A.
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:
a. 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.
b. 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
c. 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.
B.
When women with endometriosis-related infertility seek treatment, they are often advised to try ovarian stimulation with or without intrauterine insemination (IUI) as a first option. However, it’s important to clarify the reality and set the record straight. In vitro fertilization (IVF) offers distinct advantages and a higher chance of success compared to IUI. Let’s explore why IVF should often be considered as the primary approach for women with endometriosis.
1. The Toxic Pelvic Factor:
Endometriosis causes the lining of the uterus to grow outside the uterus. As these deposits bleed over time, they release toxins into the pelvic secretions. These toxins coat the peritoneum, the membrane that covers the abdominal and pelvic organs. When eggs are released from the ovaries, they must pass through these toxic secretions to reach the sperm in the fallopian tubes. The toxins alter the egg’s envelopment, making it less receptive to fertilization. This explains why women with endometriosis are far less likely to conceive naturally, following ovulation induction or after surgical attempts to eliminate the condition. Consider the following: .
• Ovulation induction with or without intrauterine insemination (IUI) is commonly recommended for women with mild to moderately severe endometriosis. However, while fertility drugs can stimulate the growth of multiple follicles, ovulatory women (including those with mild to moderately severe endometriosis) usually ovulate only one egg a time. Therefore, the use of fertility drugs in such cases doesn’t significantly improve pregnancy potential.
• Surgery to remove endometriotic deposits or adhesions: Surgical removal of visible endometriotic lesions in mild to moderate endometriosis does not usually improve pregnancy potential significantly. This is because endometriosis is an ongoing process, with new lesions constantly developing. Even after the visible lesions are removed, invisible lesions continue to release toxins that can compromise natural fertilization. In contrast, IVF bypasses the toxic pelvic environment by retrieving eggs from the ovaries, fertilizing them outside the body, and transferring resulting embryos to the uterus. This makes IVF the preferred treatment for endometriosis-related infertility.
2. The Immunologic Factor:
Approximately one third of women with endometriosis also have an immunologic implantation dysfunction (IID) related to the activation of uterine natural killer cells (NKa). This requires selective immunotherapy with Intralipid infusions or heparinoids, which can be effectively implemented in combination with IVF.
3. Ovarian endometriomas :
Women, who have advanced endometriosis, often have endometriotic ovarian cysts, known as endometriomas. These cysts contain decomposed menstrual blood that looks like melted chocolate. Hence the name “chocolate cysts”. These space-occupying lesions inside the ovaries can activate ovarian connective tissue (stroma or theca) resulting in an overproduction of male hormones (especially testosterone). An excess of ovarian testosterone can severely compromise follicle and egg development in the affected ovary. Endometriomas of >1 cm in size should in my opinion be addressed because in my opinion, they can and do adversely affect the quality of eggs produced in the affected ovary. We confirmed this effect in a study where we evaluated egg quality in a number of women who had one or more endometriomas involving one ovary while the contralateral ovary was unaffected. We were able to show that those eggs aspirated from follicles in the endometrioma-affected ovary were of markedly reduced quality (and, the embryos and blastocysts they propagated were fewer in number and of markedly reduced quality as compared to those harvested from the un affected ovary.
• Conventional surgical treatment performed to remove endometriomas involvers laparoscopy or laparotomy with aspiration of the cyst content followed by complete removal and/or ablation/obliteration of the cyst wall. This should be done at least 6 weeks in advance of egg retrieval, in my opinion. Such treatment is associated with pain and a risk of surgical complications.
• An alternative approach which I and my colleagues first reported on more than 2 decades ago, known as Ovarian Sclerotherapy is a highly effective, inexpensive and safe outpatient method for treating endometriomas in women planning to undergo IVF. The process involves needle aspiration of the “chocolate colored” liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline hydrochloride into the cyst cavity. Such treatment will, more than 75% of the time result in disappearance of the lesion within 6-8 weeks. Ovarian sclerotherapy can be performed under local anesthesia or under conscious sedation. It is a safe and effective alternative to surgery for definitive treatment of recurrent ovarian endometriomas in a select group of patients planning to undergo IVF. It is in my opinion, unfortunate that Ovarian Sclerotherapy is not readily available in this country.
I am not suggesting that all women with infertility-related endometriosis should automatically resort to IVF. Quite to the contrary…. In spite of having reduced fertility potential, many women with mild to moderate endometriosis can and do go on to conceive on their own (without treatment). It is just that the chance of this happening is so is much lower than normal.
IVF is by far the most successful approach to dealing with endometriosis-related infertility , especially when it comes to women above the age of 35 years, those who have moderate or severe disease and for women who have DOR. Understanding how endometriosis affects IVF outcomes can help make informed decisions about treatment. By providing a more favorable environment for fertilization and implantation. IVF offers much higher success rates when compared to ovulation induction with or without IUI or surgical correction. Simply put……If you’re facing infertility due to endometriosis, it’s worth considering IVF as the first line of treatment to increase your chances of having a baby.
GS
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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) ; http://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
2. 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\
