A cohort study on IVF outcomes in infertile endometriosis patients: the effects of rapamycin treatment

Research question Can rapamycin, used as an anti-senescence drug before IVF cycles, improve the IVF outcomes of women with endometriosis by reducing oxidative stress and senescence? Design This retrospective analysis involved 168 endometriosis patients undergoing two successive IVF cycles. The treatment group (n = 80) received 3 months of rapamycin before the second IVF cycle, while the non-treatment group (n = 88) had no adjuvant treatment. The first and second IVF cycles were compared between and within groups. Follicular fluid from both IVF cycles (treatment group n = 28, non-treatment group n = 32) were tested for senescence-associated and oxidative stress-related markers. Results Comparing the follicular fluid from the second cycles, the rapamycin treatment group showed decreased markers of oxidative stress (8-hydroxydesoxyguanosine, malondialdehyde) and increased antioxidant markers (superoxidase dismutase, glutathione peroxidase) (all P < 0.001); the expression of senescence-related markers p16 and p21 was also significantly lower in the treatment group than in the non-treatment group (P < 0.001). Comparing the second IVF cycles, the treatment group needed fewer days of ovarian stimulation, with increased numbers of oocytes obtained and mature oocytes compared with the non-treatment group (all P < 0.001). Furthermore, rates of fertilization, implantation and clinical pregnancy were significantly higher in the treatment group (P = 0.008, 0.034 and 0.038 respectively), as was the live birth rate (P = 0.003). No structural abnormalities were seen in fetuses born to women treated with rapamycin. Conclusions This study suggested an association between short-term rapamycin treatment and improved pregnancy outcomes via IVF. This result needs to be further investigated in prospective randomized controlled clinical trials.