Human Reproduction vol.10 no.10 pp.2541-2544, 1995 Gonadotrophin-releasing hormone agonist compared with human chorionic gonadotrophin for ovulation induction after clomiphene citrate treatment E.Shalev 1 , Y.Geslevich, M.Matilsky and M.Ben-Ami Fertility Unit, Department of Obstetrics and Gynecology, Central Emek Hospital, Afula 18101, Israel 'To whom correspondence should be addressed The objective of this study was to compare hormonal response, luteal phase adequacy and pregnancy and abortion rates in patients randomized to receive human chorionic gonadotrophin (HCG) or gonadotrophin- releasing hormone agonist (GnRHa) during ovulation cycles stimulated by clomiphene citrate. Anovulatory patients received either one s.c. dose of tryptorelin (0.1 mg; n = 104) or one i.m. dose of HCG (10 000 IU; n = 106) after clomiphene citrate stimulation had induced enlarged ovarian follicles (>17 nun in diameter). A short-lived, transitory increase in serum luteinizing hormone (98 ± 9 IU/1) and follicle-stimulating hormone (30 ± 5 IU/1) concentrations was measured at 12 h following the injection of GnRHa, and these concentrations returned to baseline levels by 36 h post-injection. Midluteal progesterone con- centrations were similar in both groups (>10 ng/ml), and the mean luteal phase duration was also not significantly different (13 days). There were no significant differences in the mean number of pregnancies (12.0 versus 12.6% per cycle) and the abortion rate (18.2 versus 12.5%) between the GnRHa- and HCG-treated groups respectively. There were no complications related to treatment in either group. The results show that a relatively low dose of GnRHa can be used in place of HCG to induce ovulation in clomiphene citrate-treated patients. Key words: clomiphene citrate/GnRH agonist/HCG/ovulation induction Introduction Patients who respond but do not ovulate when treated with clomiphene citrate can be induced to ovulate by injection of human chorionic gonadotrophin (HCG; Kistner, 1966). HCG is administered when a mature follicle is visualized by real- time ultrasound. This will induce the final stages of follicular maturation and result in ovulation within 32-40 h. Although similar in action to the spontaneous, endogenous luteinizing hormone (LH) surge, HCG does not provide an identical physiological stimulation. In spontaneous cycles, LH and follicle-stimulating hormone (FSH) are secreted in a midcycle surge, whereas the injection of HCG artificially induces a physiological response similar to the LH surge (Dufau et a/., 1971; Hoff et cil., 1983). Furthermore, the much longer half-life of HCG activity has been implicated in sustained luteotropic effects, the development of multiple corpora lutea, implantation failure and early embryonic loss, possibly caused by induced supraphysiological concentrations of oestradiol and progesterone throughout the luteal phase (Gidley-Baird et al, 1986; Forman et al, 1988). In addition, HCG does not induce the FSH surge seen in spontaneous cycles (Hoff et al, 1983). The administration of gonadotrophin-releasing hormone analogues (GnRHa) in place of HCG has been shown to effectively induce ovulation in in-vitro fertilization (IVF; Gonen et al, 1990; Segal and Casper, 1992) and non-IVF situations (Tulchinsky et al, 1991; Shalev et al., 1994). The use of GnRHa may result in a more physiological response, similar to a spontaneous midcycle surge, with a sustained release of both LH and FSH for only several hours, depending on the dose administered (Dericks-Tan et al, 1977; Monroe et al, 1985). FSH stimulation may facilitate several processes that affect ovulation, including the stimulation of plasminogen activator, glycosaminoglycan secretion and the up-regulation of LH receptors in granulosa cells (Strickland and Beers, 1976; Eppig, 1979; Yanagashita et al, 1981). Markedly divergent results have been reported regarding the duration of the gonadotrophin surge and the adequacy of the luteal phase (Itskovitz-Eldor et al, 1993). The aim of this study was to compare hormonal response, luteal phase adequacy and pregnancy and abortion rates in patients randomized to receive HCG or GnRHa during ovula- tion cycles stimulated by clomiphene citrate. Materials and methods Patients A total of 250 women undergoing ovarian stimulation by clomiphene citrate during fertility treatment for anovulation, oligo-ovulation or superovulation were enrolled in our study. All couples had previously undergone an infertility evaluation, which included hormonal profiles, mechanical evaluation (hysterosalpingography, laparoscopy or a com- bination of laparoscopy and hysteroscopy), semen analysis and postcoital tests. Couples whose infertility was attributed to ovulation disturbances or considered unexplained were included in this study, while those whose infertility was a result of male factor, mechanical factor or cervical factor were excluded. Informed consent was obtained from each patient. Because of technical problems with the supply of tryptorelin during this study, 40 patients had to be excluded from the database. The remaining 210 patients were randomized to receive either HCG or GnRHa by a random number table. In all, 184 (87.6%) of the 210 patients had ovulation disturbances, while 26 (12.4%) had unexplained infertility. Both groups were divided separately into the GnRHa (92 + 12) or HCG (92 + 14) study groups. No significant © Oxford University Press 2541