Impaired Developmental Competence of Oocytes in Adult Prenatally Androgenized Female Rhesus Monkeys Undergoing Gonadotropin Stimulation for in Vitro Fertilization

Abstract

To determine whether prenatal T propionate exposure beginning gestational d 40-44 (early-treated) or 100-115 (late-treated) affects oocyte competence, five early-treated and five late-treated prenatally androgenized and five normal monkeys underwent recombinant human FSH injections with oocyte-retrieval after hCG administration. Serum FSH, LH, estradiol (E(2)), progesterone (P(4)), androstenedione (A(4)), T, and dihydrotestosterone were measured basally, during gonadotropin stimulation and at oocyte-retrieval; fasting serum glucose and insulin also were determined basally and at oocyte-retrieval. Follicle fluid sex steroids were analyzed. Oocyte number, nuclear maturity, and fertilization were comparable among female groups, but the percentage of zygotes developing into blastocysts was reduced in early-treated prenatally androgenized females. The intrafollicular P(4)/E(2) ratio was significantly elevated in early-treated prenatally androgenized females, whereas intrafollicular P(4)/A(4) and T/A(4) ratios were significantly increased in all prenatally androgenized females. Early-treated prenatally androgenized females demonstrated persistent LH hypersecretion. They also were unable to suppress circulating insulin levels during gonadotropin stimulation. Circulating sex steroid levels and serum P(4)/E(2), P(4)/A(4), and E(2)/androgen ratios were similar in all females. Early prenatal androgenization in monkeys receiving gonadotropins impairs oocyte developmental competence and seems to induce premature follicle differentiation in the presence of LH hypersecretion and relative insulin excess.

Correlation of serum Anti-Müllerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patients

“…It has been demonstrated that typically increased LH in PCOS patients suppressed FSH function, promoting premature granulose cells luteinization and follicular atresia in small antral follicles [25][26][27], which all impaired the quality of both oocyte and embryo [28,29]. Indeed, LH levels on day 3 before starting GnRH agonist medication were significantly increased in the high AMH group,and regression analysis indicated LH level was the only independent predictor of IR in our study, so the mostly elevated LH may be contribute to the decreased embryo developmental competence and consequently declined IR in the high AMH group.…”

Insulin and Messenger Ribonucleic Acid Expression of Insulin Receptor Isoforms in Ovarian Follicles from Nonhirsute Ovulatory Women and Polycystic Ovary Syndrome Patients

“…Adiposity-related effects on intrafollicular insulin concentration also might harm the oocyte because exposure of murine cumulus-oocyte complexes to insulin causes LH receptor up-regulation and reduced blastocyst development (38). Moreover, premature follicle luteinization and impaired oocyte competence accompany relative insulin excess in prenatally androgenized female rhesus monkeys undergoing gonadotropin therapy for IVF (39). In this regard, increased intrafollicular insulin concentrations were present in our women with impaired glucose tolerance, most of whom were obese, and might be responsible for the reduced fecundity previously reported in such individuals (40).…”

Pioglitazone improves insulin action and normalizes menstrual cycles in a majority of prenatally androgenized female rhesus monkeys

“…All hormones were assayed in the WPRC Hormone Assay Services Laboratory (40, 49,50). Circulating levels of total free fatty acids (51), and glycosylated hemoglobin (52) were assayed, as previously described.…”