Our cut off for egg retrievals is 47Y. Frozen embryo transfers….no definitive cut off. See below:

Age should never be a barrier to hope and fulfillment when it comes to IVF. Many women in their early to mid-40s are successfully having IVF babies using their own eggs, especially if they have a good number of eggs left in their ovaries. However, for women with diminished ovarian reserve (DOR) or those over the age of 44, where the chances of success with their own eggs are low, IVF with egg donation can be a highly successful and safe option. Let’s explore why age affects IVF outcomes and discover the possibilities that lie ahead.

The egg plays a crucial role in determining the quality of the embryo, with a “competent” egg having the best chance of developing into a healthy baby. As women age, the chances of having eggs with an irregular number of chromosomes (aneuploid) increase significantly. Fertilizing an aneuploid egg will result in an embryo with an abnormal number of chromosomes, making it unable to develop into a healthy baby.

Chromosomal abnormalities are the main cause of failed implantation, pregnancy losses, and birth defects. As women get older, the risk of chromosomal abnormalities in embryos rises, leading to lower IVF success rates. Additionally, older women may experience hormonal imbalances that further affect egg quality and development. However, personalized stimulation protocols can help protect egg quality and improve IVF outcomes by regulating hormone production and activity.

When it comes to IVF in older women, selecting the right ovarian stimulation protocol is crucial. Various protocols are available, each tailored to meet individual needs. However, certain protocols should be avoided for older women or those with DOR to optimize chances of success.

I selectively use a variety of ovarian stimulation protocols for ovarian stimulation/IVF in older women and those with DOR :

• The conventional long pituitary down-regulation protocol: This involves administering a GnRH agonist like Lupron or Buserelin for a few days prior to initiating ovarian stimulation with gonadotropins. Then, a combination of FSH-dominant gonadotropin and a small dose of Menopur is administered, and ultrasound and blood tests are done to monitor follicle development. The eggs are triggered for maturation with hCG, and the egg retrieval is scheduled for approximately 36 hours later. This protocol is often preferred for older women who have adequate ovarian reserve (AMH=>1.5ng/ml).
• The agonist/antagonist conversion protocol (A/ACP):, This is similar to the conventional long down-regulation protocol. However, instead of using an agonist, a GnRH antagonist is administered from the onset of stimulation with gonadotropins. This protocol is often preferred for older women who have moderately severe DOR (AMH=0.5-1.5ng/ml).
• A/ACP with Estrogen “priming”; For women with very severe, DORI prescribe  estrogen “priming “with skin estradiol (E2) patches or Estradiol injections administered bi-weekly. For some time before commencing gonadotropin stimulation, in an attempt to enhance ovarian response to stimulation. This protocol is sometimes used in older women who have severe DOR ( <0.5-1.5ng/ml).

In my opinion, the following ovarian stimulation protocols all promote over-exposure to LH-induced ovarian testosterone and are best avoided in older women and women with DOR, undergoing ovarian stimulation for IVF:

• Agonist “flare” protocols, which cause a surge of pituitary-LH at the wrong time.
• High dosages , LH-containing fertility drugs (e.g., menotropins such as Menopur).
• Testosterone-based supplements like Androgel.
• DHEA supplementation: DHEA is converted to testosterone in the ovaries.
• Clomiphene citrate & Letrozole, promote exaggerated pituitary LH release that can result in over-production of ovarian testosterone.
• Triggering egg maturation with too low a dosage of hCG (the ideal dosage is 10,000U of urine derived hCG) andf Recombinant DNA-derived hCG ( the ideal dosage is 500mcg of Ovidrel).

In cases where using their own eggs is no longer viable due to age and severe DOR, using donor eggs provides a fulfilling path to parenthood. Although some may initially hesitate due to the lack of genetic relation, it’s important to understand that the person who gives birth is considered the true biological parent in most cultures and legal systems. Becoming a parent through this connection can bring immense joy and fulfillment, as countless successful cases have shown.

Age may reduce the chances, but it does not eliminate the possibility of having a child through IVF. When IVF with own eggs is not an option, embracing the alternative of egg donation opens doors to highly successful and fulfilling paths to parenthood. It’s time to unlock the possibilities and embark on the journey towards creating a loving family.

 __________________________________________

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) ; 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

I invite you to visit my very recently launched “Podcast”,  “HAVE A BABY” on RUMBLE;   https://rumble.com/c/c-3304480

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\

• Treatment Options for Immunologic Implantation Dysfunction (IID):

1. Intralipid (IL) Therapy: IL is a mixture of soybean lipid droplets in water, primarily used for providing nutrition. When administered intravenously, IL supplies essential fatty acids that can activate certain receptors in NK cells, reducing their cytotoxic activity and enhancing implantation. IL, combined with corticosteroids, suppresses the overproduction of pro-inflammatory cytokines by NK cells, improving reproductive outcomes. IL is cost-effective and has fewer side effects compared to other treatments like IVIg.
2. Intravenous immunoglobulin-G (IVIg) Therapy: In the past, IVIg was used to down-regulate activated NK cells. However, concerns about viral infections and the high cost led to a decline in its use. IVIg can be effective, but IL has become a more favorable and affordable alternative.
3. Corticosteroid Therapy: Corticosteroids, such as prednisone and dexamethasone, are commonly used in IVF treatment. They have an immunomodulatory effect and reduce TH-1 cytokine production by CTL. When combined with IL or IVIg, corticosteroids enhance the implantation process. Treatment typically starts 10-14 days before embryo transfer and continues until the 10th week of pregnancy.
4. Heparinoid Therapy: Low molecular weight heparin (Clexane, Lovenox) can improve IVF success rates in women with antiphospholipid antibodies (APAs) and may prevent pregnancy loss in certain thrombophilias when used during treatment. It is administered subcutaneously once daily from the start of ovarian stimulation.
5. TH-1 Cytokine Blockers (Enbrel, Humira): TH-1 cytokine blockers have limited effectiveness in the IVF setting and, in my opinion, no compelling evidence supports their use. They may have a role in treating threatened miscarriage caused by CTL/NK cell activation, but not for IVF treatment. TH-1 cytokines are needed for cellular response, during the early phase of implantation, so completely blocking them could hinder normal implantation.

1. Baby Aspirin and IVF: Baby aspirin doesn’t offer much value in treating implantation dysfunction (IID) and may even reduce the chance of success. This is because aspirin thins the blood and increases the risk of bleeding, which can complicate procedures like egg retrieval or embryo transfer during IVF, potentially compromising its success.
2. Leukocyte Immunization Therapy (LIT): LIT involves injecting the male partner’s lymphocytes into the mother to improve the recognition of the embryo as “self” and prevent rejection. LIT can up-regulate Treg cells and down-regulate NK cell activation, improving the balance of TH-1 and TH-2 cells in the uterus. However, the same benefits can be achieved through IL (Intralipid) therapy combined with corticosteroids. IL is more cost-effective, and the use of LIT is prohibited by law in the USA.

Types of Immunologic Implantation Dysfunction (IID) and NK Cell Activation:

1. Autoimmune Implantation Dysfunction: Women with a personal or family history of autoimmune conditions like Rheumatoid arthritis, Lupus Erythematosus, thyroid autoimmune disease (Hashimoto’s disease and thyrotoxicosis), and endometriosis (in about one-third of cases) may experience autoimmune IID. However, autoimmune IID can also occur without any personal or family history of autoimmune diseases.Treatment for NK cell activation in IVF cases complicated by autoimmune IID involves a combination of daily oral dexamethasone from the start of ovarian stimulation until the 10th week of pregnancy, along with 20% intralipid (IL) infusion 10 days to 2 weeks before embryo transfer. With this treatment, the chance of a viable pregnancy occurring within two completed embryo transfer attempts is approximately 70% for women <40 years old who have  normal ovarian reserve.
2. Alloimmune Implantation Dysfunction: NK cell activation occurs when the uterus is exposed to an embryo that shares certain genotypic (HLA/DQ alpha) similarities with the embryo recipient.
   • Partial DQ alpha/HLA genetic matching: Couples who share only one DQ alpha/HLA gene are considered to have a “partial match.” If NK cell activation is also present, this partial match puts the couple at a disadvantage for IVF success. However, it’s important to note that DQ alpha/HLA matching, whether partial or total, does not cause IID without associated NK cell activation. Treatment for partial DQ alpha/HLA match with NK cell activation involves IL infusion and oral prednisone as adjunct therapy. IL infusion is repeated every 2-4 weeks after pregnancy is confirmed and continued until the 24th week of gestation. In these cases, only one embryo is transferred at a time to minimize the risk of NK cell activation.
   • Total (Complete) Alloimmune Genetic Matching: A total alloimmune match occurs when the husband’s DQ alpha genotype matches both that of the partner. Although rare, this total match along with NK cell activation significantly reduces the chance of a viable pregnancy resulting in a live birth at term. In some cases, the use of a gestational surrogate may be necessary.

Geoff Sher

___________________________________________________________________

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

I invite you to visit my very recently launched “Podcast”,  “HAVE A BABY” on RUMBLE;   https://rumble.com/c/c-3304480

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\

Provided strict criteria are applied…yes, you could use your daughter’s eggs.

Geoff Sher

________________________________________________________________

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

I invite you to visit my very recently launched “Podcast”,  “HAVE A BABY” on RUMBLE;   https://rumble.com/c/c-3304480

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\

This is not likely to be a pregnancy. However, to be certain…do a blood pregnancy test.

Geoff Sher

_______________________________________________________

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

I invite you to visit my very recently launched “Podcast”,  “HAVE A BABY” on RUMBLE;   https://rumble.com/c/c-3304480

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\

Sjogren Syndrome is likely an autoimmune condition and can be associated with an autoimmune, immunologic implantation dysfunction (IID), in my opinion.See below:

In the world of assisted reproduction, when IVF fails repeatedly or without explanation, it’s often assumed that poor embryo quality is the main culprit. However, this view oversimplifies the situation. The process of embryo implantation, which begins about six or seven days after fertilization, involves a complex interaction between embryonic cells and the lining of the uterus. These specialized cells, called trophoblasts, eventually become the placenta. When the trophoblasts meet the uterine lining, they engage in a communication process with immune cells through hormone-like substances called cytokines. This interaction plays a critical role in supporting the successful growth of the embryo. From the earliest stages, the trophoblasts establish the foundation for the exchange of nutrients, hormones, and oxygen between the mother and the baby. The process of implantation not only ensures the survival of early pregnancy but also contributes to the quality of life after birth.

There are numerous uterine factors that can impede embryo implantation potential. However, the vast majority relate to the following three (3) factors:

1. Thin uterine lining (endometrium) . A lining that is <8mm in thickness at the time of ovulation, and/ or the administration of progesterone
2. Irregularity the inner surface of the uterine cavity (caused by protruding sub-mucous fibroids, scar  tissue or polyps )

• Immunologic factors that compromise implantation

Of these 3 factors, the one most commonly overlooked (largely because of the highly complex nature of the problem) is immunologic implantation dysfunction (IID), a common cause of “unexplained (often repeated) IVF failure and recurrent pregnancy loss. This article will focus on the one that most commonly is overlooked ….namely, immunologic implantation dysfunction (IID.

There is a growing recognition that problems with the immune function in the uterus can lead to embryo implantation dysfunction. The failure of proper immunologic interaction during implantation has been implicated as a cause of recurrent miscarriage, late pregnancy fetal loss, IVF failure, and infertility. Some immunologic factors that may contribute to these issues include antiphospholipid antibodies (APA), antithyroid antibodies (ATA) , and activated natural killer cells (NKa).

• Activated natural Killer Cells (NKa):

During ovulation and early pregnancy, the uterine lining is frequented by NK cells and T-cells, which together make up more than 80% of the immune cells in the uterine lining. These cells travel from the bone marrow to the endometrium where they proliferate under hormonal regulation. When exposed to progesterone, they produce TH-1 and TH-2 cytokines. TH-2 cytokines help the trophoblast (embryo’s “root system”) to penetrate the uterine lining, while TH-1 cytokines induce apoptosis (cell suicide), limiting placental development to the inner part of the uterus. The balance between TH1 and TH-2 cytokines is crucial for optimal placental development. NK cells and T-cells contribute to cytokine production. Excessive TH-1 cytokine production is harmful to the trophoblast and endometrial cells, leading to programmed cell death and ultimately to implantation failure.

Functional NK cells reach their highest concentration in the endometrium around 6-7 days after ovulation or exposure to progesterone, which coincides with the time of embryo implantation.

It’s important to note that measuring the concentration of blood NK cells doesn’t reflect NK cell activation (NKa). The activation of NK cells is what matters. In certain conditions like endometriosis, the blood concentration of NK cells may be below normal, but NK cell activation is significantly increased.

There are several laboratory methods to assess NK cell activation (cytotoxicity), including immunohistochemical assessment of uterine NK cells and measuring TH-1 cytokines in the uterus or blood. However, the K-562 target cell blood test remains the gold standard. In this test, NK cells isolated from a woman’s blood are incubated with specific “target cells,” and the percentage of killed target cells is quantified. More than 12% killing indicates a level of NK cell activation that usually requires treatment. Currently, there are only a few Reproductive Immunology Reference Laboratories in the USA capable of reliably performing the K-562 target cell test.

There is a common misconception that adding IL (intralipid) or IVIg to NK cells can immediately downregulate NK cell activity. However, IL and IVIg cannot significantly suppress already activated NK cells. They are believed to work by regulating NK cell progenitors, which then produce downregulated NK cells. To assess the therapeutic effect, IL/IVIg infusion should be done about 14 days before embryos are transferred to the uterus to ensure a sufficient number of normal functional NK cells are present at the implantation site during embryo transfer. Failure to recognize this reality has led to the erroneous demand from IVF doctors for Reproductive Immunology Reference Laboratories to report on NK cell activity before and immediately after exposure to IVIg or IL at different concentrations. However, since already activated NK cells cannot be deactivated in the laboratory, assessing NKa suppression in this way has little clinical benefit. Even if blood is drawn 10-14 days after IL/IVIg treatment, it would take another 10-14 days to receive the results, which would be too late to be practically advantageous.

• Antiphospholipid Antibodies:

Many women who struggle with IVF failure or recurrent pregnancy loss, as well as those with a personal or family history of autoimmune diseases like lupus erythematosus, rheumatoid arthritis, scleroderma, and dermatomyositis, often test positive for antiphospholipid antibodies (APAs). Over 30 years ago, I proposed a treatment for women with positive APA tests. This involved using a low dose of heparin to improve the success of IVF implantation and increase birth rates. Research indicated that heparin could prevent APAs from affecting the embryo’s “root system” ( the trophoblast), thus enhancing implantation. We later discovered that this therapy only benefits women whose APAs target specific phospholipids (phosphatidylethanolamine and phosphatidylserine). Nowadays, longer-acting low molecular weight heparinoids like Lovenox and Clexane have replaced heparin.

• Antithyroid Antibodies ( thyroid peroxidase -TPO and antithyroglobulin antibodies (TGa)

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 (RPL). 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 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 thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects, and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance. It follows that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies. Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids subsequently often results in a significant improvement in reproductive performance in such cases.

Almost 50% of women with antithyroid antibodies do not have activated cytotoxic T lymphocytes (CTL) or natural killer cells (NK cells). This suggests that the antibodies themselves may not be the direct cause of reproductive dysfunction. Instead, the activation of CTL and NK cells, which occurs in about half of the cases with thyroid autoimmunity (TAI), is likely an accompanying phenomenon that damages the early “root system” (trophoblast) of the embryo during implantation.

Treating women who have both antithyroid antibodies and activated NK cells/CTL with intralipid (IL) and steroids improves their chances of successful reproduction. However, women with antithyroid antibodies who do not have activated NK cells/CTL do not require this treatment.

• Treatment Options for Immunologic Implantation Dysfunction (IID):

1. Intralipid (IL) Therapy: IL is a mixture of soybean lipid droplets in water, primarily used for providing nutrition. When administered intravenously, IL supplies essential fatty acids that can activate certain receptors in NK cells, reducing their cytotoxic activity and enhancing implantation. IL, combined with corticosteroids, suppresses the overproduction of pro-inflammatory cytokines by NK cells, improving reproductive outcomes. IL is cost-effective and has fewer side effects compared to other treatments like IVIg.
2. Intravenous immunoglobulin-G (IVIg) Therapy: In the past, IVIg was used to down-regulate activated NK cells. However, concerns about viral infections and the high cost led to a decline in its use. IVIg can be effective, but IL has become a more favorable and affordable alternative.
3. Corticosteroid Therapy: Corticosteroids, such as prednisone and dexamethasone, are commonly used in IVF treatment. They have an immunomodulatory effect and reduce TH-1 cytokine production by CTL. When combined with IL or IVIg, corticosteroids enhance the implantation process. Treatment typically starts 10-14 days before embryo transfer and continues until the 10th week of pregnancy.
4. Heparinoid Therapy: Low molecular weight heparin (Clexane, Lovenox) can improve IVF success rates in women with antiphospholipid antibodies (APAs) and may prevent pregnancy loss in certain thrombophilias when used during treatment. It is administered subcutaneously once daily from the start of ovarian stimulation.
5. TH-1 Cytokine Blockers (Enbrel, Humira): TH-1 cytokine blockers have limited effectiveness in the IVF setting and, in my opinion, no compelling evidence supports their use. They may have a role in treating threatened miscarriage caused by CTL/NK cell activation, but not for IVF treatment. TH-1 cytokines are needed for cellular response, during the early phase of implantation, so completely blocking them could hinder normal implantation.

1. Baby Aspirin and IVF: Baby aspirin doesn’t offer much value in treating implantation dysfunction (IID) and may even reduce the chance of success. This is because aspirin thins the blood and increases the risk of bleeding, which can complicate procedures like egg retrieval or embryo transfer during IVF, potentially compromising its success.
2. Leukocyte Immunization Therapy (LIT): LIT involves injecting the male partner’s lymphocytes into the mother to improve the recognition of the embryo as “self” and prevent rejection. LIT can up-regulate Treg cells and down-regulate NK cell activation, improving the balance of TH-1 and TH-2 cells in the uterus. However, the same benefits can be achieved through IL (Intralipid) therapy combined with corticosteroids. IL is more cost-effective, and the use of LIT is prohibited by law in the USA.

Types of Immunologic Implantation Dysfunction (IID) and NK Cell Activation:

1. Autoimmune Implantation Dysfunction: Women with a personal or family history of autoimmune conditions like Rheumatoid arthritis, Lupus Erythematosus, thyroid autoimmune disease (Hashimoto’s disease and thyrotoxicosis), and endometriosis (in about one-third of cases) may experience autoimmune IID. However, autoimmune IID can also occur without any personal or family history of autoimmune diseases.Treatment for NK cell activation in IVF cases complicated by autoimmune IID involves a combination of daily oral dexamethasone from the start of ovarian stimulation until the 10th week of pregnancy, along with 20% intralipid (IL) infusion 10 days to 2 weeks before embryo transfer. With this treatment, the chance of a viable pregnancy occurring within two completed embryo transfer attempts is approximately 70% for women <40 years old who have  normal ovarian reserve.
2. Alloimmune Implantation Dysfunction: NK cell activation occurs when the uterus is exposed to an embryo that shares certain genotypic (HLA/DQ alpha) similarities with the embryo recipient.
   • Partial DQ alpha/HLA genetic matching: Couples who share only one DQ alpha/HLA gene are considered to have a “partial match.” If NK cell activation is also present, this partial match puts the couple at a disadvantage for IVF success. However, it’s important to note that DQ alpha/HLA matching, whether partial or total, does not cause IID without associated NK cell activation. Treatment for partial DQ alpha/HLA match with NK cell activation involves IL infusion and oral prednisone as adjunct therapy. IL infusion is repeated every 2-4 weeks after pregnancy is confirmed and continued until the 24th week of gestation. In these cases, only one embryo is transferred at a time to minimize the risk of NK cell activation.
   • Total (Complete) Alloimmune Genetic Matching: A total alloimmune match occurs when the husband’s DQ alpha genotype matches both that of the partner. Although rare, this total match along with NK cell activation significantly reduces the chance of a viable pregnancy resulting in a live birth at term. In some cases, the use of a gestational surrogate may be necessary.

It should be emphasized that poor embryo quality is not always the main cause of reproductive dysfunction and that the complex interaction between embryonic cells and the lining of the uterus  plays a critical role in successful implantation. Women with personal or family histories of autoimmune disease or endometriosis and those with unexplained (often repeated) IVF failure or recurrent pregnancy loss, often have immunologic implantation dysfunction (IID as the underlying cause . For such women, it is important to understand how IID leads to reproductive failure and how selective treatment options such as intralipid (IL), corticosteroid and heparinoid therapy, can dramatically  improve reproductive outcomes. Finally, there is real hope that proper identification and management of IID can  significantly improve the chance of successful reproduction and ultimately contribute to better quality of life after birth.

Geoff Sher

________________________________________________________________

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

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

I invite you to visit my very recently launched “Podcast”, “HAVE A BABY” on RUMBLE; https://rumble.com/c/c-3304480
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\

The dosage is 25mg inserted high in the vagina 4 times daily from early in the cycle to the day of hCG or progesterone administration.

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.

Geoff Sher

________________________________________________________________

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

I invite you to visit my very recently launched “Podcast”,  “HAVE A BABY” on RUMBLE;   https://rumble.com/c/c-3304480

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\