Anovulation is a major cause of female reproductive dysfunction and can be identified in approximately 18-25% of couples presenting with infertility (Hull et al., 1985). Oligomenorrhea (arbitrarily defined as menstrual periods occurring at intervals betvveen 35 days to 6 months) or amenorrhea (menstruation intervals longer than 6 months) are common features. Whether and ho\v frequent there occasional bleedings are associated with preceding ovulatory cycles is not known. The occurence of ovulation can be established applying basal body temperature charts, the assessment of serum progesterone levels, or through the observation by ultrasound of co !laps of the pre-ovulatory follicle. While ovulatory cycles may be observed occasionally in oligomenorrheic ·women, ovulatory cycles are unlikely events in amenorrhea. 'vVell-designed longitudinal follow-up studies concerning the incidence of spontaneous conception in oligomenorrheic patients are lacking. Follov,.·-up studies performed thus far report only on pregnancies in those women who did not conceive spontaneously and subsequently seek the physician's help. Therefore, this population may be a negative selection of patients who exhibit cycle abnormalities. Obviously, induction of ovulation is required in these anovulatory patients to achieve follicular maturation, subsequent ovulation and ultimately conception. The association between oligoamenorrhea, obesity, bilateral polycystic ovaries, and hirsutism was illustrated in 1935 by Stein and Leventhal (Stein et al., 1935). A primary ovarian defect was inferred since bilateral vvedge resection of the ovary restored the cycle abnormality unexpectedly and 2 of 7 patients conceived (Stein et al., 1967). The wide variability of clinical and histologic findings associated with anovulatory state in PCOS resulted in the inability of the investigator to distinguish clinically significant and reliable characteristics of this syndrome (Goldzieher et al., 1963). Excessive androgen production was initially attributed to abnormal adrenal function. Hyperandrogenemia clue to diminished granulosa cell aromatase activity (responsible fOr the conversion of androgens to estrogens) of the polycystic ovaries (PCO) has subsequently been demonstrated (Axelrod et al., 1962). Abnormalities in the hypothalamic-pituitary-ovarian axis resulting in inappropriate FSH secretion along with luteinizing hormone (LH) hypersecretion has also been highlighted (Yen et al., 1970). Further insight in the abnormal physiology of this disorder occurred vvhen hyperandrogenism \vas demonstrated to be LH dependent (Givens et al., 1974). A landmark discovery was the association of ovarian hyperandrogenism and various causes of insulin resistance (Kahn et al., 1976) and subsequently, an association between polycystic ovaries, hyperandrogenism and hyperinsulinemia was established (Burghen et al., 1980).

amenorrhea, anovulation, female reproductive dysfunction, infertility
B.C.J.M. Fauser (Bart) , J.D.F. Habbema (Dik)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Imani, B. (2002, November 6). Prediction of ovulation induction outcome in normogonadotropic anovulatory infertility. Erasmus University Rotterdam. Retrieved from