The effect of clomid induced superovulation on human follicular and luteal function for extracorporeal fertilization and embryo transfer

Abstract

The administration of clomiphene citrate (Clomid) 150 mg/day from days 5-9 of the menstrual cycle to spontaneously ovulatory women in order to induce adequate multiple follicular development followed by timed laparoscopic aspiration of mature oocytes does not appear to impair luteal phase length or the steroid pattern of oestradiol-17 beta (E2) or progesterone (P) production as reflected by their peripheral blood concentrations. In Clomid stimulated cycles where preovular oocyte pickup (OPU) and embryo transfer (ET) occurred but no recognizable pregnancy resulted, the cycle length was 30.0 (s.e.m. = 0.3) days, the follicular phase length was 15.6 (s.e.m. = 0.3) days and the luteal phase length was 14.4 (s.e.m. = 0.3) days, which did not differ from a group of women having spontaneous ovular cycles. Following Clomid stimulation the dominant follicle was similar in size to the pre-ovulatory follicle in spontaneous uniovular cycles, but the second, third, fourth and fifth order follicles were significantly larger (P less than 0.0001). The ultimate test of luteal competence was the successful implantation of 11 concepti in 7 women (4 sets of twins) from 49 laparoscopies (14%) or 33 embryo transfers (21%). Comparisons between conceptual and non-conceptual embryo transfers following identical Clomid regimes showed no difference between plasma E2 concentrations at the time of hCG administration or the start of an endogenous LH rise; follicle volume, follicular fluid E2, P and testosterone concentrations were also not different. However, there was a trend for follicular P to be higher in the non-conceptual group indicating that advanced luteinization may hinder successful implantation. The follicular fluid androstenedione (A4) concentration was significantly lower in the conceptual group and the total androgen concentration (A4 + T) was also lower which was indicative of active aromatase activity in these follicles. It was concluded from this study that there was no indication to give exogenous hormonal support to the luteal phase, provided there was both optimal follicular growth and steroidogenic function following Clomid stimulation and that exogenous hCG was administered very close to the expected rise of LH. This observation was supported by the finding that timing of OPU based on a knowledge of the start of the LH surge was associated with a higher pregnancy rate than when hCG was administered and indicates that the endogenous mid-cycle events may permit superior maturation of the oocyte and/or permit better synchronization of endometrial maturation for implantation.