The effect of letrozole overlapped with gonadotropin on IVF outcomes in women with DOR or aged over 40 years old with repeated cycles

Abstract

Background: Evaluating the efficacy of letrozole overlapped with gonadotropin-modified letrozole protocol (mLP) for diminished ovarian reserve (DOR) or advanced-age women with repeated cycles.

Methods: This is a retrospectively registered, paired-match study including 243 women with DOR and 249 women aged over 40 years old who received in vitro fertilization (IVF) treatment. 123 women received stimulation with mLP (mLP group). GnRH agonist (GnRH-a) long, GnRH antagonist (GnRH-anta), and mild stimulation protocol were used as controls with 123 women in each group. We further analyzed 50 of 123 patients in the mLP group who have experienced more than one failed cycles with other ovarian stimulation protocols (non-mLP group). Clinical pregnancy rate (CPR), cumulative clinical pregnancy rate (CCPR), and live birth rate (LBR) were main outcomes.

Results: The CPR in the mLP group (38.46%) was significantly higher than mild stimulation (17.11%), but not significantly different from GnRH-a long (26.13%) and GnRH-anta (29.17%) group. The CCPR showed an increasing trend in the mLP group (33.33%) although without significance when compared with controls. The CCRP of GnRH-a long, GnRH-anta, mild stimulation group were 21.68%, 29.03%, and 13.04%, respectively. In women with repeated cycles, mLP achieved the higher available embryo rate (P < 0.05), the top-quality embryo rate, the CPR (P < 0.001), and the LBR (P < 0.001). Further study showed a positive correlation between testosterone and the number of oocytes retrieved in the mLP group (r = 0.395, P < 0.01).

Conclusion: The mLP may be effective for aged or DOR women who have experienced previous cycle failure by improving the quality of embryos, the CPR, and the LBR. An increasing serum testosterone level may reflect follicular growth during ovarian stimulation.

Keywords: Aged; Diminished ovarian reserve; Letrozole; Repeated cycles.

Fig. 1

Estrogen and testosterone levels during ovarian stimulation in different groups. (A-B) Estrogen level on the day when follicles of different diameters first showed up and estrogen levels when follicles over 18 mm in diameter were present on the trigger day. Data were shown as mean ± standard deviation. * in Fig. 1A represents P < 0.05 among the modified letrozole group and others. (C-D) Testosterone levels on the day when follicles of different diameters first showed up and testosterone levels when follicles over 18 mm in diameter were present on the trigger day. Data were shown as mean ± standard deviation. * P < 0.05 between or among groups. (E-F) Correlation analysis between number of oocytes retrieved or number of MII oocytes retrieved and testosterone levels on the trigger day in the modified letrozole group