Background Chemotherapy improves the survival rates of patients with various cancers but often causes some adverse effects, including ovarian damage, characterised by a decrease in primordial follicle stockpiles. Recent studies have revealed that chemotherapy may stimulate the PI3K signalling pathway, thereby resulting in accelerated primordial follicle activation and a decreased ovarian reserve. Quercetin is an inhibitor of the PI3K pathway; however, its protective effects against chemotherapy-induced follicle loss in mice have not been established. In this study, the effects of quercetin in a mouse model of cyclophosphamide-induced ovarian dysfunction were investigated. Methods C57BL/6 female mice were used for the study. Paraffin sections of mouse ovaries (n = 30 mice) were stained with haematoxylin and eosin for differential follicle counts. Apoptosis (n = 5 mice per group) was evaluated by TUNEL assay. Immunohistochemical staining for ki67 and Foxo3a (n = 5 mice per group) was performed to evaluate the activation of primordial follicles. The role of the PI3K signalling pathway in the ovaries (n = 45 mice) was assessed by western blotting. Results Quercetin attenuated the cyclophosphamide-induced reduction in dormant primordial follicles. Analysis of the PI3K/Akt/Foxo3a pathway showed that quercetin decreased the phosphorylation of proteins that stimulate follicle activation in cyclophosphamide-induced ovaries. Furthermore, quercetin prevented cyclophosphamide-induced apoptosis in early growing follicles and early antral follicles, maintained anti-Müllerian hormone levels secreted by these follicles, and preserved the quiescence of the primordial follicle pool, as determined by intranuclear Foxo3a staining. Conclusions Quercetin attenuates cyclophosphamide-induced follicle loss by preventing the phosphorylation of PI3K/Akt/Foxo3a pathway members and maintaining the anti-Müllerian hormone level through reduced apoptosis in growing follicles. Accordingly, quercetin is expected to improve fertility preservation and the prevention of endocrine-related side effects of chemotherapy.

Is it possible to use different progestins cotreatment with human menopausal gonadotrophin (hMG) in women with advanced endometriosis but normal ovulation during controlled ovarian hyperstimulation (COH) in vitro fertilization (IVF)? Whether different progestins treatments can be an alternative choice for women with severe endometriosis in considering IVF/ICSI treatment remains unknown? Design: Non-inferiority randomized clinical trial. Setting: Tertiary-care academic medical center. Population: Four hundred and fifty infertile patients with severe endometriosis undergoing IVF/ICSI between May 2016 and March 2017. Methods: Four hundred and fifty infertile patients with severe endometriosis undergoing IVF/ICSI were randomized to: medroxyprogesterone acetate +hMG; dydrogesterone +hMG; and progesterone +hMG. Ovulation was induced with a gonadotropin-releasing hormone agonist (GnRH-a) and chorionic gonadotropin (hCG). Viable embryos were cryopreserved for later transfer. Main Outcome Measures: The primary endpoint outcome was the number of oocytes retrieved. Secondary indicators included the incidence of a premature surge in luteinizing hormone (LH), the number of viable embryos, and clinical pregnancy outcomes. Results: The number of oocytes retrieved was higher in the medroxyprogesterone acetate +hMG group than the two other groups (9.3 ± 5.7 vs. 8.0 ± 4.5 vs. 7.8 ± 5.2, P = 0.021). LH levels were suppressed after a 6-day progestin treatment in the medroxyprogesterone acetate +hMG and dydrogesterone +hMG groups, but there was Guo et al. Progestins in Endometriosis and IVF a rebound of LH values in the progesterone +hMG group. No premature LH surge and ovarian hyperstimulation syndrome (OHSS) occurred. No significant differences among the three groups were observed in fertilization and pregnancy outcomes. Conclusion: It is mandatory to point out that our conclusions are valid for patients with ovarian advanced endometriosis but normal ovarian functions. These results suggest three different progestins protocols are equivalent in terms of pregnancy outcomes for women with advanced endometriosis. PPOS protocol can be an alternative choice for women with severe endometriosis and normal ovarian reserve in IVF/ICSI treatment. These methods could be tested with other populations of women with endometriosis.

Background: It is unclear whether we should focus attention on cleavage-stage embryo quality and embryo development speed when transferring single particular grade vitrified-warmed blastocysts, especially poor-quality blastocysts (grade "C"). Method: This retrospective study considered 3386 single vitrified-warmed blastocyst transfer cycles from January 2010 to December 2017. They were divided into group 1 (AA/AB/BA, n = 374), group 2 (BB, n = 1789), group 3 (BC, n = 901), and group 4 (CB, n = 322). The effects of cleavage-stage embryo quality and embryo development speed were measured in terms of clinical pregnancy and live birth rates in each group. Results: Pregnancy outcomes showed a worsening trend from groups 1 to 4; the proportion of embryos with better cleavage-stage quality and faster development speed decreased. In group 1, only the blastocyst expansion degree 3 was a negative factor in the clinical pregnancy rate (odds ratio (OR) [95% confidence interval (CI)]: 0.233 [0.091-0.595]) and live birth rate (0.280 [0.093-0.884]). In the other groups (BB, BC, and CB), blastocysts frozen on day 5 had significantly better clinical pregnancy outcomes than those frozen on day 6: 1.373 [1.095-1.722] for group 2, 1.523 [1.055-2.197] for group 3, and 3.627 [1.715-7.671] for group 4. The live birth rate was 1.342 [1.060-1.700] for group 2, 1.544 [1.058-2.253] in group 3, and 3.202 [1.509-6.795] in group 4, all Ps < 0.05). The degree of blastocoel expansion three for clinical pregnancy rate in group 2 (0.350 [0.135-0.906], P < 0.05) and day 3 blastomere number (>7) for live birth rate in group 4 (2.455 [1.190-5.063], P < 0.05) were two important factors. Conclusion: We should consider choosing BB/BC/CB grade blastocysts frozen on day 5, CB grade blastocysts with day 3 blastomere numbers (>7), and AA/AB/BA grade blastocysts with degrees of expansion (≥4) to obtain better pregnancy outcomes.