The question
My name is Polona, I'm 50 and I've done four IVF cycles, all in North Cyprus, two of them when I was 48 and two of them at 50, for the last one I changed clinics. I’m planning to do one more round with my own eggs and need some advise with the stimulation protocol, since all my doctors use only basic protocols. I listened to your webinar IVF stimmulation protocols and was really impressed, but also confussed. Most of the doctors say that you have to add more LH in older women, because they don’t have enough of it and their receptors for LH are damaged. And also most of them use Femara. I know that at my age is almost imposssible to get an euploid embryo,but want to try one more time with optimal protocol. After that, if I fail to get euploids, I want to transfer one of the donor embryos (I had tandem cycle last round).
I have PCOS, but I don't have many symptoms - I'm skinny ( but have to watch my diet and do a lot of sports), I don’t have high androgens, I think I don’t have insulin resistance, but I don't ovulate if I don't take Femara (day 3 to 7) and even Femara sometimes doesn’t help.
My latest bloodwork and AFC (after fourth IVF):
25.8.2023, day 2 (after the last IVF
FSH= 4.4 mIU/L
LH= 4.2 mIU/L )
prolactin= 6.4 microg/L
estradiol= 111.6 pmol/L
AMH= 5.60 ng/mL
AFC at day 4: 13+13=26
My bloodwork and AFC (before starting the fourth IVF):
4.5.2023, day 3:
FSH= 7.0 mIU/L (it was 12.4 in 2021)
LH= 5.8 mIU/L (it was 15.35 in 2021)
prolactin= 14.5 microg/L
estradiol= 90.9 pmol/L ( it was 33.17 in 2021)
AMH= 4.05 ng/mL ( it was 3.99 in 2021)
AFC at day 4: 7+7 =14
22.5.2023, day 21:
progesteron= 30.61 nmol/L (it was 44.77 in 2021)
testosteron= 0.14 nmol/L
I'm taking a lot of supplements for last two years and doing red light theraphy from May 2023.
My stimulation protocols and results were:
Avgust 2021:
- Gonal f 300IU for 9 days (plus Femara for first 5 days),
- adding Cetrotide from day 7
- trigger with Gonapeptyl day 10
22 collected - 7 mature - 3 fertilized - 3 frozen at day 3
After the egg collection I had HSG done and they discovered I had an Y shaped uterus and they operated and I think it is now ok.
November 2021:
the same, only a day more of Gonal f and trigger one day later
15 collected – 9 mature - 7 fertilized - 6 frozen on day 3
They did PGT on all embrios together, but only 5 chromosome FISH (13, 18, 21, X, Y), two came out normal, one was monosomy 18, X0.
I transfered all three (one by one), but didn't implant.
March 2023:
- Gonal f for 9 days (plus Femara day 1 to 5)
- adding Dabroston pills at day 7 ( instead of Cetrotide)
- trigger with Gonapeptyl at day 13 (I overslept the trigger and did it 8 hours late), they collected 11h after the trigger.
I ovulated before collecting, I think at day 7, I think because I wasn’t taking Certrotide injections, but they said, Dabrostone pills were OK.
7 collected (the big ones ovulated before collection) - 3 mature - 0 by day 3
After that failed cycle I changed the clinic, but wasn’t sure from the start if the stimulation protocol they prescribed would be ok for me (high doses of FSH). I did an estrogen priming, but my doctor didn’t read my mails and he didn’t know I did it. My follicles weren’t growing at all at the beginning (because of estrogen priming, but I didn t know at first that was the cause), I told the nurse about the estrogen priming, but I think she didn’t tell the doctor, so he just kept highering the dose of meds. At trigger day they said that there were a lot of big follicles, but then they collected only four (I still don’t know what happened to the rest, because I left right after the egg retrieval and I still didn’ t get an explanation by mail). Only two were fertilized and only one made it to day 5 to early blastocyte stage, but it was tested chaotic. They did a cytoplasmic transfer on both of them and also fertilized 7 donor eggs with the same donor sperm, but only 3 got to day 5. I still didn’t get an explanation, what was the problem, but anyway, I have three frozen donor embryos there and two frozen donor eggs. I took hGh for 8 weeks before and during the last stimulation. Last stimulation protocol and results:
July 2023, (AFC at day 3 was 10):
Day 1 to 5: Gonal f 375 IU and Femara
Day 6: Gonal f 300 IU, Meriofert 150 IU
Day 7 to 12: Gonal f 350 IU, Meriofert 150 IU
Day 13 and 14: Gonal f 350 IU, Meriofert 300 IU, Cetrotide
Day 15: trigger with Gonapeptyl, half of Ovitrelle and Cetrotide
Day 17: 4 collected – 2 fertillized- one early blastocyst at day 5, tested chaotic
If it is possible, I would be glad to have an online consultation about my case. I’m from Slovenia (Europe).
Thank you for your answer!
Answer from Dr. Geoffrey Sher
Dear Polona,
I cannot in good faith support a decision to do IVF with own eggs at 50y of age. The chance of success is virtually zero, regardless of ovarian reserve. You should exclusively be focused on egg donation.
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.
Geoff Sher
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PLEASE SHARE THIS WITH OTHERS AND HELP SPREAD THE WORD!!
Herewith are online links to 2 E-books recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)....... for your reading pleasure:
- 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\
General information only, not medical advice for your own situation. For that, book a consultation.