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 Dr. Sher,
I am 40yrs old and recently just did a IVF cycle that resulted in a BFN. They were able to get 25 eggs 18 fertilized and 10 made it to day 5. On day 5 i transfered 3 and froze the rest. They said they are not sure why it didn’t work as my levels and lining were great and so were my eggs. My cycle has just started and my doctor wants to see me tomorrow to discuss using the frozen eggs. Is there any truth that frozen is better than fresh? I have endometriosis and have had 2 natural miscarriages as well as 2 ectopic pregnancies resulting in both tubes being removed. There is scar tissues built up could that have been a factor to the eggs not attaching? I’m just scared to go through this again and be emotionally let down.
I presume you mean frozen embryos (not eggs). Yes FET is at least as succesfull (maybe more so) than fresh transfers. However, endometriosis is associated with several issues you need to consider before proceeding to FET.
Endometriosis is a condition that occurs when the uterine lining (endometrium) grows not only in the interior of the uterus but in other areas, such as the fallopian tubes, ovaries and the bowel. Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).
All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such “treatment” evoking an improvement in subsequent fertility.
It is indisputable that even the mildest form of endometriosis can compromise fertility. It is equally true that, mild to moderate endometriosis is by no means a cause of absolute “sterility”.
Rather, when compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about four to six times less likely to have a successful pregnancy.
Endometriosis often goes unnoticed for many years. Such patients are frequently, erroneously labeled as having “unexplained infertility”, until the diagnosis is finally clinched through direct visualization of the lesions at the time of laparoscopy or laparoscopy. Not surprisingly, many patients with so called “unexplained” infertility, if followed for a number of years, will ultimately reveal endometriosis.
Women who have endometriosis are much more likely to be infertile. There are several reasons for this:
•First-Ovulation Dysfunction: In about 25 – 30% of cases, endometriosis is associated with ovulation dysfunction. Treatment requires controlled ovarian stimulation (COS). The problem is that the toxic pelvic environment markedly reduces the likelihood that anything other than IVF will enhance pregnancy potential.
•Second- Toxic Pelvic environment that compromises Fertilization Endometriosis is associated with the presence of toxins in peritoneal secretions while it is tempting to assert that normally ovulating women with mild to moderate endometriosis would have no difficulty in conceiving if their anatomical disease is addressed surgically or that endometriosis-related infertility is confined to cases with more severe anatomical disease…nothing could be further from the truth. The natural conception rate for healthy ovulating women in their early 30’s (who are free of endometriosis) is about 15% per month of trying and 70% per year of actively attempting to conceive. Conversely, the conception rate for women of a comparable age who have mild or moderate pelvic endometriosis (absent or limited anatomical disease) is about 5-6% per month and 40% after 3 years of trying. As sperm and egg(s) travel towards the fallopian tubes they are exposed to these toxins which compromise the fertilization process. In fact it has been estimated that there is a 5-6 fold reduction in fertilization potential because of these toxins which cannot be eradicated. Frankly, it really does not matter whether an attempt is made to remove endometriosis deposits surgically as this will not improve pregnancy potential. The reason is that for every deposit observed, there are numerous others that are in the process of developing and are not visible to the naked eye and whether visible or not, such translucent deposits still produce toxins. This also explains why surgery to remove visible endometriosis deposits, controlled ovarian stimulation with or without intrauterine insemination will usually not improve pregnancy potential. Only IVF, through removing eggs before they are exposed to the toxic pelvic environment, fertilizing them in-vitro and then transferring the embryos to the uterus represents the only way to enhance pregnancy potential.
•Third-Pelvic adhesions and Scarring: In its most severe form, endometriosis is associated with scarring and adhesions in the pelvis, resulting in damage to, obstruction or fixation of the fallopian tubes to surrounding structures, thereby preventing the union of sperm and eggs.
•Fourth-Ovarian Endometriomas, Advanced endometriosis is often associated with ovarian cysts (endometriomas/chocolate cysts) that are filled with altered blood and can be large and multiple. When these are sizable (>1cm) they can activate surrounding ovarian connective tissue causing production of excessive male hormones (androgens) such as testosterone and androstenedione. Excessive ovarian androgens can compromise egg development in the affected ovary (ies) resulting in an increased likelihood of numerical chromosomal abnormalities (aneuploidy) and reduced egg/embryo competency”. In my opinion large ovarian endometriomas need to be removed surgically or rough sclerotherapy before embarking on IVF.
•Fifth- Immunologic Implantation Dysfunction (IID). Endometriosis, regardless of its severity is associated with immunologic implantation dysfunction linked to activation of uterine natural killer cells (NKa) and cytotoxic uterine lymphocytes (CTL) in about 30 of cases. This is diagnosed by testing the woman’s blood for NKa using the K-562 target cell test or by endometrial biopsy for cytokine analysis, and, for CTL by doing a blood immunophenotype. These NKa attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in death of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or even an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.
Advanced Endometriosis: In its most advanced stage, anatomical disfiguration is causally linked to the infertility. In such cases, inspection at laparoscopy or laparoscopy will usually reveal severe pelvic adhesions, scarring and “chocolate cysts”. However, the quality of life of patients with advanced endometriosis is usually so severely compromised by pain and discomfort, that having a baby is often low on the priority list. Accordingly, such patients are usually often more interested in relatively radical medical and surgical treatment options (might preclude a subsequent pregnancy), such as removal of ovaries, fallopian pubis and even the uterus, as a means of alleviating suffering.
Moderately Severe Endometriosis. These patients have a modest amount of scarring/ adhesions and endometriotic deposits which are usually detected on the ovaries, fallopian tubes, bladder surface and low in the pelvis, behind the uterus. In such cases, the fallopian tubes are usually opened and functional.
Mild Endometriosis: These patients who at laparoscopy or laparotomy are found to have no significant distortion of pelvic anatomy are often erroneously labeled as having “unexplained” infertility. To hold that the there can only infertility can only be attributed to endometriosis if significant anatomical disease can be identified, is to ignore the fact that, biochemical, hormonal and immunological factors profoundly impact fertility. Failure to recognize this salient fact continues to play havoc with the hopes and dreams of many infertile endometriosis patients.
TREATMENT:
The following basic concepts apply to management of endometriosis-related infertility:
1.Controlled Ovulation stimulation (COS) with/without intrauterine insemination (IUI): Toxins in the peritoneal secretions of women with endometriosis exert a negative effect on fertilization potential regardless of how sperm reaches the fallopian tubes. This helps explain why COS with or without IUI will usually not improve the chances of pregnancy (over no treatment at all) in women with endometriosis. IVF is the only way by which to bypass this problem.
2.Laparoscopy orLaparotomy Surgery aimed at restoring the anatomical integrity of the fallopian tubes does not counter the negative influence of toxic peritoneal factors that inherently reduce the chances of conception in women with endometriosis four to six fold. Nor does it address the immunologic implantation dysfunction (IID) commonly associated with this condition. Pelvic surgery is relatively contraindicated for the treatment of infertility associated with endometriosis, when the woman is more than 35 years of age. With the pre-menopause approaching, such women do not have the time to waste on such less efficacious alternatives. In contrast, younger women who have time on their side might consider surgery as a viable option. Approximately 30 -40 percent of women under 35 years of age with endometriosis will conceive with in two to three years following corrective pelvic surgery.
3.Sclerotherapy for ovarian endometriomas.: About 10 years ago I introduced “sclerotherapy”, a relatively non-invasive, safe and effective outpatient method to permanently eliminate endometriomas without surgery being required. Sclerotherapy for ovarian endometriomas involves needle aspiration of the liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline into the cyst cavity. Treatment results in disappearance of the lesion within 6-8 weeks, in more than 75% of cases so treated. Ovarian sclerotherapy can be performed under local anesthesia or under general anesthesia. It has the advantage of being an ambulatory office- based procedure, at low cost, with a low incidence of significant post-procedural pain or complications and the avoidance of the need for laparoscopy or laparotomy
4.The role of selective immunotherapy Women with antiphospholipid antibodies (APA’s) experience improved IVF birth rates when heparinoids (Clexane/Lovenox) is administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy.
a.About Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating activated natural killer cells (NKa). This effect is enhanced through the concomitant administration of corticosteroids such as dexamethasone, prednisone, and prednisolone which enhance the therapeutic effect by suppressing cytotoxic/activated T-lymphocytes (CTL). This effect of IL might is likely due to its ability to
5. In vitro fertilization is the treatment of choice for women with endometriosis. This is especially true for women more than 35 years of age or where surgery and treatment with fertility agents has proven to be unsuccessful. We anticipate that approximately 75 percent of such women will achieve the birth of one or more babies within three IVF attempts performed.
6.
?suppresses pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. In-vitro testing has shown that IL successfully and completely down-regulates activated natural killer cells (NKa) within 2-3 weeks in 78% of women experiencing immunologic implantation dysfunction. In this regard it is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.
I hope this helps!
Geoff Sher
Hello! I am 38 years old. I had have a son conceived naturally on the first round of trying in 2012. The only complication was some early bleeding (spotting weeks 5-6 and again at 15 weeks). I had a CP a few months after his birth. I waited a few months to try again and had a blighted ovum. Then I had another CP before seeing an RE and starting on progesterone supplements. Pregnant the next cycle with my daughter in 2014- no complications. Since then, I have had 3 more CPs with 100 mg q hs progesterone supplementation for a total of 5 CP plus the blighted ovum and 2 healthy children. We conceived on the 1st try 7/8 times so no problem there. I have had some mid cycle bleeding since my daughter’s birth in 2014 and so used Letrozole this last attempt. The mid cycle bleeding resolved but I did have some mild bleeding after intercourse about 7 dpo on the last cycle (also the most recent CP cycle). My FSH is 6.9- all other 3 day labs and routine labs totally normal. normal BMI, don’t smoke or drink, avoid caffeine, no medical problems, normal 28 day cycle etc. I also take Inositol supplements, Vit D, and fish oil.
Based on my history and reading I suspect that I have some type of hormone fluctuation that is hostile to implantation and it may have worsened with aging. I was thinking of asking to up my progesterone (on 100 mg suppository q hs now) and perhaps check my endometrial lining thickness or add a med to promote thickening as a next step.
Any thoughts or help is appreciated. I am very thankful for my 2 healthy children, but would love to add a 3rd to our family if it is possible and I know time is short with my age.
Thank you!
It is possible that you have dysfunctional ovulation. Tou need to discuss this with your RE. Perhaps ovulation dysfunction will be necessar5y, but first the nature ofr the problem needs to be determined.
Geoff Sher
Hi, I already posted couple of queries here, and I got fruitful answers from you. Thank you so much.
This is my FET Cycle. ET was done on 30th July 2016.
I had my 6 weeks scan today at 6W4D, below are the details:
FHR: 112 bpm
Gestational Sac: 19 x 7 mm
Yolk sac: 4.1 mm
My doctor told me that fetal heart rate quite low at 6W4D. She asked me to go for another round of scan next week, if there is any chance of heart rate picks up.
Is 112 bpm low? I am worried.
I would not be over-concerned right now. Give it a week as suggested and hopefully all will turn out well.
Geoff Sher
Dear Dr. Sher,
I have a 5 yo son from ICSI2 (I was 31) and a 2 yo old daughter from ICSI4 ( I was 34). I had one chemical pregnancy prior to my daughter but otherwise had BFN (recurrent implantation failure). We have MFI and I have a very high AMH but do not meet criteria for PCOS. Earlier this year my AMH had dropped to about 6 on the US scale (40-ish here, previously I had been at 80) and my FSH had increased to 8. I am now 40. We discovered that I am heterozygous for MTHFR and PAI-1 and I was started on high-dose folate (and given a prescription LMWH after transfer). I had an endometrial scratch prior to restarting treatments. For ICSI5 we did a natural start (no BCP) agonist cycle and I was stimulated initially with Gonal 150 which was decreased at day 5 to 112.5 (E2 562 or 2067 on the European scale) and we added some LH later in the cycle. My E2 was around 10K (35K in Swiss units) on CD13, I believe. The follicles were mostly large (perhaps 22-24 mm if memory serves me right) when we triggered with a 1/2 dose of HCG. We retrieved 39 follicles on CD 15 which led to 20 zygotes, 3 PGS normals and 3 indeterminate (Swiss law permits only polar body testing). There was no fresh transfer due to OHSS (E2 around 10K or 36K on CD13). FET1 (natural start medicated) was a 3dt of 2 polar-body PGS normals and had excellent betas but I lost the pregnancy at 5wk3d with hemorrhaging while on LMWH, estrogen and progestin (2h after a beta of 6K). FET2 (1 normal, 1 indeterminate) was a BFN. We have 2 indeterminates left to transfer and I am trying to plan the next step. My husband is not willing to do DE and I am running out of steam. I know I make lots of eggs but the quality has always been limited and age is not on my side. I have heard of human growth human improving egg quality but I worry about worsening OHSS. Do you have any ideas on how to improve my egg quality without increasing the number of eggs retrieved? Thanks in advance!
I see that my math was off for my first 2 children – my eggs were 33 and 36 for those pregnancies, respectively!
In my opinion this is largely a problem with ovarian stimulation. I do not think you need DE. Besides that won’t alter the MF (if this is indeed a factor in your case).
When it comes to stimulating women who are at risk of OHSS,, my approach is consistently to use a long pituitary down-regulation protocol with an agonist, coming off 1-2 months on the BCP. The latter is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen release. I then stimulate with low dosage FSHr to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day and watch for the # of follicles and [E2] starting on the 7th day of COS. If there are > 25 follicles, I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. Then, provided the [E2] is >2500pg/ml, I stop the agonist and the gonadotropin stimulation and follow the E2 (only) daily, without doing further US examinations. The [E2] will almost invariably climb and I watch it go up (regardless of how high the concentration of E2reaches) and track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then ever), I administer 10,000U hCGu or hCGf (Ovidrel/Ovitrel-500mcg) as the “trigger” and perform an egg retrieval 36h later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris and eggs without a cumulus will not readily fertilize on their own. All fertilized eggs are cultured to blastocyst (up to 6 days). And up to two (2) are transferred transvaginally under US guidance.
The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs.
Use of the above approach avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon.
I do not use antagonists in high responders (e.g., PCOS) because it interferes with the assay of E2 (often causing the value to be understated), a valuable index in assessing risk for the development of severe/critical OHSS. I also do not believe in the agonist trigger to prevent OHSS. The reason is that the magnitude of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the oocyte aneuploidy index.
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
•Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
•Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
•“Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
•The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
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.
My 30-year-old daughter just recently underwent IVF due to male factor infertility. Fourteen eggs were retrieved and 12 fertilized. Out of the 12 fertilized embryos, only 3 made it to blastocysts. Two were transferred and 1 was frozen. Of the 2 that were transferred, 1 implanted but resulted in a silent miscarriage at 11 weeks. Since the embryos seemed to have been either immature or genetically altered, should we trust that 1 remaining frozen embryo and do a FET or start a new fresh cycle?
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).
Hope this helps!
Geoff Sher