Follicular Fluid Steroid Levels in Dysmature and Mature Follicles from Spontaneous and Hyperstimulated Cycles in Normal and Anovulatory Women*

Abstract

Follicular maturity and atresia have been defined previously, both hormonally and microscopically, in normal ovulatory women. Ovarian hyperstimulation with clomiphene citrate and human menopausal gonadotropins in normal women is carried out for the purpose of aspirating oocytes from several large follicles for in vitro fertilization. Alterations in follicular fluid (FF) hormone levels occur with hyperstimulation regimens, and some of these large follicles (>18 mm) appear morphologically atretic. We have used the term dysmature to describe those large follicles that have an abnormal oocyte morphological appearance and cannot be fertilized in vitro. Mature follicles have been defined by their size, their oocyte morphological appearance, and their ability to be fertilized in vitro. FF from small (2–3 mm) and large (>18 mm) mature and dysmature follicles were obtained from 10 untreated ovulatory women. Mature and dysmature follicles also were obtained from clomiphene and human menopausal gonadotropin-treated normal (n = 11) and anovulatory (n = 5) women. In untreated cycles, the FF steroid content of the small follicles characterized these follicles to be atretic. FF from dysmature follicles from spontaneous untreated cycles had higher concentrations of dihydrotestosterone, 5α-androstane-3α,17‟3-diol, and 17‟3-estradiol (E₂) and lower progesterone (Prog) and Prog to E2 ratios (P < 0.05). Compared to mature follicles from untreated patients, hyperstimulated mature follicles from ovulatory women had higher FF E2 concentrations and lower Prog to E₂ ratios (P < 0.05). In ovulatory patients, the FF concentrations of testosterone were higher and FF Prog and Prog to E₂ ratios were lower (P < 0.05) in the dysmature than in the mature follicles. Mature follicles from hyperstimulated ovulatory patients and those from hyperstimulated anovulatory patients were similar except for lower FF Prog, higher FF E₂, and lower Prog to E₂ ratios in the anovulatory group. Dysmature follicles from hyperstimulated anovulatory patients had lower FF androstenedione and dihydrotestosterone, but were generally similar to mature follicles. The percentages of dysmature follicles occurring among all large (>18 mm) follicles that were aspirated were similar in ovulatory (34%) and anovulatory (45%) patients. FF steroid concentrations did not correlate with serum levels of testosterone and E2 at the time of follicle aspiration in any patient group. In conclusion, FF androgen concentrations in folliclse hyperstimulated were unrelated to morphological maturity. FF Prog to E2 ratios correlated best with maturity as well as subsequent fertilizability. In anovulatory patients, FF Prog to E2 ratios were low, even in mature follicles. Morphological and functional atresia can be distinguished from dysmaturity by FF hormonal patterns.