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 !
I am 36 (living in Germany) and on my way to our first ivf+imsi. We Chose this path because of my husband’s sperm Quality (only 7% Forward moving guys). I was checked and re-checked for the last 3 years and other that a homa-index of 2,8 (max Limit 2,6) there is nothing wrong with me. All bloodwork came always good out. I am dealing now with the question: how many embrios should we tranfer when the time Comes? I have read so many pros and cons that i am totally confused… should we make the decision ONLY based on my Age and Transfer 2 or should we start with just one? I have to mention we lost a Baby back in 2014 at 6 weeks of pregnancy. My doctor said it is possible it was an ectopic that didn’t stick.
I would very much appreciate your opinion, thank you!
The decision as to 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. Unfortunately however, there is a major downside to transferring multiple embryos, namely an inevitable increase in the rate of multiple pregnancies/births which in turn result in a marked increase in both maternal and neonatal (newborn) complications. You see….. multiple pregnancies – especially high order gestations (triplets and greater) – significantly increase the risk of pregnancy-induced complications such as miscarriage, pregnancy high blood pressure, [preeclampsia], premature placenta separation [placental abruption], placenta previa [front-lying placenta]. It also margedly increases the likelihood of premature birth, low birth weight, perinatal death and morbidity (including but not limited to severe neurologic complications).
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 (see below) 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 much more likely than their day-3 counterparts to be competent. Embryos that do not reach blastocyst are in more than 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 egg/ embryo selection represents a real break through in the IVF arena. NGS allows for identification of ALL 23 pairs of the chromosomes,pr 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 NGStesting 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.
Vitrification (Ultrarapid 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 more than 95%. Impressively, birth rates following the transfer of thawed, pre-vitrified embryos hardly differ from those using fresh embryos.
The Hippocratic Oath, decrees 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.
Good luck!
Geoff Sher
Hi Dr. Sher!
I recently completed my first round of IVF with ICSI due to male factor infertility. My husband and I are both 32. They retrieved 38 eggs (34 mature) and we’re going to do a FET to prevent OHSS. 28 of the eggs fertilized. By day 3, we had about 14 6-8 cell, grades 1 and 2.
On Day 5, they said that we had 8 blastocysts and they were going to wait and see if they had become expanded blastocyst. On Day 6, they all had arrested except two poor quality embryos that did not end up making it to freeze.
We were so upset and shocked. We never saw this coming. What do you think the problem is? If we try another cycle, will it happen again? Where do we go from here? Any advice you can give us? Thanks so much for your help!!
We have a daughter together from an IUI, but DH’s sperm has gone down since then.
Here are the exact grade and embryos at Day 3.
Three 4-Cell Grade 3/4
Four 6-Cell Grade 2/3
Seventeen 8-Cell
3 Grade 1
10 Grade 2
3 Grade 3
1 Grade 4
Three 12-Cell Grade 1/2
Thanks again for your help!! We are so devastated and don’t know what to do!
Embryos that do not develop to expanded blastocysts by day 6 post-fertilization are almost always “incompetent” and would not have prpagated a bay anywa Very often this is due to the protocol used for ovarian stimulation and its implementation. This needs to be critically reviewed, becauae at 32Y and with good ovarian reserve this usually would not happen.
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)
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•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?
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•Why did my IVF Fail
I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.
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
My son and daughter-in-law are going through IVF (unexplained infertility & she is 37). They harvested 5 eggs last Wed., March 2, all of which fertilized by the following morning. As of today, March 7, they have biopsied and frozen one. The clinic says the other 4 are still growing and should be ready to be biopsied and frozen soon. Does this sound like normal protocol ? By “soon” I don’t know if that meant soon as in “today” or when. Would it be unusual to wait more than 5 days to freeze ? Under what circumstances would they biopsy ? Does this mean testing for abnormalities ? Thank you in advance for your time and info.
* they will inseminate after her next cycle.
It does sound regular. Those who biopsy late, do so as soon as the blastocyst stage is reached and some get there by day 5…Others on day 6.
Geoff Sher
My protocol (that we hopefully start on this cycle) is
– starting day 21 – Progynova twice a day (estradiol) until the bleeding starts
– starting day 3 of the next cycle Puregon 225 for 4 days
– day 7 – scan and discuss if i Need more Puregon and for how Long. This day we will also decide when to start Orgalutran and Cetrotide (one of each per day)
– we will Trigger with Decapetyl and Predalon and after 36 hours we harvest the eggs.
Hi I am currently going through IVF process where we were told that the issue was due to the males sperm shape. I was just told today that they saw fluid and that I have Hydrosalpinx. From what I googled this can happen to women if they have had a STD or a myomectomy. I had a myomectomy to remove fibroids back in 2011 I believe. My fertility Dr wants to set me up to have surgery/laperscopy. She said this will determine what’s causing the fluid or blockage. I was scheduled to have s transfer done this month with my already retrieved frozen embryos. She said that she does not want to take the chance of continuing with the transfer and risk the fluid pushing the embryo and being wasted with transfer ending up not successful. Is this common? Should I go through with surgery? Is this my best option? Is this my only option? Any advise you can give is greatly appreciated
I occur with that position by your RE.
Good luck!
Geoff Sher
Hello Dr Sher! I am heartbroken over my results-please read.
I am 40 years old with high fsh and very low amh. I had my period a few days back and on day 2 fsh was 11.9 while e2 was 46pg/ml. My afc was 3. I decided to try a low stimulation cycle for the first time. So i am taking 75iu of puregon and 75iu of menopur.
I was doing ok. First scan(day 5 of stims) e2 was 380 whole lh was 10. I had 3 follicles at 12mm.
Second scan(day 6 of stims) e2 was 529 while Lh jumped to 24! I had 3 follicles at 14, 14, 16.
I was told to start ganirelix that evening.
I took ganirelix on Saturday and Sunday evening.
Today i had my 3rd scan. E2 dropped to 171 while Lh is 10.6. P4 is today at 1.3ng/ml(it was 0.92 on day 1 of stims). The follicles are actually bigger at 18, 19, 19.
I was told not to increase stims. I was also told to add an extra ganirelix injection in the morning of the trigger day. I thought that if someone takes ganirelix in the evening -like i do-there is no need to add one in the morning of the trigger day.
I am so confused now. What happened? Did i ovulate? Why did e2 drop so? Why are the follicles bigger but e2 went horribly low? Should i cancel? Should i increase stims and if so by how much? Should i add that extra ganirelix injection in the morning of the trigger day?
My dr is open to my suggestions but i have no idea what to suggest right now. Please advice me. Thank you.
Respectfully,in my opinion, I think that what has happened here is “premature luteinization” linked to the protocol you used for stimulation. A minimal stimulation protocol at 40Y of age with DOR, is in my opinion not optimal.
Older women, women and those with with diminished ovarian reserve, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
The developing eggs of women who have increased LH activity (older women, women with diminished ovarian reserve, and those with PCOS) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
You need a modified, robust, long pituitary down-regulation protocol. I would use an agonist/antagonist conversion protocol with human growth hormone (HGH) augmentation and would recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing)-normal blastocysts, to make hay while the sun still shines.
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)
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•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?
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.
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