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.
I am 39years old. I started my first IVF procedure this month with stimulation and the scan at intervals showed enough follicles being produced , on the 14th day , there was egg retirval and sadly the doctor told me that the whole egs where empty. I have been devasted since then and having been wandering why it was so. though the doctor said the stimulation will be repeated with close monitoring and increased drugs. . am worried, pls doctor Sher, is there hope for a better result?
Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.
This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”
Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, 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.
There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.
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.
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
•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?
•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.
•Fertility Preservation (FP) Through Freezing/Banking Human Eggs
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.
Hi Dr Sher, my periods have suddenly become short and light. They only last 1.5 days instead of 3-5 days and they are also very light. My periods have been light for about 5-6 months now but my lining has been fine. The month before last my line was suddenly a lot thinner than normal 6.8mm but a month later it was back to normal 11mm. What could be causing this? What can I do about it? Thanks so much in advance.
Dysfunctional ovulation is likely the cause. However, with ovarian stimulation this could be negated. Discuss with your RE.
Geoff Sher
Dear Dr Sher,
My genetic testing says I am a carrier of immediate fragile X (29 and 50 repeats). I gave birth to my first child when I was 32 years old and got pregnant the second time almost at 36 but it was abnormal and I lost my second baby (D&C surgery at 16 weeks) in 2013. Since then more than 4 years, I have tried actively with 3 IUI, and 1 IVF and also taking Co q10, prenatal vitamins and sometimes DHEA 75 mg, but never get pregnant again. I researched information about my fragile X genetic disorder and according to NIH, some studies show that women with about 44 to 54 CGG repeats, known as an intermediate (or gray zone) mutation, can also have features of Fragile X-associated primary ovarian insufficiency. If this is the case, do you think because of my genetic disorder with fragile X, I might have early menopause or fertility problem and cannot conceive with my own eggs? If so, do you think I should consider donor egg in my case? I am almost 41 years old. My doctor concluded that my case is unexplained infertility. All the tests of my husband and mine came back normal. Your insight and response is greatly appreciated. Thank you so much for your time, Dr Sher. I look forward to your reponse.
I suggest we talk!
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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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.
•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)
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•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.
•IVF: Selecting the Best Quality Embryos to Transfer
•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
•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.
Hi! I am a recent ivf patient and had egg retrieval 8-29. 21 eggs, 13 fertilized but only 2 blasts and one has tested abnormal. They said most all that fertilized had a lot of fragmentation and that it could be an egg quality issue.
I do have a pea sized prolactinoma diagnosed 2012. Im on bromocryotine since 2012 and my prolactin levels are normal while on medication. I am going to try another round of stims and another retrieval and I’m hoping for better results. I’m going to take ubiquinol to try and improve quality but I don’t know what else to do?! My doctor says dhea and myoinositol probably won’t help me. I mentioned adding a growth hormone to my next cycle and he doesn’t seem to think that will help either.
I don’t get it. I had 21 eggs! Why am I having such poor luck? I just turned 30. Husband tested normal so there’s no issue there. Am I having these issues because of the prolactinoma? Even though the levels have been managed for 5 years? What advice can you give me?
Thank you!!
I took 150 menopur, 75 gonal to start which increases to 150 on about day four of stims, added cetrotide day 6 to prevent ovulating early then triggered with ovidrel day 9 I believe. Retrieval was 36 hours later. While on stims I took bromocryotine to manage prolactin as normal and levothyroxine so we can get thyroid under 2 for transfer.
Aside from age and ovarian reserve, it is the protocol used for ovarian stimulation that impacts egg/embryo competency.
My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
I strongly recommend that you visit https://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
• “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
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 Dr. Sher,
I have endometriosis. Should I undergo immunology testing before a frozen pgs tested embryo transfer? Or do you recommend trying a certain number of pgs tested embryo transfers before immunology testing?
Thank you,
Erin
In my opinion, all women with endometriosis, regardless of its severity should undergo immunologic assessment before contemplating embryo transfer.
More than half of women who have endometriosis harbor antiphospholipid antibodies (APA) that can compromise development of the embryo’s root system (trophoblast). In addition and far more serious, is the fact that in about one third of cases endometriosis, regardless of its severity is associated with NKa and cytotoxic uterine lymphocytes (CTL) which can seriously jeopardize implantation. This immunologic implantation dysfunction (IID) is diagnosed by testing the woman’s blood for APA, for NKa (using the K-562 target cell test or by endometrial biopsy for cytokine activity) and, for CTL (by a blood immunophenotype). Activated NK cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.
Women who harbor APA’s often experience improved IVF birth rates when heparinoids (Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. NKa is treated with a combination of Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa.
The therapeutic effect of IL/steroid therapy is likely due to an ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. IL/steroids down-regulates NKa within 2-3 weeks of treatment the vast majority of women experiencing immunologic implantation dysfunction. In this regard IL is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.
The toxic pelvic environment caused by endometriosis, profoundly reduces natural fertilization potential. As a result normally ovulating infertile women with endometriosis and patent Fallopian tubes are much less likely to conceive naturally, or by using fertility agents alone (with or without intrauterine (IUI) insemination. The only effective way to bypass this adverse pelvic environment is through IVF. I am not suggesting here that all women who have endometriosis require IVF! Rather, I am saying that in cases where the condition is further compromised by an IID associated with NKa and/or for older women(over 35y) who have diminished ovarian reserve (DOR) where time is of the essence, it is my opinion that IVF is the treatment of choice.
Geoff Sher
Thank you Dr. Sher. So I should get a blood test for Apa, nka, and ctl? Is this all? If I get the blood test for Nka do I need the endometrial biopsy, too?
Thank you,
Erin