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Inclusion of standard and low-dose gonadotropin releasing hormone-analog (short protocol) in controlled ovarian hyperstimulation regimens in normogonadotropic patients aged 40-48 years who are undergoing in vitro fertilization

We aimed to compare the efficiency of three controlled ovarian hyperstimulation protocols in achieving superovulation in normogonadotropic patients aged 40 years or more, who were undergoing in vitro fertilization (IVF) treatment. This was a prospective randomized clinical study, carried out in the Infertility and IVF Unit of an academic tertiary hospital. A total of 219 normogonadotropic patients (serum follicular stimulating hormone level < 15 mIU/ml) aged 40-48 years, with regular menstrual cycles, were randomly allocated to one of three short follicular protocols: menotropins only (group A), menotropins plus a mini-dose of gonadotropin releasing hormone (GnRH)-analog (600 μg/day) (group B), or menotropins plus a standard dose (900 μg/day) of a GnRH-analog (group C). Those cycles that reached the stage of oocyte retrieval (67, 70 and 71cycles, respectively) were analyzed. The mean daily dose of menotropins needed for ovarian stimulation was higher when GnRH-analog was used (groups B and C) (p < 0.02; ANOVA), although there was no significant difference in the time of human chorionic gonadotropin injection (average: cycle day 11). Peak estradiol levels (p < 0.02), number of oocytes retrieved (3.9, 5.4 and 5.5 oocytes/cycle, respectively, p < 0.02) and number of embryos transferred (1.6, 1.8 and 2.1 embryos/cycle, respectively, p < 0.05) were higher when GnRH-analog was included in the controlled ovarian hyperstimulation protocol. The IVF treatment resulted in 19 pregnancies (9.1% implantation rate), with a similar distribution among all three groups (11.9%, 8.6% and 7.0%). However, a higher miscarriage rate was noted in the menotropins-only group (67.5% vs. 33.3% and 40.0% of pregnancies). No differences were observed in any of the aforementioned variables between the mini-dose and standard dose GnRH-analog groups (groups B and C). In conclusion, controlled ovarian hyperstimulation before IVF treatment in normogonadotropic patients aged 40 years or more is more effective when a GnRH-analog (short protocol) is included in the treatment regimen. In this selected group of patients, reducing the daily dose of GnRH-analog does not improve the treatment results.