Objective:To evaluate the clinical pregnancy outcomes of progesterone elevation cycles with follicular phase gonadotropin-releasing hormone agonist (GnRH-a) long-acting protocol and luteal phase GnRH-a short-acting protocol.Methods:In this retrospective cohort study, data of patients who received in vitro fertilization/intracytoplasmic sperm injecion (IVF/ICSI) treatment with fresh cleavage phase embryo transferred and follicular phase GnRH-a long-acting protocol or luteal phase GnRH-a short-acting protocol at the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2018 were analyzed. We matched the above patient cycles with age, basal follicle-stimulating hormone (FSH) and number of transplanted embryos using propensity score matching (PSM). There were 1748 cases received long-acting protocol (group A) and 1751 cases received short-acting protocol (group B). According to the different concentrations of progesterone on human chorionic gonadotropin (hCG) injection day, patients were divided into four subgroups: <1.00 μg/L (group 1), 1.00-1.25 μg/L (group 2), 1.25-1.75 μg/L (group 3) and 1.75-3.00 μg/L (group 4). We compared the different items among subgroups in group A and group B including clinical pregnancy, miscarriage rate, and so on. Results:The clinical pregnancy rate of group A was higher than that of group B [65.5% (1145/1748) vs. 53.6% (938/1751), P<0.001], and the live birth rate of group A was higher than that of group B [55.7% (973/1748) vs. 44.0% (770/1751), P<0.001], both of the differences were statistically significant. The clinical pregnancy rate of subgroup A4 [56.6% (82/145)] was significantly lower than that of subgroup A1 [66.8% (725/1086), P=0.010] and subgroup A2 [69.3% (167/241), P=0.008]. In group B, the clinical pregnancy rate of subgroup B3 and subgroup B4 [43.6% (68/156), 30.8% (12/39)] was significantly lower than that of subgroup B1 [55.4% (728/1315)] and subgroup B2 [55.2% (127/230)], the differences were statistically significant (subgroup B3 vs. subgroup B1, P=0.003; subgroup B4 vs. subgroup B1, P=0.002; subgroup B3 vs. subgroup B2, P=0.016; subgroup B4 vs. subgroup B2, P=0.004). Adjusted for confounding factors, the results of multi-factor logistics analysis showed that: compared with subgroup A1, other subgroups (subgroup A2: OR=1.090, 95% CI=0.787-1.509, P=0.606; subgroup A3: OR=0.809, 95% CI=0.588-1.114, P=0.194; subgroup A4: OR=0.675, 95% CI=0.456-1.000, P=0.050) in group A had no statistically significant difference in clinical pregnancy rate. Compared with subgroup B1, the clinical pregnancy rate of subgroup B4 was significantly lower in group B ( OR=0.410, 95% CI=0.199-0.843, P=0.015). Conclusion:After PSM matching, the clinical pregnancy rate and the live birth rate of follicular phase GnRH-a long-acting protocol were better than those of luteal phase GnRH-a short-acting protocol. The follicular phase GnRH-a long-acting protocol had better tolerance to the negative effects of high progesterone than that of luteal phase GnRH-a short-acting protocol.

Objective:To evaluate the clinical pregnancy outcomes of progesterone elevation cycles with follicular phase gonadotropin-releasing hormone agonist (GnRH-a) long-acting protocol and luteal phase GnRH-a short-acting protocol.Methods:In this retrospective cohort study, data of patients who received in vitro fertilization/intracytoplasmic sperm injecion (IVF/ICSI) treatment with fresh cleavage phase embryo transferred and follicular phase GnRH-a long-acting protocol or luteal phase GnRH-a short-acting protocol at the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2018 were analyzed. We matched the above patient cycles with age, basal follicle-stimulating hormone (FSH) and number of transplanted embryos using propensity score matching (PSM). There were 1748 cases received long-acting protocol (group A) and 1751 cases received short-acting protocol (group B). According to the different concentrations of progesterone on human chorionic gonadotropin (hCG) injection day, patients were divided into four subgroups: <1.00 μg/L (group 1), 1.00-1.25 μg/L (group 2), 1.25-1.75 μg/L (group 3) and 1.75-3.00 μg/L (group 4). We compared the different items among subgroups in group A and group B including clinical pregnancy, miscarriage rate, and so on. Results:The clinical pregnancy rate of group A was higher than that of group B [65.5% (1145/1748) vs. 53.6% (938/1751), P<0.001], and the live birth rate of group A was higher than that of group B [55.7% (973/1748) vs. 44.0% (770/1751), P<0.001], both of the differences were statistically significant. The clinical pregnancy rate of subgroup A4 [56.6% (82/145)] was significantly lower than that of subgroup A1 [66.8% (725/1086), P=0.010] and subgroup A2 [69.3% (167/241), P=0.008]. In group B, the clinical pregnancy rate of subgroup B3 and subgroup B4 [43.6% (68/156), 30.8% (12/39)] was significantly lower than that of subgroup B1 [55.4% (728/1315)] and subgroup B2 [55.2% (127/230)], the differences were statistically significant (subgroup B3 vs. subgroup B1, P=0.003; subgroup B4 vs. subgroup B1, P=0.002; subgroup B3 vs. subgroup B2, P=0.016; subgroup B4 vs. subgroup B2, P=0.004). Adjusted for confounding factors, the results of multi-factor logistics analysis showed that: compared with subgroup A1, other subgroups (subgroup A2: OR=1.090, 95% CI=0.787-1.509, P=0.606; subgroup A3: OR=0.809, 95% CI=0.588-1.114, P=0.194; subgroup A4: OR=0.675, 95% CI=0.456-1.000, P=0.050) in group A had no statistically significant difference in clinical pregnancy rate. Compared with subgroup B1, the clinical pregnancy rate of subgroup B4 was significantly lower in group B ( OR=0.410, 95% CI=0.199-0.843, P=0.015). Conclusion:After PSM matching, the clinical pregnancy rate and the live birth rate of follicular phase GnRH-a long-acting protocol were better than those of luteal phase GnRH-a short-acting protocol. The follicular phase GnRH-a long-acting protocol had better tolerance to the negative effects of high progesterone than that of luteal phase GnRH-a short-acting protocol.

Objective To investigate the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA)supplementation on brain edema,autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats and the related mechanisms.Methods TBI rat models were established using Feeney's method.Seventy-two SD rats were divided into 4 groups using random number table:sham operation group,TBI group,ω-3 PUFA supplementation group (TBI + ω-3 group) and autophagy inhibitor 3-methyladenine group (TBI + 3-MA group) (all n =18),each group was further divided into 3 sub-groups (n =6) corresponding to 3 time points (days 1,3,and 7 after TBI).On each of the 3 time points,we measured rat behavioral outcomes with modified neurologic severity score (mNSS) tests;brain water content was measured with wet-dry weight method.The mRNA and protein expressions of autophagy-related factors (LC3-Ⅱ and Beclin-1) in TBI cerebral cortex were determined by immunohistochemistry staining,reverse transcription-polymerase chain reaction and Western blot on day 3 after TBI.Results Compared with the sham group,on days 1,3,and 7 after injuary,the TBI group,the TBI + ω-3 group,and the TBI + 3-MA group had significantly higher mNSS scores (TBI group:12.42±0.27vs.1.34±0.32,12.07±0.27vs.1.16±0.29,10.22±0.39vs.1.22±0.30;TBI+ω-3 group:12.05 ±0.23 vs.1.34 ±0.32,11.38 ±0.21 vs.1.16±0.29,8.20 ±0.21 vs.1.22±0.30;TBI +3-MA group:11.93 ±0.20 vs.1.34 ±0.32,11.09 ±0.19 vs.1.16 ±0.29,7.93 ±0.17 vs.1.22 ± 0.30;all P =0.00) and brain water content [TBI group:(79.82 ± 0.61) ％ vs.(71.87 ± 0.43) ％,(83.04±0.42)％ vs.(72.13 ±0.53)％,(75.12 ±0.72)％ vs.(71.78 ±0.38)％;TBI+ω-3 group:(76.81 ±0.63)％ vs.(71.87 ±0.43)％,(79.39 ±0.59)％ vs.(72.13 ±0.53)％,(73.86 ±0.38)％ vs.(71.78 ±0.38)％;TBI+3-MAgroup:(75.98 ±0.49)％ vs.(71.87 ±0.43)％,(77.14 ±0.46)％ vs.(72.13 ±0.53)％,(72.24 ±0.37)％ vs.(71.78 ±0.38)％;all P =0.00].The mRNA and protein expressions of LC3-Ⅱ and Beclin-1 in the brain were also significantly higher on day 3 in the TBI group,the TBI + ω-3 group,and the TBI + 3-MA group (all P =0.00).Compared with the TB1 group,on day 3 and day 7 after injury,the TBI + ω-3 group and the TBI + 3-MA group had significantly lower mNSS scores (TBI + ω-3 group:11.38±0.21 vs.12.07±0.27,P=0.04,8.20±0.21 vs.10.22±0.39,P=0.01;TBI+3-MA group:11.09±0.19vs.12.07 ± 0.27,P=0.01,7.93 ± 0.17 vs.10.22±0.39,P=0.00).Ondays1,3,and 7,compared with the TBI group,the TBI + ω-3 group and the TBI + 3-MA group had significantly lower brain water content [TBI + ω-3 group:(76.81 ± 0.63) ％ vs.(79.82 ± 0.61) ％,P =0.04,(79.39 ±0.59)％ vs.(83.04±0.42)％,P=0.01,(73.86±0.38)％ vs.(75.12±0.72)％,P=0.03;TBI+3-MAgroup:(75.98 ±0.49)％ vs.(79.82 ±0.61)％,P=0.01,(77.14 ±0.46)％ vs.(83.04 ±0.42)％,P =0.00,(72.24 ± 0.37) ％ vs.(75.12 ± 0.72) ％,P =0.02].On day 3,the TBI + ω-3 group and the TBI + 3-MA group had significantly reduced LC3-Ⅱ and Beclin-1 mRNA expression compared with the TBI group (TBI +ω-3 group:P=0.04,P =0.01;TBI +3-MA group:P =0.01,P =0.00) and protein expression (TBI+ω-3 group:P=0.01,P=0.03;TBI +3-MA group:both P=0.00).Conclusion ω-3 PUFA supplementation could markedly reduce brain edema and improve neurological functions after TBI,showing a neuroprotective effect,possibly through inhibiting TBI-induced autophagy responses.