ObjectiveThe aim was to study the impact of coronavirus disease 2019 (COVID-19) convalescence on female fertility and laboratory and clinical outcomes in fresh assisted reproductive technology (ART) cycles.MethodsIn this retrospective cohort study, we analyzed data from 294 patients who had recovered from COVID-19 and who underwent fresh ART cycles between January and March 2023 (COVID-19 group). This group was compared with 631 patients who underwent similar ART cycles in the same period in 2022 but without having been infected with COVID-19 (non-COVID-19 group). The analysis focused on comparison of basic demographic characteristics and laboratory parameters of patients in each group. The primary outcome measure was the clinical pregnancy rate, which was examined to assess the impact of COVID-19 infection on the efficacy of ART treatment.ResultsBasal follicle-stimulating hormone (FSH) levels were significantly lower and antral follicle count (AFC) was markedly higher in the COVID-19 group compared to the non-COVID-19 group (P<0.001 and P=0.004, respectively). The predominant ovarian stimulation protocol in the COVID-19 group was GnRH antagonists (64.85%, P<0.001), with a reduced gonadotropin (Gn) dosage and duration in comparison to the non-COVID-19 group (P<0.05). Although the number of blastocysts formed was lower in the COVID-19 group (P=0.017), this group also exhibited a higher blastocyst freezing rate and a higher rate of high-quality embryos per retrieved oocyte (P<0.001 and P=0.023, respectively). Binary logistic regression analysis indicated that COVID-19 convalescence did not significantly impact clinical pregnancy rates in fresh transfer cycles (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 0.68-1.96, P=0.5874). However, smooth curve-fitting and threshold effect analysis revealed an age-related decline in clinical pregnancy rates in both groups, more pronounced in the COVID-19 group, for women aged over 38 years, with the likelihood of clinical pregnancy decreasing by 53% with each additional year of age (odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.61–1.08, P=0.1460; odds ratio [OR] = 0.47, 95% CI = 0.21–1.05, P=0.0647).ConclusionsOur findings present no substantial evidence of adverse effects on clinical pregnancy outcomes in fresh ART cycles in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) during the period of convalescence from COVID-19. However, age emerges as a significant factor influencing these outcomes. Notably, for women above 38 years of age, the likelihood of clinical pregnancy in patients with a prior COVID-19 infection decreased by 53% with each additional year. This highlights the importance of considering maternal age, especially in the context of COVID-19, when evaluating the likelihood of successful pregnancy following ART treatments.

Accumulating evidence has suggested that men exposed to air pollution are associated with decreased sperm quality, and seminal plasma plays a pivotal role in maintaining sperm viability. However, the role of seminal plasma in air pollution related sperm quality decline remain unestablished. In current study, we recruited 524 participants from couples who underwent in vitro fertilization treatment due to female factors at a fertility clinic in China from March to August 2020. Conventional sperm parameters, total antioxidant capacity (T-AOC), malondialdehyde (MDA) and testosterone were measured using semen samples. The six main air pollutants (PM2.5, PM10, NO2, SO2, CO, O3) during four key periods of sperm development (meiotic stage, spermiogenesis stage, epididymal stage and total sperm cycle period) were estimated using inverse distance weighting method. Multiple linear regression models were employed to investigate the exposure-outcome relationships. And we found that PM10 exposures were negatively related to sperm total motility and the exposures of PM2.5 and PM10 were inversely associated with sperm progressive motility during epididymal stage. Furthermore, PM2.5 and PM10 exposures were positively associated with seminal plasma MDA and PM10 was negatively related to seminal plasma T-AOC during epididymal stage. PM2.5, PM10 and CO exposures during total sperm cycle period might relate to increased seminal plasma testosterone. Mediation analysis indicated seminal plasma MDA and T-AOC partially mediated PM10 associated reduction of sperm motility during epididymal stage. Our study suggested MDA and T-AOC of seminal plasma played a role in air pollution associated decline of sperm motility.

Epidemiological studies have established an association between chronic exposure to PM2.5 and male infertility. However, the underlying mechanisms were not fully revealed. In this study, we established mice models exposed to PM2.5 for 16 weeks, and a significant decrease in sperm quality accompanied by an increase in testosterone levels were observed after PM2.5 exposure. Moreover, treatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, effectively mitigated PM2.5-induced testicular dysfunction in mice. And lipid peroxidation and ferritin accumulation were found to be significantly increased in Leydig cells of testes with a PM2.5-dose dependent manner. Further investigations revealed that TM-3 cells, a mouse Leydig cell line, were prone to ferroptosis after PM2.5 exposure, and the cell viability was partly rescued after the intervention of Fer-1. Furthermore, our results supported that the ferroptosis of TM-3 cells was attributed to the upregulation of ferredoxin 1 (FDX1), which was the protein transferring electrons to cytochrome P450 family 11 subfamily A member 1 to aid lysing cholesterol to pregnenolone at initial of steroidogenesis. Mechanically, PM2.5-induced FDX1 upregulation resulted in cellular ROS elevation and ferrous iron overload, which together initiated an autoxidation process of polyunsaturated fatty acids in the cell membrane of Leydig cells until the accumulated lipid peroxides triggered ferroptotic cell death. Simultaneously, upregulation of FDX1 promoted steroidogenesis and let to an increased level of testosterone. In summary, our work suggested that FDX1, a mediator involving steroidogenesis, was a key regulator in PM2.5-induced Leydig cells ferroptosis.

Objective To evaluate the pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) protocol for patients with endometrioma underwent in vitro fertilization/intra-cytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). Design Observational retrospective cohort study. Setting University affiliated reproductive center. Study Participants 605 infertile patients with endometrioma underwent IVF/ICSI-ET from January 2016 to March 2021 were included in this study. Methods Multivariable logistic regression analyses were conducted to determine the independent effect of controlled ovarian stimulation (COS) protocols on reproductive outcomes of first embryo transfer (ET) cycles. The live birth was primary outcome, the implantation rate, biochemical pregnancy, clinical pregnancy and ongoing pregnancy were secondary outcomes. Results Compared to PPOS protocol, the probability of implantation showed no significant difference with ultra-long gonadotrophin-releasing hormone agonist (GnRHa) protocol and gonadotrophin-releasing hormone antagonist (GnRHant) protocol (OR 1.7, 95% CI 0.9-3.1, OR 1.2, 95% CI 0.7-2.1, respectively). The PPOS protocol was correlated with a significantly lower biochemical pregnancy and clinical pregnancy than ultra-long GnRHa protocol in the multivariable logistic regression analysis (OR 2.3, 95% CI 1.1-4.9, OR 2.4, 95% CI 1.1-5.3, respectively). However, there was no significant difference in terms of biochemical pregnancy, clinical pregnancy and ongoing pregnancy between PPOS and GnRHant protocol (OR 1.4, 95% CI 0.7-2.7, OR 1.3, 95% CI 0.7-2.4, OR 1.1, 95% CI 0.6-2.3, respectively). In addition, compared to PPOS protocol, ultra-long GnRHa protocol and GnRHant protocol demonstrated no statistical difference in ongoing pregnancy (OR 2.0, 95% CI 0.9-4.5, OR 2.1, 95% CI 0.6-2.3, respectively). Notably, the ultra-long GnRHa protocol was associated with a significant higher probability of live birth than PPOS protocol both in crude analysis and multivariable logistic regression analysis (OR 2.6, 95% CI 1.3-5.1, OR 2.5, 95% CI 1.1-5.7, respectively). Nevertheless, no statistical difference was found in live birth between PPOS and GnRHant protocol either in crude analysis and multivariable logistic regression analysis (OR1.2, 95% CI 0.6-2.3, OR 1.2, 95% CI 0.6-2.5, respectively). Conclusions Based on the reproductive outcomes of the first ET cycles in patients with endometrioma, PPOS protocol may associated with inferior reproductive outcomes in terms of biochemical pregnancy, clinical pregnancy and live birth than ultra-long GnRHa protocol. However, there was no significant difference in implantation rate, clinical pregnancy, ongoing pregnancy and live birth between PPOS and GnRHant protocol.

Background: Congenital anomalies (CAs) are the leading causes for children's disabilities and mortalities worldwide. The associations between air pollution and CAs are not fully characterized in fetuses born by in vitro fertilization (IVF) who are at high risk of congenital anomalies. Methods: We conducted a cross-sectional study including 16,971 IVF cycles from three hospitals in Hebei Province, China, 2014-2019. Air quality data was obtained from 149 air monitoring stations. Individual average daily concentrations of PM2.5, PM10, NO2, SO2, CO, and O3 were estimated by spatiotemporal kriging method. Exposure windows were divided into 5: preantral follicle period, antral follicle period, germinal period, embryonic period and early fetal period. Logistic generalized estimating equations were used to estimate the associations between air pollutants and overall or organ-system specific congenital anomalies. Negative control exposure method was used to detect and reduce bias of estimation. Results: We found increasing levels of PM2.5 and PM10 were associated with higher risk of overall congenital anomalies during early fetal period, equating gestation 10-12 weeks (OR: 1.05, 95% CI: 1.02-1.09, p = 0.013 for a 10 mu g/m3 increase of PM2.5; OR: 1.03, 95% CI: 1.01-1.06, p = 0.021 for a 10 mu g/m3 increase of PM10). Cleft lip and cleft palate were associated with PM10 in germinal period and early fetal period. The CAs of eye, ear, face and neck were related to CO in preantral follicle stage. We did not find an association between chromosome abnormalities and air pollution exposure. Conclusions: We concluded that ambient air pollution was a risk factor for congenital anomalies in the fetuses conceived through IVF, especially exposure in early fetal period.

Objective:To explore the relationship between different gestational weeks of transvaginal ultrasound-guided fetal reduction and abortion in patients with multiple pregnancies after embryo transfer, and to seek the best gestational age for fetal reduction.Methods:The datas of 486 pregnant women with multiple pregnancies after embryo transfer in the Second Hospital of Hebei Medical University from January 2012 to December 2020 were retrospectively analyzed. The relationship between gestational weeks of fetal reduction and abortion rate was analyzed by curve fitting, threshold effect and multivariate logistic regression analysis.Results:After adjusting for age, infertility type, infertility years, number of births, abortion times, body mass index(BMI), various infertility and sterility factors, endometrial thickness on the day of transformation, monozygotic twins and reduction methods, when the gestational age was less than 8.43 weeks, the abortion rate increased significantly with the increase of reduction gestational age, and the abortion rate increased by 221% ( OR=3.21, 95% CI=1.47-6.99, P=0.003 3). When the gestational age of reduction ≥8.43 weeks, the abortion rate tended to be stable and did not increase ( OR=0.81, 95% CI=0.54-1.22, P=0.317 7); meanwhile, in stratified analysis, the OR value of the BMI ≥24 kg/m 2 was 12.38, and that of BMI <24kg/m 2 was 1.91, P=0.053 9. Conclusions:There is a non-linear relationship between gestational age and abortion rate of ultrasound-guided multiple pregnancy reduction in patients with embryo transfer. The abortion rate increases significantly with the increase of gestational age before 8.43 weeks of gestation. It is recommended to carry out the operation as early as possible before 8 weeks of pregnancy. The effect of BMI on the abortion rate of patients with fetal reduction needs further study.

目的探讨胚胎移植三胎妊娠后于孕早期行不同减灭数目减胎术对围产期母婴的影响。方法回顾性分析胚胎移植后三胎妊娠患者于孕早期行多胎妊娠减胎术后保留单胎和保留双胎共282例孕妇的资料,依据保留胎儿数将减胎组分为减至单胎组28例、减至双胎组254例。同时采用倾向性评分匹配法（PSM）与同期胚胎移植后未行减胎的单胎或双胎妊娠研究对象分别进行1∶3匹配。匹配完成后,共846例作为对照组,其中单胎对照组84例、双胎对照组762例。对4组患者的一般资料、妊娠结局、新生儿体质量及围产期并发症进行比较,并采用Logistic回归进一步做敏感性分析。结果 （1）减胎组的流产率、晚期流产率、围产期并发症发生率高于对照组（P均＜0.01）,平均分娩孕周短于对照组（P=0.01）,平均足月产儿体质量（P＜0.01）、足月产率（P=0.016）,剖宫产率（P=0.037）低于对照组;（2）减至单胎组剖宫产率低于减至双胎组（P=0.001）,平均分娩孕周长于减至双胎组（P＜0.01）,平均足月产儿体质量高于减至双胎组（P＜0.01）;单胎对照组流产率、早期流产率、足月产率、足月产儿及早产儿体质量高于双胎对照组（P均＜0.01）,早产率低于双胎对照组（P＜0.01）。结论妊早期行多胎妊娠减胎术并未增加早产、出生缺陷风险,但流产、围产期并发症及低体质量儿的发生风险增加。三胎妊娠后行多胎妊娠减胎术保留至单胎者比保留至双胎者,有更好的妊娠结局。

Maternal exposure to air pollution is associated with poor reproductive outcomes in in vitro fertilization (IVF). However, the susceptible time windows are still not been known clearly. In the present study, we linked the air pollution data with the information of 9001 women receiving 10,467 transfer cycles from August 2014 to August 2019 in The Second Hospital of Hebei Medical University, Shijiazhuang City, China. Maternal exposure was presented as individual average daily concentrations of PM2.5, PM10, NO2, SO2, CO, and O3, which were predicted by spatiotemporal kriging model based on residential addresses. Exposure windows were divided to five periods according to the process of follicular and embryonic development in IVF. Generalized estimating equation model was used to evaluate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for association between clinical pregnancy and interquartile range increased average daily concentrations of pollutants during each exposure period. The increased PM2.5 (adjusted OR = 0.95, 95% CI: 0.90, 0.99), PM10 (adjusted OR = 0.93, 95% CI: 0.89, 0.98), NO2 (adjusted OR = 0.89, 95% CI: 0.85, 0.94), SO2 (OR = 0.94, 95% CI: 0.90, 0.98), CO (adjusted OR = 0.93, 95% CI: 0.89, 0.97) whereas decreased O3 (OR = 1.08, 95% CI: 1.02, 1.14) during the duration from preantral follicles to antral follicles were the strongest association with decreased probability of clinical pregnancy among the five periods. Especially, women aged 20-29 years old were more susceptible in preantral-antral follicle transition stage. Women aged 36-47 years old were more vulnerable during post-oocyte retrieve period. Our results suggested air pollution exposure during preantral-antral follicle transition stage was a note-worthy challenge to conceive among females receiving IVF.

目的 探讨卵母细胞玻璃化冷冻在临床应用中的可行性和有效性. 方法 回顾性分析2012年1月至2018年12月在我院生殖医学中心行卵母细胞玻璃化冷冻复苏后行ICSI的37例患者(共37个周期)的临床资料(观察组).采用倾向性评分(PSM)匹配方法按1∶5匹配选择同期在本中心行新鲜卵母细胞ICSI的179例患者(共181个周期)为对照组,比较两组患者的受精率、卵裂率、可利用胚胎率、临床妊娠率、种植率、流产率及活产率等妊娠结局. 结果 (1)两组患者的一般资料比较均无显著性差异(P＞0.05).(2)观察组玻璃化冷冻卵母细胞的复苏率为95.3％(344/361).两组患者的2PN受精率比较无显著性差异(P＞0.05);观察组的2PN卵裂率(94.9％ vs.99.0％)、可利用胚胎率(48.1％ vs.58.2％)显著低于对照组(P＜0.01).(3)观察组37个周期胚胎移植后,获得20例妊娠,活产19例,分娩25例健康婴儿,无出生缺陷儿发生;对照组181个周期胚胎移植后,获得95例妊娠,活产81例,分娩113例活婴,有1例出生缺陷儿.两组患者的种植率、临床妊娠率、流产率、宫外孕率及活产率比较均无显著性差异(P＞0.05). 结论 卵母细胞玻璃化冷冻保存可获得较好的复苏率,解冻后行ICSI虽然卵裂率和可利用胚胎率略有下降,但并不影响受精率和妊娠结局.对于取卵日男方因各种原因不能提供精液的女性患者,卵母细胞玻璃化冷冻是一个较好的生育力保存方法.

目的 探讨全反式维甲酸(all-trans-retinoic acid,atRA)在脂多糖(lipopolysaccharide,LPS)诱导的附睾上皮细胞炎性反应中的作用及分子机制.方法 以LPS诱导附睾上皮细胞建立炎症模型,给予不同浓度的atRA、atRA受体抑制剂处理,以及转染转化生长因子β1(Transforming growth factorβ1,TGF-β1)的小干扰RNA,敲低细胞中内源性TGF-β1的表达,采用实时荧光定量PCR检测细胞中炎性因子白细胞介素1β(interleukin-1β,IL-1β)、白细胞介素6(interleukin-6,IL-6)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和TGF-β1的mRNA表达水平,酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测细胞上清中IL-1β、IL-6、TNF-α的分泌量,Western blot方法 检测附睾上皮细胞中TGF-β1的蛋白表达水平.结果 LPS组附睾上皮细胞中IL-1β、IL-6和TNF-αmRNA的表达水平明显高于对照组,给予不同浓度的atRA处理后小鼠附睾上皮细胞的炎性因子IL-1β、IL-6和TNF-αmRNA的表达水平明显降低,呈浓度梯度依赖性(P<0.01).LPS组附睾上皮细胞培养基上清中IL-1β、IL-6和TNF-α含量明显高于对照组,给予不同浓度的atRA处理后小鼠附睾上皮细胞培养基上清中IL-1β、IL-6和TNF-α含量明显降低,呈浓度梯度依赖性(P<0.01).LPS组小鼠附睾上皮细胞中TGF-β1 mRNA的表达水平明显低于对照组,给予不同浓度atRA处理后小鼠附睾上皮细胞中TGF-β1 mRNA的表达水平明显升高,呈浓度梯度依赖性(P<0.01).Si-TGF-β1组TGF-β1 mRNA表达水平明显低于Si-Ctl组(P<0.01).atRA+Si-Ctl+LPS组小鼠附睾上皮细胞IL-1β、IL-6和TNF-αmRNA相对表达量低于Control+LPS组,atRA+Si-TGF-β1+LPS组小鼠附睾上皮细胞IL-1β、IL-6和TNF-αmRNA相对表达量明显高于atRA组(P<0.01).atRA+Si-Ctl+LPS组小鼠附睾上皮细胞培养液上清中IL-1β、IL-6和TNF-α含量低于Control+LPS组,atRA+Si-TGF-β1+LPS组小鼠附睾上皮细胞培养液上清中IL-1β、IL-6和TNF-α含量明显高于atRA组(P<0.01).atRA组小鼠附睾上皮细胞中维甲酸α受体(retinoic acid receptor alpha,RARα)和维甲酸β受体(retinoic acid receptor beta,RARβ)mRNA相对表达量明显高于Normal组(P<0.01).atRA组TGF-β1 mRNA相对表达量明显高于Control组,atRA+BMS 195614组TGF-β1 mRNA相对表达量明显低于atRA组(P<0.01).结论 atRA可以抑制LPS诱导小鼠附睾上皮细胞炎性反应,其分子机制可能是通过与RARα受体结合上调TGF-β1的表达而抑制其抗炎反应.

目的 探讨核因子-κB(NF-κB)/白细胞介素1β(IL-1β)在脂多糖(LPS)诱导小鼠附睾炎中的作用机制.方法 40只雄性小鼠按随机数字表法分为3组,LPS组30只,磷酸盐缓冲液(PBS)组(对照)5只,LPS+JSH-23组5只.LPS组小鼠于造模0、6、12、24、48h及3周,PBS组、LPS+JSH-23组分别于造模3周采用颈椎脱臼法处死,收集血清及附睾;观察LPS小鼠血清、附睾IL-1β浓度及mRNA表达水平变化,同时比较LPS组与PBS组造模3周后附睾精子常规参数,以及3组小鼠附睾NF-κB p65蛋白表达及血清、附睾IL-1β浓度及附睾组织mRNA表达水平,血清睾酮浓度.结果 与0h比较,LPS组小鼠6、12、24h血清、附睾IL-1β浓度及附睾组织mRNA表达水平明显升高,且呈时间依赖性(P＜0.05);至48h开始降低(P＜0.05).造模3周,LPS组精子总数、活动精子百分比、前向运动精子百分比、非前向运动精子百分比较PBS组均明显降低(均P＜0.05),不活动精子百分比高于PBS组(均P＜0.05).与PBS组比较,LPS组小鼠附睾组织NF-κB p65蛋白表达上调(P＜0.05),LPS+JSH-23组明显下调(P＜0.05).与PBS组比较,LPS组小鼠血清、附睾IL-1β浓度及附睾组织mRNA表达水平均明显升高(均P＜0.05),LPS+JSH-23组较LPS组明显降低(均P＜0.05).LPS组小鼠血清睾酮浓度较PBS组明显降低(P＜0.05),LPS+JSH-23组较LPS组明显升高(P＜0.05).结论 LPS能显著诱导小鼠附睾炎中IL-1β表达,而NF-κB抑制剂能有效抑制LPS诱导小鼠附睾炎中炎症因子IL-1β的产生,进而抑制小鼠附睾的炎性反应.

目的 探讨核因子E2相关因子2(nuclear factor E2-related factor,Nrf2)、醌氧化还原酶(triphosphopyridine nucleotide quinine oxidoreductase,NQO1)在肾透明细胞癌中的表达及其意义.方法 应用免疫组织化学法检测52例肾透明细胞癌及正常肾组织(癌旁＞ 4cm处正常肾组织,病理学检测证实)Nrf2、NQO1蛋白的表达,采用逆转录聚合酶链反应法检测36例肾透明细胞癌及正常肾组织Nrf2、NQO1mRNA的表达.结果 肾透明细胞癌组织Nrf2、NQO1蛋白及mRNA的表达明显高于正常肾组织(P＜0.05).同时Nrf2蛋白表达与NQO1蛋白表达呈正相关(rs=0.594,P＜0.05).结论 Nrf2与NQO1在肾透明细胞癌中表达升高,可能成为评价肾透明细胞癌发生、发展的生物学指标.