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 Doctor Sher,
I am currently 34 and partner also 34- undergoing IVF treatment in Germany. As per our doctors me and my husband do not have any fertility issue and are capable of natural conception. Having said this – we have been trying to conceive since almost 3 years now with 2 failed IUI and 1 failed IVF cycle last year. During my last IVF they were able to retrieve 10 eggs out of which 5 fertilized and one blast was transferred at day 5 and other 4 was frozen. Resulted in high OHSS afterwards and BFN. However when they tried to thaw the frozen embryos all degenerated and hence nothing left to transfer. That’s how 2nd fresh IVF was planned. This month we underwent the 2nd IVF treatment with the same protocol like 1st IVF however the outcome was not convincing. I had 8 fully matured follicles – and my doctor could retrieve 7 eggs with 5 Ocytes. As per my doctor she could extract eggs from all the follicles as 2 of my follicles were behind the uterus during surgery. Only 1 could fertilize however it was a slow growing embryo – only 4 cells on day 4. Doctors are not very positive about the result. What do you think? is there any hope this embryo might implant by any chance? I developed mild OHSS 3 days after the transfer after taking 1500 units of HCG injection. I am confused on the next steps if this IVF fails. Shall I try a 3rd one in the same clinic next cycle or go back to IUI trusting our biological stats are okay. All input will be highly appreciated.
My first suspicion is that you need to have your protocol used for ovarian stimulation thoroughly reviewed and perhaps revised. However, please consider the following also:
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).
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and 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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•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)
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•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
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.
What is the maximum number of day-5/day-6 embryos that you would transfer, no PGS, on a healthy 43 year old? Eggs were retrieved when I was 42.5 yrs and 43.25 years old. Can frozen embryos be easily transported from one clinic to another? Thank you.
Indeed frozen embryos can readily and safely be transported.
The decision on how many embryos to transfer confronts most IVF physicians and their IVF patients. It is driven by a goal that both share in common, namely that of optimizing the chance of IVF treatment resulting in pregnancy. Clearly, the more embryos transferred, the greater the likelihood of success. However, there is overwhelming evidence to show that the more embryos transferred to the mother’s uterus, the greater the risk of a multiple pregnancy resulting and the higher the multiple, the higher the risk to both mother and babies. Pregnancy complications such as miscarriage, pre-eclampsia, late pregnancy bleeding, an increased incidence of cesarean section, post-delivery hemorrhage etc., are all much more prevalent, placing the mother at risk. Preterm delivery is also much more likely to occur and the earlier the baby is born, the less equipped it is to cope with extrauterine existence, placing it at great risk of complications such as respiratory distress, impaired neurologic and visual development and necrotizing enterocolitis …..to name but a few . While such complications do occur with a twin pregnancy, their incidence and severity increases exponentially with high order multiples (triplets or greater). In fact, in such cases the likelihood that at least one of the babies not surviving the ravages of premature delivery or being left severely developmentally impaired is about 50:50.
Since the higher the number of embryos transferred the greater the chance of a multiple pregnancy, it is incumbent on the treating physician to minimize the number he/she delivers into the uterine cavity with IVF. When deciding on the number of embryos to transfer, the patient’s chance for success (her prognosis) needs to be considered. The younger the woman, the better the microscopic quality of the embryos (their grade), the stage of development of the embryos (cleaved or blastocyst) , the chromosomal integrity of available embryos as assessed by preimplantation genetic sampling (PGS); and the number of supernumerary embryos left over for cryopreservation (freezing) and storage, are factors that should all be taken into consideration. In general, it is recommended that fewer embryos that have reached the blastocyst stage (day 5-6 after fertilization) be transferred than if the transfer were to be done earlier at the cleavage stage (day 2-3 after fertilization). This is because, the further an embryo has advanced in development the greater the likelihood that it will propagate a viable pregnancy.
Consider the fact that when comparing singleton with twin and triplet pregnancies:
Twins have 3-times, and triplets, a 6-times greater perinatal mortality rate.
Twins have 6-times, and triplets, an 11-times greater likelihood of developing cerebral palsy.
Twins are 50% and triplets 80% more likely to be born prematurely.
Mothers of twins are 3-times, and mothers of triplets, 7-times more likely to experience serious pregnancy-induced complications.
The anguish of losing one or more of your children at birth or watching them endure a life-long disability is a situation no parent would wish to face, yet it is a frequent consequence of multiple births. Why then do so many IVF practitioners still insist on transferring multiple embryos at a time? The following are the main reasons for this:
Most infertile patients simply do not perceive any great risk associated with multiple gestations, especially when it comes to twins. In fact most, consider multiple pregnancy to be a “bonus”…a favorable outcome. Faced with the high emotional and financial cost associated with IVF treatment, most couples prefer to complete their families in one attempt so as to “maximize the use of their resources.” In fact, when asked, almost 90% of couples undergoing IVF in the United States are desirous of having twins. Some are even interested or covet having high order multiples (triplets or beyond). Education is urgently needed to make IVF candidates fully aware of the risks associated with multiple gestations.
The inability to differentiate between embryos that will propagate a healthy pregnancy (i.e. “competent” embryos) and those that will not (“incompetent” embryos): Most IVF patients erroneously believe that a “pretty”, embryo (one given a high grade because it fulfils the microscopic criteria of “good quality”) should invariably make a baby. This is simply not the case. Consider the fact that such a microscopically “good quality” embryo from a 30-year-old has about an 8-times greater chance of resulting in a normal birth than would an identical looking embryo of a 45 year old! This confronts IVF practitioners with a “damned if you do, damned if you don’t” situation; driven by patient pressure to achieve a pregnancy and by competing market forces, they still too often choose to transfer multiple embryos, often with disastrous results. It is generally true that declining egg/embryo “competency”with advancing age justifies transferring more embryos in older women – especially in those over 40 years of age – but this still needs to be carefully measured against the risk of multiple gestations.Not only is multiple gestation the most common complication of infertility treatment, it has also become the most costly in terms of its social impact. If all of the factors associated with multiple gestations are considered, including the costs of antenatal maternal hospitalization, neonatal intensive care for premature infants, as well as the costs of chronic medical care, rehabilitation and special education, the projected annual cost of IVF-associated multiple gestations in the United States is approximately $1.5 billion as compared to about $550 million for all the other IVF cycles performed.
On the positive side is the fact that the last decade has seen a slight but significant decline in the IVF twin pregnancy rate from about 25% to about 22%, as well as a decline in the incidence of triplets from 5% to about 3%. Still, IVF multiple birth rates are about ten times higher than those associated with natural conception. Clearly, multiple pregnancy (especially high-order multiples) represents a complex problem that can no longer be justified as an acceptable outcome following IVF treatment.
Most in the IVF field are in agreement that it is probably best not to transfer more than 2 embryos at a time in younger women. The reason is that embryos derived from the eggs of a young woman (under 35 years) are much more likely to lead to a pregnancy than are those derived from older women. That is why most IVF programs in the United States therefore recommend transferring up to 2 embryos at a time in such cases. For women over 40, many still transfer 3 or even 4 embryos. For those between 35 and 40 years of age, 2-3.
What About Single Embryo Transfers: Advances in IVF technology have brought the noble goal of transferring a single embryo at a time without reducing the chance of a successful IVF, well within reach. Numerous studies have demonstrated that the cumulative birth rate after single embryo transfer (SET), followed by subsequent transfers of individually thawed left-over embryos, is as effective in achieving pregnancy as implanting multiple embryos at one time. And by this approach the risk of multiple births can be virtually eliminated. Moreover, using the SET approach, more than 80% of women under 40 years of age will deliver babies within first four single embryo transfers. At the same time, SET’s would likely cut the cost of health care per IVF baby by about $50,000 per live-birth.
A recent study found that, compared with singleton deliveries, the costs for twins, triplets and higher-order deliveries are approximately four, 11 and 18 times greater, respectively – mostly due to maternal and neonatal complications.
When we use the term “competent” embryo, we mean one which, upon being transferred to a “receptive” or “hospitable” uterus, will in most cases propagate a viable gestation. By far the single most important determinant of embryo “competency” is its karyotype (the number of chromosomes present). Aneuploid embryos (those with too many or too few chromosomes) are uniformly “incompetent” while “euploid” embryos (those with the correct number) are by and large “competent.” An incompetent embryo will not result in a normal pregnancy. In most cases it will either fail to implant or will miscarry early on. It follows that the ability to efficiently identify competent embryos for selective individual transfer would likely represent a “game changer” in the IVF arena.
In the past, the ability to select competent embryos for transfer has been thwarted by:
a. Lack of reliability of microscopic morphologic (appearance) embryo grading.
b. The inability of traditional pre-implantation genetic diagnosis/sampling (PGD/s) and chromosomal evaluation (karyotyping) by conventional Fluorescence In-Situ Hybridization (FISH) to be able to access all of the embryo’s chromosomes.
Let’s take a look at the merit and reliability of several current methods used to select the best embryo(s) for transfer:
•Microscopic Embryo Grading: Currently, most IVF centers culture embryos in groups and then perform a single microscopic evaluation (at 2, 3 or 5-6 days) prior to embryo transfer of one or more to the uterus. This approach is limited in scope and in its ability to reliably discriminate between “competent” and “incompetent” embryos, since chromosomally abnormal embryos are often identical in appearance to those that are normal. Embryos should be at 2 to 4 cells at 48 hours after egg retrieval and about 6-9 cells by 72 hours. The cells in an embryo are also referred to as “blastomeres.” Ideally the blastomeres should be of even size, and there should be less than 20% fragmentation, or blebbing. This is where portions of the embryo’s cells have broken off and are found lying free as debris inside its substance .Most IVF clinics “grade” each embryo using one of many scoring systems. Unfortunately, there is no agreement at all as to which system to use. But regardless of the microscopic grading system used, one thing is certain…they all lack reliability because they cannot evaluate the chromosomal integrity of the embryo.
•Blastocyst Embryo Transfer: A blastocyst is an embryo which has developed to the point of having 2 different cell components and a fluid cavity. Human embryos, in culture in an IVF lab, or developing naturally in the female body, usually reach the blastocyst stage by day 5 or 6 after fertilization. Many “incompetent” embryos are culled out as the embryo progresses to the blastocyst stage. Thus, those embryos that make it to blastocyst are far more likely than their day 2-3 counterparts to be competent. Embryos that do not reach blastocyst are in about 90% of cases chromosomally abnormal (aneuploid) and would not have been worthy of transfer earlier on anyway. Routinely taking embryos to blastocyst is thus a good idea since, if they do not make it, they are incompetent anyway.By waiting five or six days post fertilization to select and transfer only blastocysts to the uterus, we can improve the likelihood that those being transferred are the “competent” ones.
•Preimplantation Genetic Sampling (PGS) using Next Generation Gene Sampling (NGS) : This very promising method for embryo selection represents a real breakthrough in the IVF arena. NGS allows for identification of all 23 pairs of the chromosomes, providing a reliable method for differentiating between “competent” and “incompetent” embryos. Even without CGH embryo selection, “one embryo/one healthy baby” is now even more attainable. However, the introduction of CGH has made embryo selection much more scientific, virtually removing the incentive to transfer multiple embryos at a time. One of the perceived disadvantages of CGH embryo selection is the cost of such testing. However, while the performance of egg/embryo PGS does increase the cost per cycle of IVF, it actually lowers the “cost per IVF baby”. Since NGS testing requires several days to complete, the use of this technology usually requires that advanced embryos (blastocysts) be frozen and stored (cryostored) in a subsequent cycle. The separation of an IVF cycle into two separate phases to achieve this objective is referred to as Staggered-IVF (St-IVF). Cryostoring blastocysts allows sufficient time for the CGH testing to be completed.
•Embryo Vitrification (Ultra-rapid Freezing): Until about a decade ago, cryopreservation of human embryos had been somewhat problematic because it caused ice crystals to form inside the embryo, damaging or destroying it. The recent introduction of ultra-rapid freezing or vitrification (read the article on vitrification here) has changed all that. With vitrification, embryos are so rapidly frozen that no ice forms, yielding a post-thaw embryo survival rate of about 90%. Impressively, birth rates following the transfer of thawed, pre-vitrified embryos hardly differ from those using fresh embryos.
The Hippocratic Oath, states that the cardinal rule of medicine is “primum non nocera” (“foremost do no harm”). Since multiple pregnancy is the most serious complication of Assisted Reproductive Medicine, and IVF has been responsible for a virtual explosion in the incidence of twins and higher order multiples, those of us that practice medicine in this arena have a solemn responsibility to educate our patients and then to restrict the number of embryos we transfer at one time. Central to achieving this goal is to optimize the ability to select the most “competent” embryos for transfer.
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and 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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•The Role of Nutritional Supplements in Preparing for IVF
•Measuring and Interpreting Blood hCG to Assess Pregnancy Viability Following ART Treatments.
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
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 there,
I’m sure you get this question many times, but I am stressing out and need some peace of mind. I had unprotected sex on the nights of April 1st and April 6th. I took Plan B on April 7th, within 8 hours of ejaculation. My period ended on April 1st. On the 11th I was bleeding again, to the point where I had to use a tampon. This lasted for 2 days. As this was going on, I was in a very mentally intense training program for work and was preparing for graduation on the 12th and moving back home after a month of being away. What is the likelihood that I am pregnant, or that the bleeding 2 weeks after my original period end date be from the stress of the program and possibly my body trying to adjust to the cycle of the other girls I was around? Thank you for your help.
I doubt that you are pregnant….but of course cannot be certain.
Geoff Sher
Dear Dr Sher,
My HCG is .8 but I am not pregnant. Could this be for Menopur and how much HCG does 75 Menopur give the body?
It could be residual hCG from the menopur.
Geoff Sher
Hi Dr. Scher:?I am about to start preparing my body for a frozen embryo transfer, and my doctor’s usual protocol is 3 weeks of birth control, estrogen patch/pills, protestrone injections, progesterone shots, however my doctor’s office can’t fit me into their next cycle so he can either do 10-12 days of birth control (and get me into the earlier cycle-which he said he does not prefer) or do 5 weeks straight of birth control. Can doing 5 weeks straight of birth control hurt the outcome of everything? It worries me to go on it straight for so long. I’d love your opinion!!
No! 5 weeks of BCP straight will in my opinion not have any deleterious effects.
Geoff Sher
Thanks for your response Dr. Sher! I have one last question..I had 12 eggs removed, 8 were mature, 5 fertilized, and then all 5 made it to blastocyst. I was planning on doing PGS (since I had recurrent miscarriages), but the embryologist did not feel comfortable biopsying the embryos. Is there any correlation with 6 day blastocysts and them being chromosomally normal? Have a lot of the chromosomal abnormalities been weeded out by then? Statistically should I have some normal embryos out of my 5? I’m bummed to not have gotten the PGS testing.