Abstract

Abstract Study question Evaluating the efficacy of modified letrozole protocol (mLP) for diminished ovarian reserve (DOR) or advanced age women. Summary answer The modified letrozole protocol provides another option for women with DOR or advanced age, especially those who experienced ovarian stimulation previously. What is known already For years, numerous methods have been conducted to obtain better outcomes in women with advanced age or DOR. Increasing doses of gonadotropin (Gn), exogenous luteinizing hormone (LH) or growth factor (GH) supplementation, and various kinds of controlled ovarian stimulation (COS) protocols were reported. However, there is still no consensus due to the contradictory reports of comparable reproductive outcomes. During ovarian stimulation, estrogen and androgen are important in the recruitment of primordial follicles and promotion of follicular growth at the preantral and antral stages across different species. Study design, size, duration This is a paired-match study including 243 women with DOR and 249 women aged over 40 years old who received in vitro fertilization (IVF) treatment. Participants/materials, setting, methods 123 women received stimulation with mLP. GnRH agonist (GnRH-a) long, GnRH antagonist (GnRH-anta), and mild stimulation protocol were used as controls with 123 women in each group. Clinical pregnancy rate (CPR) and cumulative clinical pregnancy rate (CCPR) were main outcomes. Main results and the role of chance 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. 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 13.01%, respectively. In women with repeated cycles, mLP achieved higher available embryo rate and top-quality embryo rate. Further study showed positive correlation between testosterone and the number of oocytes retrieved in mLP group (r = 0.395, P< 0.01). Limitations, reasons for caution It is a retrospective study which resulted in minor bias among mLP and the other control protocols. Although we have already paired for age and AMH, the presence of biases cannot be totally excluded. Further prospective studies need to be done to validate the effect of mLP. Wider implications of the findings The modified letrozole protocol may be effective for women with DOR or advanced age, especially those who have experienced previous cycle failure. An increasing serum testosterone level may play a role and reflect follicular growth during ovarian stimulation. Trial registration number not applicable

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