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.