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.
Hello Geoffrey Sher
We are a childless couple who are married and living in Norway. She is 40 years old, 184 cm tall and he is 47 years old and 204 cm tall. We have a reasonably healthy lifestyle without smoking and alcohol or other drugs. She has allergies to fish and shellfish, egg white in vaccines, perfumes, ammonia. Her sister has the same allergies + nuts, orange and arthritis. Their mother also had arthritis, and struggled to keep their pregnancies.
We’ve tried to have a child since February 2013. Prior to this relationship, she had four miscarriages, 2 times in 6-7 week, 1 time in week 9 and 1 time in week 12, the first miscarriage were in June 2003 and the last one just now last week. Now we have tried 4 times with ICSI, but it always ends with spontaneous aborts after 5-8 weeks. We have become pregnant the natural way 12 times (they ended after 5-7 weeks). The total of 20 pregnancies have ended in miscarriage. Every miscarriage has these symptoms: High fever (alternating feeling ice cold and very hot) for 2-5 days. Eventually comes the severe pain in the uterus for about one day, and this ends with cramping in the uterus and excessive bleeding.
Doctors have not identified any reason for the abortions, when the uterus and all associated organs are fine and no problems with mucosa. During ICSI, we have had1-2 good embryos, and these have been inserted into the uterus. Doctors could not find any reason why we should not have children, they think we have just been unlucky, but they suspect it may have something with the immune system to do.
All 4 ICSI tries have been done the same way:
She used Synarella nasal spray for 6-8 weeks, MENOPUR 450 IU + Klexane 40 IU for 12 days, Prednisone 20 mg and 250 IU Ovitrelle for ovulation 36 hours before egg retrieval. 3 days of embryo before insertion. Afterwards she spent 3 tablets 100mg Lutinus for 2 weeks to test and afterwards one tablet per day.
What do you think is the reason for the miscarriages?
Is there anything that we could have done differently?
Could this have something to do with the immune system?
Why does she gets a fever and pain each time she becomes pregnant?
Is there treatment or medication that can help us to pregnancy that you can recommend?
Sincerely
I started IVF treatment on the 1Dec 2016. Started taking Yasmin till today. I have gotten clots in my left leg. Had doppler scan and was negative but my leg is so painful when I walk. When I sit and put it up it subsides after a few minutes. If I stand it gets very sore. I have been on clexane 60mg now for 2 weeks. When will my leg start feeling better? Now that I have stopped taking yasmin? It started not long after I started yasmin. This is normal I hear and shld feel better shortly so I can continue with my IVF. Am using donor egg. I am 41yrs. Thank you for your advice in advance. I will see Dr tomorrow morning.
If you have deep vein thrombosis as the cause, the doppler test should be +ve.
Discuss with your RE.
Geoff Sher
Dr Sher,
Thank you very much for your reply about the premature luteinization that happened during my last cycle, it was very helpful. Would you add Ganirelix to the long Lupron protocol to ensure the LH is fully suppressed? If so, what day would you begin the Ganirelix? Thank you.
Yes! I would do the agonist/antagonist conversion protocol (A/ACP).
Geoff Sher
Dear Dr. Sher, I cannot thank you enough for all the work you do in helping people with fertility problems and answering all the questions. I asked one before already – whether it is possible or not for AFC to drop markedly after taking Primolut Nor due to cyst drainage + Utrogestan as luteal phase support in the next cycle. Indeed you were right in your answer because my AFC has bounced back. Now I would like to ask you to shed some more light on our situation as we are struggling to make a good decision regarding IVF. We live in Europe, but in a poor country, and will have to cover the entire expense ourselves so it is extremely important to throw everything we’ve got in the first attempt as this might very well be the only one (plus eventual EFTs if possible).
I am a 43 year old woman, and my husband is 49 years old. We have only been trying to conceive for about a year, so we don’t have a long history of infertility (together or separately). We live a rather healthy albeit a sedentary lifestyle – no smoking, drinking etc. All my hormones are good: AMH is 2,44 ng/ml, FSH 7,00 and LH 6,23, E2 53 on CD4, and so is his spermiogram. I had three IUIs – one stimulated in June (Clomiphene 50mg x2 for 5 days), one spontaneous in August, and the third also from natural cycle just a week ago. I have had an endometrioma on my right ovary for at least three years. It was about 4 cm big back in June when I underwent the stimulation. At the time it was only a suspected endometrioma. My response to stimulation was good – 4 big follicles on the left ovary and 2 on the right. My AFC on the left ovary is 10ish normally (down to 2-4 for two cycles after medication) and 1-3 on the right ovary.
In October I had a cyst drainage (it grew to 6 cm – Clompihene?) which confirmed the endometrioma. The cyst is now reduced to 4 cm. At the same time hysteroscopy was done – all fine except for 8-9 mm septum which was resected, and while I wasn’t really convinced that it needed messing with, I wanted removing all potential obstacles and problems ahead of time as we don’t have it on our side. Also I am taking 750mg Glucofage daily as well as Inofolic for insulin resistence (mild). In addition, I have a heterozygous MTHFR mutation and 4G/4G genotype of PAI-1. At the moment I am taking only aspirin 100mgx1 daily for it; the doctor said she would put me on Fraxiparine after IVF (do you think that’s ok or should I start taking it in advance?).
Now we are about to do an IVF. We have been talking with two different clinics and they both suggest long protocol due to endometriosis. One suggested the following therapy: diphereline 0,1 mg daily – midluteal start, and Fostimon from day 2, the dosage would be determined later. And the other is recommending the following protocol: dipherelin 3 mg shot on day 21, and then US to check downregulation on day 12 after menstruation and then stimulation with 3 amps of Gonal+2 amps of Menopur. Isn’t this rather late to be checking for downregulation? We were practically set on the second clinic as they are more experienced, more succesfull and specialize in older women but I am now a bit worried about this. Can you please help? I know you recommend agonist/antagonist conversion protocol for older women but we might only have the option to chose clinics not ask for protocols. In case I have to chose between these two options, which one would you recommend? What other factors are crucial for chosing a clinic beside the protocol? Also, would it be ok to start with diphereline while being possibly pregnant although with very small chances?
1. Endometriosis and IVF:
When women with infertility due to endometriosis seek treatment, they are all too often advised to first try ovarian stimulation (ovulation Induction) with intrauterine insemination (IUI) ………as if to say that this would be just as likely to result in a baby as would in vitro fertilization (IVF). Nothing could be further from reality It is time to set the record straight. And hence this blog!
Bear in mind that the cost of treatment comprises both financial and emotional components and that it is the cost of having a baby rather than cost of a procedure. Then consider the fact that regardless of her age or the severity of the condition, women with infertility due to endometriosis are several fold more likely to have a baby per treatment cycle of IVF than with IUI. It follows that there is a distinct advantage in doing IVF first, rather than as a last resort.
So then, why is it that ovulation induction with or without IUI is routinely offered proposed preferentially to women with mild to moderately severe endometriosis? Could it in part be due to the fact that most practicing doctors do not provide IVF services but are indeed remunerated for ovarian stimulation and IUI services and are thus economically incentivized to offer IUI as a first line approach? Or is because of the often erroneous belief that the use of fertility drugs will in all cases induce the release (ovulation) of multiple eggs at a time and thereby increase the chance of a pregnancy. The truth however is that while normally ovulating women (the majority of women who have mild to moderately severe endometriosis) respond to ovarian stimulation with fertility drugs by forming multiple follicles, they rarely ovulate > 1 (or at most 2) egg at a time. This is because such women usually only develop a single dominant follicle which upon ovulating leaves the others intact. This is the reason why normally ovulating women who undergo ovulation induction usually will not experience improved pregnancy potential, nor will they have a marked increase in multiple pregnancies. Conversely, non-ovulating women (as well as those with dysfunctional ovulation) who undergo ovulation induction, almost always develop multiple large follicles that tend to ovulate in unison. This increases the potential to conceive along with an increased risk multiple pregnancies.
So let me take a stab at explaining why IVF is more successful than IUI or surgical correction in the treatment of endometriosis-related infertility:
1.The toxic pelvic factor: Endometriosis is a condition where the lining of the uterus (the endometrium) grows outside the uterus. While this process begins early in the reproductive life of a woman, with notable exceptions, it only becomes manifest in the 2ndhalf of her reproductive life. After some time, these deposits bleed and when the blood absorbs it leaves a visible pigment that can be identified upon surgical exposure of the pelvis. Such endometriotic deposits invariably produce and release toxins” into the pelvic secretions that coat the surface of the membrane (the peritoneum) that envelops all abdominal and pelvic organs, including the uterus, tubes and ovaries. These toxins are referred to as “the peritoneal factor”. Following ovulation, the egg(s) must pass from the ovary (ies), through these toxic secretions to reach the sperm lying in wait in the outer part the fallopian tube (s) tube(s) where, the sperm lie in waiting. In the process of going from the ovary(ies) to the Fallopian tube(s) these eggs become exposed to the “peritoneal toxins” which alter s the envelopment of the egg (i.e. zona pellucida) making it much less receptive to being fertilized by sperm. As a consequence, if they are chromosomally normal such eggs are rendered much less likely to be successfully fertilized. Since almost all women with endometriosis have this problem, it is not difficult to understand why they are far less likely to conceive following ovulation (whether natural or induced through ovulation induction). This “toxic peritoneal factor impacts on eggs that are ovulated whether spontaneously (as in natural cycles) or following the use of fertility drugs and serves to explain why the chance of pregnancy is so significantly reduced in normally ovulating women with endometriosis.
2.The Immunologic Factor: About one third of women who have endometriosis will also have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). This will require selective immunotherapy with Intralipid infusions, and/or heparinoids (e.g. Clexane/Lovenox) that is much more effectively implemented in combination with IVF.
3.Surgical treatment of mild to moderate endometriosis does not usually improve pregnancy potential:. The reason is that endometriosis can be considered to be a “work in progress”. New lesions are constantly developing. So it is that for every endometriotic seen there are usually many non-pigmented deposits that are in the process of evolving but are not yet visible to the naked eye and such evolving (non-visible) lesions can also release the same “toxins that compromise fertilization. Accordingly, even after surgical removal of all visible lesions the invisible ones continue to release “toxins” and retain the ability to compromise natural fertilization. It also explains why surgery to remove endometriotic deposits in women with mild to moderate endometriosis usually will fail to significantly improve pregnancy generating potential. In contrast, IVF, by removing eggs from the ovaries prior to ovulation, fertilizing these outside of the body and then transferring the resulting embryo(s) to the uterus, bypasses the toxic pelvic environment and is therefore is the treatment of choice in cases of endometriosis-related infertility.
I am not suggesting that all women with infertility-related endometriosis should automatically resort to IVF. Quite to the contrary…. In spite of having reduced fertility potential, many women with mild to moderate endometriosis can and do go on to conceive on their own (without treatment). It is just that the chance of this happening is so is much lower than normal.
In young ovulating women (< 35 years of age ) with endometriosis, who have normal reproductive anatomy and have fertile male partners, expectant treatment is often preferable to IUI or IVF. However, for older women, women who (regardless of their age) have any additional factor (e.g. pelvic adhesions, ovarian endometriomas, male infertility, IID or diminished ovarian reserve-DOR) IVF should be the primary treatment of choice. 2.Why might IVF have failed? 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). 3. IVF in older women: In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”. Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”. Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced). I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”. I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
•Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•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
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.
Geoff Sher
Hi Dr Sher,
I recently watched one of your video blogs on Facebook and found it very interesting!! I’ve just had a failed cycle of IVF as it resulted in a chemical pregnancy.. We were told that our embryos were bad quality (out of 8 mature eggs we got 2 low grade blastocysts 2BC and 4CC) I’ve just checked the box and the dose of Ovitrelle I used was 250MCG and I was taking Buserelin throughout the cycle. Everything you advise against in your vlog… Could this be the reason we landed up with such poor quality embryos? I have a relatively low AMH for my age so I can’t imagine there were any concerns about me over stimulating. This was my 4th cycle – 3 of which have ended in early miscarriage/ chemical pregnancy. I am very keen to get a better idea of your prices so we can weigh up the pros and cons of travelling to the states to see you for our next cycle (we live in the U.K.) as you are the first Dr I’ve come across who really seems to know his stuff! …And that gives me hope!! Thank you so much for all your informative v/blogs… I have found them extremely helpful!!
I should also mention that my infertility is due to severe stage 4 endometriosis which I’ve had surgically removed over 2 years ago. I had drastic, nerve sparring surgery where part of my bowel was removed due to the severity of the desease but my ovaries were not effected as it was mainly in other organs like my bowel and bladder… I’ve been tested for NK cells which were normal but 1 of the genes which codes for blood clotting and folic acid absorbtion (MTHFR) was abnormal (only 1 of the genes so I was told this was not nessecarily an issue but used clexane on the cycle before this one and it resulted in the only negative of all my cycles, so I never revisited this for my most recent cycle which may have been a mistake. My husband and I have been trying for a baby for over 10 years…