REDUCED PREOVULATORY GRANULOSA-CELL STEROIDOGENESIS IN WOMEN WITH ENDOMETRIOSIS

To examine the cause of altered follicular fluid steroid levels and lo wer in vitro fertilization rate observed in infertile women with minor endometriosis, we have compared the production of estradiol (aromatas e activity) and progesterone of freshly isolated granulosa cells (3 h. incubation) from such women and a control group with tubal or unexpla ined infertility, having IVF during unstimulated or gonadotropin-stimu lated cycles. As previously observed, mature oocytes from women with e ndometriosis had a reduced fertilization and cleavage rate ill via vit ro in unstimulated cycles (19/37[51%] vs. 69/94[73%], p<0.05) and stim ulated cycles (20/37[57%] vs. 32/39[82%], p<0.01). Median [95%CI] basa l aromatase activity was lower in endometriosis compared with control in unstimulated cycles (2.84[2.03-3.49] pmol E(2)/10(3) cell/3h, n=31 vs. 3.63[2.72-3.49], n=55, p=0.057) and stimulated cycles (0.31[0.16-0 .50], n=14 vs. 0.99[0.70-1.52], n=20, p<0.001). Progesterone productio n followed a similar pattern in unstimulated (0.56[0.50-0.89] pmol/10( 3) cells/3h, n=29 vs. 1.23[0.69-1.54], n=52,) and stimulated (0.37[0.2 0-0.73], n=16 vs. 0.95[0.72-1.17], n=21) cycles (p<0.05). Addition of FSH, LH or hCG (30ng/mL) to the incubation medium enhanced progesteron e production 2 to 3-fold, but had no effect on aromatase activity. Our results indicate a defect in granulosa cell steroidogenesis associate d with endometriosis, which could affect oocyte function and explain t he reduction in fertilizing capacity and subsequent competence of the corpus luteum, and the associated subfertility.