Over 43y of age, egg donation is advisable because with advancing age, egg quality declines starting at 35 y and really accelerating after 40Y. At a younger age, egg donation should also be seriously contemplated in women who have VERY depleted ovarian reserve (AMH=,0.2ng/ml).

Egg donation is when a woman donates her eggs for assisted reproduction or research purposes. In assisted reproduction, it usually involves using IVF technology, where the eggs are fertilized in a lab. Unfertilized eggs can also be frozen for future use. Egg donation is a form of assisted reproductive technology (ART) involving a third party.

For women who can’t get pregnant with their own eggs due to disease or low ovarian reserve, egg donation offers a realistic chance of becoming parents. It has clear benefits. First, young donors often provide more eggs than needed for a single IVF cycle, resulting in extra embryos that can be frozen for later use. Second, eggs from young donors are much less likely to have chromosomal abnormalities, reducing the risk of miscarriage and birth defects like Down’s syndrome.

Around 10%-15% of IVF procedures in the United States involve egg donation, mostly for older women with diminished ovarian reserve or for menopausal women. A much smaller percentage are performed on younger women who have premature ovarian failure or repeated IVF failures with low-quality eggs or embryos. Another rapidly emerging reason for egg donation is same-sex couples, mainly female, who want to share the experience of parenting, with one partner providing the eggs and the other receiving them. 

Most egg donation in the U.S. is done through licensed egg donor agencies or frozen egg banks, where anonymous donors are recruited. Sometimes recipients seek known donors through an agency, but this is less common and often done through private arrangements. Close family members are often approached as donors. Recipients may want to know or meet their egg donor to become familiar with their physical traits, intellect, and character, but anonymous donors are more common in the U.S. Recipients using anonymous donors are usually more open about the child’s conception when disclosing to family and friends. 

Donor agencies and Egg Banks provide detailed profiles and information about each donor for recipients to choose from. The recipient interacts with the egg donor program or Egg Bank in-person, over the phone, or online. After narrowing down choices, the recipient shares medical records with their IVF physician for consultation and examination. The process is facilitated by nurse coordinators who address all clinical, financial, and logistical aspects. Donor selection and matching are completed during this time. 

Egg donor agencies and egg banks typically prefer donors under 35 years old with normal ovarian reserve to minimize risks. Having a history of successful pregnancies or live births gives confidence in the donor’s reproductive potential. However, due to the shortage of donors, strict criteria like previous successful pregnancies cannot always be met. 

Sometimes donors may blame infertility on complications from the egg retrieval process, leading to legal actions. Evidence of trouble-free pregnancies provides comfort to the egg donor program when selecting a donor.

Screening Egg Donors

Genetic Screening: Many egg donor programs now use genetic screening panels to test for various genetic disorders. They follow the recommendations of the American Society of Reproductive Medicine (ASRM) and screen prospective donors for a host ( a panel) of conditions such as sickle cell trait or disease, thalassemia, cystic fibrosis, and Tay Sachs disease. About 90% of programs offer consultation with a geneticist.

Psychological/Emotional Screening: Recipient couples value compatibility with their chosen egg donor in terms of emotions, physicality, ethnicity, culture, and religion. Psychological screening is important in the United States. Since most donors are anonymous, it’s essential for the donor agency or IVF program to assess the donor’s commitment and motivation for providing this service. Some donors may not cope with the stress and stop their stimulation medication without informing anyone, causing the cycle to be canceled. 

Donor motivation and commitment need to be assessed carefully. Recipients in the U.S. often consider the “character” of the prospective egg donor as significant, believing that flaws in character may be genetically passed on. However, character flaws are usually influenced by environmental factors and unlikely to be genetically transmitted. 

Donors should undergo counseling, screening, and selective testing by a qualified psychologist. If needed, they should be referred to a psychiatrist for further evaluation. Tests like the MMPI, Meyers-Briggs, and NEO-Personality Indicator may be used to assess personality disorders. If significant abnormalities are found, the prospective donor should be automatically disqualified.

When choosing a known egg donor, it’s important to ensure that she is not coerced into participating. Recipients considering a close friend or family member as a donor should be aware that the donor may become a permanent and unwanted participant in their new family’s life.

Drug Screening: Due to the prevalence of substance abuse, we selectively perform urine and/or serum drug testing on our egg donors.

Screening for Sexually Transmitted Diseases (STDs): FDA and ASRM guidelines recommend testing all egg donors for STDs before starting IVF. While it’s highly unlikely for DNA and RNA viruses to be transmitted to an egg or embryo through sexual intercourse or IVF, women infected with viruses like hepatitis B, C, HTLV, HIV, etc., must be disqualified from participating in IVF with egg donation due to the remote possibility of transmission and potential legal consequences. 

Prior or existing infections with Chlamydia or Gonococcus suggest the possibility of pelvic adhesions or irreparably damaged fallopian tubes, which can cause infertility. If such infertility is later attributed to the egg retrieval process, it can lead to litigation. Even if an egg donor or recipient agrees to waive legal rights, there is still a potential risk of the offspring suing for wrongful birth later in life.

Screening Embryo Recipients

Medical Evaluation: Before starting infertility treatment, it’s important to assess a woman’s ability to safely carry a pregnancy and give birth to a healthy baby. This involves a thorough evaluation of cardiovascular, hepatorenal, metabolic, and reproductive health.

Infectious Screening: It is crucial to screen embryo recipients for infectious diseases. If the cervix is infected, introducing an embryo transfer catheter can transmit the infection to the sterile uterine cavity, leading to implantation failure or miscarriage in the early stages of pregnancy.

Immunologic Screening: Some autoimmune and alloimmune disorders can affect the success of implantation. To prevent treatment failure, it is advisable to evaluate the recipient for immunologic implantation dysfunction (IID) and in some cases, test both the recipient and sperm provider for alloimmune similarities that could affect implantation.

Disclosure and Consent: Full disclosure about the egg donation process, including medical and psychological risks, is necessary. Sufficient time should be dedicated to addressing questions and concerns from all parties involved. 

It’s important for all parties to seek independent legal advice to avoid conflicts of interest. Consent forms are reviewed and signed by the donor and recipient independently.

Types of Egg Donation

Conventional Egg Donation: This is the standard process for egg donor IVF. The menstrual cycles of the donor and recipient are synchronized using birth control pills. Both parties undergo fertility drug stimulation, allowing for precise timing of fresh embryo transfer. The success rate for pregnancy through this method is over 50% per cycle.

Donor Egg Bank: In this approach, eggs from young donors are frozen and stored for later use in IVF and embryo transfer. Frozen egg banks offer access to non-genetically tested eggs. While it provides convenience, there are minimal financial benefits. 

Through an electronic catalogue, recipients can select and purchase 1-5 frozen eggs. These eggs are fertilized through intracytoplasmic sperm injection (ICSI), and up to 2 embryos are selectively transferred, resulting in a 30-40% pregnancy rate without the risk of multiple pregnancies. This method reduces the cost, inconvenience, and risks associated with conventional fresh egg donor cycles. It is important for the recipient couple to be made aware that frozen eggs are slightly less likely to result in viable embryos as compared to fresh eggs and that the pregnancy rate using frozen eggs is also somewhat lower.

Preimplantation Genetic Screening/Testing for Aneuploidy (PGS/PGT):

The use of PGS/PGT to select embryos for transfer in IVF with egg donation is a topic of debate. Since most egg donors are under 35 years old, about 60-70% of embryos created from their eggs will likely have the correct number of chromosomes (euploid). This means that transferring up to two “untested” embryos from these donors should result in similar pregnancy rates compared to using PGS/PGT for embryo selection. However, it may in the future, become possible and practical to perform PGS/PGT on eggs for selective banking in the future. This could lead to improved success rates using banked eggs that have been tested for chromosomal abnormalities.

Egg Donation with Frozen Embryo Transfer (FET): Advances in embryo cryopreservation technology have made FET cycles a preferred method for many fertility specialists and patients. Whether or not embryos have undergone PGS/PGT testing, they are frozen as blastocysts and transferred in a subsequent FET cycle. This approach is more convenient, less complicated logistically, and can significantly improve the chances of successful pregnancy.

Financial Considerations in the United States:

The cost of an egg donor cycle involves various expenses. The average fee paid to the egg donor agency per cycle is typically between $2,000 – $8,000. Additional costs include psychological and clinical pre-testing, fertility drugs, and donor insurance, which range from $3,000 to $6,000. The medical services for the IVF treatment cycle can cost between $8,000 and $14,000. The donor stipend can vary widely, ranging from $5,000 to as high as $50,000, depending on the specific requirements of the recipient couple and supply-demand factors. Consequently, the total out-of-pocket expenses for an egg donor cycle in the United States ranges from $15,000 to $78,000, making it financially challenging for most couples in need of this service.

To address the growing gap between the need for affordable IVF with egg donation, various creative approaches have emerged. Here are a few examples:

• Egg Banking: As mentioned earlier, egg banking is a method where eggs are preserved and stored for future use.
• Egg Donor Sharing: This approach involves splitting the cost between two recipients, who then share the eggs for transfer or freezing. However, the downside is that there may be fewer eggs available for each recipient.
• Egg Bartering: In this scenario, a woman undergoing IVF can exchange some of her eggs with the clinic in return for a reduction in her IVF fee. This arrangement can be problematic because if the woman donating her eggs fails to conceive while the recipient does, it may cause emotional distress and potential complications in the future.
• Financial Risk Sharing: Some IVF programs offer a refund of fees if the egg donation is unsuccessful. This option is preferred by many recipient couples as it helps to spread the financial risk between the providers and the couple.

Moral, Legal, and Ethical Considerations:

In most States in the USA, the “Uniform Parentage Act” protects the recipient couple from legal disputes relating to parental claims by the donor. This “act” which states that the woman who gives birth to the child is legally recognized as the mother has generally prevented legal disputes over maternal custody in cases of IVF with egg donation. While a few states have less clear laws on this matter, there have been no major legal challenges so far.

The moral, ethical, and religious implications of egg donation vary and greatly influence the cultural acceptance of this process. In the United States, the prevailing attitude is that everyone is entitled to their own opinion and should have their views respected as long as they don’t infringe on the rights of others.

Looking ahead, there are important questions to consider. Should we cryopreserve and store eggs or ovarian tissue from a young woman who wishes to delay having children? Would it be acceptable for a woman to give birth to her own sister or aunt using these stored eggs? Should we store ovarian tissue across generations? Additionally, should egg donation primarily be used for stem cell research or as a source of spare body parts? If we decide to pursue these avenues, how do we ensure proper checks and balances? Are we willing to go down a slippery slope where the dignity of human embryos is disregarded, and the rights of human beings are compromised? Personally, I hope not.

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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) ; 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\

We have the required resources to do this.

Geoff Sher

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

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

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

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\

There is no uniformity here. A dosage ranging from 8U per day to 20U per day is probably fine. I start the omnitrope with ovarian stimulation and discontinue on the day of the “trigger”.

Geoff Sher

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• IVF and the use of Supplementary Human Growth Hormone (HGH) : Is it Worth Trying and who needs it?

Older women and those who have diminished ovarian reserve (DOR) have greater difficulty in conceiving naturally or through assisted reproductive technology (ART). This is largely due to an inevitable increase in egg aneuploidy (numerical chromosome irregularity). However, although less significant than the rising increase in egg aneuploidy, advancing age and DOR are both also associated with non-chromosomal egg deterioration involving a decline in mitochondrial activity as well  as a progressive reduction in the  ability of the granulosa cells that line the inside of the follicle to respond to FSH stimulation.

Getting older women and those with DOR to respond optimally to ovarian stimulation often represents a serious challenge. Many will fail to respond adequately to standard ovarian stimulation regimens, requiring any individualized and strategic approach to ovarian stimulation…. one that regulates and limits exposure of ovarian follicles and eggs to LH-induced local male hormones (predominantly testosterone). This, in my opinion is best addressed by using a modified long pituitary down regulation protocol with an agonist (e.g. Lupron/Buserelin/Superfact) coming off a birth control pill. Thereupon, as soon as the period starts, the agonist is supplanted by an antagonist (e.g. Cetrotide/Orgalutron/Ganirelix) and stimulation with recombinant FSH (Follistim/Gonal-F/Puregon) along with a small amount of menotropin (e.g. Menopur) until t optimal follicle development prompts initiation of the hCG trigger. More than 15 years ago, I reported on the observation that in some women with severe DOR, the addition of intramuscular administration of estradiol valerate (i.e. Delestrogen) prior to and during gonadotropin stimulation (i.e. “estrogen priming”) is capable of further enhancing follicle growth .

More recently, researchers have shown that the administration of human growth hormone (HGH), as an adjunct to ovarian stimulation, can enhance follicle response in older women and those with DOR. Two basic mechanisms have been proposed: a) enhanced response to FSH by up-regulating the FSH receptors on follicular granulosa cells and, b) through a direct effect of HGH on the egg itself whereby mitochondrial activity is enhanced.  Human eggs do have receptors to HGH but eggs retrieved from older women show decreased expression of such receptors (as well as a reduced amount of functional mitochondria. It was recently observed that some such women treated with HGH, show a marked increase in egg functional mitochondria along with improved egg quality.

 ________________________________________________________

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\

Respectfully, I do not concur with the suggested approach. You have recurrent pregnancy loss. I suggest you read the articles I wrote , below and then seriously consider calling my assistant, Patti Converse at 702-533-to set up an online consultation with me to discuss your case in detail.

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A. UNDERSTANDING RECURRENT PREGNANCY LOSS ( RPL): CAUSES AND SOLUTIONS.

When it comes to reproduction, humans face challenges compared to other mammals. A significant number of fertilized eggs in humans do not result in live births, with up to 75% failing to develop, and around 30% of pregnancies ending within the first 10 weeks  (first trimester). Recurrent pregnancy loss (RPL) refers to two or more consecutive failed pregnancies, which is relatively rare, affecting less than 5% of women for two losses and only 1% for three or more losses. Understanding the causes of pregnancy loss and finding solutions is crucial for those affected. This article aims to explain the different types of pregnancy loss and shed light on potential causes.

Types of Pregnancy Loss: Pregnancy loss can occur at various stages, leading to different classifications:

1. Early Pregnancy Loss: Also known as a miscarriage, this typically happens in the first trimester. Early pregnancy losses are usually sporadic, not recurring. In over 70% of cases, these losses are due to chromosomal abnormalities in the embryo, where there are more or fewer than the normal 46 chromosomes. Therefore, they are not likely to be repetitive.
2. Late Pregnancy Loss: Late pregnancy losses occur after the first trimester (12th week) and are less common (1% of pregnancies). They often result from anatomical abnormalities in the uterus or cervix. Weakness in the cervix, known as cervical incompetence, is a frequent cause. Other factors include developmental abnormalities of the uterus, uterine fibroid tumors, intrauterine growth retardation, placental abruption, premature rupture of membranes, and premature labor.

Causes of Recurrent Pregnancy Loss (RPL): Recurrent pregnancy loss refers to multiple consecutive miscarriages. While chromosomal abnormalities are a leading cause of sporadic early pregnancy losses, RPL cases are mostly attributed to non-chromosomal factors. Some possible causes include:

1. Uterine Environment Problems: Issues with the uterine environment can prevent a normal embryo from properly implanting and developing. These problems may include inadequate thickening of the uterine lining, irregularities in the uterine cavity (such as polyps, fibroid tumors, scarring, or adenomyosis), hormonal imbalances (progesterone deficiency or luteal phase defects), and deficient blood flow to the uterine lining.
2. Immunologic Implantation Dysfunction (IID): IID is a significant cause of RPL, contributing to 75% of cases where chromosomally normal embryos fail to implant. It involves the immune system’s response to pregnancy, which can interfere with successful implantation.
3. Blood Clotting Disorders: Thrombophilia, a hereditary clotting disorder, can disrupt the blood supply to the developing fetus, leading to pregnancy loss.
4. Genetic and Structural Abnormalities: Genetic abnormalities are rare causes of RPL, while structural chromosomal abnormalities occur infrequently (1%). Unbalanced translocation, where part of one chromosome detaches and fuses with another, can lead to pregnancy loss. Studies also suggest that damaged sperm DNA can negatively impact fetal development and result in miscarriage.

IMMUNOLOGIC IMPLANTATION DYSFUNCTION AND RPL:

Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA). But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States. Alloimmune IID, (i.e., where antibodies are formed against antigens derived from another member of the same species), is believed to be a common immunologic cause of recurrent pregnancy loss. Autoimmune IID is often genetically transmitted. Thus, it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly, the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage. Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction. However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated natural killer cells (NKa) and cytotoxic lymphocytes (CTL B) in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.

DIAGNOSING THE CAUSE OF RPL.

In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus, I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients. Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include Karyotyping (chromosome analysis) both prospective parents Assessment of the karyotype of products of conception derived from previous miscarriage specimens Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.) Hysterosalpingogram (dye X-ray test) Hysteroscopic evaluation of the uterine cavity Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.) Immunologic testing to include Antiphospholipid antibody (APA) panel Antinuclear antibody (ANA) panel Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies) Reproductive immunophenotype Natural killer cell activity (NKa) assay (i.e., K562 target cell test) Alloimmune testing of both the male and female partners

TREATMENT OF RPL

• Treatment for Anatomic Abnormalities of the Uterus: 

This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated. Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin. sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures. Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.

Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: 

Modalities such as intralipid (IL), intravenous immunoglobulin-G (IVIG),  heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction. The Use of IVF in the Treatment of RPL In the following circumstances, IVF is the preferred option: When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed and in cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.  The reason for IVF being a preferred approach when immunotherapy is indicated is that in order to be effective, immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic screening/ testing (PGS/T), with tests such as next generation gene sequencing (NGS), can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGS/T requires IVF to provide access to embryos for testing. There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha gene matching ( where there is a complete genotyping match between the male and female partners) where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy. Conclusion:

 Understanding the causes of pregnancy loss is crucial for individuals experiencing recurrent miscarriages. While chromosomal abnormalities are a common cause of sporadic early pregnancy losses, other factors such as uterine environment problems, immunologic implantation dysfunction, blood clotting disorders, and genetic or structural abnormalities can contribute to recurrent losses. By identifying the underlying cause, healthcare professionals can provide appropriate interventions and support to improve the chances of a successful pregnancy. The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

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B. WHY IVF SHOULD BE REGARDED AS A TREATMENT OF CHOICE FOR INFERTILE WOMEN WITH ENDOMETRIOSIS.

 When women with endometriosis-related infertility seek treatment, they are often advised to try ovarian stimulation with or without  intrauterine insemination (IUI) as a first option. However, it’s important to clarify the reality and set the record straight. In vitro fertilization (IVF) offers distinct advantages and a higher chance of success compared to IUI. Let’s explore why IVF should often be considered as the primary approach for women with endometriosis.

1. The Toxic Pelvic Factor:

Endometriosis causes the lining of the uterus to grow outside the uterus. As these deposits bleed over time, they release toxins into the pelvic secretions. These toxins coat the peritoneum, the membrane that covers the abdominal and pelvic organs. When eggs are released from the ovaries, they must pass through these toxic secretions to reach the sperm in the fallopian tubes. The toxins alter the egg’s envelopment, making it less receptive to fertilization. This explains why women with endometriosis are far less likely to conceive naturally, following ovulation induction or after surgical attempts to eliminate the condition. Consider the following: .

• Ovulation induction with or without intrauterine insemination (IUI) is commonly recommended for women with mild to moderately severe endometriosis. However, while fertility drugs can stimulate the growth of multiple follicles, ovulatory women (including those with mild to moderately severe endometriosis) usually ovulate only one egg a time. Therefore, the use of fertility drugs in such cases doesn’t significantly improve pregnancy potential.
• Surgery to remove endometriotic deposits or adhesions: Surgical removal of visible endometriotic lesions in mild to moderate endometriosis does not usually improve pregnancy potential significantly. This is because endometriosis is an ongoing process, with new lesions constantly developing. Even after the visible lesions are removed, invisible lesions continue to release toxins that can compromise natural fertilization. In contrast, IVF bypasses the toxic pelvic environment by retrieving eggs from the ovaries, fertilizing them outside the body, and transferring resulting embryos to the uterus. This makes IVF the preferred treatment for endometriosis-related infertility.

1. The Immunologic Factor:

Approximately one third of women with endometriosis also have an immunologic implantation dysfunction (IID) related to the activation of uterine natural killer cells (NKa). This requires selective immunotherapy with Intralipid infusions or heparinoids, which can be effectively implemented in combination with IVF.

1. Ovarian endometriomas :

Women, who have advanced endometriosis, often have endometriotic ovarian cysts, known as endometriomas. These cysts contain decomposed menstrual blood that looks like melted chocolate. Hence the name “chocolate cysts”. These space-occupying lesions inside the ovaries  can activate ovarian connective tissue (stroma or theca) resulting in an overproduction of male hormones (especially testosterone). An excess of ovarian testosterone can severely compromise follicle and egg development in the affected ovary. Endometriomas of >1 cm in size should in my opinion be addressed because in my opinion, they can and do adversely affect the quality of eggs produced in the affected ovary. We confirmed this effect in a study where we  evaluated egg quality in a number of women who had one or more endometriomas involving one ovary while the  contralateral ovary was unaffected. We were able to show that those eggs aspirated from follicles in the endometrioma-affected ovary were of markedly reduced  quality (and, the embryos and blastocysts they propagated were fewer in number and of markedly reduced quality as compared to those harvested from the un affected ovary.

• Conventional surgical treatment performed to remove endometriomas involvers laparoscopy or laparotomy with aspiration of the cyst content followed by complete removal and/or  ablation/obliteration  of the cyst wall. This should be done at least 6 weeks in advance of egg retrieval, in my opinion.  Such treatment is associated with pain and a risk of surgical complications.
• An alternative approach which I and my colleagues first reported on more than 2 decades ago, known as Ovarian Sclerotherapy is a highly effective, inexpensive and safe outpatient method for treating endometriomas in women planning to undergo IVF. The process involves needle aspiration of the “chocolate colored”  liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline hydrochloride into the cyst cavity. Such treatment will, more than 75% of the time result in disappearance of the lesion within 6-8 weeks. Ovarian sclerotherapy can be performed under local anesthesia or under conscious sedation. It is a safe and effective alternative to surgery for definitive treatment of recurrent ovarian endometriomas in a select group of patients planning to undergo IVF. It is in  my opinion, unfortunate that Ovarian Sclerotherapy is not readily available in this country.

I am not suggesting that all women with infertility-related endometriosis should automatically resort to IVF. Quite to the contrary…. In spite of having reduced fertility potential, many women with mild to moderate endometriosis can and do go on to conceive on their own (without treatment). It is just that the chance of this happening is so is much lower than normal.

IVF is by far the most successful approach to dealing with endometriosis-related infertility , especially when it comes to women above the age of 35 years, those who have moderate or severe disease and for women who have DOR. Understanding how endometriosis affects IVF outcomes can help make informed decisions about treatment. By  providing a more favorable environment for fertilization and implantation. IVF offers much  higher success rates when compared to ovulation induction with or without  IUI or surgical correction. Simply put……If you’re facing infertility due to endometriosis, it’s worth considering IVF as the first line of treatment to increase your chances of having a baby

__________________________________________________________________

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\

Please post in English!

GS

It is possible

Molar pregnancy or hydatidiform mole — is a benign tumor that occurs in the uterus. It starts when an egg is fertilized, but instead developing into a normal, conceptus + placental tissue, the placenta tissue develops into a mass of small cysts. Here, the root system (trophoblast) of the embryo which under normal conditions develops into the placenta that connects the baby to the mother. With molar pregnancy, the roots of the trophoblast (chorionic villi) undergo cystic degeneration and when the woman bleeds, these cystic structures are passed in dark blood, giving rise to the common description of “white currants floating in red currant jelly”.

The condition usually presents with one or more of the following:

• Vaginal bleeding in the first trimester
• Very high beta hCG levels early on in pregnancy
• Exaggerated pregnancy symptoms and pernicious intractable vomiting (hyperemesis gravidarum)
• Rapid (often painful) enlargement of the early pregnant uterus
• Ultrasound evidence of a typical “snow storm pattern)

A molar pregnancy can have serious complications. It can become invasive (an invasive mole or chorioadenoma destruens) and permeate the uterine wall or it can (albeit rarely) develop into a rare form of cancer known as choriocarcinoma.

Molar pregnancies are rare (about 1:2000 pregnancies) and having occurred.it infrequently (<1:1000) recurs in the same woman. It is at least twice as common among Asian women. On rare occasions (1%) a twin pregnancy will comprise of a normal baby and a mole. In about 20%-40% of cases the healthy baby will survive to delivery.

There are two types of molar pregnancies: a) the complete molar pregnancy: Here there’s no embryo or normal placental tissue is present. b) . A partial molar pregnancy, there is a developing embryo present but it is abnormal and non-viable, but there can be some “normal” placental tissue present as well.

“Complete Hydatidiform Molar Pregnancies” occur when an egg that has no chromosomal material (anuclear) is fertilized by a sperm and thereupon divides in two and propagates haphazard tissue growth. Like normal pregnancies, the complete mole has 46 chromosomes (two sets of 23), i.e., it is diploid.  However, unlike with normal fertilization, where one set of chromosomes comes from the mother and the other set from the father, both sets of chromosomes come from the father in the case of a complete molar pregnancy. This results from duplication of a sperm’s chromosomes after it has fertilized an “inactive” egg.  Since an embryo that has a YY karyotype is not viable, the chromosome gender of the complete molar pregnancy is invariably XX (female). Accordingly, with IVF, if one selectively only transfers only male (XY) embryos, the possibility of a complete molar pregnancy can be virtually eliminated.

A “Partial Molar Pregnancy” on the other hand, most often results from an egg being fertilized by 2 separate sperm, such that instead of the resulting embryo comprising 46 chromosomes (23 from the egg + 23 from the sperm), it instead has 69 chromosomes (23 from the egg + 46 from 2 separate sperm). However, it can also happen where one sperm fertilizes an egg, but one group of 23 chromosomes duplicates …again resulting in 3 groups of 23 chromosomes (triploidy)…..for a total of 69 chromosomes. Thus with partial moles, the sex chromosome configuration will be XXY or XYY. Partial moles can thus be avoided through selectively fertilizing an egg by intracytoplasmic sperm injection (ICSI), where a single sperm is injected, and thereupon performing PGD on the embryo(s) to exclude triploidy.

Persistent trophoblastic disease refers to the situation where following treatment to remove a molar pregnancy some molar tissue is retained and starts to grow again. It occurs in 8-10% of molar pregnancies. In such cases the woman will usually need to undergo chemotherapy

Treatment involves complete emptying of the uterus as soon as the diagnosis is made – even in cases where a spontaneous passage of the molar tissue appears to be complete. The reason is to avoid the development of an invasive mole (where the uterine wall is permeated by remaining tissue), and to limit the development of choriocarcinoma a very malignant tumor that invades the uterus and can spread rapidly via the blood system to bone, lungs, brain and other sites. Fortunately this cancer does respond well to hysterectomy, removal of ovaries plus aggressive chemotherapy.

In the vast majority of properly managed cases however, outcome after treatment is usually excellent. In cases where the beta hCG level fails to drop appropriately following evacuation of the uterus, chemotherapy will usually be curative. Close follow-up with serial quantitative blood hCG testing, ultrasound and/or Magnetic Resonance Imaging (MRI) is essential. After successful treatment, the woman must use very effective contraception for at least 6 to 12 months, so as to avoid pregnancy in order to allow for proper follow-up.

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

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

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

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\