Answer:

Absolutely you can!

Please call my assistant, Patti at 702-533-2691 and she will set you on the right course.

Good luck with the move!

Geoff Sher

Answer:

Here is some informaion on the effect of Hashimoto’s on embryo implantation.

Unfortunately I would need a lot more information to recommend a protocol for you. I suggest you contact Patti at concierge@sherIVF.com  and set up an online consultation to talk it through with me.

 

Geoff Sher

_________________________________________________________

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.

 

Answer:

I understand your confusion, but if you intend to do surrogacy again, it is important that you be evaluated for an implantation disorder.

If you would like to consult with me on this , I suggest you email my assistant, Patti Converse  (concierge@sherIVF.com)  and set  up an online consultation with me to discus.

Geoffrey Sher MD

 

• IMPLANTATION DYSFUNCTION

Implantation dysfunction is often overlooked as a significant reason for IVF failure. This is especially true when IVF failure is unexplained, or when there are recurring pregnancy losses or underlying issues with the uterus, such as endo-uterine surface lesions, thin uterine lining (endometrium), or immunological factors.

IVF success rates have been improving in the past decade. Currently, in the United States, the average live birth rate per embryo transfer for women under 40 years old using their own eggs is about 2:5 per woman undergoing embryo transfer. However, there is a wide range of success rates among different IVF programs, varying from 20% to almost 50%. Based on these statistics, most women in the United States need to undergo two or more IVF-embryo transfer attempts to have a baby. Many IVF practitioners in the United States attribute the differences in success rates to variations in expertise among embryology laboratories, but this is not entirely accurate. Other factors, such as differences in patient selection, the failure to develop personalized protocols for ovarian stimulation, and the neglect of infectious, anatomical, and immunological factors that affect embryo implantation, are equally important.

Approximately 80% of IVF failures occur due to “embryo incompetency,” mainly caused by ( irregularities in chromosome number (aneuploidy), which is often related to the advancing age of the woman, diminished ovarian reserve ( DOR) but can also be influenced by the ovarian stimulation protocol chosen, and sperm dysfunction (male infertility). However, in around 20% of cases with dysfunction, failure is caused by problems with embryo implantation.

This section will focus on embryo implantation dysfunction and IVF failure which in the vast majority of cases is caused by:

1. Anatomical irregularities of the inner uterine surface:

1. •  Surface lesions such as polyps/fibroids/ scar tissue
   • endometrial thickness

1.  Immunologic Implantation Dysfunction ( IID)lesions

1. • Autoimmune IID
   • Alloimmune IID

 

1. ANATOMICAL IMPLANTATION DYSFUNCTION
2. a) Surface lesions such as polyps/fibroids/ scar tissue

When there are problems with the structure of the uterus, it can lead to difficulties in getting pregnant. While uterine fibroids usually don’t cause infertility, they can affect fertility when they distort the uterine cavity or protrude through the lining. Even small fibroids located just beneath the lining and protruding into the cavity can decrease the chances of the embryo attaching. Multiple fibroids within the uterine wall that encroach upon the cavity can disrupt blood flow, impair estrogen delivery, and prevent proper thickening of the lining. These issues can be identified through ultrasound during the menstrual cycle’s proliferative phase. Any lesion on the uterine surface, such as submucous fibroids, adhesions, endometrial polyps, or placental polyps, can interfere with implantation by causing a local inflammatory response similar to the effect of an intrauterine contraceptive device (IUD).

Clearly, even small uterine lesions can have a negative impact on implantation. Considering the high costs and emotional toll associated with in vitro fertilization (IVF) and related procedures, it is reasonable to perform diagnostic tests like hysterosalpingography (HSG), fluid ultrasound examination (hysterosonogram), or hysteroscopy before starting IVF. Uterine lesions that can affect implantation often require surgical intervention. In most cases, procedures like dilatation and curettage (D&C) or hysteroscopic resection are sufficient. Rarely a laparotomy may be needed. Such interventions often lead to an improvement in the response of the uterine lining.

Hysterosonogram( HSN/saline ultrasound) is a procedure where a sterile saline solution is injected into the uterus through the cervix using a catheter. Vaginal ultrasound is then used to examine the fluid-filled cavity for any irregularities that might indicate surface lesions like polyps, fibroid tumors, scarring, or a septum. When performed by an expert, HSN is highly effective in detecting even the smallest lesions and can supplant hysteroscopy in certain cases. HSN is less expensive, less invasive/traumatic, and equally effective as hysteroscopy. The only drawback is that if a lesion is found, hysteroscopy may still be needed for treatment.

Hysteroscopy is a diagnostic procedure performed in an office setting with minimal discomfort to the patient. It involves inserting a thin, lighted instrument called a hysteroscope through the vagina and cervix into the uterus to examine the uterine cavity. Normal saline is used to distend the uterus during the procedure. Like HSN, hysteroscopy allows for direct visualization of the inside of the uterus to identify defects that could interfere with implantation. We have observed that around one in eight IVF candidates have lesions that need attention before undergoing IVF to optimize the chances of success. I strongly recommend that all patients undergo therapeutic surgery, usually hysteroscopy, to correct any identified issues before proceeding with IVF. Depending on the severity and nature of the problem, hysteroscopy may require general anesthesia and should be performed in a surgical facility equipped for laparotomy if necessary.

1. b) Thickness of the uterine lining (endometrium)

As far back as In 1989, I and my team made an important discovery about using ultrasound to assess the thickness of the endometrium during the late proliferative phase of both “ natural” and hormone-stimulated cycles. The assessment helped predict the chances of conception. We found that an ideal thickness of over 9mm at the time of ovulation , egg retrieval or with the commencement of progesterone therapy in embryo recipient cycles ( e.g., IVF with egg donation, gestational, surrogacy and embryo adoption) was associated with optimal implantation rates, while an endometrial thickness of less than 8 mm was associated with failure to implant or early pregnancy loss in the vast majority of cases. An endometrium measuring <8mm was almost invariably associated with failure to implant or early pregnancy loss in the while an endometrium measuring 8 to 9 mm was regarded as being intermediate, and while pregnancies did occur in this range, the rates were only slightly lower than with an optimal lining of 9 mm

A “poor” uterine lining typically occurs when the innermost layer of the endometrium (basal or germinal endometrium) is unable to respond to estrogen by developing a thick enough outer “functional” layer to support successful embryo implantation and placental development. The “functional” layer, which accounts for two-thirds of the total endometrial thickness, is shed during menstruation if pregnancy does not occur.

The main causes of a poor uterine lining are:

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 childbirth.
   • Surgical trauma caused by aggressive dilatation and curettage (D&C).

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

1. • Prolonged (back to back) use of clomiphene citrate for ovarian stimulation or…
   • Prenatal exposure to diethylstilbestrol (DES), a drug given to prevent miscarriage in the 1960s.

1. Overexposure of the uterine lining to male hormones produced by the ovaries or administered during ovarian stimulation (primarily testosterone):

1. • Older women, women with DOR (poor responders), and women with polycystic ovarian syndrome (PCOS) often have increased biological activity of luteinizing hormone (LH), leading to testosterone overproduction by the ovarian connective tissue (stroma/theca). This effect can be further amplified when certain ovarian stimulation protocols were high doses of menotropins ( e.g., Menopur) are used.

1. Reduced blood flow to the basal endometrium caused by:

1. • Multiple uterine fibroids, especially if they are located beneath the endometrium (submucosal).
   • Uterine adenomyosis, which involves extensive abnormal invasion of endometrial glands into the uterine muscle.

In 1996 I introduced the Vaginal administration of Sildenafil (Viagra) to improve endometrial thickening. The selective administration of Sildenafil has shown great promise in improving uterine blood flow and increasing endometrial thickening in cases of thin endometrial linings. When administered vaginally, it is quickly absorbed and reaches high concentrations in the uterine blood system, diluting as it enters the systemic circulation. This method has been found to have minimal systemic side effects. However, it is important to note that Viagra may not be effective in all cases, as some cases of thin uterine linings may involve permanent damage to the basal endometrium, rendering it unresponsive to estrogen.

Severe endometrial damage leading to poor responsiveness to estrogen can occur in various situations. These include post-pregnancy endometritis (inflammation after childbirth), chronic granulomatous inflammation caused by uterine tuberculosis (rare in the United States), and significant surgical injury to the basal endometrium (which can happen after aggressive D&C procedures).

 

2. 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 6-7days 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 Intravenous gammaglobulin (IVIg) to NK cells can immediately downregulate NK cell activity. However, neither 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 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.
6. 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.
7. 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. Humans have 23 pairs of chromosomes: one set from the sperm and one set from the egg that created us. Our sixth pair of chromosomes each contain DQ alpha genes. Again, one of these genes is from the sperm and one is from the egg that created us.

Like the genes for eye color, DQ alpha/HLA gene combinations differ between people. Thus, the male (whose  sperm created an embryo is likely to have different DQ alpha/HLA gene combinations than the potential mother . However, there are rare situations in which the male and the female partners have  DQ-alpha/HLA gene combinations are the same.

 

The endometrial immune system is programmed to accept embryos with different DQ alpha/HLA gene combinations than its own. This is known as “alloimmune recognition.” So, if the man shares a similar DQ alpha/HLA gene combination with the woman, and his sperm creates an embryo that tries  to implant , her endometrial immune system will see the embryo’s DQ alpha/HLA gene as “too similar” to its own and assume it is a foreign body.

 

Usually, this will lead to NK/T cell activation, the overproduction of TH-1 cytokines, and reproductive failure (i.e., infertility, and pregnancy loss). The severity with which this occurs is an important determinant of whether total implantation failure will occur or whether there would remain enough residual trophoblastic activity that would allow the pregnancy to limp along until the nutritional supply can no longer meet the demands of the pregnancy, at which point pregnancy loss occurs.

 

In cases of paternal-maternal DQ alpha/HLA matching, it will often take several pregnancies for NK cell activation to build to the point that women with alloimmune implantation dysfunction will present with clinical evidence of implantation dysfunction. Sometimes it starts off with one or two live births, whereupon NK/T cell activity starts to build, leading to one or more early miscarriages. Eventually the NK/T cell activation is so high that subsequent pregnancies can be lost before the woman is even aware that she was pregnant at all. At this point, she is often diagnosed with secondary, “unexplained” infertility and/or “unexplained” IVF failure.

 

Alloimmune Implantation Dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/T cell activation.

 

There are two types of DQ alpha/HLA genetic matching: 

• 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

 

Answer:

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

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

 

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

 If you would like to  have an online consultation with me, please email Patti Converse at concierge@sherivf.com  and she will arrange it for you.

Geoffrey Sher MD

Sher Fertility Solutions (SFS)

 

 

Answer:

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

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

 

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

 If you would like to  have an online consultation with me, please email Patti Converse at concierge@sherivf.com  and she will arrange it for you.

Geoffrey Sher MD

Sher Fertility Solutions (SFS)

_______________________________________________________________________

·      Endometriosis and infertility :

A Practical, Real-World Guide to Smart, Evidence-Based Treatment Decisions

Geoffrey SherMD

____________________________________________________________________________________

 

INTRODUCTION: THE HIDDEN EPIDEMIC IN INFERTILITY

 

Endometriosis is one of the most common—and most underappreciated—causes of infertility worldwide.

 

It affects approximately 6–10% of women of reproductive age, yet in the infertility population, its prevalence rises dramatically—being present in 20–40% of women seeking fertility care. In many practices, it is one of the most frequently encountered underlying conditions.

 

Despite this, it is often misdiagnosed, underestimated, or entirely overlooked!

Bye be good. Did you send it to thank you

Part of the problem lies in its deceptive nature.

 

Endometriosis is not simply a structural disease that can be seen, removed, and cured. Rather, it is a dynamic, biologically active condition that affects reproduction at multiple levels—many of which are invisible to routine testing.

 

⸻

 

A Disease That Often Goes Unseen

 

In its earliest stages, endometriosis may exist in a microscopic or preclinical form:

• Lesions may be translucent and invisible
• Laparoscopy may fail to detect them
• Standard fertility tests remain normal

 

Yet, even in this “invisible” state, it can significantly impair fertility.

 

This is why so many women are labeled with “unexplained infertility”—when in reality, the explanation is present but hidden.

 

⸻

 

Age and Natural History

 

Endometriosis is typically a disease that emerges and progresses over time.

• It is relatively uncommon in women under 25
• Its prevalence increases through the 30s
• It becomes even more common in the late 30s and early 40s

 

This progression reflects its nature as a chronic, evolving condition, rather than a sudden-onset disease.

 

⸻

 

Why Does Endometriosis Occur?

 

The exact cause of endometriosis remains incompletely understood, but several theories exist:

 

1. Retrograde Menstruation (Most Widely Accepted)

Menstrual blood flows backward through the fallopian tubes into the pelvic cavity, carrying endometrial cells that implant and grow.

 

However, since retrograde menstruation occurs in many women who do not develop endometriosis, additional factors must be involved.

 

2. Immune Dysfunction

Some women may have an altered immune response that:

• Fails to clear misplaced endometrial cells
• Allows them to implant and proliferate

 

3. Genetic Predisposition

Endometriosis often runs in families, suggesting a hereditary component.

 

4. Stem Cell and Metaplastic Theories

Certain cells in the pelvis may transform into endometrial-like tissue under specific conditions.

 

⸻

 

Epidemiologic Observations

 

An interesting and often under-discussed observation is the variation in prevalence across populations.

 

Endometriosis appears to be:

• Less commonly reported in indigenous African populations
• More prevalent in Caucasian populations
• Increasingly recognized among women of African descent living in Western societies

 

The reasons for this are not fully understood but may involve:

• Environmental exposures
• Lifestyle and dietary factors
• Delayed childbearing
• Differences in access to diagnosis
• Genetic susceptibility

 

While these observations are real, they remain incompletely explained and an area of ongoing research.

 

⸻

 

More Than Infertility: The Miscarriage Link

 

Endometriosis does not only reduce the chance of conceiving—it may also increase the risk of early pregnancy loss.

 

In many cases:

• Fertilization occurs
• Implantation begins
• The pregnancy is lost so early that it goes unrecognized

 

This is often due to immunologic implantation dysfunction, a key concept discussed later.

 

⸻

 

The Central Misconception

 

Many women are told:

 

“You have mild endometriosis—you should still get pregnant.”

 

And yet, they do not.

 

Why?

 

Because endometriosis does not primarily impair fertility through what we can see—it does so through what we cannot see.

 

Its most important effects occur at the:

• Microscopic
• Biochemical
• Immunologic level

 

These mechanisms interfere with:

• Fertilization
• Embryo development
• Implantation

 

⸻

 

Purpose of This Guide

 

This booklet is designed to:

• Demystify endometriosis
• Explain how it truly affects fertility
• Provide a clear, rational, and biologically sound treatment strategy

 

The goal is not aggressive treatment.

 

The goal is precise, informed, and individualized care.

 

⸻

 

UNDERSTANDING THE DISEASE

 

Endometriosis is a chronic condition in which tissue resembling the uterine lining grows outside the uterus.

 

It most commonly involves:

• The ovaries
• Fallopian tubes
• Pelvic peritoneum
• Uterosacral ligaments
• . Pouch of Douglas/cul de sac

 

These implants respond to hormones and bleed cyclically—but the blood cannot exit the body.

 

This leads to:

• Chronic inflammation
• Adhesions
• Endometriomas
• Distortion of pelvic anatomy

 

⸻

 

THE MASTER OF DISGUISE

 

One of the most important truths:

 

Endometriosis can impair fertility long before it becomes visible.

 

This “invisible phase” is responsible for many cases of unexplained infertility.

 

⸻

 

THE PRIMARY MECHANISM: A TOXIC ENVIRONMENT

 

The dominant mechanism is not anatomical—it is biochemical.

 

Endometriotic implants release inflammatory substances into pelvic fluid.

 

As the egg travels from ovary to tube:

• It is exposed to these toxins
• The zona pellucida is altered
• Sperm binding is impaired

 

Fertilization becomes inefficient—even when everything appears normal.

 

⸻

 

THE MAGNITUDE OF IMPACT

 

Normal fertility:

• ~15–20% per month
• ~80% per year

 

With endometriosis:

• ~2–4% per month

 

A 5–6 fold reduction in fertility

 

⸻

 

WHY SURGERY RARELY HELPS FERTILITY

 

Endometriosis is:

• Progressive
• Microscopic
• Recurrent

 

Removing visible lesions does not eliminate:

• Hidden disease
• Ongoing inflammation

 

Surgery should be reserved for symptoms—not fertility enhancement alone.

 

⸻

 

WHY IUI AND STIMULATION FALL SHORT

 

They increase egg number—but not fertilization efficiency.

 

The egg still passes through a hostile environment.

 

⸻

 

WHY IVF WORKS

 

IVF bypasses the toxic pelvic environment entirely.

 

Fertilization occurs outside the body.

 

This is the single most important advantage in endometriosis-related infertility.

 

⸻

 

ENDOMETRIOMAS: A CRITICAL TARGET

 

Endometriomas:

• Reduce egg quality
• Disrupt ovarian function
• Complicate IVF

 

Cysts >2 cm should generally be treated

 

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SCLEROTHERAPY: A FERTILITY-PRESERVING SOLUTION

 

Ethanol sclerotherapy:

• Drains cyst
• Destroys lining
• Preserves ovarian tissue

 

A safer alternative to surgery

 

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IMMUNOLOGIC IMPLANTATION DYSFUNCTION (IID)

 

Occurs in ~30% of cases.

 

Leads to:

• Implantation failure
• Early miscarriage

 

Requires:

• Diagnosis
• Targeted immunotherapy

 

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THE SEED AND SOIL PRINCIPLE

• Embryo = seed
• Uterus = soil

 

Both must be optimized.

 

⸻

 

WHY GnRH AGONISTS ARE OVERUSED

 

They suppress estrogen—but may impair uterine receptivity.

 

Often counterproductive before IVF

 

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MODERN DIAGNOSIS

• Ultrasound
• MRI
• Receptiva (BCL6)

 

Laparoscopy often unnecessary.

 

⸻

 

THE ROLE OF PGT-A

 

Selects chromosomally normal embryos.

 

Improves outcomes.

 

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A SMART STRATEGY

1. Suspect early
2. Diagnose intelligently
3. Avoid unnecessary surgery
4. Treat endometriomas (sclerotherapy)
5. Use IVF when appropriate
6. Optimize stimulation
7. Use PGT-A
8. Evaluate IID
9. Treat before transfer

 

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FINAL PERSPECTIVE

 

Endometriosis is a biological—not just structural—disease.

 

Success comes from precision, not aggression.

 

⸻

 

CLOSING MESSAGE

 

Hope is not a strategy.

 

Understanding biology—and acting on it—is.

 

With the right approach, most women with endometriosis can achieve a healthy pregnancy.

 

 

 

Answer:

I am afraid it is not a good idea. But perhaps I can help determine if anything can be done to access better embryos for you.

 

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

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

 

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

 If you would like to  have an online consultation with me, please email Patti Converse at concierge@sherivf.com  and she will arrange it for you.

Geoffrey Sher MD

Sher Fertility Solutions (SFS)