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.
hi I’ve just completed my first egg collection and was wondering what day is the best for implantation day 3 or day 5 as they have asked in the clinic which one I would prefer?
With IVF, embryos may be transferred at the cleaved stage, 2 days following fertilization (2-4 cell stage) or 3 days post-fertilization (5-10 cell stage or alternatively, 5-6 days following fertilization, at the blastocyst stage (>100 cells). Blastocyst embryo transfer thus requires extending the embryo culturing duration for an additional 2-3 days.
With blastocyst transfer, the chance of pregnancy is significantly higher than with cleaved embryo transfers. This is because many numerically chromosomally abnormal (aneuploid) embryos arrest in development before they reach the blastocyst stage.
Previously (and to a large extent even today), IVF doctors and embryologists have intuitively believed that the uterus provides a more “natural” and favorable environment for embryo development, than the petri dish and incubator and accordingly have held that the sooner an embryo is transferred to the uterus, the better off it would be. By this belief an embryo transferred as on day 2 -3 post-fertilization rather than as a blastocyst (on day 5 or 6) would have a better chance of resulting in a live birth. We now know this to be erroneous.
Background information: Before the freshly fertilized egg, starts to cleave (divide), it is called a zygote. After the first 24 hours, (Day 1) the embryo has divided into 2 cells. By Day 2 the embryo has 4 cells blastomeres and by the third day, there should be between 6 and 9 cells. Up to that point, embryonic development is under the control of maternal genes in the egg. Around the 8 cell stage, the embryo’s own genes (embryonic genome) begin to take over control of development. By the fourth day, the embryo has between 16 and 32 cells. At this point it looks like a mulberry and is called a morula. Until the morula stage, all of the embryo’s cells are the same and are “totipotential” (i.e. they have the ability to ultimately develop into any tissue or organ type). By day 5 post-fertilization, differentiation of the embryo begins. A fluid-filled cavity blastocoel forms in the center of the conglomerate of blastomeres. This blastocoel will eventually become the amniotic sac and the fluid surrounding the conceptus in the uterus.
The cells around the outside of the morula develop into the trophectoderm, which will eventually form the placenta and fetal membranes, while the cells on the inside of the morula aggregate and group together to form the inner cell mass, which ultimately develops into the fetus. This complex creation is now called a blastocyst. By this stage the embryo comprises more than 100 cells. As the blastocoel fills with fluid, the blastocyst expands, its walls thin out and it eventually breaks through (hatches) its envelopment zona pellucida. The trophectoderm then begins to invade the uterine lining (implantation) by the 6th to 8th day after ovulation (or egg retrieval in the case of IVF treatment).
Human embryos are very fickle. They have specific metabolic requirements in order to survive. The earliest type of artificial embryo culture media developed for IVF purposes was relatively simple in composition and could only support limited embryonic development in the Petri dish and incubator. Thus, the majority of embryos cultured in such media could only survive to the third day, whereupon their development would usually arrest. Subsequent improvements in media composition allowed for more reliable embryo development to the third day…which became and remained the standard time at which embryos were transferred for more than two decades.
In the mid-1990s, researchers in Australia, Scandinavia and the USA simultaneously developed a new generation of culture media that could support the growth of embryos to the fifth or sixth day. This development was based on a clearer appreciation of the metabolic needs of the early embryo. Now, contingent upon the age of the egg provider, approximately 30-40% of morphologically “good quality” day 3 embryos (comprising 5-9 cells with minimal/no fragmentation) can be grown to the blastocyst stage using such advanced culturing methods.
A few years ago I and my research partner, Levent Keskintepe PhD, reported on the fact that embryos that failed to develop into blastocysts were almost always aneuploid and incapable of propagating a viable pregnancy (i.e. “incompetent”). However, not all embryos that developed into expanded blastocyst were chromosomally normal and “competent”. As such, embryos that fail to develop in the laboratory to the expanded blastocyst (advanced preimplantation) stage by day 5-6 post-fertilization, would not have developed into a viable pregnancy had they been transferred to the uterus earlier on in the cleaved stage (day 2-4 post-fertilization). Accordingly, there is in my opinion, little justification for transferring embryos that have not developed into fully expanded blastocysts by day 5-6 post-fertilization. Since many aneuploid (“incompetent” embryos are culled out during the developmental stage, it follows that blastocysts are much more likely to be “competent” than are cleaved, earlier stage embryos. Thus blastocyst transfer reduces the incentive on the part of IVF doctors to transfer multiple embryos in order to bolster their success rates, and the process this reduces the risk of high order multiple pregnancies (triplets or greater) with its incumbent risks to both mother and babies.
As mentioned earlier on, the older the egg provider, the lower the chance that her fertilized eggs with develop into blastocysts. In fact, in spite of the introduction of specialized culture systems and other new techniques, at best (even in younger women) 40% of “good quality” day 3 embryos (those that are 6-9 cells and have little fragmentation) will develop into expanded blastocysts by day 5-6 post-fertilization in younger women. And the blastocyst conversion rate declines rapidly as the woman ages beyond 35 years, such that by age 40 years, the conversion rate is about 15-20% and by 43 years of age it is <10-15%. Since blastocysts are much more likely than cleaved embryos to implant following embryo transfer (ET), the transfer of 1-2 good quality blastocysts will in any age category, proportionately yield a far better IVF success rate
The new found ability to safely freeze blastocysts using a new ultra-rapid process known as vitrification which does not compromise their subsequent (post-thaw) ability to propagate a viable pregnancy, has led to many IVF programs to preferentially cryobank vitrified blastocysts for transfer in one or more subsequent frozen embryo transfer (FET) cycles. Also, the introduction of Preimplantation genetic sampling (PGS) with full numerical chromosomal assessment (full karyotyping) using methods such as comparative genomic hybridization (CGH) and next generation gene sequencing or (NGS) now permits the identification and selective transfer of only the most competent blastocysts, thereby improving IVF outcome substantially. This allows many older women and those with diminished ovarian reserve(DOR) who are averse to doing egg donation-IVF, to have their embryos biopsied and then bank (stockpile) their embryos over several cycles, in the hope of subsequently transferring only those that are determined through PGS to be the most “competent” ones
For all these reasons (and there are probably many others) most IVF centers of excellence have graduated from transferring cleaved embryos to blastocyst transfers.
Other than patient preference and easing pressure on doctor and/or patient, there is in my view seldom a justification for transferring embryos on day 2 or day 3. In light of the aforementioned revelations and developments I therefore hold that blastocyst transfer should be the embryo transfer method of choice.
Geoff Sher
PH: 702-533-2691
What is your opinion on the Endometrial Receptivity Array biopsy, which determines if embryos are being transferred in the wrong implantation window? a lot of women with previous implantation failure are getting pregnant by adding or subtracting a day of progesterone before FET because their ERA biopsy is coming back as “pre-receptive” or “post-receptive”? I am interested in this technology as I’ve had a few failed FET recently with CGH normal embryos, but I also have 2 children from prior FET with the regular 5 day window. Do you think if I’ve had 2 successes with the previous 5 day window, an ERA biopsy makes sense for me? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601169/
I do not believe it helps because testing the endometrium in a different cycle to that which the transfer of embryos is effected, makes no sense to me….Besides there is to my knowledge no convincing evidence of efficacy.
Geoff Sher
Hi, I recently had my first cycle using 50mg of clomid from days 3-7. I believe I ovulated early on cycle day 8-9 and on an ultrasound on day 10, I had a LUF. A blood test the day next showed progesterone at 3.6 suggesting “ovulation” had occurred and the LUF was not remaining from a previous cycle. I did not take an hcg trigger because we missed ovulation, and my doctor did not want me taking it as a post-ovulation supplement because he was afraid it may grow the LUF. Anyway, next cycle we are scheduling earlier monitoring and will be administering the 10000 hcg as a trigger. Is there any other suggestion you would make to avoid another LUF and help with pregnancy? I avoid taking nsaids already and my lining already looked good probably because I am on an estradiol patch.
Yes! You cannot easily control this with clomiphene. It occurs in about 20% of cases…especially in women who have diminished ovarian reserve. Thus have your ovarian reserve tested by measuring AMH and basal FSH/LH and E2. Then I suggest that if you do have DOR, you consider moving to IVF as your could be running out of time on the biological clock!. At the very least I would move to gonadotropin stimulation using a long down-regulation protocol.
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.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•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
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to IVF
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•Induction of Ovulation With Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
•Clomiphene Induction of Ovulation: Its Use and Misuse!
•Intrauterine Insemination
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.
thank you for this blog in being able to share our concerns it is greatly appreciated, my wife had hcg levels on day 11 at 714 and day thirteen at 1380 and here we are on day 17 and my wife started bleeding this morning very lightly and then it stopped when we contacted our doctor the ivf coordinator told us she was confident in our pregnancy she did prescribe something (levothyroxine) for my wife’s thyroid which the tsh levels were higher than they would’ve like for a pregnant woman but not dangerous, well she started bleeding again this evening more than we would like. Should we be concerned she isn’t experiencing any unusual cramping just whatever she had been experiencing since she got pregnant. should we be concerned
The rise in hCG level seems reasonable. s long as the bleeding is painless and not excessive she could still be OK.
Time will tel!
I will be praying for you both!
Geoff Sher
Hi Dr. Sher,
I recently did an IVF cycle with PGS testing due to a chromosome inversion I have. Out of 7 blastocysts, we had 4 come back euploid. We just did a FET with our top graded embryo and got a positive beta but the ended in a chemical pregnancy. I have had 4 previous chemical pregnancies that I know of. My question is, would you suspect an immune issue after miscarrying a “normal” embryo?
Thanks for your time.
Hannah
It would definitely need to be ruled out, in my opinion.
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.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•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 Approach
•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.
•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?
•Blastocyst Embryo Transfers Should be the Standard of Care in IVF
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•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:
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF.
•The Role of Nutritional Supplements in Preparing for 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.