Maximizing Correction of Infertility with Moderate to Marked Diminished Egg Reserve in Natural Cycles by Up-Regulating Follicle Stimulating Hormone Receptors
Check JH,Choe JK
Published August 29, 2022Gynecology & Reproductive Health, 6(4), 1-7
Check, J. H., & Choe, J. K. (2022). Maximizing Correction of Infertility with Moderate to Marked Diminished Egg Reserve in Natural Cycles by Up-Regulating Follicle Stimulating Hormone Receptors. Gynecology & Reproductive Health, 6(4), 1-7. https://doi.org/10.33425/2639-9342.1197
Check JH, Choe JK. Maximizing Correction of Infertility with Moderate to Marked Diminished Egg Reserve in Natural Cycles by Up-Regulating Follicle Stimulating Hormone Receptors. Gynecol Reprod Health. 2022;6(4):1-7. doi:10.33425/2639-9342.1197
Check, Jerome H., and Jung K. Choe. "Maximizing Correction of Infertility with Moderate to Marked Diminished Egg Reserve in Natural Cycles by Up-Regulating Follicle Stimulating Hormone Receptors." Gynecology & Reproductive Health, vol. 6, no. 4, 2022, pp. 1-7.
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Review reports live births in natural cycles despite low egg reserve
A 2022 review by two physicians reports live births in natural cycles among women with low egg reserve. Their first pilot treated five women with ovarian failure. Two of the five women delivered a healthy baby. The authors suggest high-dose FSH drugs may harm implantation.
Key Findings
Five women with ovarian failure were treated in the authors' first pilot. Two conceived and delivered a healthy baby, two did not ovulate, and one ovulated in both treatment cycles without conceiving.
The authors' first 100 cases (1990) covered ages 19 to 47, median 34, all with a year or more without periods. About 50% of pregnancies in the series ended in miscarriage.
In a cited IVF study of the authors' technique, live delivery with low reserve was 80% as likely as with normal reserve under 35, 70% at 36-39, 50% at 40-42.
In women with 1 year of infertility and a luteal phase defect as the only finding, 24 of 31 conceived with luteal phase support alone, against 3 of 27 given follicle-maturing drugs.
The authors cite case reports of live deliveries in women who appeared to be in overt menopause, at ages 45 and 46.5.
Interpretation
This review reports live births in natural cycles among women with low egg reserve, including some cases of overt menopause. The authors think high doses of FSH drugs turn off FSH receptors needed for implantation. They think natural cycles let those receptors recover, restoring the chance of pregnancy. The findings support larger studies of this approach.
RRM Context
Restorative reproductive medicine asks why ovulation or implantation fails in a given couple. The review asks that question about low egg reserve. The authors think long-term high FSH turns off receptors on follicle cells, and that follicles may respond once receptors return. They limit the idea to women whose only infertility finding is low reserve.
Our editorial summary of this paper, not the article's abstract.
Abstract
Many infertility specialists advise women with diminished oocyte reserve (DOR) that their remaining oocytes probably are of poor quality similar to women of advanced reproductive age. There have been studies, especially employing in vitro fertilization-embryo transfer (IVF-ET), showing very poor live delivered pregnancy rates despite the transfer of morphologically normal embryos in women even with mild DOR. However, other data suggests that the low pregnancy rates are related to the use of high dosages of follicle stimulating hormone (FSH) drugs which down-regulate some key FSH dependent enzymes, cytokines, or proteins required for proper embryo implantation. Some studies have shown that techniques that favor FSH receptor up-regulation, rather than down-regulation, can provide the chance of live delivery 80% as well in women ≤ 35 with DOR, 70% for women 36-39, and 50% for women 40-42. Though some infertility specialists will encourage women whose only infertility issue is DOR, who reject the initial suggestion to consider donor oocytes, to proceed immediately with IVF-ET to maximize success, pregnancies are quite possible with natural conception. Thus, it seems imprudent to make couples undergo the financial burden of IVF-ET in the absence of a significant tubal or male factor problem. Not only have live deliveries occurred in women with DOR, using the principle described to achieve a mature dominant follicle followed by proper luteal phase support, with serum FSH levels over 100 mIU/mL, but also serum Anti-Mullerian Hormone (AMH) levels that were undetectable. This even applies to women in overt menopause where FSH up-regulation was achieved by negative feedback to the pituitary using ethinyl estradiol inhibiting FSH release, or down-regulation of hypothalamic-pituitary stimulation of FSH production by using gonadotropin releasing hormone agonists or antagonists.
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