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Embarking on the journey of IVF often raises questions about the likelihood of success and the quality of embryos. While it’s challenging to predict outcomes due to various factors, there’s hope and information to guide you.

Firstly, the key to fertilization potential lies in the chromosomal integrity of the egg. Women in their twenties or early thirties have a higher chance of having eggs with the required number of chromosomes for a healthy pregnancy. However, as age advances, this percentage decreases, emphasizing the importance of timely decisions.

Secondly, embryos that don’t develop into blastocysts are usually chromosomally abnormal and are not suitable for transfer, as they may lead to implantation issues or miscarriages. Not all blastocysts are guaranteed to be chromosomally normal, and this likelihood decreases with the age of the woman. Understanding this helps set realistic expectations.

While species and genetic factors play a role in egg quality, our choice of a controlled ovarian stimulation (COS) protocol also matters. Selecting the right COS protocol is crucial, especially for older women, those with diminished ovarian reserve (DOR), and those with polycystic ovarian syndrome. An individualized approach to optimize follicle growth and egg quality can significantly impact IVF outcomes.

In a natural ovulation cycle, hormonal changes are finely tuned to support healthy follicle development and egg maturation. When undergoing IVF, it’s essential to avoid disrupting this delicate balance. The Human Chorionic Gonadotropin (hCG) “trigger shot” should be carefully timed to enhance the chances of success.

In summary, understanding the influence of age, genetics, and COS protocols on egg quality is crucial for a successful IVF journey. The decision-making process becomes even more critical for older women or those facing specific fertility challenges. By embracing personalized approaches and staying informed, you can navigate the path of IVF with hope and optimism.

• 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.

• STAGGERED IVF WITH PGS/PGT: A MAJOR BREAK-THROUGH IN THE TREATMENT OLDER WOMEN AND THOSE WITH DIMINISHED OVARIAN RESERVE

“Staggered  (ST) IVF refers to the process whereby embryos are intentionally  frozen and cryobanked for elective transfer to the uterus  in a subsequent cycle”. 

Doctors often start with less invasive treatments for women over 40 who have patent fallopian tubes before considering IVF. They prescribe fertility drugs and may try artificial insemination. The reason is that IVF is more expensive, but it's also more likely to lead to a successful live birth. When we think about the true cost of having a baby, IVF can actually be a more cost-effective choice.

IVF has proven to be far more successful than other treatments, regardless of a woman's age or the cause of infertility. For example, for women under 35 with healthy tubes and a fertile partner, the chance of having a baby through IUI is less than 15% per attempt. But with IVF, the chances rise to about 40-45%. This difference becomes even more significant as a woman gets older. For women in their mid-40s, the chance of success with IUI drops to less than 3%, while IVF offers a 10-15% chance.

This doesn't mean all women with healthy tubes and fertile partners should choose IVF over other options. However, for women in their 40s or those with diminished ovarian reserve (DOR), time is precious, and IVF may be the best choice. As a woman ages, the risk of miscarriage and having a chromosomally abnormal baby, increases. At age 30, the risk of miscarriage is about 15%, and the chance of having a baby with Down syndrome is less than 1 in 1000. But in the mid-40s, the risk of miscarriage exceeds 40%, and the chance of having a baby with Down syndrome becomes 1 in 60-80.

Staggered IVF and Preimplantation Genetic Sampling /Testing (PGS/PGT) with/without Embryo Banking offers real hope to older infertile women and those with DOR,  as an alternative to IVF or egg donation. It involves multiple IVF procedures, biopsy of potentially viable embryos for PGS, cryobanking the embryos until several blastocysts have been collected, and then conducting genetic testing using Next Generation Gene Sequencing (NGS). Once the PGS/PGT results are known, the woman can return in a subsequent cycle for the transfer of up to two PGS/PGT-normal embryos to her uterus. Embryo banking with Staggered IVF and selective transfer of chromosomally healthy embryos greatly improves the success rate per embryo transferred, reaching as high as 50%. It also reduces the risk of miscarriage by 5-6 times and minimizes the chance of having a baby with chromosomal birth defects like Down syndrome.

As a woman ages, the competency of her eggs declines rapidly, resulting in diminished ovarian reserve. This reduces fertility, increases the risk of miscarriage, and raises the likelihood of chromosomal birth defects. IVF maximizes the number of available eggs and allows for genetic testing of resulting embryos, improving outcomes. Staggered IVF, Embryo Banking, and PGS/PGT are excellent tools that enhance pregnancy rates, reduce miscarriage risks, and minimize the chance of chromosomal birth defects. We strongly recommend this approach for women undergoing IVF in the following situations:

• Older women (>39y), 
• Women who (regardless of age) have DOR,
• Women with known transmittable genetic defects
• Chromosomal testing for gender selection,
• Women with recurrent pregnancy loss and
• Those with unexplained IVF failure

Embryo banking with staggered IVF and PGS/PGT represents a major breakthrough in the field of Assisted Reproduction ., one that offers hope primarily to older infertile women and those with diminished ovarian reserve. This method involves multiple IVF procedures, genetic testing of embryos, and cryobanking until several viable embryos are collected. By transferring only chromosomally healthy embryos, the success rate per embryo transferred can reach as high as 50%, significantly reducing the risk of miscarriage and chromosomal birth defects. For women facing the challenges of advancing age and diminished ovarian reserve, this advanced IVF technique provides an inspiring opportunity to improve pregnancy rates, minimize risks, and increase the chance of a healthy baby.

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

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

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

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\