Refractory acute T-lymphoblastic leukemia (T-ALL), which is characterized by a low sensitivity to conventional induction therapy and poor prognosis, poses significant challenges during treatment. This study reported a case of refractory T-ALL patient with mutations in the JAK1, JAK3, and STAT5B genes from Nanjing University’s Gulou Hospital. Following an unsuccessful course of standard VDLP regimen chemotherapy, the treatment was modified to include ruxolitinib in combination with venetoclax and azacitidine. Subsequent to this therapy, the patient achieved bone marrow minimal residual disease (MRD) negativity. Notably, pleural effusion and mediastinal mass significantly improved the post-chest cavity infusion of dexamethasone combined with etoposide at the same stage. The patient also underwent allogeneic hematopoietic stem cell transplantation upon achieving bone marrow remission and was followed up until January 2024. Ruxolitinib combined with venetoclax and azacytidine has shown promising efficacy and safety in treating refractory T-ALL harboring the JAK1, JAK3, and STAT5B mutations, providing a novel therapeutic approach for such patients.

Objective:To compare the cumulative live birth rates per oocyte retrieval cycle in patients with normal ovarian response between the gonadotropin-releasing hormone agonist (GnRH-a) long protocol and the progestin-primed ovarian stimulation (PPOS) protocol.Methods:A retrospective cohort study was conducted in Centre of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine between January 2017 and December 2019. Women who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment with normal ovarian reserve and <40 years of age were included. Other inclusion criteria included regular menstrual cycles, serum follicle-stimulating hormone level <10 U/L, and the antral follicle count >5. The primary outcome was the cumulative live birth rate (CLBR) within 18 months from the start of ovarian stimulation. Results:A total of 995 patients were included in the study, with 509 patients in the PPOS group and 486 patients in the GnRH-a long group. Both groups had almost comparable demographic and cycle stimulation characteristics except for duration of infertility which was shorter in the PPOS group [3 (2,4) years] than in the GnRH-a long group [3 (2,5) years, P=0.015]. In the GnRH-a long group, 372 patients (77%) underwent fresh embryo transfer, resulting in 218 clinical pregnancies and 197 live births. The clinical pregnancy rate, the ongoing pregnancy rate, and the live birth rate per embryo transfer cycle were 58.6% (218/372), 54.0% (201/372) and 53.0% (197/372), respectively. No fresh embryo transfer was performed in the PPOS group. During the study period, there were 662 frozen-thawed embryo transfer (FET) cycles in the PPOS group and 257 FET cycles in the GnRH-a long group. The PPOS group had a live birth rate of 31.1% (206/662) per FET cycle, which was notably lower than the GnRH-a long group [42.8% (110/257), OR=0.727; 95% CI: 0.607-0.871; P<0.001]. The implantation rate of all FET cycles in the PPOS group was also lower than that in the GnRH-a long group [29.2% (293/1 004) vs. 34.5% (157/455), OR=0.846, 95% CI: 0.721-0.992; P=0.041]. CLBRs after one complete IVF/ICSI cycle including fresh and subsequent FET cycles within 18 months follow up were significantly lower in the PPOS group [40.5% (206/509)] than in the long agonist group [63.2% (307/486), OR=0.641, 95% CI: 0.565-0.726]. Compared with the PPOS group, the GnRH-a long group had a significantly shorter duration from the start of ovarian stimulation to pregnancy and live birth ( P<0.001). In Kaplan-Meier analysis, the CLBR was significantly higher in the GnRH-a long group than in the PPOS group (long rank test, P<0.001). Adjusted Cox-regression analysis revealed stimulation protocol adopted was strongly associated with the CLBR ( OR=1.917, 95% CI: 1.152-3.190, P=0.012). Conclusion:Progestin primed ovarian stimulation was associated with a lower cumulative live birth rates and a long time to pregnancy/live birth than the long agonist protocol in women with a normal ovarian reserve.

Objective:To compare the cumulative live birth rates per oocyte retrieval cycle in patients with normal ovarian response between the gonadotropin-releasing hormone agonist (GnRH-a) long protocol and the progestin-primed ovarian stimulation (PPOS) protocol.Methods:A retrospective cohort study was conducted in Centre of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine between January 2017 and December 2019. Women who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment with normal ovarian reserve and <40 years of age were included. Other inclusion criteria included regular menstrual cycles, serum follicle-stimulating hormone level <10 U/L, and the antral follicle count >5. The primary outcome was the cumulative live birth rate (CLBR) within 18 months from the start of ovarian stimulation. Results:A total of 995 patients were included in the study, with 509 patients in the PPOS group and 486 patients in the GnRH-a long group. Both groups had almost comparable demographic and cycle stimulation characteristics except for duration of infertility which was shorter in the PPOS group [3 (2,4) years] than in the GnRH-a long group [3 (2,5) years, P=0.015]. In the GnRH-a long group, 372 patients (77%) underwent fresh embryo transfer, resulting in 218 clinical pregnancies and 197 live births. The clinical pregnancy rate, the ongoing pregnancy rate, and the live birth rate per embryo transfer cycle were 58.6% (218/372), 54.0% (201/372) and 53.0% (197/372), respectively. No fresh embryo transfer was performed in the PPOS group. During the study period, there were 662 frozen-thawed embryo transfer (FET) cycles in the PPOS group and 257 FET cycles in the GnRH-a long group. The PPOS group had a live birth rate of 31.1% (206/662) per FET cycle, which was notably lower than the GnRH-a long group [42.8% (110/257), OR=0.727; 95% CI: 0.607-0.871; P<0.001]. The implantation rate of all FET cycles in the PPOS group was also lower than that in the GnRH-a long group [29.2% (293/1 004) vs. 34.5% (157/455), OR=0.846, 95% CI: 0.721-0.992; P=0.041]. CLBRs after one complete IVF/ICSI cycle including fresh and subsequent FET cycles within 18 months follow up were significantly lower in the PPOS group [40.5% (206/509)] than in the long agonist group [63.2% (307/486), OR=0.641, 95% CI: 0.565-0.726]. Compared with the PPOS group, the GnRH-a long group had a significantly shorter duration from the start of ovarian stimulation to pregnancy and live birth ( P<0.001). In Kaplan-Meier analysis, the CLBR was significantly higher in the GnRH-a long group than in the PPOS group (long rank test, P<0.001). Adjusted Cox-regression analysis revealed stimulation protocol adopted was strongly associated with the CLBR ( OR=1.917, 95% CI: 1.152-3.190, P=0.012). Conclusion:Progestin primed ovarian stimulation was associated with a lower cumulative live birth rates and a long time to pregnancy/live birth than the long agonist protocol in women with a normal ovarian reserve.

Objective:To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle between gonadotropin-releasing hormone (GnRH) antagonist protocol and progestin-primed ovarian stimulation (PPOS) protocol in patients aged 20-50 years.Methods:A retrospective cohort study was conducted to analyze 3 752 infertile patients aged 20-50 years who received in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). They used either GnRH antagonist protocol or PPOS protocol at the Center of Assisted Reproduction in Shanghai First Maternity and Infant Hospital from January 2017 to April 2021. One to one propensity score matching (PSM) was used to match the population characteristics. Baseline, clinical and laboratory characteristics, as well as pregnancy outcomes were compared between the two groups. The differences of CLBR was analyzed by multivariate logistic regression and subgroup analysis. Results:After matching, 1 466 patients (733 in each group) were included in the analysis. No significant differences were detected in age, body mass index, infertility type, cause and duration of infertility, number of stimulation cycles, basal follicle-stimulating hormone, number of antral follicles and composition ratio of insemination methods between the two groups ( P>0.05). Serum estradiol level [1 700.30 (1 011.76, 2 580.50) ng/L] and luteinizing hormone (LH) level [1.95 (1.07, 5.27) U/L] on trigger day were significantly lower in GnRH antagonist group than in PPOS group [2 056.50 (884.08, 3 601.59) ng/L, P=0.010; 3.00 (1.51, 5.00) U/L, P<0.001]. The cycle cancellation rate of PPOS group [30.56% (224/733)] was significantly higher than that of GnRH antagonist group [18.83% (138/733), P<0.001]. The numbers of oocytes obtained, available embryos and good-quality embryos were similar to those in GnRH antagonist group (all P>0.05). For each embryo transfer cycle, the implantation rate [16.97% (207/1 220) vs. 21.42% (266/1 242)], the clinical pregnancy rate [21.78% (188/863) vs. 27.38% (233/851)], the onging pregnancy rate [16.11% (139/863) vs. 21.62% (184/851)] and the live birth rate [15.06% (130/863) vs. 20.80% (177/851)] were significantly lower in PPOS group than in GnRH antagonist group ( P=0.010, P=0.012, P=0.004 and P=0.002, respectively). The CLBR of PPOS group was significantly lower than that of GnRH antagonist group [17.74% (130/733) vs. 24.15% (177/733), P=0.003]. Multivariate logistic regression analysis showed that ovarian stimulation protocol was an independent risk factor for CLBR [ OR=1.42, 95% CI: 1.03-1.95, P=0.032]. The results of subgroup analysis showed that the CLBR of PPOS group was significantly lower than that of GnRH antagonist group in the population aged ≤35 years and underwent non-first IVF/ICSI cycle [21.35% (111/520) vs. 28.93% (151/522), P=0.005; 7.85% (41/522) vs. 12.23% (62/507), P=0.019]. Conclusion:Compared with PPOS regimen, antagonist regimen can improve the CLBR per oocyte cycle in infertile patients aged 20-50 years, and is more significant in women aged ≤35 years and non-first oocyte collection patients.

Objective:To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle between gonadotropin-releasing hormone (GnRH) antagonist protocol and progestin-primed ovarian stimulation (PPOS) protocol in patients aged 20-50 years.Methods:A retrospective cohort study was conducted to analyze 3 752 infertile patients aged 20-50 years who received in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). They used either GnRH antagonist protocol or PPOS protocol at the Center of Assisted Reproduction in Shanghai First Maternity and Infant Hospital from January 2017 to April 2021. One to one propensity score matching (PSM) was used to match the population characteristics. Baseline, clinical and laboratory characteristics, as well as pregnancy outcomes were compared between the two groups. The differences of CLBR was analyzed by multivariate logistic regression and subgroup analysis. Results:After matching, 1 466 patients (733 in each group) were included in the analysis. No significant differences were detected in age, body mass index, infertility type, cause and duration of infertility, number of stimulation cycles, basal follicle-stimulating hormone, number of antral follicles and composition ratio of insemination methods between the two groups ( P>0.05). Serum estradiol level [1 700.30 (1 011.76, 2 580.50) ng/L] and luteinizing hormone (LH) level [1.95 (1.07, 5.27) U/L] on trigger day were significantly lower in GnRH antagonist group than in PPOS group [2 056.50 (884.08, 3 601.59) ng/L, P=0.010; 3.00 (1.51, 5.00) U/L, P<0.001]. The cycle cancellation rate of PPOS group [30.56% (224/733)] was significantly higher than that of GnRH antagonist group [18.83% (138/733), P<0.001]. The numbers of oocytes obtained, available embryos and good-quality embryos were similar to those in GnRH antagonist group (all P>0.05). For each embryo transfer cycle, the implantation rate [16.97% (207/1 220) vs. 21.42% (266/1 242)], the clinical pregnancy rate [21.78% (188/863) vs. 27.38% (233/851)], the onging pregnancy rate [16.11% (139/863) vs. 21.62% (184/851)] and the live birth rate [15.06% (130/863) vs. 20.80% (177/851)] were significantly lower in PPOS group than in GnRH antagonist group ( P=0.010, P=0.012, P=0.004 and P=0.002, respectively). The CLBR of PPOS group was significantly lower than that of GnRH antagonist group [17.74% (130/733) vs. 24.15% (177/733), P=0.003]. Multivariate logistic regression analysis showed that ovarian stimulation protocol was an independent risk factor for CLBR [ OR=1.42, 95% CI: 1.03-1.95, P=0.032]. The results of subgroup analysis showed that the CLBR of PPOS group was significantly lower than that of GnRH antagonist group in the population aged ≤35 years and underwent non-first IVF/ICSI cycle [21.35% (111/520) vs. 28.93% (151/522), P=0.005; 7.85% (41/522) vs. 12.23% (62/507), P=0.019]. Conclusion:Compared with PPOS regimen, antagonist regimen can improve the CLBR per oocyte cycle in infertile patients aged 20-50 years, and is more significant in women aged ≤35 years and non-first oocyte collection patients.