Dr. Sher,
I just recently finished my first ivf cycle, to find out this afternoon that I am having a chemical pregnancy. I was taking 1 cc of PIO and 4 mg of Estrace. At 5 days past transfer, I went in to my dr for with bright red spotting, and when they ran my blood, they found that my progesterone levels were extremely low (20). This comes after my levels were in the thousands after my retrieval. My Dr upped me to 1.5 PIO, 3 days later my levels had raised a bit, bit the dr still has no idea why my body isn’t absorbing the PIO. He’s sure that this is the reason my pregnancy failed. I have heard of people getting PIO and suppositories, is this something that you would recommend? Any idea why my levels will not rise even with daily injections?

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Dr. Geoffrey Sher

In my opinion, a low progesterone is the consequence (rather than the cause) of a failing implantation.

Geoff Sher

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Deborah

Dear Dr. Sher, I am almost 48 and preparing for my first ever FET using a 6 day BB blastocyst (PGD tested). I made the blast at age 44. This last year my cycles went from 27-28 days the first half of the year to most cycles now at 25 days, with a few 26, 27 or 29 days thrown in. I would rather not do a Lupron cycle. What would you recommend in my case? This is my last chance. Thanks

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Dr. Geoffrey Sher

I personally would advise against natural cycle FET at your age. You need to use hormone therapy coming off a BCP in my opinion…whether you use Lupron overlap (which I believe to be preferable) or not.

Frozen Embryo Transfer (FET): A frozen embryo transfer cycle is initiated by administering an oral contraceptive (OC) to the recipient. This is later overlapped with Lupron daily for 5-6 days. The OC is then withdrawn, but the daily Lupron injections are continued until the onset of menstruation. Next, the Lupron dosage is reduced and intramuscular (IM) estradiol valerate (Delestrogen) is administered every 3 days. The objective of the estradiol is to achieve and sustain an optimal plasma E2 concentration of 500pg/ml-1000pg/ml and a 9mm endometrial lining as assessed by ultrasound examination. Intramuscular and/or intravaginal progesterone is administered daily starting about 6 days prior to the FET and continued along with twice weekly IM Delestrogen until the 10th week of pregnancy or until it has been confirmed that the patient is not pregnant.
Daily oral dexamethasone commences with the Lupron start and continues until a negative pregnancy test or until the completion of the 8th week of pregnancy. Then it is tapered down and discontinued. The recipient also receives prophylactic oral antibiotics starting with the initiation of Progesterone therapy, until the day after ET. Usually we would thaw vitrified blastocysts with the objective of having 1, 2 or 3 for transfer; depending on a couple’s stated preference. Commencing on the day following the ET, the patient inserts a vaginal progesterone suppository daily and this is continued until the completion of the 8th week of pregnancy or until a negative pregnancy test.
As an alternative regimen for women who cannot tolerate intramuscular Progesterone (PIO), we prescribe either Crinone vaginal gel or Endometrin vaginal inserts according to protocol. If you’d like to explore one of these options, talk to your physician. For blastocyst FET’s, the blood pregnancy tests are performed 13 days and 15 days after the first progesterone administration is commenced.

Good luck!

Geoff Sher

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Mark

In your opinion is it necessary to monitor progesterone levels after the 10th week mark with a normal ultrasound? How can one be certain that the placenta is producing the necessary amount to sustain the pregnancy?

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Kyle Koepp

We did a FET (5 day) on Nov 11. Our clinic wants us to stay on estradiol (oral) 8mg daily and PIO 2ml daily until 14 weeks (Jan 29). My wife has circulation problems (Raynauds) and regular headaches. We are wanting to possibly wein down sooner based on her risk of clotting and the side effects she has been having. We have been confused about the 10 weeks you suggest. Would that be from the date of the transfer?

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Angel

Dear Dr Sher,
I just turned 43, I have a 3 year old we conceived on clomid at 39. We desire to have sibling for our son. It’s the deepest desire in my heart. So I just attempted my first ivf cycle. We have been actively trying for 2 years clomid first year then from 41-42 we did 3 IUIS. We have never miscarried. We finally turned to ivf to give it a shot. I did microdose lupron flare protocol.
I got 6 eggs collected, 4 fertilized, 3 embryos all transfered on day 3. A fresh embryo transfer. I am waiting a few more days till I test to see results. If it is not successful do you think i should move on to embryo adoption? I just discovered you see patients in LA. We live there. We have already spent so much $. Do you ever have trials you need woman over 40 for. Also do u suggest a second cycle with my own eggs? Thank you for your advice! Your articles are incredible!
x Angel

Dr. Geoffrey Sher

Age is definitely a factor here.

This having been said, it is hard to give advice when you may not have the resources to do what otherwise might be the best way to go. There is no doubt that egg donation or embryo adoption (if the embryo provider was young and/or had the embryos tested through PGT-A)would be more likely by far to succeed. But, given your history, it might be worth trying another cycle with own eggs, perhaps using a different protocol for ovarian stimulation.

The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

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

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

______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

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Geoff Sher

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