This study was designed to compare both the effectiveness and safety of two low-dose gonadotrophin regimens (step-up versus sequential step-up and step-down) for ovulation induction in polycystic ovarian syndrome (PCOS) patients. In all, 56 infertile clomiphene citrate-resistant PCOS patients were included in this prospective randomized study. A total of 38 cycles were conducted with a classic step-up protocol, whereas for 35 cycles the follicle-stimulating hormone (FSH) threshold dose was reduced by half when the leading follicle reached 14 mm in diameter (sequential protocol). Serum oestradiol, progesterone and luteinizing hormone concentrations and follicular growth rate were evaluated during the cycle. At the time of human chorionic gonadotrophin administration, cycles treated with sequential protocol exhibited significantly lower oestradiol concentrations [434 +/- 45 versus 593 +/- 67 pg/ml (mean +/- SEM)] and the number of medium-sized (14-15 mm) follicles was significantly reduced (0.3 +/- 0.1 versus 0.8 +/- 0.2) compared with cycles treated with the classic step-up protocol. Moreover, in these cycles serum luteal oestradiol concentrations were decreased significantly (350 +/- 77 versus 657 +/- 104 pg/ ml) compared with the classic step-up protocol. A sequential step-up and step-down protocol seems to be a safe and effective regimen for ovulation induction in PCOS patients. Decreasing the FSH dose following step-up follicular selection may be an alternative method to avoid multifollicular development.

In a short-term protocol, the influence of progestogen pretreatment upon the oestradiol flare-up (delta E2) induced by gonadotrophin-releasing hormone agonist (GnRHa) was assessed in relation to in-vitro fertilization (IVF) outcome in 90 cycles programmed (n = 52) or not (n = 38) by norethisterone (10 mg/day for 12-20 days). Patients pretreated by progestogen had a significantly lower delta E2 value than patients without pretreatment (delta E2 = 26 +/- 5 versus 61 +/- 8 pg/ml, P = 0.003). It could be related to a lower gonadotrophic response for luteinizing hormone (LH) (delta LH = 9 +/- 0.8 versus 14.5 +/- 2.2 IU/l, P = 0.01). The IVF outcome (final oestradiol, number of oocytes or embryos) was similar in both groups and delta E2 was well correlated with these final parameters in each group. A significant rise in serum progesterone was observed only in patients without pretreatment (delta P = 1.1 +/- 0.2 versus 0.1 +/- 0.1 ng/ml, P < 0.0001). Thus norethisterone pretreatment decreases the oestradiol flare-up and prevents the early increase of progesterone (by avoiding some rescue of the corpus luteum or some luteinization of small developing follicles) but does not influence the outcome of the IVF cycle. In clinical practice, evaluation of the hormonal flare-up for predicting IVF outcome must take into account any pretreatment prescription.

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The cytometry of 545 oocytes was evaluated during subzonal insemination (SUZI; 85 attempts), on day 0 (egg retrieval and SUZI), day 1 and day 2 (embryo transfer). On day 0, the egg and oolemma diameters (mean ± SD) were 164.0 ± 19.6 urn and 114.2 ± 16.8 u5m respectively. The zona thickness was 17.8 ± 13.4 urn and correlated with the oolemma diameter (r = 0.24, p < 0.001). The fertilisation rate was significantly lower for the smaller oocytes (less than 108 urn diameter) compared with the larger oocytes (over 108 urn) (9.8% vs 21.2% respectively; p < 0.05). There was little variation in oocyte diameter according to nuclear status. However, oocyte diameter increased significantly between day 0 and day 1 (p < 0.001) for both fertilised and unfertilised oocytes. Six different indications for SUZI were investigated in detail: three with non-specific (normal and subnormal sperm with in vitro fertilization failure, oligoasthenospermia) and three with specific sperm defects (flagellar dyskinesia, absence of outer dynein arms, antisperm antibodies). Oocytes from the non-specific defect groups had significantly smaller diameters than the others (p < 0.05). The mean fertilisation rate was related to the mean oolemma diameter for the groups with non-specific sperm defects and the group lacking dynein arms (LODA) (r = 0.91, p < 0.05). Eggs from the groups of patients with LODA and those with antisperm antibodies had thicker zona pellucida than others (p < 0.05). These findings suggest that in addition to nuclear criteria of maturity, the growth of oocytes is an important factor for fertilising ability. Insufficient development of the ooplasm may contribute to fertilisation failure, particularly when sperm with functional defects are used. In contrast, a thick zona pellucida may prevent sperm with specific anomalies such as LODA or antisperm antibodies from penetrating into the perivitelline space.