Optimizing Fertility in Primary Ovarian Insufficiency: Case Report and Literature Review

Abstract

Primary ovarian insufficiency (POI) is a clinical spectrum of ovarian dysfunction. Overt POI presents with oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. Overt POI involves chronic health problems to include increased morbidity and mortality related to estradiol deficiency and the associated osteoporosis and cardiovascular disease as well as psychological and psychiatric disorders related to the loss of reproductive hormones and infertility. Presently, with standard clinical testing, a mechanism for Overt POI can only be identified in about 10% of cases. Now discovery of new mechanisms permits an etiology to be identified in a research setting in 25-30% of overt cases. The most common genetic cause of Overt POI is premutation in FMR1. The associated infertility is life altering. Oocyte donation is effective, although many women prefer to conceive with their own ova. Surprisingly, the majority who have Overt POI still have detectable ovarian follicles (70%). The major mechanism of follicle dysfunction in Overt POI has been histologically defined by a prospective NIH study: inappropriate follicle luteinization due to the tonically elevated serum LH levels. A trial of physiologic hormone replacement therapy, clinically proven to suppress the elevated LH levels in these women, may improve follicle function and increase the chance of ovulation. Here, we report the case of a woman with Overt POI diagnosed at age 35 years. To attempt pregnancy, she elected a trial of intrauterine insemination (IUI) in conjunction with follicle monitoring and physiologic hormone replacement therapy. She conceived on the eighth cycle of treatment and delivered a healthy baby. Our report calls for a concerted effort to define the best methods by which to optimize fertility for women who have POI.

Keywords: hormone replacement therapy; intrauterine insemination; luteinized follicles; pregnancy; primary ovarian insufficiency.

Figure 1

(A) Luteinized follicle containing a structure suggestive of an ovum undergoing degeneration (hematoxylin and eosin stain; magnification, ×150). (B) Higher magnification of the putative ovum (hematoxylin and eosin stain; magnification, ×250). (C) Higher magnification of the same follicle showing luteinized cells characterized by their larger size, abundant eosinophilic cytoplasm, and prominent nucleus (hematoxylin and eosin stain; magnification, ×250).

Figure 2

Serum estradiol correlated with maximum follicle diameter in normal women but not in women with Overt POI. (A) Each point represents the findings in 1 of 10 normal women with regular menses examined during the follicular phase. Two congruent points are noted by (2). (B) Each point represents the findings in a patient with overt POI who had an ovarian follicle detected by sonogram (37 sonograms in 27 patients). There are 8 congruent points (Nelson et al., 1994).

Figure 3

Serum estradiol response to stimulation with 300 IU FSH. (A) Control women, women with Overt POI, and women with overt POI segregated by the absence or presence of an antral follicle 8 mm in diameter or greater (^***P < 0.0001 vs. baseline). (B) Change in serum estradiol levels at 24 h.

Figure 4

(A) Mean (SEM) percentage change from screening in the femoral neck BMD. (B) Mean (SEM) percentage change from screening in the lumbar spine BMD (Popat et al., 2014).