DEVELOPMENT OF LUTEINIZED GRAAFIAN-FOLLICLES IN PATIENTS WITH KARYOTYPICALLY NORMAL SPONTANEOUS PREMATURE OVARIAN FAILURE

Despite having amenorrhea and markedly elevated serum gonadotropin lev els, some women with karyotypically normal spontaneous premature ovari an failure, nevertheless, have ovarian follicles that function intermi ttently. Graafian follicles capable of responding to these high FSH le vels are faced with high serum LH levels as well, which might induce i nappropriate luteinization and prevent normal follicle function. We ex amined this possibility using weekly blood sampling and sonography in 65 patients. Nearly 50% of our patients demonstrated ovarian follicle function [serum estradiol, >183 pmol/L (50 pg/mL)] during a median of 4 months of observation (range, 2-6 months). However, during this obse rvation, only 16% achieved an ovulatory serum progesterone level [>9.5 nmol/L (3.0 ng/mL)]. We imaged an antral follicle by sonography in ov er 40% of patients (27 of 65), and serum estradiol was significantly g reater when an antral follicle was present. The follicles in these pat ients were not functioning normally, however. In contrast to normal wo men, patients with ovarian failure had poor correlation between follic le diameter and serum estradiol. We biopsied these antral follicles in 6 patients and found luteinized Graafian follicles in all cases. Ther efore, luteinized Graafian follicles account for at least 60% of the a ntral structures imaged (95% confidence limit). Thus, inappropriate lu teinization of Graafian follicles appears to be a major pathophysiolog ical mechanism in patients with karyotypically normal spontaneous prem ature ovarian failure.