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 dr Sher I just did my first ivf in February with 12 eggs 8 were mature and six was the starting count.. on day five I was left with three and two were transferred the other stopped developing so I’m left with none to freeze. I’m 38&1/2. Should I try again or go straight to donor eggs is that my better option for successful outcome? Thanks in advance!
Hi Nicole!
This is a huge decision and to respond authoritatively, I need to have MUCH MORE information.
I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Hi Dr Sher, at what age do you recommend a woman’s blastocysts be PGS testing? I recall reading that you had changed your stance on this before a certain age due to the phenomenon whereby they correct themselves after implantation (mosaicism.) At what age do you consider the cut off age for this?
About a decade ago, I, along with my associate, Levent Keskintepe PhD were the first to introduce full chromosome Preimplantation Genetic Sampling/Screening (PGS) into the IVF clinical realm to try and identify euploid embryos whose cells contained the required 46 chromosomes (23 pairs) necessary to render them potentially “competent” to propagate viable pregnancies. Aneuploid embryos (those that have more or less than a total of 46 chromosomes) are by and large considered to be “incompetent”, far less likely to propagate a viable pregnancy and thus largely unworthy of being transferred to the uterus.
Initially the primary method used for PGS was, comparative genomic hybridization (CGH). The methodology was not without certain problems. A few years ago, new and improved technology known as next generation gene sequencing (NGS) emerged. This has since all but replaced other methodologies. Gene sequencing determines the precise order of nucleotides within a DNA molecule. It includes any method or technology that is used to determine the order of the four bases—adenine, guanine, cytosine, and thymine—in a strand of DNA.
The widely held belief is that the ideal time to biopsy embryos for PGS is when they reach the most advanced stage of preimplantation development (the blastocyst stage) by 5-6 days post-fertilization. At this point several cells are microsurgically removed from the embryo’s outer cellular layer (trophectoderm-TE), processed and subjected to PGS analysis. The blastocysts are ultra-rapidly frozen (vitrified) and held for future dispensation in a subsequent frozen embryo transfer (FET) cycle, once test results are known.
Access to several cells through TE biopsy provides more DNA for reliable analysis that can be attained through the testing of a single cell removed from a day-2-3 cleaved embryo. It is this plus the belief that the hypercellular blastocyst is far less likely to be damaged through such microsurgical intervention than would be the case with a 4-10 cell, day-3 cleaved embryo that has led to the preferred timing for biopsy to be on day 5-6 blastocysts..
When PGS testing was first introduced, initial results were most-encouraging. Embryo implantation rates of >50% and birth rates of 50-60% when up to two euploid blastocysts were transferred, were being reported. In addition, the reported incidence of miscarriages and chromosomal birth defects was likewise greatly reduced. In fact, we were so encouraged that most of us predicted that a time would come where full embryo karyotyping through PGS would become a routine part of IVF. But alas…..we were soon to be disappointed when following the widespread introduction of PGS testing success rates started dropping. This was especially the case when PGS was performed on embryos derived from the eggs of older women and women with severely diminished ovarian reserve (DOR). With further investigation it began to dawn upon us that:
a)Chromosomal numerical integrity, while being the most important determinant of embryo “competency” was likely not the only factor that impacted embryo “competency”. Indeed advancing age was revealed to increase the incidence of embryo aneuploidy, independent of embryo karyotype and this is probably linked to non-chromosomal, genetic and metabolomic factors that might also be age-related.
b)Independent of embryo competency, there are many variables, that can and also do determine IVF outcome and these are often outside the control of the embryology/genetic laboratory. They include selection and implementation of individualized protocols for controlled ovarian stimulation (COS), endometrial factors that determine embryo implantation (e.g. anatomical an immunologic implantation dysfunction), technical skill of the physician performing embryo transfer etc.
c)Not all PGS-aneuploid embryos are “incompetent”. Some are mosaic (see elsewhere) and these are often capable of “autocorrecting” upon being transferred to the uterus, and propagating healthy babies.
Example A: Under optimal conditions embryo “competency” is determined by age and the protocol used for COS. In women <36Y of age roughly 1:2 blastocysts will likely be euploid “competent” and were such an embryo be gently and expertly transferred to a “receptive” uterine environment, the chance of a viable pregnancy should about 55-60%. This means that when ET is performed in such ideal IVF candidates, the chance of it resulting in a live birth should be about 27%-30% per embryo.
Example B: Conversely, when it comes to a woman in her mid-forties, the chance of an embryo being “competent” is probably < 1:8-10. And, the age-adjusted chance of such a Euploid embryo propagating a live birth is (for reasons cited above) theoretically well below 60% (perhaps around 40%-45%). This extrapolates to a baby rate of no more than 4%-5% per blastocyst transferred. Using the above examples: In Example A: Given that about 50% of the eggs (and thus resulting embryos) of young women are euploid and competent, the transfer up to 2 non-PGS tested blastocysts would likely yield the same results as would the transfer of a single PGS-tested euploid blastocyst. It follows that a patient/couple who are capable and willing to engage a twin pregnancy (which would occur in roughly 25% of such cases), might get as good a result by simply transferring two (2) untested blastocysts and in the process avoid the additional cost of PGS. In Example B: Conversely, the chance of a viable pregnancy in a woman in her mid-40’s would likely be 8-10 times greater when a “competent”, PGS-euploid blastocyst is selectively transferred as compared to when a non-PGS tested blastocyst is transferred to the uterus (4% versus 40%). Albeit that PGS-testing of blastocysts derived from fertilization of an older woman’s eggs is less reliable than for younger counterparts, there would be a distinct benefit/advantage in pre-selecting euploid, “competent” blastocysts for transfer in such cases. Since older women often also have DOR and thus produce fewer eggs/embryos, such women should benefit inordinately from the selective “stockpiling” (banking) of PGS-biopsied blastocysts (vitrification) over several cycles of IVF for collective PGS testing and the subsequent selective transfer of only the most “competent” ones to the uterus with FET. In conclusion, it is my considered opinion that PGS-embryo selection only be considered in the following circumstances: 1.Women over the age of 39Y and those who, regardless of age have significant DOR, are running out of eggs and time, and need to “make hay while the sun shines”! 2.Unexplained IVF failure. 3.Certain cases of recurrent pregnancy loss (RPL). 4.Family gender balancing cases 5.Women who have alloimmune implantation dysfunction (IID) with activation of uterine natural killer cells (NKa)…see elsewhere. 6.Where karyotyping reveals one or other partner to have a balanced chromosomal translocation 7.Known or anticipated specific genetic abnormalities When selectively used PGS is an excellent tool to improve implantation potential and IVF outcome (see above). While PGS provides a new and unique method for selecting the ideal embryos to be transferred, it is not a panacea when it comes to identifying “competent embryos”. There are factors other than numerical chromosomal integrity (karyotype) that can and do influence embryo “competency”, profoundly. PGS embryo selection is in my opinion currently over-used. This is especially the case when it comes to younger women with normal ovarian reserve. Unless the dust is allowed to settle such that this remarkable technology is properly applied, it is my belief that it stands the risk of progressively falling into disrepute. If you are interested in my advice or medical services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Dear doctor,
I am 40 years old and pregnant for the 2. time. No previous abortion. I have a question about slow rising HCG. Week 6+0 HCG. 1550. Week 7+0 HCG 3750. Week 7+5 6250 .
Spot bleeding start week 7+1 and ongoing after 3 weeks. TVS shows intrauterine pregnancy but a week smaller and it should be after the last period. Fine HR 164 week 7+5. Can you say where the bleeding could come from? I did not got an answer from my doctor. Tnhank you in advance for you answer.
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.
I would not worry about the slight lag. It could well catch up. Check again in 1 week.
Please keep me in the loop!
Good luck and G-d bless!
Geoff Sher
Would you treat a woman who is 43 and AMH is 0.03? What are the chances of a successful IVF in this scenario? Thank you!
Yes I would …However, I would caution you that the chance of success (given age and DOR) ids small with own eggs. No doubt, egg donation is the best way to go. However, if in spite of this advice you insist on trying with own eggs then please consider the following:
The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
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
•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
•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.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•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
•Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
•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 Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
•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
•How Many Embryos should be transferred: A Critical Decision in IVF.
•The Role of Nutritional Supplements in Preparing for IVF
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•IVF Egg Donation: A Comprehensive Overview
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Hi i have to take my trigger injection tonight and have discovered i was only prescribed 5000 units of gonasi yet in protocol it says 10000 units of gonasi and now im worried that it will be failed cycle. We have been messed around with hospital before just today we were up for an appointment i asked did i need bloods for the progesterone levels and was told no, at 4pm we were called to make the 2 hour jojrney back to the hospital to get a blood test done. I was very annoyed and now im worried that their negligence will affect our cycle.
Ideal egg development sets the scene for optimal egg maturation that occurs 36-42h prior to ovulation or egg retrieval. Without prior optimal egg development (ovogenesis), egg maturation will be dysfunctional and most eggs will be rendered “incompetent” and unable upon fertilization to propagate viable embryos. In IVF, optimal ovogenesis requires the selection and implementation of an individualized approach to controlled ovaria stimulation (COS). Thereupon, at the ideal time, maturational division of the egg’s chromosomes (i.e. meiosis) is “triggered” through the administration of hCG or an agonist such as Lupron, which induces an LH surge. The, dosage and timing of the “trigger shot” profoundly affects the efficiency of meiosis, the potential to yield “competent (euploid) mature (M2) eggs, and as such represents a rate limiting step in the IVF process .
“Triggering meiosis with Urine-derived hCG (Pregnyl/Profasi/Novarel) versus recombinant hCG (Ovidrel): Until quite recently, the standard method used to “trigger” egg maturation was through the administration of 10,000 units of hCGu. Subsequently,, a DNA recombinant form of hCGr (Ovidrel)was introduced and marketed in 250 mcg doses. But clinical experience strongly suggests that 250 mcg of Ovidrel is most likely not equivalent in biological potency to 10,000 units of hCG. It probably only has 50%-70%of the potency of a 10,000U dose of hCGu and as such might not be sufficient to fully promote meiosis, especially in cases where the woman has numerous follicles. For this reason, I firmly believe that when hCGr is selected as the “trigger shot” the dosage should best be doubled to 500 mcg at which dosage it will probably have an equivalent effect on promoting meiosis as would 10,000 units of hCGu. Failure to “trigger” with 10,000U hCGu or 500mcg hCGr, will in my opinion increase the likelihood of disorderly meiosis, “incompetent (aneuploid) eggs” and the risk of follicles not yielding eggs at egg retrieval (“empty follicles”). Having said this, it is my personal opinion that it is unnecessary to supplant hCGu with hCGr since the latter is considerably more expensive and is probably no more biopotent than the latter.
Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the dosage of hCG administered as a trigger in the hope that by doing so the risk of critical OHSS developing will be lowered. It is my opinion, that such an approach is not optimal because a low dose of hCG (e.g., 5000 units, hCGu or 250mcg hCGr) is likely inadequate to optimize the efficiency of meiosis particularly when it comes to cases such as this where there are numerous follicles. It has been suggested that the preferential use of an “agonist (Lupron) trigger” in women at risk of developing severe ovarian hyperstimulation syndrome could potentially reduce the risk of the condition becoming critical and thereby placing the woman at risk of developing life-endangering complications. It is with this in mind that many RE’s prefer to trigger meiosis by way of an “agonist (Lupron) trigger rather than through the use of hCG. The agonist promptly causes the woman’s pituitary gland to expunge a large amount of LH over a short period of time and it is this LH “surge” that triggers meiosis. The problem with using this approach, in my opinion, is that it is hard to predict how much LH will be released in by the pituitary gland. For this reason, I personally prefer to use hCGu for the trigger, even in cases of ovarian hyperstimulation hyperstimulated, with one important proviso…that being that is she underwent “prolonged coasting” in order to reduce the risk of critical OHSS, prior to the 10,000 unit hCGu “ trigger”.
The timing of the “trigger shot “to initiate meiosis: This should coincide with the majority of ovarian follicles being >15 mm in mean diameter with several follicles having reached 18-22 mm. Follicles of larger than 22 mm will usually harbor overdeveloped eggs which in turn will usually fail to produce good quality eggs. Conversely, follicles less than 15 mm will usually harbor underdeveloped eggs that are more likely to be aneuploid and incompetent following the “trigger”.
Geoff Sher