If the embryo is aneuploid, there is no merit in keeping it. Frankly, trying with own eggs at 45y with such severely diminished ovarian reserve is ill-advised. You need an egg donor.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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:
- 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.
- 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
- 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.
- 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.
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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:
- From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) ; http://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
- Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link ;https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
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\
