Changjun Zhang

Objective: To evaluate the dynamics of serum medroxyprogesterone acetate (MPA) concentrations and their influence on serum progesterone (P) levels and pregnancy outcomes in the progestin-primed ovarian stimulation (PPOS) protocol. A total of 116 patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the PPOS protocol were included. Serum MPA levels were measured on the third, fifth, and seventh days of MPA use; on the day of human chorionic gonadotropin (hCG) trigger; and two and five days after oocyte pick-up (OPU).Results: The serum MPA concentration was 2.26 ± 2.11 nmol/L on the hCG trigger day, 0.37 ± 0.40 nmol/L two days after OPU, and zero five days after OPU. There were no statistically significant differences in P levels on the hCG trigger day, total dosage of Gn, duration of Gn, number of oocytes retrieved, number of mature oocytes, fertilization rate, blastocyst progression rate, CPR, ectopic pregnancy rate, early pregnancy loss rate, or live birth rate (LBR) between the two cohorts (P > 0.05).Conclusion(s): Serum concentrations of MPA had no effect on serum P levels or pregnancy outcomes in patients undergoing the PPOS protocol.

Objective: To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis.Design: A retrospective cohort study.Setting: Tertiary-care academic medical center.Population: A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020.Methods: A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed.Main outcome measures: The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate.Results: We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E₂) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups.Conclusion: The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.

Objective: To explore the effects of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women. Design: Retrospective cohort study. Setting: Tertiary-care academic medical center. Population: We studied 3173 infertile women undergoing their first IVF/ICSI treatment from 2017 to 2020. Methods: Propensity score matching (PSM) analysis was performed with 1:1 in 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively. Main outcome measures: Incidence of premature luteinizing hormone (LH) surges and number of oocytes retrieved. Results: We created a perfect match of 581 patients in each group. The dosage of MPA, premature LH surge, progesterone (P) level and LH level on the hCG trigger day and LH level on the day after hCG trigger were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group. The E ₂ level on the hCG trigger day, the duration of Gn, the number of oocytes retrieved were lower in the LE + fixed MPA group than in the LE + degressive MPA group. Conclusions: Using degressive MPA dose combined with LE could reduce the total MPA dosage and premature LH surge and increase the number of oocytes retrieved in women undergoing the PPOS protocol. Funding: National Natural Science Foundation of China (82101726) and Innovation and Entrepreneurship Training Program for students of Hubei University of Medicine (X202110929037 and S202110929032). Keywords: progestin primed ovarian stimulation, medroxyprogesterone acetate, letrozole, controlled ovarian stimulation.

ObjectivesTo explore the effect of abnormally elevated serum alanine aminotransferase (ALT) on pregnancy outcomes in patients with moderate and severe ovarian hyperstimulation syndrome (OHSS) at disease onset. MethodsThis was a single-center retrospective cohort study conducted between January 1, 2014 and October 31, 2021. A total of 3550 fresh in vitro fertilization/intracytoplasmic sperm injection embryo transfer cycles were included, using Golan's three-degree, five-level classification to diagnose patients with OHSS. According to the patient's ALT level after diagnosis of OHSS, 123 (3.46%) patients with moderate-to-severe OHSS were divided into two groups. A control group included 3427 (96.54%) non-OHSS patients, and 91 (2.56%) abnormal ALT patients were matched with the control group for propensity scores. ResultsThere was no difference in baseline data between the abnormal ALT and matched control groups. The incidence of obstetric complications was significantly higher in the abnormal ALT group than in the matched control group (P < 0.05). After adjusting for confounding factors, the incidence of obstetric complications in the abnormal ALT group was still higher than that in the normal ALT group (P < 0.05). ConclusionIn patients with moderate and severe OHSS, higher ALT levels resulted in an increased risk of obstetric and neonatal complications.

Research question: What are the influencing factors of the average blastomere number of all embryos in D3 patients and the association with a live birth rate in the transfer cycle? Methos: A total of 7420 fresh embryo transferred cycles of patients who underwent IVF-ET in the Reproductive Medicine Center, Renmin Hospital, Hubei University of Medicine from January 2016 to December 2021 were selected retrospective observed. Results: According to the average blastomeres number in all embryos on day 3 following oocyte retrieval, the patients were split into five groups: 5.00 group (747 cases), 5.01-6.00 group (1763 cases), 6.01-7.00 group (3052 patients), 7.01-8.00 group (1646 cases), and >8 groups (212 patients). The average number of blastomere on D3 was negatively associated (P Conclusion: An average blastomere number between 7.01 and 8.00 is associated with higher LBR in D3 fresh embryo transfer cycle, when the average blastomeres in D3 embryos are less than 5.7 to reduce the live birth rate of the transfer cycle.

Background: In an in vitro fertilization (IVF) cycle, the embryo ends its wandering time and begins the process of implantation into the uterine cavity on the seventh day after oocyte pick-up (OPU + 7), which is closer than OPU + 5 to the time of nidation. Therefore, measuring the oestradiol (E2)/progesterone (P) ratio on OPU + 7 may be helpful for predicting pregnancy outcomes. Methods: This is a retrospective cohort study of 2,257 women undergoing a follicular-phase depot gonadotropin-releasing hormone agonist (GnRH-a) protocol for in vitro fertilization /intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh blastocyst embryo transfer cycles at a university-affiliated fertility center between January 2016 and April 2021. First, 2,257 women were split into two groups based on clinical pregnancy for analyzing the levels of E₂ and P and the E₂/P ratio on the day of OPU + 2, OPU + 5 and OPU + 7. And then 2,257 cycles were stratified into three groups based on E₂/P ratio tertiles on OPU + 7: the low group (1.3–15.7 pg/ng), middle group (15.7–28.8 pg/ng), and high group (28.8–487.2 pg/ng). The threshold effect of the E₂/P ratio on OPU + 7 on live birth was investigated using a two-piecewise linear regression model and a smoothing function curve. Results: The level of P in the clinical pregnancy group were lower than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (201.9 ± 71.6 ng/ml vs 213.1 ± 77.6 ng/ml, 89.5 ± 88.5 ng/ml vs 99.5 ± 94.9 ng/ml, P < 0.05). The E₂/P ratio in the clinical pregnancy group were higher than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (8.4 ± 6.5 pg/ng vs 8.0 ± 6.8 pg/ng, 32.3 ± 38.5 pg/ng vs 25.2 ± 31.0 pg/ng, P < 0.01). The E₂/P ratio on OPU + 7 was positively associated with positive hCG (adjusted OR = 1.01; 95% CI, 1.01–1.02; P < 0.0001), clinical pregnancy (adjusted OR = 1.01; 95% CI, 1.00–1.01; P = 0.0067) and live birth (adjusted OR = 1.01; 95% CI, 1.00–1.01; P < 0.001), and a nonlinear correlation was observed between the E₂/P ratio and LBR on OPU + 7. Conclusions: A higher E₂/P ratio is associated with a higher LBR, but the E₂/P ratio should be maintained within a suitable range.

Background: The gonadotropin-releasing hormone agonist (GnRH-a) has been used in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles for a long time. This paper evaluates the efficacy and safety of two commonly used protocols (follicular-phase depot GnRH-a protocol and daily mid-luteal long GnRH-a protocol) in normal responders undergoing IVF/ICSI using propensity score matching (PSM) analysis. Methods: A total of 6,816 infertile women treated within the period from January 2016 to September 2020 were stratified into cohorts. A total of 2,851 patients received the long-acting group (depot GnRH-a protocol), and 1,193 used the short-acting group (long GnRH-a protocol) after the data-selection process. PSM was utilized for sampling by up to 1:1 nearest neighbour matching to adjust the numerical difference and balance the confounders between groups. The primary outcome was the live birth rate (LBR). Multivariable logistic analysis was used to evaluate the difference between these two protocols in relation to the LBR. Result(s): In this study, 1:1 propensity score matching was performed to create a perfect match of 964 patients in each group. After matching, the blastocyst formation rates, oestradiol (E₂) value on Day hCG + 9, progesterone (P) value on Day hCG + 9, implantation rates, clinical pregnancy rates, and LBR were more favourable in the depot GnRH-a protocol than in the long GnRH-a protocol (P < 0.05). However, the moderate or severe OHSS rates were higher in the depot group than in the long group (P < 0.001). There were no significant differences in endometrial thickness, luteal support medication, early pregnancy loss rates, mid- and late-term pregnancy loss rates, or foetal malformation rates between the two protocols. Conclusion(s): Compared with the daily short-acting GnRH agonist protocol, the follicular-phase depot GnRH-a protocol might improve LBRs in normogonadotropic women without discernible differences in luteal function and child health.

The aim of this retrospective analysis was to explore whether an elevated ALT level before pregnancy is associated with a reduction in live birth rate after IVF-FET.Retrospective observational stud...

Objective: This study is aimed to examine the associations between embryo outcomes and serum sex hormone-binding globulin (SHBG) changes during progestin-primed ovarian stimulation (PPOS) protocols in IVF/ICSI cycles. Research methods: This study included 2790 eligible consecutive cycles of patients aged 21–53 years undergoing PPOS treatment. Multivariable linear regression analysis was performed to explore the association between SHBG changes and embryo outcomes. Results of the study: Our results showed that the SHBG-increase rate on the HCG day and in the late follicular phase were positively and linearly correlated with available embryos in day3, with adjusted regression coefficients (β) for the SHBG-increase rate on the HCG day, in the late follicular phase were 0.6 (0.4, 0.9), 0.4 (0.2, 0.6), but in the middle follicular phase and in the early follicular phase, this correlation was not significant (p > 0.05). Conclusion: Our results indicate that serum SHBG increment may serve as a biomarker of the developmental potential of the oocytes from patients undergoing the PPOS protocol.

What is known and Objective To compare the characteristics and efficacy of progestin-primed ovarian stimulation (PPOS) protocol plus letrozole versus PPOS protocol alone for patients with normal ovarian function who received in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) assisted pregnancy treatment. Methods From 1 October 2017 to 1 October 2019, 576 patients who underwent IVF/ICSI cycles received PPOS protocol with or without letrozole in the Center of Reproductive Medicine, Renmin Hospital of Shiyan City were included in this retrospective cohort study. The PPOS group included 249 patients who received PPOS protocol alone, and the combined treatment group included 327 patients who received PPOS protocol plus letrozole. The general data and laboratory indicators were detected and used as baseline data. In addition, evaluation of related indicators was performed, including days of gonadotropin (Gn) duration, total amount of dose of Gn and medroxyprogesterone acetate (MPA), hormone levels on the trigger day, number of oocytes retrieved and mature eggs, fertilization rate, cleavage rate, blastocyst formation rate, high-quality embryo rate, methods of endometrial preparation, stage of embryo transfer, endometrial thickness, the number of embryo transfer, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, abortion rate, ectopic pregnancy rate and live birth rate. The risk factors affecting clinical pregnancy rate were detected by binary Logistic regression analysis. Results and discussion In this study, we found that baseline level of Anti-Müllerian hormone (AMH) was significantly higher in combined group compared with PPOS group (p < 0.05). The days of Gn duration in combined group were significantly longer than that in PPOS group (p < 0.05), and the total amount of dose of Gn and MPA in combined group was significantly less than that in PPOS group (p < 0.05). The levels of luteinizing hormone (LH) and progesterone in combined group were significantly higher than that in PPOS group on the trigger day (p < 0.05). The number of oocytes retrieved and mature eggs in combined group was significantly more than that in PPOS group (p < 0.05). Meanwhile, the fertilization rate, cleavage rate and blastocyst formation rate in combined group were significantly higher than that in PPOS group (p < 0.05). There was no significant difference in the characteristics of endometrial preparation and embryo transfer, as well as the pregnancy outcomes. The results of logistic regression analysis showed that stage (p < 0.001) (OR = 0.281, 95% CI: 0.187, 0.422) and number (p < 0.001) (OR = 0.333, 95% CI: 0.196, 0.567) of embryos transfer were risk factors for clinical pregnancy rate. What is new and Conclusion Compared with PPOS protocol alone, letrozole combined with PPOS can achieve similar embryo and pregnancy outcomes while reducing the amount of Gn and MPA, which has a higher cost performance and is worth promoting. Stage and number of embryos transfer are risk factors for clinical pregnancy rate.