The question
Hi,
I have done 4 rounds of egg freezing at 3 different clinics.
First round- 30 follicles growing, 15 retrieved but only 6 mature. I believe I was triggered to early as the majority of eggs were less than 16mm on day of trigger (only 6 were above). 375 gonal f and trigger of ovitrelle.
Second cycle. New clinic. Less follicles growing, 8 retrieved, 7 mature. The eighth one was matured in the lab for 2 hours and became mature so they froze that too. Dosage changed daily based on bloods but was around 150 Fostimon and 150 Meriofert. Trigger 10000 gonasi.
I then moved to a clinic abroad as I’m an expat so chose a clinic closer to me than my home country (U.K.)
Third cycle- about 14 follicles growing, 12 retrieved, 7 mature. They froze the 5 immature ones as well and will thaw these earlier when I come to use them to see if they can mature in the lab. 300 gonal f and 150 menopur. Dual trigger of 0.2 decapatyl and 7500 hcg.
Forth cycle- 21 follicles growing, 14 retrieved, 8 mature. They have again also frozen the 6 immature eggs. 300 folliculin and 150 humog. Trigger 0.2 decapatyl and around 8000 hcg.
My AMH never stays consistent. It has gone from 8.2 to 6.4, to 2.9 and then up to 9.6. No doctor can suggest why my AMH fluctuates. Instead they said to focus on the fact I get around 7 mature eggs each cycle.
My first 3 cycles were completed at the age of 34. And my last cycle at the age of 35 and 2 months.
My questions:
Why am I getting so many immature eggs? Does this suggest that my egg quality is poor? Should I also be concerned about the quality of my mature eggs? I’ve been told they look good quality.
How likely is it that the immature eggs will mature after thawing? Was there any point in the clinic freezing them?
Will 28/29 mature eggs be enough to give me the best chances of at least two children. Ideally I always wanted more children but I guess I need to rely on also getting pregnant naturally to give me the best chances. Should I consider another round?
Why does my AMH fluctuate?
In an ideal world I would have liked to have frozen a couple of years earlier but Covid meant this wasn’t possible. So it left me doing my cycles at the age of 34/35.
Any professional insight you have would be greatly appreciated.
Many thanks,
Emma
Answer from Dr. Geoffrey Sher
It seems as if you have produced enough "mature" eggs to give you a shot. However, as to the reason for so many immature egg cells, consider the following:
One of the commonest questions asked by patients undergoing IVF relates to the likelihood of their eggs fertilizing and the likely “quality of their eggs and embryos. This is also one of the most difficult questions to answer. On the one hand many factors that profoundly influence egg quality; such as the genetic recruitment of eggs for use in an upcoming cycle, the woman’s age and her ovarian reserve, are our outside of our control. On the other hand the protocol for controlled ovarian stimulation (COS) can also profoundly influence egg/embryo development and this is indeed chosen by the treating physician.
First, it should be understood that the most important determinant of fertilization potential, embryo development and blastocyst generation, is the numerical chromosomal integrity of the egg. While sperm quality does play a role, this is a relatively minor one unless there is severe sperm dysfunction. Human eggs have the highest rate of numerical chromosomal irregularities (aneuploidy) of all mammals. In fact, only about two thirds of the eggs of women in their twenties or early thirties, have the required number of chromosomes (euploid), without which upon fertilization they cannot propagate a normal pregnancy. As the woman advances into and beyond her mid-thirties, the percentage of eggs that are euploid declines progressively such that by the age of 40 years, only about one out of five or six eggs is likely to be chromosomally normal and by the time she reaches her mid-forties less than one in ten of her eggs will be euploid. This is due to the effect of “wear and tear” on eggs that are in the ovaries from before birth and which once they are gone, no treatment can replenish .
Second; embryos that fail to develop into blastocysts are almost always aneuploid and not worthy of being transferred to the uterus because they will either not implant, will miscarry or propagate a chromosomally abnormal baby (e.g. Down syndrome). However, it is incorrect to assume that all embryos reaching the blastocyst stage will be euploid (“competent”). Bear in mind that a high percentage of aneuploid embryos will succumb during early development and never attain blastocyst status while the few that do reach blastocyst might appear to morphologically normal while in fact they are aneuploid. It is a fact that embryos which fail to develop into blastocysts within 6 days of fertilization are almost invariably aneuploid and “incompetent “. It follows that blastocysts are far more likely to be competent than are earlier (cleaved embryos). What is also true is that the older the woman, the less likely it is that any given blastocyst will be “competent”. As an example, a morphologically pristine blastocyst derived from the egg of a 30-year-old woman would have about a 50:50 chance of being euploid and a 30% chance of propagating a healthy, normal baby, while a microscopically comparable blastocyst-derived through fertilization of the eggs from a 40+year-old, would be far less likely to be euploid and/or capable of propagating a healthy baby.
While the effect of species on the potential of eggs to be euploid at ovulation is genetically preordained and nothing we do can alter this equation, there is, unfortunately, a lot we can (often unwittingly) do to worsen the situation by selecting a suboptimal protocol of controlled ovarian stimulation (COS). This, by creating an adverse intraovarian hormonal environment will often disrupt normal egg development and lead to a higher incidence of egg aneuploidy than otherwise might have occurred. Older women, women with diminished ovarian reserve (DOR) and those with polycystic ovarian syndrome are especially vulnerable in this regard .It is believed that this is in large part is attributable to increased LH- induced over-production of ovarian testosterone which is common in older women, those who (regardless of their age) have DOR and in most women who have PCOS.
During the normal, ovulation cycle, small amounts of androgens (male hormones such as testosterone), are produced by the ovarian stroma (tissue surrounding ovarian follicles). Testosterone is vital for follicular growth and egg development. However, over-production of testosterone often has the reversed effect and can adversely affect follicle growth, egg development and IVF outcome. It is thus essential that ovarian stimulation protocols be tailored and individualized so as to avoid exposure to excessive ovarian androgen (testosterone) so as to optimize follicle growth and egg development. It is in my opinion, also important to avoid the administration of androgens (testosterone-containing drugs), the administration products that can provoke additional LH production by the pituitary gland (e.g., Lupron/Buserelin/Superfact/clomiphene/Letrozole) as well as overdosing with LH-containing fertility drugs (e.g., Menopur and Luveris), in older women, those with DOR and in cases of PCOS.
In summary, it is important to understand the influence species, age of the woman as well as the effect of the COS protocol can have on egg/embryo quality and thus on IVF outcome. The selection of an individualized protocol for ovarian stimulation is one of the most important decisions that the RE has to make and this becomes even more relevant when dealing with older women, those with diminished ovarian reserve (DOR) and women with PCOS. Such factors will in large part determine egg competency, fertilization potential, the rate of blastocyst generation and indeed IVF outcome.
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ADDITIONAL INFORMATION:
I am attaching online links to two E-books which I 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
- “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
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General information only, not medical advice for your own situation. For that, book a consultation.