Reproductive Technology

Reduced Intrafollicular Androstenedione and Estradiol Levels in Early-Treated Prenatally Androgenized Female Rhesus Monkeys Receiving Follicle-Stimulating Hormone Therapy for In Vitro Fertilization

Abstract

To determine whether prenatal testosterone propionate exposure beginning gestational days 40-44 (early-treated) or 100-115 (late-treated) affects follicular steroidogenesis during recombinant human FSH treatment, 5 early-treated and 4 late-treated prenatally androgenized and 5 normal female rhesus monkeys were studied. All monkeys underwent recombinant human FSH injections, without human chorionic gonadotropin administration, followed by oocyte retrieval. Serum FSH, LH, estradiol, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone and dihydrotestosterone were measured basally, during recombinant human FSH therapy and at oocyte retrieval. Follicle fluid sex steroids, oocyte fertilization and embryo development were analyzed. Circulating FSH, estradiol, 17-hydroxyprogesterone, androstenedione and dihydrotestosterone levels increased similarly in all females. Serum LH levels decreased from basal levels in normal and late-treated prenatally androgenized females, but were unchanged in early-treated prenatally androgenized females. Serum progesterone levels at oocyte retrieval were comparable to those before FSH treatment in all females. All prenatally androgenized females showed reduced follicle fluid levels of androstenedione and estradiol, but not progesterone or dihydrotestosterone. Intrafollicular T concentrations also were significantly lower in late-treated compared to early-treated prenatally androgenized females or normal females. In early-treated prenatally androgenized females, but not the other female groups, intrafollicular androstendione and estradiol levels were reduced in follicles containing oocytes that failed fertilization or produced zygotes with cleavage arrest before or at the 5- to 8-cell embryo stage. Therefore in monkeys receiving rhFSH therapy alone, without human chorionic gonadotropin administration, early prenatal androgenization reduced follicular fluid concentrations of estradiol and androstenedione in association with abnormal oocyte development, without having an effect on progesterone, testosterone or dihydrotestosterone concentrations.