Please re-post in English!

Geoff Sher

It is the thickness of the endometrium pre-ovulation that matters.

Good luck!

Geoff Sher

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Back in 1989, I conducted a study that examined how the thickness of a woman’s uterine lining, known as the endometrium, affected the successful implantation of embryos in IVF patients. The study revealed that when the uterine lining measured less than 8mm in thickness by the day of the “hCG trigger” in fresh IVF cycles, or at the start of progesterone therapy in embryo recipient cycles (such as frozen embryo transfers or egg donation IVF), the chances of pregnancy and birth were significantly improved. In my opinion, an ideal estrogen-promoted endometrial lining should measure at least 9mm in thickness, while a lining of 8-9mm is considered “intermediate.” In most cases, an estrogenic lining of less than 8mm is unlikely to result in a viable pregnancy.

A “poor” uterine lining typically occurs when the innermost layer of the endometrium, called the basal or germinal endometrium, fails to respond to estrogen and cannot develop a thick enough outer “functional” layer to support optimal embryo implantation and placenta development. The “functional” layer makes up two-thirds of the total endometrial thickness and is the layer that sheds during menstruation if no pregnancy occurs.

The main causes of a “poor” uterine lining include:

1. Damage to the basal endometrium due to:

1. • Inflammation of the endometrium (endometritis) often resulting from retained products of conception after abortion, miscarriage, or birth.
   • Surgical trauma caused by aggressive uterine scraping during procedures like D&C.

1. Insensitivity of the basal endometrium to estrogen due to:

1. • Prolonged or excessive use of clomiphene citrate.
   • Prenatal exposure to diethylstilbestrol (DES), a drug given to pregnant women in the 1960s to prevent miscarriage.

1. Overexposure of the uterine lining to ovarian male hormones, mainly testosterone, which can occur in older women, women with diminished ovarian reserve, and women with polycystic ovarian syndrome (PCOS) who have increased LH biological activity. This hormonal imbalance leads to the overproduction of testosterone in the ovary’s connective tissue, further exacerbated by certain ovarian stimulation methods used in IVF.
2. Reduced blood flow to the basal endometrium, often caused by:

1. • Multiple uterine fibroids, especially those located beneath the endometrium (submucosal).
   • Uterine adenomyosis, an abnormal invasion of endometrial glands into the uterine muscle.

“The Viagra Connection”

Eighteen years ago, I reported on the successful use of vaginal Sildenafil (Viagra) in treating women with implantation dysfunction caused by thin endometrial linings. This breakthrough led to the birth of the world’s first “Viagra baby.” Since then, thousands of women with thin uterine linings have been treated with Viagra, and many have gone on to have babies after multiple unsuccessful IVF attempts.

Viagra gained popularity in the 1990s as an oral treatment for erectile dysfunction. Inspired by its mechanism of action, which increases penile blood flow through enhanced nitric oxide activity, I investigated whether vaginal administration of Viagra could improve uterine blood flow, deliver more estrogen to the basal endometrium, and promote endometrial thickening. Our findings confirmed that vaginal Viagra achieved these effects, while oral administration did not provide significant benefits. To facilitate treatment, we collaborated with a compound pharmacy to produce vaginal Viagra suppositories.

In our initial trial, four women with a history of poor endometrial development and failed conception underwent IVF treatment combined with vaginal Viagra therapy. The Viagra suppositories were administered four times daily for 8-11 days and stopped 5-7 days before embryo transfer. This treatment resulted in a rapid and significant improvement in uterine blood flow, leading to enhanced endometrial development in all four cases. Three of these women subsequently conceived. In 2002, I expanded the trial to include 105 women with repeated IVF failure due to persistently thin endometrial linings. About 70% of these women responded positively to Viagra therapy, with a notable increase in endometrial thickness. Forty-five percent achieved live births after a single cycle of IVF with Viagra treatment, and the miscarriage rate was only 9%. Women who did not show improvement in endometrial thickness following Viagra treatment did not achieve viable pregnancies.

When administered vaginally, Viagra is quickly absorbed and reaches the uterine blood system in high concentrations. It then dilutes as it enters the systemic circulation, explaining why treatment is virtually free from systemic side effects.

It is important to note that Viagra may not improve endometrial thickness in all cases. Approximately 30-40% of women treated may not experience any improvement. In severe cases of thin uterine linings where the basal endometrium has been permanently damaged and becomes unresponsive to estrogen, Viagra treatment is unlikely to be effective. This can occur due to conditions such as post-pregnancy endometritis, chronic inflammation resulting from uterine tuberculosis (rare in the United States), or extensive surgical damage to the basal endometrium.

In my practice, I sometimes recommend combining vaginal Viagra administration with oral Terbutaline (5mg). Viagra relaxes the muscle walls of uterine spiral arteries, while terbutaline relaxes the uterine muscle itself. The combination of these medications synergistically enhances blood flow through the uterus, improving estrogen delivery to the endometrial lining. However, it’s important to monitor potential side effects of Terbutaline such as agitation, tremors, and palpitations. Women with cardiac disease or irregular heartbeat should not use Terbutaline.

Approximately 75% of women with thin uterine linings respond positively to treatment within 2-3 days. Those who do not respond well often have severe inner ( (basal) endometrial lining damage, where improved uterine blood flow cannot stimulate a positive response. Such cases are commonly associated with previous pregnancy-related endometrial inflammation, occurring after abortions, infected vaginal deliveries, or cesarean sections.

Viagra therapy has been a game-changer for thousands of women with thin uterine linings, allowing them to successfully overcome infertility and build their families.

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PLEASE SHARE THIS WITH OTHERS AND HELP SPREAD THE WORD!!

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) ; http://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\

Please Repost in English!

Geoff Sher

• Asherman Syndrome is a medical condition characterized by severe intrauterine adhesions, also known as synechiae. These adhesions can cause significant damage to the basal layer of the endometrium, the part of the uterus responsible for developing the uterine lining (endometrium) under the influence of hormones like estrogen and progesterone. When the basal endometrium is severely affected, it can lead to  a reduction in menstrual flow (hypomenorrhea) or complete cessation of menstruation (amenorrhea), and infertility.

  Causes of Asherman Syndrome

  The most common cause of Asherman Syndrome is inflammation of the uterine lining, a condition called endometritis. This inflammation often occurs after childbirth (post-partum) , after an incomplete miscarriage or post-abortal. However, it can also result from uterine surgeries, such as the removal of fibroid tumors (myomectomy) that encroach upon or penetrate the uterine cavity.

  Treatment for Asherman Syndrome

  The primary treatment for Asherman Syndrome involves a procedure called hysteroscopic resection. During this procedure, a telescope-like instrument is introduced through the vagina and cervix into the uterine cavity. This allows surgeons to directly remove as much scar tissue as possible and free any adhesions that have fused the walls of the uterine cavity together. The goal is to uncover viable basal endometrium and promote its growth to cover the surface of the uterine cavity. In some cases, a small balloon may be placed in the uterine cavity for a short period to prevent adhesion recurrence. Women undergoing this treatment typically receive supplemental estrogen to encourage endometrial growth.

  Fertility Complications

  Asherman Syndrome can lead to scarring and blockage of the uterine entrance to the fallopian tubes. This blockage often affects the ability of the uterus to support embryo implantation. In rare cases, pregnancy can occur in the fallopian tubes, leading to an ectopic pregnancy. Ectopic pregnancies are dangerous and require early diagnosis and treatment to prevent severe intra-abdominal bleeding.

  A Glimmer of Hope: Viagra Suppositories

  Recent research has explored the use of Viagra vaginal suppositories to improve blood flow and enhance the delivery of estrogen to the endometrium. This innovative approach has shown promise in improving endometrial development, especially in cases where traditional treatments have failed. Approximately 75% of women who struggled with poor endometrial development, often after multiple failed IVF attempts, experienced positive results with this treatment. Some of these women successfully conceived and went on to deliver healthy babies, providing renewed hope for those facing infertility challenges.

  Challenges and Considerations

  However, for women with extensive damage to the basal endometrium due to Asherman Syndrome, improving blood flow with Viagra may not be sufficient in achieving the necessary endometrial development. In such cases, it’s essential for women to consider alternative options, including adoption or gestational surrogacy, to fulfill their dreams of parenthood.

  In conclusion, Asherman Syndrome is a complex condition that can have a profound impact on a woman’s reproductive health. While treatments like hysteroscopic resection and innovative approaches with Viagra offer some hope, the severity of the condition may necessitate exploring alternative paths to parenthood. It’s crucial for individuals facing this challenge to consult with their healthcare providers to determine the best course of action for their unique circumstances.

• Geoff Sher
• ———————————————————————————————————-

PLEASE SHARE THIS WITH OTHERS AND HELP SPREAD THE WORD!!

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) ; http://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\

Understanding the impact of age and 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 older women an those 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. Age and Ovarian Reserve: Chronological age plays a vital role in determining the quality of eggs and embryos. As women age, there is an increased risk of aneuploidy (abnormal chromosome numbers) in eggs and embryos, leading to reduced 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 older women or those with DOR, ovarian stimulation protocols that down-regulate LH activity before starting gonadotropins are necessary to improve egg/embryo quality and IVF outcomes.
3. Individualized Ovarian Stimulation Protocols: Although age is a significant factor in aneuploidy, it is possible to prevent further 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 for Older Women or Those with DOR: Certain ovarian stimulation protocols may not be suitable for older women or those 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(PGS/T): PGS/T is a valuable tool for identifying chromosomal abnormalities in eggs and embryos. By selecting the most competent (euploid) embryos, PGS/T significantly improves the success of IVF, especially in older women or those with DOR.

Understanding the impact of advancing age and declining ovarian reserve on IVF outcomes is essential when making decisions about fertility treatments. Age-related factors can affect egg quality and increase the likelihood of aneuploid embryos with resultant IVF failure. Diminished ovarian reserve (DOR) further complicates the process. By considering these factors, 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.

PLEASE SHARE THIS WITH OTHERS AND HELP SPREAD THE WORD!!

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) ; http://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\

Geoff Sher

Please re-post this question in English!

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

Geoff Sher