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.
In my recent hysteroscopy done on CD 8, my uterine cavity was filled with a lot of white fluffy material that was not there in previous hysteroscopies. It was removed and tested to be “benign proliferative endometrium with focal glandular and stroma breakdown.”
Have you seen this before? If it grows back, do you think it should be removed again before my upcoming FET or is it not an impediment as long as the rest of the uterine wall looks healthy? I am concerned the embryo might get lost in the tissue overgrowth, be crowded out, or can’t easily find a good landing place. There were also some blood clots mixed in the tissue.
I appreciate your expertise!
As long as it is not endometrial pathology and there are no adhesions inside the uterine cavity, it is likely to be insignificant in my opinion.
Geoff Sher
Hi Dr. Sher,
Do you think endometrial scratches work?
If so, what is the best timing before FET?
I understand the exact placement of the embryos is paramount to implantation success. Where in the endometrium cavity do you like to place the embryos for FET?
Thanks!
I have absolutely no belief in the endometrial scratch porocedure and do not do it.
The ideal location for embryo placement is about 1cm below the roof of the uterine cavity.
Good luck and G-d bless!
Geoff Sher
Dear Dr. Sher,
I am a fragile x permutation carrier with amh of 0.36 and amenorrhea. I have a very low BMI. I recently began an ivf cycle after being on birth control pills for 13 days. I have failed to respond to six days of gonal-f and menopur. The gonal-f was increased from 300 units to 450 units for the last three days. My e2 level was under 5 pgmol at baseline and after three days of stimulation. I have an antral follicle count of four (all still unmeasurable).
Do you believe it is possible that the use of birth control was ill timed? I would like to determine whether it is possible that this apparent lack of response may be overcome in a future cycle with a modified protocol. Any guidance that you may be kind enough to give would be most appreciated.
Many thanks in advance,
Nicola.
In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Women 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 effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, 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 women 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 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, https://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
Addendum:
Fragile X syndrome: Which IVF Candidates Should be Tested and How Should Results be Interpreted?
Geoffrey Sher MD
Fragile X syndrome occurs in individuals who carry the gene, FMR1 on an X-chromosome. This condition is inherited as a dominant X-linked disorder. With a dominant disorder, the condition results when there is only one copy of the altered gene in each cell.
Fragile syndrome occurs twice as frequently in males (1:1,200) as compared to females (1:2,500) A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. The Fragile X gene, FMR1, can be passed on in a family by individuals who have no apparent signs of this genetic condition. In some families, a number of members appear to be affected, whereas in other families a newly diagnosed individual may be the first family member to exhibit symptoms.
By and large, Fragile X syndrome results from a mutation in the FMR1 gene where a segment, known (CGG triplet repeat), is expanded. Under normal circumstances, the CGG triplet is repeated from 5 to approximately 55 times. In contrast, those who have Fragile X syndrome will have more than 200 repeats. CGG segments prevent the FMR from propagating the formation of a specific protein needed to protect against the development of Fragile X syndrome. Thus over-expression of CGG triplet (>200 times) on an X chromosome represents a degree of loss of this “protective protein” as to lead to the development of fragile X syndrome. Since boys have only one X chromosome, Fragile X syndrome tends to manifest much more severely in males than in females, (who have two X chromosomes).
In a normal population, the number of repeated FMR1 genes varies from 5 to about 55. Those with 55 to 200 repeats of the CGG segment are said to have an FMR1 premutation (carriers”). In women, this is liable to increase to >200 repeats in the developing eggs. Accordingly, such women are at increased risk of having a child with fragile X syndrome. Conversely, when passed by men to the next generation, CGG repeats either remain the same in size or shorten. This is why men with a permutation do not transmit the disease. However they do transmit the permutation which if carried to a subsequent female offspring can result in them transmitting Fragile X syndrome in subsequent generations.
Both males and females with fragile X pre-mutation are by and large intellectually and physically normal in outward appearance. Some may manifest with mild but often socially harmful intellectual or behavioral symptoms,. They are however usually not infertile.
Some men with a premutation are at risk of developing a manifestation of fragile X-associated tremor/ataxia syndrome (FXTAS) a condition characterized by loss of balance, tremors and memory loss. It occurs in some older male carriers of the gene. Heart bone and skin problems are also often present. Age distribution is a s follows: Seventeen percent (17%) of males aged 50-59 years, in 38 percent of males aged 60-69 years, in 47 percent of males aged 70-79 years, and in 75 percent or males aged 80 years or older. Some female premutation carriers may have diminished ovarian reserve (DOR), premature ovarian failure and FXTAS.
It is important to bear in mind that women who have approximately 55 to 200 repeats. There is no clear cut-off between the upper limit of normal and the lower limit of the premutation range. Accordingly, cases with 45-55 repeat copies fall into the so called “gray zone.” In some cases, premutations expand from generation to generation such that over time they ultimately express as full Fragile X syndrome. The larger the premutation in cases that fall in the “gray zone”, the greater is the risk of subsequent expansion to a full mutation in the offspring.
Boys with full FMR1 mutation (Fragile X syndrome) will almost routinely have moderately severe mental retardation. They will tend to have a characteristic facial appearance with a long face, enlarged cranium, protruding ears and an elongated face with a protuberant chin and forehead. Affected boys after puberty tend also to experience enlargement of the scrotum and laxicity of joints. There will also usually be characteristic behavioral problems such as lack of impulse control, temper tantrums, delay in speech and language development and perseverative speech. Hand biting, hand flapping and attention deficit /hyperactivity are other common manifestations. Fragile X syndrome is also the most common known cause of autism or “autistic-like” behaviors.
Girls with Fragile X on the other hand, tend to only have mild mental retardation. Women who have fewer repeats of the FMR-1 gene usually do not have mental retardation but often will have prematurely diminishing of ovarian reserve (DOR) with early menopause and infertility. Both men and women may develop FXTAS.
While most males with full blown clinical fragile X syndrome are mentally retarded and exhibit some or all the physical and behavioral characteristics, only about one third of females are mentally retarded. Another one third are partially mentally impaired, and the remaining third are unaffected.
Fragile X syndrome is diagnosed through DNA testing of cells using one of two methods:
1.Polymerase Chain Reaction (PCR) or
2.Southern blot analysis
Both methods exhibit a high degree of interpersonal variability and thus when it comes to interpreting results, there are significant limitations. This is especially the case when diagnosing a “carrier state.” Interpretation is further complicated by the presence of other fragile sites in the same region of the X chromosome.
It is recommended that in the following circumstances, patients undergoing assisted reproduction be tested for Fragile-X:
•All mentally challenged individuals, those who are autistic, and in cases of developmental delay
•Women with unexplained premature reduction in ovarian reserve or premature ovarian failure (menopause)
•Individuals who have physical or behavioral characteristics of fragile X syndrome
•Those with a family history of fragile X syndrome
•Those with a family history of mentally challenged male or female relatives where no definitive cause has been ascertained.
•Offspring of known carrier mothers
Prenatal diagnosis can be made by 2nd trimester amniocentesis, which yields definitive results. In contrast, results obtained from 1st trimester chorionic villus sampling (CVS) should be interpreted with caution, because the status of the FMR1 gene often will not fully manifest in chorionic villi until the second trimester.
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Hi Dr. Sher.
I am 37. Have AMH 5.7. Had four follicles at collection, three eggs collected, two have fertilised. Tomorrow I will find out how they are and if I should have a two day transfer or wait and try to grow them to blastocyte. I could have them both put back but I’m not sure about that. I have to decide if I should go tomorrow for a two day transfer or wait till day 5. (If they are still ok that is by the morning) What would you advise?
Embryo transfer (ET) is undoubtedly a rate limiting factor when it comes to IVF outcome. In fact, in my opinion, it is the single most important procedural step in IVF. Optimal performance of ET takes practice, confidence, dexterity, timing, gentility and skill. Of all the hands-on procedures involved in the IVF process, embryo transfer is by far the most difficult to teach. In fact, any women fail to conceive simply because the practicing physician did (could) not perform this procedure optimally.
The issue of whether it is better to transfer early (day 2-3,post fertilization) cleaved embryos rather than (day 5-6) blastocysts continues to rage. Here I wish to focus on the reasons why I favor transferring blastocysts.
Not too long ago, it was believed that the sooner an embryo was transferred into the “natural environment” of the uterus, the greater would be the chance of it implanting and propagating a viable pregnancy. Thus most IVF physicians advocated day 2 or day 3 embryo transfers preferentially. About 20 years ago, we began to realize that there was no validity to the belief that an embryo would develop better and have a greater chance of propagating a baby by being inside the uterus earlier than it would by being allowed to first develop into a blastocyst in an incubator. About a decade later, it was realized that cleaved embryos that fail to develop into blastocysts are with few exceptions numerically chromosomally “incompetent” (aneuploid) such that had they been transferred earlier, they almost certainly would not have developed into blastocysts and would not have propagated a pregnancy anyway. Now most of us practicing in this field believe it to be preferential to selectively transfer blastocysts rather than earlier cleaved embryos. Don’t get me wrong! I am not saying that there is never a place for doing earlier pre-blastocyst transfers. Patients that only have one or two cleaved embryos available might as well transfer them early.
The recent popularization of full preimplantation genetic sampling (PGS) using methods such as comparative genomic hybridization (CGH), next generation gene sequencing (NGS) and SNP array, now allow us to identify those blastocysts that are the most “competent”. Selective transfer of such embryos improves the implantation rate per embryo by a factor of 2-3.
It is important to bear in mind that morphologically good looking day 3 embryos/blastocysts that are determined microscopically to be of a “high grade” , are by no means always numerically chromosomally “competent” euploid , and the likelihood of such embryos being “competent” diminishes progressively with advancing age of the woman. Only through the performance of full PGS can his age-related discrepancy be reduced.
While it would be acceptable to me to transfer 2 PGS-untested blastocysts to women under 39 years, and to transfer 3 to older women, I would not recommend transferring more than 2 PGS-normal embryos at any age.
The following are arguments in favor of performing blastocysts transfers:
•By waiting to day 5-6 many unworthy, many aneuploid and “incompetent” embryos can be culled out, thereby allowing for the transfer of fewer embryos and minimizing the risk of high order multiple pregnancies.
•Diagnostic Advantages:
o Failure of the expected number of cleaved embryos to advance to the blastocyst stage of development in culture, raises the suspicion of underlying inherent embryo “incompetence”, which is usually (but not exclusively) egg-related rather than due to a sperm factor. While age of the woman is the most important factor involved, it can also be due to the wrong protocol of ovarian stimulation being used).
oIt facilitates the performance of PGS to identify and then selectively transfer only most “competent” (euploid) blastocysts. In such cases, provided there is no underlying uterine implantation dysfunction implantation and pregnancy rate is enhanced significantly.
Of course, for the treating physician it is far less stressful not have to have to confront a patient with her having no surviving embryos to transfer. The avoidance of this has in my opinion, in the past, been one of the main reasons why IVF practitioners have elected to transfer cleaved embryos rather than blastocysts. But such a policy is usually not in the in the patients’ best interest. In my opinion, it is far better to advise the patient to do a blastocyst transfer since that is almost always in their best interest.
Hope this helps!
Geoff Sher
PH: 800-780-7437
Dr. I just wanted to ask my last menstrual period is august 1,2017-so im expecting my next period on the 26th. I got my period but only for one day..after a few days i use hpt….and it came out with a very blurred lines but showing positive…i test again after two days and its really positive….i got docs appt…and the urine test shows negative…and the doc says my hcg level is too low at about 25000….so i took blood test and its positive.but when i went to a maternty hospital the urine test is negative….pls advice me do you think im pregnant?thank you in advance
It clearly suggests that you conceived. Howsoever, the viability of the pregnancy needs still to be established. i suggest you orange for an ultrasound, sooner rather than later.
Good luck!
Geoff Sher