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Hi Dr Sher,
My husband (35yrs and has cabvd) and I (29yrs) live in the UK and have undergone two embryo transfers, the second was on a frozen natural cycle. Both failed. As far as i know i don’t have any reproductive issues. We have one more embryo still frozen (four were viable from the ivf treatment – two transferred on first attempt and one on 2nd transfer – leaving one remaining). Given our circumstances do you think we should continue with natural cycle transfers, or if not, what other interventions can be considered and at what point do you think other investigations need to happen? Many thanks
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 think, after giving consideration to the above, you will need another FET. However, I would suggest that it be done under hormonal therapy, rather than with a natural cycle.
Geoff Sher
Apologies for the lack of details in previous question. The first transfer was two 5 day blastocysts and the remaining were frozen on day 6. I was told my womb lining and other ovulation factors were sufficient to have an unmedicted cycle. I was told to wait 14 days before doing a home pregnancy test. My period came just prior to testing on both occassions which further confirmed negative results. I have read it is possible to have a very early miscarriage but I’m not sure how this could be ascertained or if indeed it was the case in our situation. Your guidance would be very much appreciated. Kind regards.
I am 37 & have very low AMH (2.5pmol) and even with a AMH of 4pmol at age 35 I still got 16 mature eggs frozen with Puregon/Orgalutran stims 2yrs ago. This year with AMH at 2.5 I got only 6 eggs on a menopure/Orgalutran cycle which got 1 blastocyst banked. Next cycle this year was back to Puregon/Orgalutran and got 10 mature eggs to freeze. How reliable is AMH as an indication of reserve & response since I have responded very well. My basal FSH has been between 5 – 7IU/L for past 2 years consistently and AFC of between 12-15follicles for past 2 years. This all contradicts the AMH! My results are in such contrast to my poor AMH. How many eggs is considered a good yield per cycle & subsequently how many eggs are needed on average to make one day 5/6 blastocyst? And would you suggest I carry on with the Puregon/Orgalutran protocol since it has been successful versus the menopur/Orgalutran?
Hi Dr Sher, firstly thank you so much for your blog, it’s so informative and I’ve learned so much from you. We have just had our 6th transfer of a PGS tested normal embryo and unfortunately had another chemical pregnancy. That’s now 1 ectopic, 2 very early chemicals and 3 negative cycles. I don’t have any confirmed immune issues, however I was on intralipids 12 days before transfer and again on the morning of transfer as well as 5mg steroids moving up to 20mgs a few days before transfer and also daily clexane and still this didn’t work. We are lucky enough to have 9 PGS embryos left so we know our issue is implantation. Our embryos are always top grade AA. My lining is always a struggle, on a fresh cycle it’s usually between 7mm-8mm at the time of trigger and between 8mm-9mm the day of transfer. I’ve had 3 FETs cancelled as my lining responds poorly despite high dose of estrogen and other FETs my lining is just under 7mm at the time of progesterone and between 7mm-8.5mm on the day of transfer. My clinic feels the next step is the ERA test (endometrial receptivity test) as my lining may not be receptive at the time of transfer. Do you think this is a good option? I am worried our only option is surrogacy! My question is, I see on your website you recommend viagra but as I am living in Ireland, I can’t get it here. Can you tell me is it possible for me to order some from Ireland and if so, so you know where I can get it from? I presume I will need to use it for the ERA test as you need to mimic the meds I would be using for the actual transfer. Thank you for taking the time for reading my message, I am feeling so hopeless and the moment and the only thing keeping me going is our 9 beautiful embryos. I really look forward to hearing from you. Kindest regards, Joanne
I understand your dilemma, but I strongly suspect that this is an implantation dysfunction…most likely endometrial thickness-related but possibly an incorrectly diagnosed immune component. The endometrial thickness MUST be taken on the day of the “trigger” or the day that progesterone therapy starts. It has no prognostic merrit if measured on the day of ET. I do not believe in the merit of ERA. The lining needs to be ideally >9mm . 8-9 mm is a “gray zone” and <8mm is almost always associated with negative outcome. You will need compounded vaginal Viagra.
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 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
•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:
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to 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.
Dr. Sher
I would appreciate your advice on my case,we have been trying for a year -I am 31yr and my Day 3 Testing was : FSH 11.15, AMH 2.74, Estradiol 30.06, Progesterone Day 21 8.96, Thyroid 1.53. we did genetic screening and it came back normal. Do you recommend we try clomid+IUI or go straight to IVF. Also what other supplements should I take to improve my chances. I was also wondering if I should do egg cryopreservation because of my FSH.
Thank you
If all else is normal, I would suggest 3 attempts at gonadotropin-IUI cycles before going to IVF.
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
•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.
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!
•Micro-IVF: Often Preferable to Ovarian Stimulation with or Without IUI
•The Role of Gender Selection in 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.
My sister is suffering from brown discharge during her first week of pregnancy (IVF) but she has experienced two miscarriages in the past. What does this mean? Is she miscarrying again? p.s i’m live in Australia.
Vaginal bleeding occurs in about 25% of all pregnancies. When it happens, it almost invariably raises the concern of pregnancy loss (miscarriage). Bleeding can also be a sign of a tubal (ectopic) pregnancy, and in cases where the distended Fallopian tube ruptures it can precipitate a life-threatening crises. However, a small amount of painless vaginal bleeding can also be the result of normal embryo implantation (i.e. implantation bleeding) or it can result a local erosion of the vagina or cervix and/or trauma during intercourse.
Notwithstanding, in virtually all cases the occurrence of early pregnancy vaginal bleeding congers concerns or even alarm regarding the possibility of miscarriage. And when this happens to women who conceived following infertility treatment, the alarm often turns into panic. However, the truth is that in most such cases the bleeding soon stops and the pregnancy proceeds unabated to the birth of a healthy baby. However, because some do progress and end in miscarriage, and in most cases, only time will tell how things will ultimately turn out, we use the term “threatened miscarriage” to describe such early bleeding. The term “inevitable miscarriage” is used once symptoms and signs confirm a miscarriage is in progress. The term “complete miscarriage” is used if all products of conception are passed, leaving the uterus “empty”. An “incomplete miscarriage” refers to cases where some products remain retained in the uterus.
Miscarriage: Mild painless vaginal bleeding (often referred to as “spotting”) is usually due to hormonally induced eversion of the glandular cells that line the inner cervical canal, such that erosion develops on the outer part of the cervix that protrudes onto the vagina. The everted glandular tissue is fragile and susceptible to contact trauma, brought about sexual penetration or the insertion of vaginal suppositories. Since such local bleeding does not involve the developing conceptus located inside the uterus it is almost always innocuous. The diagnosis of a local cause of bleeding requires visual inspection of the vagina and cervical inlet a speculum examination. Thereupon, provided that the pregnancy has advanced beyond 5-6 weeks, a concomitant sonogram could confirm the presence of an unaffected pregnancy. Patients are advised to be more careful in inserting vaginal suppositories and to avoid sexual penetration until the bleeding has stopped for at least 1 week.
Sometimes bleeding occurs behind the conceptus inside the uterus (retrochorionic bleeding). Some blood will usually track down through the cervix and into the vagina. A speculum examination will often reveal blood tracking into the vagina through the cervical canal and a sonogram will reveal the presence of a retrochorionic blood clot. Although such retrochorionic bleeding can become an inevitable miscarriage, it often abates and over time the blood clot in the uterus absorbs, and the pregnancy continues normally. Treatment involves careful observation, avoidance of aspirin and other non-steroidal anti-inflammatory medications, bed rest and avoidance of vaginal penetration until the condition stabilizes, is essential.
While mild painless vaginal bleeding is usually innocuous, bright red bleeding that increases in amount and is accompanied by escalating pain is another matter altogether. It often suggests an impending inevitable miscarriage.
Before the 7th week of pregnancy a normally rising blood hCG (pregnancy hormone) titers is a comforting indicator that the pregnancy is more than likely progressing normally. Likewise, the detection of a normal heartbeat detected by ultrasound examination done after the 7th week of pregnancy is a very reassuring finding. However, even such findings by no means exclude the possibility of an inevitable miscarriage.
The causes of a miscarriage are multiple and diverse. However in most cases it is due to the developing conceptus being chromosomally/genetically abnormal. However, early miscarriages that reoccur more than twice in a row (Recurrent Pregnancy Loss-RPL) often suggest of an underlying implantation problem that could be due to a poorly developed uterine lining (endometrium) or immunologic dysfunction involving activated immune cells known as uterine natural killer (NK) and/or T-cells. Treatment requires an accurate diagnosis of the cause and selective therapy.
An ectopic pregnancy must be excluded: .Bleeding in the first 2-3 months of pregnancy especially if associated with the sudden onset of acute abdominal pain that is aggravated by movement and is accompanied by right shoulder tip pain, and light headedness or fainting could point to a bleeding ectopic pregnancy (one that is located in a Fallopian tube, outside the uterus) . The condition can be life endangering and warrants an immediate trip to the hospital as it often requires emergency surgery.
Molar pregnancy: Molar pregnancies are due to rapid overgrowth of the trophoblastic tissue that forms the placenta. Although infrequent they can cause early vaginal bleeding in pregnancy. Bleeding from molar pregnancies is often present with typical bleeding which resembles “red currents floating in a red jelly”. Bleeding from a molar pregnancy can either painful or painless. The condition is often associated with severe vomiting in early pregnancy, disproportionate enlargement of the uterus, and very elevated blood levels of hCG. Ultrasound evaluation, often reveals a rather characteristic snow-storm like image.
Patients with vaginal bleeding are often told to stay in bed. While this might reduce visible blood loss, there is no tangible evidence that it will prevent a miscarriage. Unfortunately, there is no definite treatment for this kind of bleeding in the early stages of pregnancy. Alas, in most cases only time will provide the answer.
Good luck!
Geoff Sher