I am not overly concerned. The le3vels often tail off somewhat around this time. Do an US confirmation ASAP.

Good luck!

Geoff Sher

I honestly doubt that this is what has caused your miscarriages,. But discuss it with your primarybcare OB/GYN.

Geoff Sher

Your elevated TSH could indicate an underlying hypothyyroid state which could be due to an autoimmune condition andf your low AMH points towards iminished ovarian reserve (DOR:

• 1. Thyroid Autoimmunity (TAI) & Immunologic Implantation Dysfunction (IID)

Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss. The condition is 5-10 times more common in women than in men.

In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies. The increased prevalence of hypothyroidism and TAI in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities.

While being the main cause of hypothyroidism TAI is more often present independent of coexisting clinical or hormonal features of hypothyroidism. Regardless of whether or not hormonal or clinical evidence of hypothyroidism is present or whether a woman with Hashimoto’s disease is successfully treated with thyroid hormone supplementation, women who have thyroid antibodies are often afflicted with reproductive dysfunction (infertility and early or late pregnancy loss).

We reported on the fact that 47% of women with TAI (regardless of the absence or presence of clinical hypothyroidism) have CTL and activated NKa cells and that such women often present with reproductive dysfunction. We also reported that appropriate treatment with IL and steroids, often results in viable pregnancies in such cases.

The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo.

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• 2.ADDRESSING DIMINISHING OVARIAN RESERVE (DOR) IN IVF

Understanding the impact of ovarian reserve on the success of in vitro fertilization (IVF) is crucial when it comes to reproductive health. This article aims to simplify and clarify these concepts, emphasizing their significance in the selection of ovarian stimulation protocols for IVF. By providing you with this information, we hope to shed light on the importance of considering these factors and making informed decisions regarding fertility treatments.

1. The Role of Eggs in Chromosomal Integrity: In the process of creating a healthy embryo, it is primarily the egg that determines the chromosomal integrity, which is crucial for the embryo’s competency. A competent egg possesses a normal karyotype, increasing the chances of developing into a healthy baby. It’s important to note that not all eggs are competent, and the incidence of irregular chromosome numbers (aneuploidy) increases with age.
2. Meiosis and Fertilization: Following the initiation of the LH surge or the hCG trigger shot, the egg undergoes a process called meiosis, halving its chromosomes to 23. During this process, a structure called the polar body is expelled from the egg, while the remaining chromosomes are retained. The mature sperm, also undergoing meiosis, contributes 23 chromosomes. Fertilization occurs when these chromosomes combine, resulting in a euploid embryo with 46 chromosomes. Only euploid embryos are competent and capable of developing into healthy babies.
3. The Significance of Embryo Ploidy: Embryo ploidy, referring to the numerical chromosomal integrity, is a critical factor in determining embryo competency. Aneuploid embryos, which have an irregular number of chromosomes, are often incompetent and unable to propagate healthy pregnancies. Failed nidation, miscarriages, and chromosomal birth defects can be linked to embryo ploidy issues. Both egg and sperm aneuploidy can contribute, but egg aneuploidy is usually the primary cause.
4. Embryo Development and Competency: Embryos that develop too slowly or too quickly, have abnormal cell counts, contain debris or fragments, or fail to reach the blastocyst stage are often aneuploid and incompetent. Monitoring these developmental aspects can provide valuable insights into embryo competency.
5. Diminished Ovarian Reserve (DOR): As women advance in their reproductive age, the number of remaining eggs in the ovaries decreases. Diminished ovarian reserve (DOR) occurs when the egg count falls below a certain threshold, making it more challenging to respond to fertility drugs effectively. This condition is often indicated by specific hormone levels, such as elevated FSH and decreased AMH. DOR can affect women over 40, but it can also occur in younger

Why IVF should be regarded as treatment of choice for women who have diminished ovarian reserve ( DOR):

Understanding the following factors will go a long way in helping you to make an informed decision and thereby improve the chances of a successful IVF outcome.

1. Ovarian Reserve: While chronological age plays a vital role in determining the quality of eggs and embryos [there is an increased risk of egg aneuploidy (irregular chromosome number) in eggs,  leading to reduced embryo competency. Additionally, women with declining ovarian reserve (DOR), regardless of their age, are more likely to have aneuploid eggs/embryos. Therefore, it is crucial to address age-related factors and ovarian reserve to enhance IVF success.
2. Excessive Luteinizing Hormone (LH) and Testosterone Effects: In women with DOR, their ovaries and developing eggs are susceptible to the adverse effects of excessive LH, which stimulates the overproduction of male hormones like testosterone. While some testosterone promotes healthy follicle growth and egg development, an excess of testosterone has a negative impact. Therefore, in both older women or those who (regardless of their age) have DOR, ovarian stimulation protocols that down-regulate LH activity before starting gonadotropins are necessary to improve egg/embryo quality and IVF outcomes.
3. It is possible to regulate the  decline in egg/embryo competency by tailoring ovarian stimulation protocols. Here are my preferred protocols for women with relatively normal ovarian reserve:

1. Conventional Long Pituitary Down Regulation Protocol:

• Begin birth control pills (BCP) early in the cycle for at least 10 days.
• Three days before stopping BCP, overlap with an agonist like Lupron for three days.
• Continue daily Lupron until menstruation begins.
• Conduct ultrasound and blood estradiol measurements to assess ovarian status.
• Administer FSH-dominant gonadotropin along with Menopur for stimulation.
• Monitor follicle development through ultrasound and blood estradiol measurements.
• Trigger egg maturation using hCG injection, followed by egg retrieval.

1. Agonist/Antagonist Conversion Protocol (A/ACP):

• Similar to the conventional long down regulation protocol but replace the agonist with a GnRH antagonist from the onset of post-BCP menstruation until the trigger day.
• Consider adding supplementary human growth hormone (HGH) for women with DOR.
• Consider using “priming” with estrogen prior to gonadotropin administration

1. Protocols to Avoid in Women with DOR: Certain ovarian stimulation protocols may not be suitable for women with declining ovarian reserve:

• Microdose agonist “flare” protocols
• High dosages of LH-containing fertility drugs such as Menopur
• Testosterone-based supplementation
• DHEA supplementation
• Clomiphene citrate or Letrozole
• Low-dosage hCG triggering or agonist triggering for women with DOR

Preimplantation Genetic Screening/Testing for aneuploidy (PGS/PGTA): PGS/PGTA is a valuable tool for identifying chromosomal abnormalities in eggs and embryos. By selecting the most competent (euploid) embryos, PGS/PGTA significantly improves the success of IVF, in women with DOR.

Understanding the impact of declining ovarian reserve on IVF outcomes is essential when making decisions about fertility treatments. Diminished ovarian reserve (DOR) can affect egg quality and increase the likelihood of aneuploid embryos with resultant IVF failure. By considering this factor, you can make informed choices and work closely with fertility specialists to optimize your chances of success. Remember, knowledge is power, and being aware of these aspects empowers you to take control of your reproductive journey.

If you would like to discuss your case with me , email my assistant (702-533-2691 and set up an online  consultation with   me,

I would need much more information.

If you would like to discuss your case with me , email my assistant (702-533-2691 and set up an online  consultation with   me,

Empty Follicle Syndrome” is a misleading term because follicles always contain eggs. However, some eggs may have difficulties detaching and being retrieved. This is more likely to happen when multiple attempts are needed to retrieve an egg from a follicle, indicating the egg may have chromosomal abnormalities.

The hormonal environment created during controlled ovarian stimulation plays a significant role in egg development. In certain cases, follicles may not release their eggs during retrieval, leading to the misconception of “empty” follicles.

This situation is most commonly encountered in older women, those with diminished ovarian reserve (DOR), and women with polycystic ovarian syndrome (PCOS). To address this problem, personalized protocols for controlled ovarian stimulation and careful administration of the hCG trigger shot are important.

The hCG trigger shot is given after optimal ovarian stimulation to initiate the process of reducing the number of chromosomes in the egg. It also helps the egg detach from the follicle’s inner wall. This allows for easier retrieval during the egg retrieval procedure.

Women with increased LH activity, such as older women, those with DOR, and women with PCOS, are more susceptible to the negative effects of LH-induced ovarian testosterone. Excessive LH activity can compromise egg development and increase the chances of chromosomal abnormalities. Medications like clomiphene and Letrozole can stimulate LH release, and certain drugs containing LH or hCG can have negative consequences.

Individualizing the controlled ovarian stimulation protocol, determining the correct dosage and type of hCG trigger, and administering it at the right time are crucial. The recommended dosage of urinary-derived hCG products is 10,000 units, while for recombinant DNA-derived hCG, the optimal dosage is 500 micrograms. A lower dosage of hCG can increase the risk of chromosomal abnormalities in the eggs and negatively impact the outcome of IVF.

Understanding the role of LH activity, the effects of medications on hormone release, and the importance of personalized protocols are vital. By optimizing these factors, the risk of failed egg retrieval and “empty follicle syndrome” can be minimized, improving the chances of successful IVF outcomes.

If you would like to discuss your case with me , email my assistant (702-533-2691 and set up an online  consultation with   me,

I would need to consult directly with your daughters re ovarian stimulation. If you are interested, please reach outv to my assistant, Patti Converse (702-533-2691 ). Below is an article I wrote on Fragile-X FYI.

• Fragile X syndrome: Which IVF Candidates Should be Tested and How Should Results be Interpreted?

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 more  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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Herewith are  online links to 2  E-books recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1. From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) ; https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link ;https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

If you are interested in having an online consultation with me, please contact my assistant, Patti Converse at 702-533-2691 or email her at concierge@sherivf.com\