• 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.

_____________________________________________________________________________

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\

So sorry for the delay but our website went down.

Please contact my assistant, Patti (concierge@sherIVF.com and set up on online consultation with me to discuss.

• EGG BANKING:

“The bottom line is that because of the traumatic effect of freezing on egg viability and “competency” the statistical chance of each frozen/ thawed egg ultimately resulting in a baby is only at best 6-8%. So, while success rates following the transfer of embryos derived from frozen eggs have indeed improved substantially over the last 5-10 years, they remain significantly lower than when embryos derived through fertilization of fresh (not frozen) eggs, are transferred.\”

Since the birth of the 1st “frozen egg baby” in the mid 1980’s, fewer than 3,000 births resulting from the fertilization of thawed eggs have been reported, worldwide. Compare this to > 4.5 million IVF babies born worldwide in the same time period, and > 2,000,000 babies resulting from the transfer of frozen embryos. Harvesting eggs for freezing typically involves giving a woman fertility drugs to stimulate her ovaries to produce multiple eggs, and then harvesting those eggs from her ovaries using ultrasound guided needle aspiration. In average cases (where the mean age of the woman is <36y), it takes about one cycle of fertility drug administration to harvest 10 to 15 eggs.

Presently, in cases where embryos derived from the eggs of women under 35years are frozen, survive the thaw and are transferred to the uterus, the birth rate per embryo transfer is about 35%. In those cases where the eggs were derived from women between 35y and 40y of age, the birth rate is about 25-30% per embryo transfer (ET) procedure. For women of >40y the comparable birth rate per ET is about 10-15%.

While on the face of it, this sounds like a reasonable outcome (especially when it comes to younger women), it should be borne in mind that many eggs do not survive the freeze/thaw and a significant number of those that survive, fail to fertilize. Moreover, of those that do fertilize, a significant percentage fail to progress to the expanded blastocyst stage of development (regarded as being the ideal stage for ET).  That is why depending on their age, women who elect to bank their eggs for fertility preservation (FP) are encouraged to undergo as many egg retrieval procedures as needed in to bank 12-20 eggs before having some degree of confidence, of ultimately being rewarded with a live birth. Since the percentage of eggs that are chromosomally normal (euploid) and “competent”) declines with advancing age, the older the woman becomes, the greater will be the number of eggs (and egg retrieval procedures) needed. . 

In young women, less 50% of eggs are euploid and by the  mid-forties, that percentage drops to below <10%, it follows that potential for a successful outcome using frozen eggs  largely hinges on their chromosomal integrity (“competency”). It follows that ultimately, the success of IVF outcome using frozen eggs will in large part center around the widespread introduction of technology that will provide the ability to accurately identify eggs that are numerically chromosomally normal (“euploid”) and are thus the ones most likely, upon being fertilized and transferred to the uterus,  to propagate a live birth.

In 2005 we became the first to evaluate the chromosomal integrity of the egg, prior to freezing it. We used a procedure where an envelopment of egg chromosomes (the 1^st polar body)  which  is expelled from the egg nucleus following a spontaneous (or GnRHa-induced ) LH surge  or the administration of an hCG “trigger”, is removed (biopsied) and subjected to numerical chromosome analysis. “Competent” (euploid) eggs are those that have precisely 23 chromosomes. Such euploid eggs are then selectively frozen for subsequent banking and dispensation. We were able to show that the likelihood that the transfer of embryos derived through the fertilization of such eggs, improves the baby rate per frozen egg by a factor of 4  . It follows that the selective freezing of only  euploid (“competent”) eggs  could dramatically improve results with egg banking. It would also be most helpful in assisting women undergoing egg banking to determine how many eggs to stockpile for future dispensation with the expectation of ultimately achieving a viable birth. This would be especially helpful in older women and those who have diminished ovarian reserve (DOR) and accordingly would have fewer competent eggs available. The problem is that this process is presently cost0-prohibitive and as such has not been adopted in the present-day clinical armamentarium.

• Indications for egg freezing:
  1. Female fertility preservation (FP)

This refers to the process whereby a woman’s eggs are frozen (cryopreserved) and banked for future use. It has been estimated that the potential demand for FP using frozen eggs exceeds that for conventional IVF by a factor of 4-6 times. The need addresses:

• • • • Women who face a looming prospect of losing their ovarian function – either because of impending menopause, pending surgical removal of their ovaries, and/or exposure to radiation therapy and/or chemotherapy,
      • Women who anticipate delaying or deferring childbearing, ,because of :
        • Career demands
        • Not being ready to commit to a permanent relationship.
        • They feel that by deferring egg banking the ever-advancing biological clock might later render them less able or unable to conceive.
      • Women/couples undergoing in vitro fertilization who are opposed to embryo freezing on moral, ethical or religious grounds.

While the demand for FP is growing rapidly, a word of caution is appropriate here: Women need to be encouraged to bank their eggs at a younger age (<35y) where their chance of the eggs frozen being euploid (“competent”) is greatest and…older women should be cautioned that their ability to propagate viable (usable) eggs diminishes with advancing age. Regardless of age, all should be made aware of the fact that it could take several egg retrievals to generate enough frozen eggs to provide a reasonable chance of subsequently having a baby. Finally, in my opinion, women of >40y (especially those with diminished ovarian reserve-DOR) should be advised against egg banking, primarily because of the inevitability of an age-related decline in egg “competency”. Perhaps some time in the future,  the banking of PGS-tested, euploid embryos will become available to such women and improve their ability to make rational decisions as to whether they should embark on egg banking for fertility preservation (FP).

_____________________________________________________________

• IVF WITH EGG DONATION: A REVIEW

Introduction:

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.

________________________________________________________________________________________________________________________________

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\

_____________________________________________

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 a great deal to discuss! I suggest that you contact my assistant, Patti (concierge@sherIVF.com ) and set up a time to discuss online.

• ADDRESSING ADVANCING AGE AND DIMINISHING OVARIAN RESERVE (DOR) IN IVF

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

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

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

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

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

1. Conventional Long Pituitary Down Regulation Protocol:

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

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

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

1. Protocols to Avoid for Older Women or Those with DOR: Certain ovarian stimulation protocols may not be suitable for older women or those with declining ovarian reserve:

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

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

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

• EGG/ EMBRYO QUALITY IN IVF & HOW SELECTION OF THE IDEAL PROTOCOL FOR OVARIAN STIMULATION INFLUENCES  EGG/EMBRYO QUALITY AND  OUTCOME.

The journey of in vitro fertilization can be a rollercoaster of emotions for many patients. Often times they have to face the harsh reality that the number and quality of eggs retrieved has fallen short of their expectations. Then, should fertilization of these eggs not propagate  chromosomally normal (euploid), “competent” embryos suitable for transfer to the uterus, many such patients find themselves in a state of emotional distress. They grapple with the inevitable questions of why this happened and how to prevent it from occurring again in the future. This article aims to delve into these queries, providing insights, rational explanations, and therapeutic options. It is an invitation to explore the light at the end of the tunnel. Readers are urged to carefully absorb the entirety of the article in the hope of finding valuable information and renewed hope.

• The Importance of Chromosomal Integrity: While sperm quality is an important factor, egg quality is by far the most important when it comes to the generation of embryos that are capable of propagating healthy babies (“competent”). In this regard, chromosomal integrity of the egg and embryo, although it is not the only factor , is certainly the main determinant of such competency.
• The woman’s age: About two thirds of a woman’s eggs in her twenties or early thirties have the correct number of chromosomes, which is necessary for a healthy pregnancy. As a woman gets older, the percentage of eggs with the right number of chromosomes decreases. By age 40, only about one in every 5-6 eggs is likely to be normal, and by the mid-forties, less than one in ten eggs will be normal.
• Ovarian Reserve (number of available in the ovaries): A woman is born with all the eggs she will ever have. She starts using these eggs when she begins ovulating during puberty. At first, the eggs are used up quickly, but as she gets older, the number of eggs starts to run out. Her brain and pituitary gland try to stimulate the production of more eggs by increasing the output of Follicle Stimulating Hormone (FSH), but unfortunately, this often doesn’t work. When the number of remaining eggs in her ovaries falls below a certain level (which can be different for each woman), her FSH level rises, and production of the ovarian hormone, AMH decreases. This is the start of diminishing ovarian reserve (DOR). Most women experience the onset of DOR in their late 30s or early 40s, but it can happen earlier for some. The lower the ovarian reserve, the lower the AMH level will be, and the fewer eggs will be available for harvesting during IVF-egg retrieval. In such cases, a higher dosage of fertility drugs might be needed to promote better egg production in future attempts. . On the other hand, higher AMH levels mean more eggs are available, and lower doses of fertility drugs are usually needed. DOR is commonly associated with increased bioactivity of pituitary gland-produced LH. This LH activates production of ovarian male hormones (androgens)…predominantly testosterone by ovarian connective tissue (stroma) . While a small amount of  ovarian testosterone is absolutely necessary for optimal follicle and egg development, excessive ovarian testosterone will often access the follicle , and compromise both egg quality and follicle growth and development. In some cases, rapidly increasing  LH-release (“premature LH-surge”) with excessive induced ovarian testosterone can lead to “premature luteinization”  of the follicles with cessation in growth and even to“ premature ovulation”.
• Importance of Individualized Controlled Ovarian Stimulation (COS) Protocol: It’s not surprising that DOR is more common in older women, but regardless of age, having DOR makes a woman’s eggs more likely to be compromised during controlled ovarian stimulation (COS). The choice of the COS protocol is crucial to preventing unintentional harm to egg and embryo quality. The wrong protocol can disrupt normal egg development and increase the risk of abnormal embryos. That’s why it’s important to tailor the COS protocol to each individual’s needs. This helps optimize follicle growth and the quality of eggs and embryos. The timing of certain treatments is also important for successful outcomes.
• Embryo Competency and Blastocyst Development: Embryos that don’t develop into blastocysts by day 6 after fertilization are usually chromosomally abnormal or aneuploid (”incompetent”) and not suitable for transfer. However, not all blastocysts are guaranteed to be normal and capable of developing into a healthy baby. As a woman gets older, the chances of a her embryos being chromosomally normal blastocyst decreases. For example, a blastocyst from a 30-year-old woman is more likely to be normal compared to one from a 40-year-old woman.

The IVF stimulation protocol has a big impact on the quality of eggs and embryos especially in women with DOR. Unfortunately, many IVF doctors use the same COS “recipe approach” for everyone without considering individual differences. Using personalized protocols can greatly improve the success of IVF. While we can’t change genetics or reverse a woman’s age, a skilled IVF specialist can customize the COS protocol to meet each patient’s specific needs.

GONADOTROPIN RELEASING HORMONE AGONISTS (GNRHA) AND GNRH-ANTAGONISTS:

• Gonadotropin releasing hormone agonists (GnRHa). Examples are  Lupron, Buserelin, Superfact, and Decapeptyl . These are commonly used to launch  ovarian stimulation cycles. They work by initially causing a release of pituitary gonadotropins, followed by a decrease in LH and FSH levels within 4-7 days. This creates a relatively low LH environment when COS begins, which is generally beneficial for egg development. However, if GnRHa are administered starting concomitant with gonadotropin stimulation (see GnRHa –“flare protocol” -below) it can cause an immediate surge in LH release, potentially leading to high levels of ovarian testosterone that can harm egg quality, especially in older women and those with diminished ovarian reserve (DOR).
• Gonadotropin releasing hormone antagonists (GnRH-antagonists) : Examples are Ganirelix, Cetrotide, and Orgalutron. GnRH antagonists (take days   work quickly (within hours) to block pituitary LH release. Their purpose is to prevent excessive LH release during COS. In contrast, the LH-lowering effect of GnRH agonists takes several days to develop. Traditionally, GnRH antagonists are given starting on the 5th-7th day of gonadotropin stimulation. However, in older women and those with DOR, suppressing LH might happen too late to prevent excessive ovarian androgen production that can negatively impact egg development in the early stages of stimulation. That’s why I prefer to administer GnRH-antagonists right from the beginning of gonadotropin administration.

USING BIRTH CONTROL PILLS TO START OVARIAN STIMULATION:

Patients are often told that using birth control pills (BCP) to begin ovarian stimulation will suppress the response of the ovaries. This is true, but only if the BCP is not used correctly. Here’s the explanation:

In natural menstrual cycles and cycles stimulated with fertility drugs, the follicles in the ovaries need to develop receptors that respond to follicle-stimulating hormone (FSH) in order to properly respond to FSH stimulation. Pre-antral follicles (PAFs) do not have these receptors and cannot respond to FSH stimulation. The development of FSH responsivity requires exposure of the pre-antral follicles to FSH for several days, during which they become antral follicles (AFs) and gain the ability to respond to FSH-gonadotropin stimulation. In regular menstrual cycles, the rising FSH levels naturally convert PAFs to AFs. However, the combined BCP suppresses FSH. To counter this suppression, we need to promote increased  FSH production several days before starting COS. This allows the orderly conversion from PAFs to AFs, ensuring proper follicle and egg development.

GnRHa causes an immediate surge in FSH release by the pituitary gland, promoting the conversion from PAF to AF. Therefore, when women take the BCP control pill to launch a cycle of COS, they need to overlap the BCP with a GnRHa for a few days before menstruation. This allows the early recruited PAFs to complete their development and reach the AF stage, so they can respond appropriately to ovarian stimulation. By adjusting the length of time, the woman is on the birth control pill, we can regulate and control the timing of the IVF treatment cycle. Without this step, initiating ovarian stimulation in women coming off birth control pills would be suboptimal.

PROTOCOLS FOR CONTROLLED OVARIAN STIMULATION (COS):

• GnRH Agonist Ovarian Stimulation Protocols:

• • The long GnRHa protocol: Here, a GnRHa (usually Lupron or Superfact) is given either in a natural cycle, starting 5-7 days before menstruation, overlapping with the BCP for three days. Thereupon,  the pill is stopped, while daily  GnRHa injections continue until menstruation occurs (usually 5-7 days later). The GnRHa causes a rapid rise in FSH and LH levels. This is followed about 3-4 days later , by a progressive decline in FSH and LH to near zero levels,  with a concomitant drop in ovarian estradiol and progesterone. This, in turn triggers uterine withdrawal bleeding (menstruation) within 5-7 days of starting the GnRHa administration. Gonadotropin treatment is then initiated while daily GnRHa injections continue to maintain a relatively low LH environment. Gonadotropin administration continues until the hCG “trigger” (see below).
  • Short GnRH-Agonist (“Flare”) Protocol: This protocol involves starting hormone therapy and using GnRH agonist at the same time. The goal is to boost FSH so that with concomitant stimulation with FSH-gonadotropins  + the GnRHa-induced surge in pituitary gland FSH release, will augment follicle development. However, this surge also leads to a rise in LH levels, which can cause an excessive production of ovarian male hormones (e.g., testosterone). This could potentially adversely affect the quality of eggs, especially in women over 39 years old, those with low ovarian reserve, and women with PCOS or DOR who already have increased LH sensitivity. In this way, these “flare protocols” can potentially decrease the success rates of IVF. While they are generally safe for younger women with normal ovarian reserve, I personally avoid using this approach on the off chance that even patients with normal ovarian reserve, might experience poor egg quality.

• GnRH Antagonist-Ovarian Stimulation Protocols:

• • Conventional GnRH Antagonist Protocol: In this approach, daily GnRH antagonist injections are  given from the 5th to the 8th day of COS with gonadotropins to the day of the “trigger” (see below). Accordingly, although rapidly acting to lower LH , this effect of GnRH- antagonist only starts suppressing LH from well into the COS cycle which means the ovarian follicles are left exposed and unshielded from pituitary gland -produced, (endogenous) LH during the first several days of stimulation. This can be harmful, especially in the early stage of COS when eggs and follicles are most vulnerable to the effects of over-produced LH-induced excessive ovarian testosterone. Therefore, I believe the Conventional GnRH Antagonist Protocol is not ideal for older women, those with low ovarian reserve, and women with PCOS who already have elevated LH activity. However, this protocol is acceptable for younger women with normal ovarian reserve, although I personally avoid using this approach on the off chance that even patients with normal ovarian reserve, might experience poor egg quality.

It’s important to note that the main reason for using GnRH antagonists is to prevent a premature LH surge, which is associated with poor egg and embryo quality due to follicular exhaustion. However, calling it a “premature LH surge” is misleading because it actually represents the culmination of a progressive increase in LH-induced ovarian testosterone. A better term would be “premature luteinization”. In some such cases, the rise in LH can precipitate “premature ovulation”.

• Agonist/Antagonist Conversion Protocol (A/ACP): I recommend this protocol for many of my patients, especially for older women and those with DOR or PCOS. The woman starts by taking a BCP for 7-10 days. This overlapped with a GnRHa for 3 days and continued until menstruation ensues about 5-7 days later. At this point  she “converts” from the GnRH-agonist to a GnRH-antagonist (Ganirelix, Orgalutron, or Cetrotide). A few days after this conversion from agonist to antagonist, COS with  gonadotropin stimulation starts. Both the antagonist and the gonadotropins are continued together until the hCG trigger. The purpose is to suppress endogenous LH release throughout the COS process and so  avoid over-exposure of follicles and eggs to LH-induced  excessive ovarian testosterone which as previously stated, can compromise egg and follicle growth and development.   Excessive ovarian testosterone can also adversely affect estrogen-induced growth of the uterine lining (endometrium). Unlike GnRH-agonists, antagonists do not suppress ovarian response to the gonadotropin stimulation. This is why the A/ACP is well-suited for older women and those with diminished ovarian reserve.
• A/ACP with estrogen priming: This is a modified version of the A/ACP protocol used for women with very low ovarian reserve (AMH=<0.2ng/ml). Estrogen priming is believed to enhance the response of follicles to gonadotropins. Patients start their treatment cycle by taking a combined birth control pill (BCP) for 7-10 days. After that, they overlap daily administration of a GnRH agonist with the BCP for 3 days. The BCP is then stopped, and the daily agonist continues until menstruation ensues (usually 5-7 days later). At this point, the GnRH agonist is supplanted by daily injections of  GnRH antagonist and  Estradiol (E2) “priming” begins using E2 skin patches or intramuscular estradiol valerate injections twice weekly, while continuing the GnRH antagonist. Seven days after starting the estrogen priming COS begins using recombinant FSHr such as Follistim, Gonal-F or Puregon) +menotropin (e.g., Menopur) . The estrogen “priming” continues to the day of the “trigger” (see below).  Egg retrieval is performed 36 hours after the trigger.

Younger women (under 30 years) and women with absent, irregular, or dysfunctional ovulation, as well as those with polycystic ovarian syndrome (PCOS), are at risk of developing a severe condition called Ovarian Hyperstimulation Syndrome (OHSS), which can be life-threatening. To predict this condition, accurate daily blood E2 level monitoring is required.

TRIGGERING “EGG MATURATION PRIOR TO EGG RETRIEVAL”

• The hCG “trigger”: When it comes to helping eggs mature before retrieval, one of the important decisions the doctor needs to make is choosing the “trigger shot” to facilitate the process. Traditionally, hCG (human chorionic gonadotropin) is derived from the urine of pregnant women (hCGu) while a newer recombinant hCG (hCGr), Ovidrel was recently  introduced. The ideal dosage of hCGu is 10,000U and for Ovidrel, the recommended dosage is 500mcg. Both have the same efficacy. The “trigger” is usually administered by intramuscular injection, 34-36 hours prior to egg retrieval.

Some doctors may choose to lower the dosage of hCG if there is a risk of severe ovarian hyperstimulation syndrome (OHSS). However, I believe that a low dose of hCG (e.g., 5000 units of hCGu or 250 mcg of hCGr ( Ovidrel) might not be enough to optimize egg maturation, especially when there are many follicles. Instead, I suggest using a method called “prolonged coasting” to reduce the risk of OHSS.

• Using GnRH antagonist alone or combined with hCG as the trigger: Some doctors may prefer to use a GnRH- agonist  trigger instead of hCG to reduce the risk of OHSS. The GnRHa “trigger” acts by inducing a “surge of pituitary gland-LH. However, it is difficult to predict the amount of LH that is released in response to a standard agonist trigger. In my opinion, using hCG is a better choice, even in cases of ovarian hyperstimulation, with the condition that “prolonged coasting” is implemented beforehand.
• Combined use of hCG + GnRH agonist: This approach is better than using a GnRH agonist alone but still not as effective as using the appropriate dosage of hCG.
• Timing of the trigger: The trigger shot should be given when the majority of ovarian follicles have reached a size of more than 15 mm, with several follicles measuring 18-22 mm. Follicles larger than 22 mm often contain overdeveloped eggs, while follicles smaller than 15 mm usually have underdeveloped and potentially abnormal eggs.

SEVERE OVARIAN HYPERSTIMULATION SYNDROME (OHSS) & “PROLONGED COASTING”

OHSS is a life-threatening condition that can occur during controlled ovarian stimulation (COS) when the blood E2 (estradiol) level rises too high. It is more common in young women with high ovarian reserve, women with polycystic ovarian syndrome (PCOS), and young women who do not ovulate spontaneously. To prevent OHSS, some doctors may trigger egg maturation earlier, use a lower dosage of hCG, or “trigger” using a GnRHa. However, these approaches can compromise egg and embryo quality and reduce the chances of success.

To protect against the risk of OHSS while optimizing egg quality, Physicians can use one of two options. The first is “prolonged coasting,” a procedure I introduced more than three decades ago. It involves stopping gonadotropin therapy while continuing to administer the GnRHa until the risk of OHSS has decreased. The precise timing of “prolonged coasting” is critical. It should be initiated when follicles have reached a specific size accompanied and the  blood estradiol has reached a certain peak.  The second option is to avoid fresh embryo transfer and freeze all “competent” embryos for later frozen embryo transfers (FETs) at a time when the risk of OHSS has subsided. By implementing these strategies, both egg/embryo quality and maternal well-being can be maximized.

In the journey of fertility, a woman is blessed with a limited number of eggs, like precious treasures awaiting their time. As she blossoms into womanhood, these eggs are gradually used, and the reserves start to fade. Yet, the power of hope and science intertwines, as we strive to support the development of these eggs through personalized treatment. We recognize that each woman is unique, and tailoring the protocol to her individual needs can unlock the path to success. We embrace the delicate timing, understanding that not all embryos are destined for greatness. With age, the odds may shift, but our dedication remains steadfast, along with our ultimate objective, which is  to do everything possible to propagate  of a normal pregnancy while optimizing the  quality of that life after birth and all times, minimizing risk to the prospective parents.

______________________________________________________________________

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\

Absolutely. This is your only option…in my opinion.

Geoff Sher.

• IVF WITH EGG DONATION: A REVIEW

Introduction:

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.

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\