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Multiple pregnancies still constitute a major and relatively frequent complication of induction of ovulation by human menopausal gonadotrophins (HMG) despite the increasing sophistication of monitoring techniques. In order to define specific variables which may be associated with multiple pregnancies, we have compared 51 multiple pregnancy cycles to 51 consecutive control singleton pregnancy cycles, following HMG induction of ovulation. The aetiology and classification of anovulation, duration of infertility, total amount of HMG utilized per cycle and the duration of stimulation were not associated with an increase in the rate of multiple pregnancy. Basal serum oestradiol levels and its periovulatory pattern were remarkably similar in the singleton and multiple pregnancy groups. The mean age of the multiple pregnancy group (29.4 +/- 4.4 years) was significantly lower than the mean age of the singleton pregnancy group (31.6 +/- 5.3 years) (P less than 0.05). In the multiple pregnancy group, there were significantly more cycles with intermediate sized (15-17 mm). (P less than 0.002), small sized (12-14 mm). (P less than 0.02) and immature follicles (less than 12 mm) (P less than 0.03), at the time of human chorionic gonadotrophin (HCG) administration, as compared with the singleton pregnancy group. Furthermore, a direct linear correlation was observed between the number of intermediate sized follicles and number of implanted embryos. The presence of intermediate sized follicles at the time of HCG administration after HMG induction of follicular maturation is predictive of, and independently associated with, a higher incidence of multiple pregnancy.

The results of subzonal sperm insertion (SUZI) have been retrospectively analysed in a subset of patients with normal sperm counts who were found to require SUZI because of poor or absent fertilization of zona-intact oocytes. This patient group is of particular interest because male factor-related infertility cannot be due to insufficient numbers of spermatozoa reaching the oocytes. Thus, failed fertilization can be attributed to deficiencies in one or more steps in the fertilization process, and SUZI provides a method of distinguishing defects of zona pellucida penetration from gamete fusion. A total of 26 such patients were treated identically to and concurrently with a much larger group of SUZI candidates who typically suffered from oligozoospermia, and fertilization results were compared. Fertilization rates after SUZI were higher in patients with normal counts than in oligozoospermic patients (51 and 26% respectively), indicating that the proportion of spermatozoa capable of fusing with the oocyte is the same or higher in the group with normal counts. In addition, nearly all SUZI procedures led to fertilization (23/26), with two out of three failed fertilizations occurring in cases where two or less oocytes were manipulated, results which further indicate that failed fertilization in these patients is not due to a defect at the level of gamete fusion. These findings suggest that infertility in these patients is based upon the inability of the spermatozoa to reach the oolemma and thus, that their fertility defect resides at the step of zona penetration.

Late follicular phase levels of 17 beta-oestradiol (E2) and progesterone (P) in serum were studied during the induction of follicular maturation with human menopausal gonadotrophin (HMG) (n = 23) and HMG-clomiphene citrate (CC) (n = 18). For each patient one hormonal profile was studied between 6 days to 2 h before administration of human chorionic gonadotrophin (HCG). Ultrasonographic follicular measurement at the time of evaluation demonstrated preovoulatory ovarian follicles of various number and size in all patients studied. Sixteen endometrial biopsies were performed at the time of evaluation (eight for each subgroup), before HCG administration. Mean late follicular phase levels of E2 did not differ significantly between the two groups (436 +/- 348 and 475 +/- 267 pg/ml for the HMG and HMG-CC groups respectively). The mean progesterone levels in the HMG-CC group (1.233 +/- 0.67 ng/ml) was significantly higher than that for the HMG group of (0.86 +/- 0.55 ng/ml, P less than or equal to 0.04). The mean time interval between ovulation and HCG administration for the two groups was 2.5 and 2.4 days for the HMG and HMG-CC groups, respectively. In all eight biopsies taken from the HMG group, various stages of endometrial proliferation were demonstrated. Premature glandular secretory transformation and oedematous stroma were observed in three out of eight biopsy specimens obtained from the HMG-CC group. Taken together, these results demonstrate that subtle or full premature luteinization in the late follicular phase occurs more frequently with the use of HMG-CC for induction of follicular maturation.

Serum levels of progesterone and estradiol at early, middle, and late luteal phases were compared in nonfertile cycles in which only ovulation occurred to those in cycles in which ovulation was verified by conception. Two groups of patients were studied: 33 normal ovulatory women (12 of whom conceived) and 28 women who underwent induction of ovulation (8 of whom conceived). In each group, mean midluteal levels of progesterone and estradiol were essentially similar in nonfertile and fertile cycles. In fertile cycles the late luteal levels of both steroids were higher than their respective midluteal values, whereas the late luteal values dropped in the nonfertile cycles. The late luteal rise in estradiol was found to be a more sensitive indicator of pregnancy than that of progesterone. The progesterone/estradiol ratio was stable during the luteal phase of fertile and nonfertile cycles. The ratio in spontanecus cycles was 34.4 ± 4.7 and only 17.9 ± 4.3 in induced cycles. This marked decrease suggests an impairment of steroid metabolism in women who require induction of ovulation.

A retrospective analysis was performed on 64 cycles stimulated with human menopausal gonadotrophin and/or pure follicle-stimulating hormone (FSH) and oestrogen (E2) levels. The increase in serum E2 on the day of HCG administration did not correlate (r = 0.05) with the number of preovulatory oocytes (preovs) or with an increase or decrease in serum FSH (r = 0.31). However, the change in serum FSH showed a significant correlation with the number of preovs (r = -0.95, P = 0.013). The probability of obtaining two or more preovs was relatively greater (1.47x) than that of other IVF patients, when there was a drop in FSH of 5% on the day of human chorionic gonadotrophin administration.