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.
Dear Dr Sher
Thankyou for your response, I would just like to ask clarification on whether a drug such as Prostap( shutting down normal menustrual cycle) would have any adverse effects on eggs, due to the strength of such a drug.
Kind Regards
S
All gonadotropin releasing hormone (GnRH) agonists act by rapidly expunging reservoirs of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. GnRH agonists can be administered by intramuscular injection (e.g. Lupron, Postap, Superfact,Buserelin) or through intranasal administration (Nafarelin, Synarel). The intramuscular route which insures more even absorption is preferred.
At Sher-IVF we prescribe leuprolide acetate (Lupron/Postap) to launch moist IVF-controlled ovarian hyperstimulation (COH) cycles. Lupron is very similar in structure to gonadotropin releasing hormone (GnRH) . As such, its initial effect, (for about 2-4days or so), is to stimulate the pituitary gland to produce both LH and FSH .As soon as the pituitary starts to recognize the difference in chemical structure between the Leuprolide and normal GnRH, it profoundly reduces its output of biologically active LH and FSH production. This is referred to as “pituitary down-regulation” and the effect continues for as long as Lupron/Postap therapy is maintained uninterrupted. The initial increase in FSH and LH production during the first 4-6 days of leuprolide therapy is accompanied by a transient, but very significant increase in estrogen release by the ovary. The initial rise in LH and FSH production results in a rise in estradiol, and the subsequent pituitary “down-regulation” is followed by a precipitous fall in blood estrogen levels, until gonadotropin or estrogen administration commences.
The reason that agonists are administered to women receiving Gonadotropin therapy for IVF is because of its ability to suppress LH and so prevent a premature rise in LH which is most likely to occur in older women or those with have diminished ovarian reserve. When this happens, the cells lining the follicles undergo premature change (premature luteinization), compromising further follicle development and egg/embryo quality. Such premature premature luteinization (previously referred to as “premature LH surge”) severely compromises further follicle development as well as egg/embryo quality. Women with reduced ovarian reserve (who are resistant to ovarian stimulation) are most susceptible to this happening
There is often talk of “agonists “over-suppressing” ovarian response to gonadotropins. The reason for this concern is that agonists probably compete with FSH for receptor binding sites on the granulosa cells that line the ovarian follicles and produce estrogen…and so can blunt ovarian follicle response to FSH. However, since antagonists apparently do not exert the same effect, by supplanting Lupron/Postap with an antagonist prior to starting gonadotropin therapy), avoids this problem (see the agonist/antagonist conversion protocol -A/ACP is below). While both antagonists land s block LH activity, antagonists do so much more rapidly (within hours) than agonists (within a few days).
Use of Lupron/Postap to launch COS for IVF: At Sher-IVF we launch controlled ovarian stimulation (COS) for IVF by putting the woman on a birth control pill (BCP) for 10-25 days, to suppress ovarian response to FSH/LH. Thereupon, Lupron/Postap is overlapped with the BCP for 2-4 days. Then thee BCP is discontinued and daily Lupron/Postap therapy is continued until menstruation ensues. By varying the length of time on Lupron it is possible to control the timing of the onset of menstruation and reduces the incidence of cycle cancellation due to ovarian cyst formation. Menstruation will usually occur 4-7 days after stopping the BCP. Thereupon, one of two variations in approach is taken. Either the long Lupron/Postap approach or the agonist/antagonist conversion protocol (A/ACP) is used. With the A/ACP, Lupron/Postap is supplanted by low dosage antagonist therapy. In both cases daily Gonadotropin (FSH and LH) injections are concomitantly initiated and continued with the agonist or antagonist until the day of the hCG trigger. In some cases of markedly diminished ovarian reserve, we preempt the initiation of gonadotropin therapy with “estrogen priming”. It involves twice weekly injections of estradiol valerate for 8-10 days and then we initiate Gonadotropins therapy which is continued until more than 50% of the developing follicles reach at least 12mm in diameter. The addition of estrogen in this way could improve ovarian response to gonadotropins as well as endometrial response to estrogen stimulation. In both the long Lupron/Postap approach and the A/ACP daily shots of antagonist or antagonist are continued up to the day of the hCG trigger. The egg retrieval (ER) is performed 35-37 hours following hCG administration.
Some clinicians, when faced with the risk of OHSS developing will deliberately elect to reduce the dosage of hCG administered as a trigger in the hope that by doing so the risk of critical OHSS developing will be lowered. It is my opinion, that such an approach is not optimal because a low dose of hCG (e.g., 5000 units, hCGu or 250mcg hCGr) is likely inadequate to optimize the efficiency of egg maturational division (meiosis), particularly when it comes to cases such as this where there are a large number of developed follicles.
Lupron/Postap (Agonist) “Flare (Short” Protocol: Some IVF physicians advocate the use of GnRHa (Lupron/Postap)- flare protocols in which the administration of Lupron/Postap, therapy begins at the same time that ovarian stimulation with gonadotropins is started (usually with the onset of menstruation). The proposed benefit of such an approach is that the GnRHa will cause the woman’s pituitary gland to release large amounts of follicle stimulating hormone (FSH), which would augment the administered dosage of FSH and thereby synergizing the growth of ovarian follicles. The problem associated with this “flare” approach is that concurrent with the GnRHa-induced FSH luteinizing hormone (LH) also surges. In older women and those who have diminished ovarian reserve, the out-pouring of LH can cause the ovarian connective tissue (stroma or theca) which produces excessive male hormones (predominantly, testosterone). While some testosterone is essential for optimal follicle growth, too much testosterone can compromise its development as well as egg/embryo quality. Since older women and women with diminished ovarian reserve often have increased LH production as well as an overgrown of ovarian stroma/theca (i.e. hyperthecosis), a further GnRHa-induced increase in LH can so elevate local ovarian testosterone levels as to severely compromise egg/ embryo “competency”.
The Lupron/Postap (Agonist) “trigger”: It has been suggested that the preferential use of an “agonist (Lupron/Postap) trigger” in women at risk of developing severe ovarian hyperstimulation syndrome (OHSS) could potentially reduce the risk of the condition becoming critical and thereby placing the woman at risk of developing life-endangering complications. The argument is that the Lupron/Postap “trigger” by causing an LH surge to occur will reduce the risk of severe complications due to OHSS. The problem with using this approach, in my opinion, is that it is hard to predict how much LH will be released in by the pituitary gland. Often times, the magnitude of the LH surge induced by Lupron/Postap, is not sufficient to promote maximum and orderly egg maturation in the 36-38 hours prior to egg retrieval. The result is that eggs are more likely to be chromosomally irregular (aneuploid) when the Lupron/Postap “trigger” is used. So, in my opinion, while the Lupron “trigger” might well reduce the severity of OHSS-related complications, this benefit often comes at the expense of egg/embryo quality and outcome. For this reason, I personally prefer to use hCG for the trigger, even in cases of ovarian hyperstimulation hyperstimulated, with one important proviso…that being that is she underwent “prolonged coasting” in order to reduce the risk of critical OHSS, prior to the 10,000-unit hCGu “trigger”.
Lupron/Postap use in embryo recipient cycles: In cases of egg donation and gestational surrogacy, embryo donation and with frozen/thawed thawed embryo transfers (FET) undergo a similar regime of BCP/agonist preparation as do those who undergo ovarian stimulation, except that instead of receiving gonadotropins injections, these women receive daily estradiol valerate injections. Thereupon, progesterone therapy (administered by intramuscular injection and/or by vaginal administration) is added for several days. The combination of estrogen and progesterone therapy prepares the uterine lining for embryo implantation. Lupron/Postap therapy is discontinued 5-7 days prior to Embryo Transfer (ET) in such cases.
There is little need to be alarmed at what at first might seem to be a complex treatment regimen. Extensive studies on non-human primates, as well as limited human evaluations, indicate that Lupron/Postap is relatively harmless to both mother and baby. The drug is eliminated from the system within hours of discontinuing its administration. At Sher-IVF we discontinue Lupron/Postap therapy at least 5-7 days prior to transferring embryos/blastocysts to the woman’s uterus. The administration of subcutaneous or trans-nasal agonist is rarely associated with significant side effects. Some women experience temporary fluctuations in mood, hot flashes, nausea, and symptoms not vastly dissimilar from PMS. No serious long-lasting side-effects have been reported.
The subcutaneous injection of Lupron/Postap is relatively painless. Unfortunately, the drug will incur a modest additional financial burden. Lupron/Postap administration as described above (for ovarian stimulation), spares women the inconvenience and frustration of unnecessary cancelled treatment cycles with gonadotropins. As such, the use of Lupron/Postap in reality reduces the overall cost of ovulation induction
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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.
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
I am using vaginal Viagra for my lining for an FET but we were unable to get the compounded suppository form in time so I am putting the regular pills vaginally. Is this a waste or can it still be effective this way? Thank you! (for reference, I’m on high dose estrogen and Lupron for FET protocol)
Also to note, I am doing 25mg pills 4x vaginally. I have been on them for 4 days and I have a lining check tomorrow. I have been on estrogen for 3 weeks tomorrow as my lining did not thicken past a 7 due to mild Ashermans from a d&c. I had a hysteroscopy in Nov 2019 to remove the scar tissue. This is my second FET cycle attempt since the hysteroscopy, the first one was cancelled due to thin lining, this is the second we are hoping to salvage with the Viagra (we did not use Viagra last time). If it does not thicken, would it be worth trying again with the suppositories? Or would it be safe enough to say with the pills that my lining will not respond to traditional estrogen therapy anymore? YOU!
Unfortunately it wont be nearly as effective! Absorbtion is the issue.
Geoff Sher
I am due to start an FET cycle in the coming days. I live in France and travel a lot for work. I am concerned about doing a transfer while this first wave of coronavirus infections is occurring and the number of cases is increasing, especially as I live in a country which shares and open border with Italy. I have read reports on how the illness effects the elderly, middle aged, and young. However I have read little about its effect on pregnant women, especially in the first and second trimesters – I suppose this is unknown. Do you think it is worth waiting until the number of cases start to go down, perhaps with warmer weather, to do an FET cycle? Do you recommend any precautions such as a pneumonia vaccine? Thank you for this wonderful forum!
That is a personal decision. I would not wait!
Good luck!
Geoff sher
(I’m sorry if tommy first attempt worked and this is a repeat)
Hi Dr. Sher,
I had a positive home pregnancy test on 1/31.
I started having light brown spotting on 2/23 and ended up going to the ER on 2/25 to check it out. My beta hcg levels were 9500 and an US showed that I had a gestational sac and a yolk sac but no visible sign of a fetal pole.
Went back to the ER 3/1 with increased bleeding (still less than a normal period) and very very light cramping. Beta hcg levels were 14400 and US showed same thing as previous, but this time they described the gestational sac as irregularly shaped and the yolk sac very tiny. I do not know if it was the same person evaluating both US or not…
I go back to an actual OB tomorrow, 3/3 for more testing and his/her diagnosis.
Do you think there is hope and I could be earlier in my pregnancy than we thought? Or do you believe this might be the situation of blighted ovum?
Thank you.
Sorry Caitlin,
This does not look very optimistic
Geoff Sher
Hi Dr Sher, I just had my testosterone levels checked and the result was 0.09 (i think it’s measured as nmol/L) my clinic would prefer it to be at 1 and so have advised me to take DHEA but having read your info here on the subject I’m not sure. Is there an optimum level of testosterone to work towards before undergoing IVF? And if I do take it, should I stop taking DHEA at a certain point before beginning my IVF meds?
I’m 42 and I’ve had 2 previous cycles of IVF, the first was unsuccessful and then i had Chicago blood work done and had a full autoimmune protocol with ICSI and conceived but miscarried before 8 weeks. A subsequent FET was unsuccessful and I’m due to start my next cycle in 6 weeks or so. Any advice about DHEA would be much appreciated! J
There are differences of opinion regarding the use of DHEA. In my opinion, it is not a good idea, especially when it comes to older women and those with diminished ovarian reserve.
Geoff Sher
P.S. If you are interested, please set up a consultation online, to discuss. To effect this, please call my assistant Patti at 702-5332691.