Mary Smith (not her real name) recently came to the office requesting egg freezing. She was thirty years old with regular menses but no lifetime partner, and she wanted to preserve her fertility. She had heard that in one month she could store up to 20 eggs to be used later at her discretion. Her friend Amy was married but wanted to delay childbearing due to career concerns. A third friend had irregular menses for two years, and no gynecologist could explain why. We evaluated each of these women, and the results revealed that each had diminished ovarian reserve.
What does diminished ovarian reserve really mean for a young woman who has yet to try to conceive and does NOT have a diagnosis of infertility? How should these women be counseled?
Now that egg freezing is NOT considered experimental, more and more women are inquiring about it. The first step includes an assessment of ovarian reserve. We start with a history of menstrual cyclicity, and perform an ultrasound to measure antral follicle count (the number of small eggs/follicles seen in the ovary at the start of menses). Lab tests look at hormones including Anti-Müllerian (AMH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), and also measure estradiol. We then begin a discussion of the process, which includes eight to twelve days of injectable gonadotropin hormone to help the antral follicles grow to maturity and ovulation, followed by transvaginal aspiration of the follicles to retrieve the eggs.
Diminished ovarian reserve is a term coined to explain the situation when a woman has few (less than five) antral follicles in her ovaries each month. The diagnosis may also be made when AMH levels are below one (suggesting a decreased chance of conception) and FSH is elevated.
I liken ovulation to a horse race — each month a certain number of eggs line up in the corral at the beginning of the menstrual cycle. For some women, there are twenty eggs at the starting gate, and for others there are less than five. At menstruation (or a few days before), the starting gun goes off and the race begins as the pituitary gland signals the ovary to release hormones; FSH to help the eggs grown and LH to help the cells surrounding the eggs make estrogen. Usually by Day Five of the cycle, the largest egg has enough machinery in its cell to continue growing without the extra input from the pituitary gland’s hormones. This message from this “lead” follicle to the pituitary gland is, “I have this race won, I don’t need any more juice.” The pituitary subsequently stops feeding the ovary with FSH and LH hormones. Over the next week, that lead egg grows, survives, and wins the race to ovulation, leaving behind the other eggs that were too small to make it to the finish line.
Women with diminished ovarian reserve have fewer eggs at the starting gate. Typically until perimenopause, ovulation continues unabated – so unless investigation is undertaken, a woman may have no indication that there are changes happening in her ovary. As time progresses, a woman with diminished ovarian reserve may notice changes to her menstrual cycles: first subtle changes, which are the shortening but increased regularity of her periods, and then on to later changes which are much less subtle, such as months of delayed or missed menses. She may also notice hot flashes and night sweats.
Response to fertility medications is markedly different in young women with diminished ovarian reserve, and so it is critical that changes to menstrual cycles, no matter how seemingly minor, should be noted.
In women with a healthy ovarian reserve, the extra FSH and LH in the form of injectable gonadotropins provided at the outset of fertility treatments gives smaller eggs the extra juice needed to reach maturity and achieve ovulation. For women with diminished ovarian reserve, since the additional eggs were not in the starting corral at the onset of menses, the extra drugs do NOT recruit any additional eggs.
Diminished ovarian reserve and infertility/subfertility are not one and the same. Egg and embryo quality is most closely associated with age, not embryo number. Women who are under 35 usually have a larger percentage of their embryos that have a normal chromosome number and thus have a very high chance of pregnancy. A young women in her 20s or early 30s with diminished ovarian reserve may not have significant fertility issues if she tries to conceive naturally.
If a young woman with diminished ovarian reserve chooses to freeze her eggs, she may not develop a significant number of mature eggs to put away in the freezer. This means that delayed childbearing that relies on egg freezing to preserve fertility may not be as successful or financially feasible for all women.
Population-based studies to see what percent of young women in their 20s and early 30s have diminished ovarian reserve have not been done. Most studies have focused on women presenting to the infertility clinic. It is not known if young 20-somethings with few antral follicles have similar or reduced pregnancy rates when trying to conceive naturally. Biologically, since egg quality and subsequent embryo quality is most closely associated with age, the presumption is that these women should have similar pregnancy rates as their age-related cohorts. The difference is as they age and there are fewer eggs in the ovary, they will reach the critical juncture to the perimenopausal transition sooner, which means they might start having anovulatory cycles (bleeding without ovulation) and infertility issues sooner.
For women like Mary Smith and her friends with diminished ovarian reserve and a desire to delay childbearing by freezing eggs, fertility options are somewhat limited and may be relatively expensive. Realistically Mary can expect two to five eggs in the freezer per cycle, and it may take several cycles (and much expense) to store the desired 20 eggs or more. For those with means, this may still be worthwhile as their alternative prospects are not favorable. The diminished ovarian reserve diagnosis is NOT synonymous with infertility; it only implies a poor response to fertility medications. A woman already in perimenopausal transition should be counseled that ovulation induction may already be a required treatment, and her symptoms combined with diminished ovarian reserve may yield much lower changes of conception. For these women, donor egg and adoption always remain a viable option for building a family.
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