The effect of human menopausal gonadotrophin and highly purified, urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down-regulated normogonadotrophic women

Abstract

It has been suggested that the luteinizing hormone (LH) activity of human menopausal gonadotrophin (HMG) preparations used for ovarian stimulation in in-vitro fertilization (IVF) may have adverse effects on reproductive outcome. In the present prospective, randomized trial of 218 infertile couples this notion was investigated. A total of 114 women were treated with Pergonal (HMG group) and 104 with Fertinorm HP (HP-FSH group). The two groups were comparable with regard to duration of infertility, cause of infertility, age and number of previous IVF attempts and all had normal basal gonadotrophin concentrations before treatment was started. A standard hormonal treatment consisting of pituitary down-regulation with gonadotrophin-releasing hormone analogue (GnRHa) for 14 days starting on cycle day 21, followed by either HMG or highly purified follicle stimulating hormone (HP-FSH), three ampoules (225 IU) per day for 7 days, was used in all cases. The daily hormone dose was thereafter individualized according to the ovarian response. A maximum of two pre-embryos were transferred after 3 days of culture. Luteal support with progesterone (300 mg per day intravaginally) was used in all cases. Serum concentrations of oestradiol, FSH and LH were measured on days 1 and 8 of stimulation and on the day of oocyte retrieval. The mean number of days of stimulation, mean number of ampoules of HMG or HP-FSH used, mean total motile sperm count on the day of oocyte retrieval and mean numbers of oocytes retrieved (13.4 versus 13.7) or pre-embryos transferred (1.8 versus 1.8) were similar for both groups. Significantly (P < 0.05) more cycles in the HP-FSH group (17 = 16%) were cancelled due to complete failure of fertilization than in the HMG group (7 = 6%). The mean fertilization rate was significantly (P < 0.05) higher in the HMG group (56%) than in the HP-FSH group (50%), and significantly more transferable pre-embryos were obtained in the HMG than in the HP-FSH group (mean: 4.0 versus 3.2; P < 0.01). Serum hormone concentrations were similar to the two groups on stimulation day 1, but differed significantly with regard to FSH, LH and oestradiol on stimulation day 8. The clinical outcome was similar in the two groups, with an ongoing pregnancy rate (> 12 weeks of gestation) per started cycle of 33% in the HMG group and 29% in the HP-FSH group. The clinical abortion rates were similar (10 and 14%), and the implantation rate was 30% in each group. In conclusion, no detrimental effect of the LH activity of HMG on the clinical outcome of IVF in GnRHa down-regulated normogonadotrophic women was found. To the contrary, some beneficial effects of HMG on fertilization rates and pre-embryo development as compared with HP-FSH were demonstrated. These effects, as well as the differences in serum hormone concentrations during ovarian stimulation, may be caused by differences in LH content and/or in the composition of FSH isoforms of the HMG and HP-FSH preparations.