Characterization of Intrafollicular Steroid Hormones, Inhibin, and Follistatin in Women with and without Polycystic Ovarian Syndrome Following Gonadotropin Hyperstimulation1

Abstract

The etiology of polycystic ovary syndrome (PCOS) is unexplained. Since no major deficiencies are reported in serum FSH or inhibin, we hypothesized that abnormal levels of a paracrine modulator of FSH action within the ovary may be associated with the arrest of follicular growth seen in the PCOS ovary. Follicular fluid aspirates were collected from women with (n = 7) or without (n = 17) PCOS during oocyte retrieval for in vitro fertilization. Aspirates were assayed for total inhibin, inhibin A (InhA), inhibin B (InhB), and follistatin (FS), as well as for estradiol, progesterone (P4), androstenedione, and total protein. Hormone levels were compared between women with and without PCOS using all aspirates (some of which were collected from multiple follicles at once) and also between aspirates containing fluid from a single follicle only (PCOS, n = 30; non-PCOS, n = 107). P4 levels were significantly (p < 0.01) reduced in PCOS versus non-PCOS women as evidenced by analysis of all follicles as well as in single-follicle aspirates only. In addition, InhA, P4, and FS increased with follicle volume, and InhB decreased significantly in non-PCOS, but not in PCOS, follicles. Therefore, although follicular development can be induced in PCOS patients with gonadotropins, hormonal responses within the ovary appear inappropriate in terms of concentrations or patterns of secretion. These data support the concept that PCOS is associated with a deficit in the paracrine control of folliculogenesis.

Increased intrafollicular androgen levels affect human granulosa cell secretion of anti-müllerian hormone and inhibin-B

“…In the present study, levels of inhibin-B in group II and III reached only approximately 60% of that observed in the control group, suggesting that androgens, which were artificially kept high by the use of aromatase inhibitor, are the cause of the attenuated granulosa cell production of inhibin-B. The inhibin-B content of preovulatory FF from women with polycystic ovary syndrome (PCOS) and healthy women who underwent ovarian stimulation with exogenous gonadotropin has been reported to be similar (11). This is in contrast to observations on FF from women with PCOS who did not receive ovarian stimulation.…”

Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence

“…Elevated inhibin B levels are closely related to an elevated risk of developing PCOS (Magoffin and Jakimiuk, 1997; Anderson et al ., 1998; Lockwood et al ., 1998). In addition, studies have shown that inhibin A and B levels are significantly reduced in the FF of women with PCOS, when compared with FF levels of size-matched follicles from NOW (Lambert-Meserlian et al ., 1997; Welt et al ., 2005). Therefore, activin, FS and inhibins bring about intra-ovarian actions through paracrine/autocrine systems, playing an important role in maintaining folliculogenesis; their imbalance may be directly correlated to the pathogenesis of PCOS, consequently impairing oocyte maturity, embryo quality and pregnancy outcome.…”

Ontogeny of the ovary in polycystic ovary syndrome

“…Inhibin A and B concentrations also are decreased in some, but not all, small PCOS follicles, despite normal amounts of activin and follistatin unbound to activin (150, 157). Although exogenous FSH stimulates the growth of PCOS follicles, intrafollicular inhibin A levels in PCOS patients receiving gonadotropin-releasing hormone (GnRH) analog/gonadotropin therapy for IVF remain reduced (158). On the other hand, serum inhibin B levels arising from the multiple small follicles are elevated in PCOS patients (159) and are suppressed by exogenous hCG and endogenous insulin (160), linking defective inhibin biosynthesis with follicular arrest, likely by reducing FSH levels (151).…”