Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Hi Dr Sher,
I have one Fallopian tube due to an ectopic pregnancy, and endometriosis. I have been off the pill for 4 years now so I know I will need fertility treatment. However, I want to be married first. I’m 31, and I’m not going to be married for another year at least. Am I leaving it too late to begin treatment? I’m hoping to begin treatment before I’m 34
Thanks
As long as your ovarian reserve is good you should be OK waiting a year or two. Have your AMH checked ASAP.
Geoff Sher
Hello Dr Sher, I read your blog and wonder what the difference is between an down reg cycle using an agonist and a down reg cycle using an agonist then switching to an antagonist, such as a ganirelix, a few days later. Doesn’t the agonist prevent ovulation? What is the benefit of switching to an antagonist (ganirelix) to stop ovulation when the agonist is doing the job of already keeping LH levels down to avoid premature ovulation?
Agonist]s in my opinion can, by competing with FSH for receptor occupancy in the follicle cells can somewhat blunt response to stimulation. Antagonists do not! Thus women with any degree of diminishing ovarian reserve are better of with the agonist/antagonist conversion protocol…in my opinion.
The use of GnRH antagonists as currently prescribed in ovarian stimulation cycles, i.e. the administration of 250mcg daily from the 6or 7th day of stimulation with gonadotropins is in my opinion problematic when used in women who have diminished ovarian reserve (DOR) (i.e. are “poor responders” to gonadotropins),. In such cases the commencement of pituitary LH suppression with GnRH antagonists 6-7 days into the stimulation fails to suppress high tonic pituitary LH in the first few days of stimulation and it is at this time , formative (early) stage of follicle/egg development early on in the most the vulnerable stage. One of the roles of LH is to promote androgen (mail hormone) production which in turn is essential (in modest amounts) for optimal follicular growth to take place. In women with high LH and/or ovarian stromal hyperplasia, the failure of conventional GnRH antagonist protocols to address this issue, results in the inevitable excessive exposure of follicles to androgens (mainly testosterone). This can adversely influence egg/embryo quality and endometrial development.
The likely reason for the traditional approach of commencing GnRH- antagonist 6-7 days after stimulation with gonadotropins commences, is to try to block the release of LH (later in the cycle) so as to try to prevent the occurrence of the so called “premature LH surge” (syn; premature luteinization), which is most commonly seen in women with DOR, who tend to be susceptible to LH-induced “follicular exhaustion” resulting in poor egg/embryo quality. But if truth be known, the term “premature LH surge” is a misnomer. Contrary to popular belief, the concept of LH rising as a “terminal event” late in the cycle is, erroneous. In fact rather than representing an isolated event, the so called “premature LH surge” is the end point of a progressive escalation in LH (“a staircase effect”) which results in increasing ovarian stromal activation with commensurate growing androgen (mainly testosterone) production. A more appropriate term would be …”Premature Luteinization”. So, trying to improve ovarian response and protect follicular exhaustion by administering Ganirelix/Cetrotide/Orgalutron starting during the final few days of ovarian stimulation is like trying to prevent a shipwreck by collision, through removing the tip of an iceberg. The use of such late GnRH-antagonist protocols in women who have a normal ovarian reserve (i.e. are “good responders”) will probably not produce such adverse effects because the tonic endogenous LH levels are low (normal) and such women are unlikely to have ovarian stromal hyperplasia.
It is my opinion that some form of pituitary blockade, either in the form of a GnRH agonist (e.g. Lupron, Buserelin, Superfact or Decapeptyl) or a GnRH antagonist (e.g. Orgalutron Cetrotide, and Ganirelix) is an essential component in ovarian stimulation of “poor responders” undergoing IVF. If this is not done, a progressive rise in LH –induced ovarian androgens (male hormones ….mainly testosterone) will often adversely affect follicle/ egg development, resulting in compromised embryo quality. However, when a GnRH antagonist is used in women with DOR, it is my belief (for reasons cited above) that it should preferably be administered from early in the cycle, at the time that gonadotropin stimulation starts and NOT 6-7 days later, as is traditionally done. In such cases, the dosage of the GnRH antagonist can in my opinion be reduced to 125mcg daily.
The long Pituitary agonist down-Regulation approach: With the long Lupron down regulation protocol the administration of the GnRH agonist begins several days in advance of commencing gonadotropin stimulation. As such, by the time gonadotropin stimulation commences, most LH has been expunged from the pituitary gland thereby avoiding over-production of ovarian androgens. However, this protocol involves continued administratio0n of the GnRH agonist throughout the stimulation phase and this is not ideal for women who have DOR where prolonged administration of GnRH agonists could blunt follicular response to ovarian stimulation with gonadotropins (perhaps by competitively binding with ovarian FSH receptors).
The agonist-Antagonist conversion protocol (A/ACP). I introduced the A/ACP for women with DOR, in order to counter the suppression effect of the traditional long Pituitary agonist down-regulation protocol.. With the A/ACP, low dose GnRH-antagonist (Ganirelix/Cetrotide Orgalutron) is commenced at the onset of menstrual bleeding that follows initiation of GnRH agonist therapy using a long-down-regulation protocol approach or at the onset of spontaneous menstruation. I currently prescribe the A/ACP to most of my IVF patients who have DOR. Results suggest that this is an optimal approach in such cases. In such cases I augment the stimulation with human growth hormone.
There is one potential draw back to the use of the A/ACP, in that the sustained use of a GnRH antagonist throughout the stimulation phase of the cycle, appears to compromise the predictive value of serial plasma estradiol measurements as a measure of follicle growth and development in that the estradiol levels tend to be much lower in comparison to cases where an agonist (e.g. Lupron) alone is used or where a “conventional” short GnRH antagonist protocol is employed. Rather than this being due to reduced production of estradiol by the ovary(ies), the lower blood concentration of estradiol seen with prolonged exposure to GnRH-antagonist, could be the result of a subtle, agonist-induced alteration in the configuration of the estradiol molecule , such that currently available commercial kits used to measure estradiol levels are rendered much less sensitive/specific. Thus when the A/ACP is employed, we rely much more heavily on ultrasound growth of follicles along with observation of the trend in the rise of estradiol levels, than on absolute estradiol values. For this reason I avoid prescribing the A/ACP in “high responders” who are predisposed to the development of severe ovarian hyperstimulation syndrome (OHSS) where accurate measurement of plasma estradiol plays a very important role in the safe management of their stimulation cycles.
The A/ACP with Estrogen priming: In women who have severe DOR (AMH=<0.1 ng/ml) I modify the A/ACP The A/ACP through incorporation of “estrogen priming” with injections of estradiol valerate (Delestrogen), given twice weekly for about a week following the initiation of the A/ACP, and prior to commencing FSH-dominant gonadotropin stimulation. I then continue this through gonadotropin stimulation. Estrogen Priming appears to further enhance ovarian response….presumably by up-regulating ovarian FSH-receptors. ”.
“Flare Protocols” in women with DOR: With the “Flare” approach, GnRH agonist (e.g. Lupron/Buserelin/Superfact/Decapeptyl) is started with the initiation of gonadotropin stimulation. The agonist causes an immediate surge in pituitary gland LH release. Thus the follicles/ eggs of women on GnRH-agonist “flare protocols” are exposed to an exaggerated Lupron-induced LH release, (the “flare effect” The increased androgen production early on in the stimulation has a deleterious effect on egg development and thus on subsequent embryo quality.
The Traditional GnRH-antagonist , ‘short protocol” in women with DOR: While the follicles/eggs of women, who receive GnRH antagonists starting 6-8 days into the stimulation cycle are exposed to endogenous LH -induced ovarian androgens( especially testosterone). While this might not be problematic in in women who have normal ovarian reserve (i.e. “normal responders”), it could be decidedly prejudicial in women with DOR (“poor responders”) where endogenous tonic LH activity is usually raised and the ovaries may be inordinately sensitive to LH. In such cases excessive exposure of follicles and eggs to androgens (mainly testosterone) could severely compromise egg development and thus embryo quality.
Use of the Birth Control Pill to set up ovarian stimulation with gonadotropins: In my practice, patients are placed on a birth control pill for 10-40 days (depending on circumstance), before commencing a long antagonist protocol (whether conventional or the A/ACP). With this approach, the agonist is overlapped with the BCP in the last few days of its usage. Thereupon daily agonist administration continues until menstruation ensues a few days later at which point, the dosage of the agonist is halved and this is continued throughout stimulation until the hCG “trigger”.
The rise in FSH that occurs in ovulating women 5-6 days prior to menses, initiates recruitment of follicles available for the upcoming cycle. The BCP by suppressing ovulation (and FSH) precludes this premenstrual rise in FSH, suppressing follicle recruitment. Premenstrual GnRH agonist administration overcomes this by inducing a premenstrual FSH surge which then serves to recruits follicles in a timely manner…for the upcoming COH cycle. Following use of the BCP (without prior overlap with agonist) the first 4-6 days of FSH administration must first recruit follicles before growing them.
When the BCP is overlapped with a GnRH agonists towards the end of the BCP cycle, it triggers a pre-menstrual pituitary release of endogenous FSH (and LH). This results in recruitment of follicles to the antral follicle stage, whereupon the initiation of gonadotropin stimulation, while continuing agonist or supplanting this with low dose antagonist (i.e. A/ACP) to prevent further LH release, will induce an uninhibited and prompt follicle growth and development.
Given that FSH is so important to antral follicle “recruitment” , since the BCP suppresses FSH, it is essential (in my opinion) that the contraceptive pill be overlapped with an agonist during the last 3 days of its use to promote FSH production. If this is omitted optimal antral follicle development will not occur, and the response to subsequent ovarian stimulation with gonadotropins will in my opinion, be suboptimal. This could result in discordant egg/follicle development, a longer period of ovarian stimulation and compromised egg/embryo quality. I believe that unless the use of a long pituitary down regulation approach is contemplated, launching ovarian stimulation coming off a BCP is best be avoided.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist 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.
•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
•Optimizing Response to Ovarian Stimulation in Women who Have Compromised Ovarian Response to Ovarian Stimulation in Women who Have Compromised Ovarian Reserve: A Personal Approach.
•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?
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,"In Vitro Fertilization, the ART of Making Babies". It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Dear Dr.Sher,
I will be starting my 5th IVF cycle in about 2 weeks. My last cycle was an FET but ended in a chemical pregnancy, the other 3 fresh cycles didn’t work.
Next week I will be doing a blood test for NK killer cells on Thursday, but I will also be getting an endometrial scratch, however that will take place on Wednesday (because that will be 7 days before my next period). Unfortunately I can’t make the appointments on the same day as when I do the blood test it’s only possible on thursdays and I should do the endo scratch on Wednesday. Do you think doing the endo scratch the day before the NK killer cells blood test will mess up the test? Or give a false reading?
If the NK killer cells comes back as high, what are my options for treatment? Is it still possible to conceive?
Also, what is the advantage/disadvantages of taking baby aspirin during a fresh IVF cycle!
Thank you for your time!
Aspirin, in my opinion, offers no benefit and does have certain disadvantages. It thins the blood so that unless you stop taking it 5-6 days prior to ER, it increases the chance of bleeding. Also for the same reason, it can increase the chance of concealed bleeding with the introduction of the ET catheter exists . You will not be aware of this happening but when it does, it can interfere with implantation.
Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1.Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2.Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3.The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4.Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a.A“ thin uterine lining”
b.A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c.Immunologic implantation dysfunction (IID)
d.Endocrine/molecular endometrial receptivity issues
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I do not believe in the value of an endometrial scratch but it should not interfere with immune test results.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist 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.
•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
•The Role of Nutritional Supplements in Preparing for IVF
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Hello Dr. sher –
When is it OK to have sex after a Successful Frozen Embryo Transfer? There are so many opinions, wait until two betas, wait for the heartbeat, wait till after 10-12 weeks. Your expert opinion would be much appreciated.
I would wait until a viable pregnancy is confirmed by ultrasound. Then provided there is no bleeding, I regular sex is encouraged.
Geoff Sher
Hi D0ctor-
Im 7.5 weeks pregnant after a FET. I’ve been trying to eat healthy, exercise and maintain a good diet. With that being said, I think it’s the progesterone (injections and suppositories) that have completely shut down my digestive system and I’m quite uncomfortable. I’ve read online it’s not safe to take Ducolax suppositories but it has worked for me before becoming pregnant, I’ve tried more benign things like stool softener and powders and glycerin suppositories, nothing works. What is your opinion on ducolax suppositories. I don’t want to do anything that would harm this baby. I’m willing to be uncomfortable if i need to. Thanks in advance.
In my opinion, Psylium (Metamucil and the like) is a healthy stool softener to use.
Geoff Sher