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Phthalate exposures, blood coagulation function, and assisted reproductive technology outcomes: Results from the TREE cohort study

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ENVIRONMENTAL RESEARCH 2025年第Pt 2期264卷 120412页

作者： Liu, Chong Liu, Chang-Jiang Tian, Wen-Qu Yao, Wen Miao, Yu Zhang, Min Yuan, Xiao-Qiong Deng, Yan-Ling Lu, Wen-Qing Li, Yu-Feng Zeng, Qiang Shanghai Jiao Tong Univ Sch Med Sch Publ Hlth Dept Environm Hlth Shanghai Peoples R China Chongqing Populat & Family Planning Sci & Technol NHC Key Lab Birth Defects & Reprod Hlth Chongqing Peoples R China Huazhong Univ Sci & Technol Tongji Hosp Tongji Med Coll Reprod Med Ctr 1095 Jiefang Ave Wuhan Hubei Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Minist Educ Key Lab Environm & HlthSch Publ Hlth Wuhan Hubei Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Sch Publ Hlth Minist Environm Protect Wuhan Hubei Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Sch Publ Hlth State Key Lab Environm Hlth incubating Wuhan Hubei Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Sch Publ Hlth Dept Occupat & Environm Hlth Wuhan Hubei Peoples R China Zhengzhou Univ Ctr Reprod Med Affiliated Hosp 3 Zhengzhou Peoples R China Emory Univ Rollins Sch Publ Hlth Gangarosa Dept Environm Hlth Atlanta GA USA

Background: Phthalate exposures have been shown to be inversely associated with reproductive success among women undergoing assisted reproductive technology (ART). However, the underlying mechanisms are unknown. Objectives: To explore blood coagulation function as the mediating role of associations between exposure to phthalates and ART outcomes. Methods: A total of 735 women from the Tongji reproductive and Environmental (TREE) study were included. Urine samples collected at recruitment were quantified for 8 phthalate metabolites, and blood clotting time and platelet indices were also determined. Generalized linear regression, logistic regression, weighted quantile sum (WQS) regression, or Bayesian kernel machine regression (BKMR) models were applied to investigate the associations among individual and mixture of phthalate metabolites, blood coagulation parameters, and ART outcomes. The mediation role of blood coagulation parameters was estimated by mediation analysis. Results: Mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), and molar sum of di(2-ethylhexyl) phthalate metabolites (& sum;DEHP) were positively associated with platelet indices. Phthalate metabolite mixture was also positively associated with platelet count (PLT), mean platelet volume (MPV), and plateletcrit (PCT), whereas inversely associated with international normalized ratio (INR). Meanwhile, PLT and PCT were inversely associated with the odds of implantation success and live birth, while prothrombin time and INR were positively associated with the odds of implantation success. Mediation analyses showed indirect effects of above-mentioned phthalate metabolites and phthalate mixture on the odds of implantation success and live birth through PLT or PCT, with the proportion mediated ranging from 3.44% to 8.96%. Conclusions: Phthalates may increase the risks of ART failure through enhancing blood coagulation fu

关键词： assisted reproductive technology Blood clotting time Phthalate Platelet indices Mediation analysis

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Establishing a predictive model for ectopic pregnancy risk following assisted reproductive technology

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BMC PREGNANCY AND CHILDBIRTH 2025年第1期25卷 1-11页

作者： Li, Jie Dai, Tiantian Liu, Yang Li, Yuanyi Chen, Tailin Chen, Xiaojun Jin, Li Fudan Univ Obstet & Gynecol Hosp Inst Reprod & Dev Shanghai Peoples R China ChangNing Matern & Infant Hlth Inst Shanghai Peoples R China Fudan Univ Sch Publ Hlth Dept Epidemiol Key Lab Publ Hlth SafetyMinist Educ Shanghai Peoples R China Shanghai Jiao Tong Univ Int Peace Maternal & Child Hlth Hosp Sch Med Dept Reprod Endocrinol Shanghai Peoples R China Shanghai Key Lab Embryo Original Dis Shanghai Peoples R China

Background The risk of ectopic pregnancy (EP) is known to increase with assisted reproductive technology (ART), but the specific risk factors are unclear. Methods We screened 6872 cycles for clinical data that met our study's inclusion criteria and conducted univariate and multivariate analyses to identify factors associated with EP and develop a nomogram prediction model for its incidence. Results The multivariate analysis demonstrated that women with polycystic ovary syndrome (PCOS) have an over two-fold increased risk of EP (aOR = 2.07, 95% CI: 1.27-3.36, P = 0.004). Frozen embryo transfer can significantly reduce the risk of EP compared to fresh embryo transfer (aOR = 2.17, 95% CI: 1.62-2.91, P < 0.001). Male infertility factor was associated with a 1.4-fold increased risk of EP (aOR = 1.39, 95% CI: 1.05-1.85,P = 0.021). Each 1 mm increase in endometrial thickness (EMT) is associated with a 15% reduction in the odds of EP(aOR = 0.86, 95% CI: 0.77-0.93, P < 0.001). Women with EP history was associated with 1.4-fold increased risk of EP (aOR = 1.41, 95% CI: 1.01-1.97, P = 0.046). A nomographic prediction model was established based on the results above. The area under the curve (AUC) for the model predicting EP following ART is 0.624, whereas in the external validation set, it is 0.618. Conclusions Our findings indicate that PCOS increases the risk of EP after ART, and fresh embryo transfer is also linked to higher EP rates. We developed a nomogram to predict and mitigate the incidence of EP. Trial registration Retrospectively registered.

关键词： Ectopic pregnancy assisted reproductive technology Polycystic ovary syndrome Prediction model Frozen embryo transfer

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Environmental pollution and human fertility: investigating the relationship between PM2.5 exposure and assisted reproductive technology outcomes

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BMC PUBLIC HEALTH 2025年第1期25卷 1-14页

作者： Li, Fei Duan, Xiaoyan Li, Mingming Gao, Yumei Kang, Yuejuan Zheng, WenJun Guo, XueYan Chen, Ying Xinxiang Med Univ PeopleS Hosp Shangqiu 1 Clin Coll Ctr Reprod Med 292 Kaixuan South Rd Shangqiu Henan Peoples R China Zhengzhou Univ Zhengzhou Henan Peoples R China

Objective To investigate the impact of seasonal variations in particulate matter with an aerodynamic diameter of 2.5 mu m or less (PM2.5) exposure on assisted reproductive technology (ART) outcomes. Methods This retrospective study, conducted at the First People's Hospital of Shangqiu, analyzed data from 13,476 patients who underwent ART procedures between February 2018 and December 2022. Patients were categorized based on seasonal PM2.5 exposure levels. A generalized additive model (GAM), linear regression analysis, and multivariate logistic regression were used to assess the relationship between PM2.5 exposure and ART outcomes, including oocyte and embryo quality, pregnancy rates, live birth rates, and miscarriage rates. Results Significant differences were observed in oocyte number, metaphase II (MII) oocyte number, transferable embryos, and good-quality embryos across seasonal PM2.5 exposure subgroups. Pregnancy rates and live birth rates also demonstrated statistically significant variations. Linear regression analysis revealed a consistent negative correlation between PM2.5 concentrations and key ART outcomes. Multivariate logistic regression analysis, adjusting for age and seasonal variations, confirmed a significant negative association between PM2.5 exposure and both pregnancy rates (OR = 0.995, 95% CI: 0.994-0.996, p < 0.001) and live birth rates (OR = 0.996, 95% CI: 0.995-0.997, p < 0.001). However, no significant relationship was found between PM2.5 exposure and miscarriage rates. GAM analysis further identified a nonlinear, threshold-like association between pregnancy outcomes and predictive factors, with significantly higher live birth rates observed in spring, summer, and autumn compared to winter. Conclusions The study complements existing evidence that exposure to PM2.5 can lead to decreased success rates of pregnancy and live births, as well as significantly impact the outcomes of ART. Future research should focus on developing strategies to mitiga

关键词： PM2.5 exposure Environmental factors Seasonal variations Pregnancy rates Live birth assisted reproductive technology

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Sperm chromatin dispersion assay reliability and assisted reproductive technology outcomes: Systematic review and meta-analysis

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ANDROLOGY 2025年第4期13卷 718-730页

作者： Kaiyal, Raneen Sawaid Karna, Keshab Kumar Kuroda, Shinnosuke Sgayer, Inshirah Shlush, Ekaterina Vij, Sarah C. Lundy, Scott D. Cannarella, Rossella Cleveland Clin Fdn Glickman Urol & Kidney Inst Dept Urol Cleveland OH 44195 USA Umass Chan Med Sch Dept Mol Cell & Canc Biol Worcester MA USA Galilee Med Ctr Dept Obstet & Gynecol Nahariyya Israel Bar Ilan Univ Azrieli Fac Med Safed Israel Univ Catania Dept Clin & Expt Med Catania Italy

Objective: Elevated sperm DNA fragmentation has potential implications for semen quality and fertility. The commonly used sperm chromatin dispersion test offers an indirect estimation but has limitations in terms of bias and variability. This study aimed to assess the reliability of the sperm chromatin dispersion assay for predicting assisted reproductive technology outcomes. Materials and methods: This systematic review included studies published until December 2023 that adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Scopus, and Google Scholar databases were searched. Various assisted reproductive technology outcomes in patients with high (>= 30%) versus low (< 30%) sperm DNA fragmentation were compared using a sperm chromatin dispersion assay and including a sub-analysis of intracytoplasmic sperm injection versus in vitro fertilization. A comprehensive meta-analysis software facilitated quantitative analysis with statistical comparisons between cases and controls. Interstudy heterogeneity was assessed, and sensitivity and publication bias tests were performed. Results: Of the 199 abstracts assessed, 64 full-text articles were screened, and 44 articles were qualitatively synthesized. Fourteen articles representing 5346 participants were quantitatively analyzed. Using the sperm chromatin dispersion assay, elevated sperm DNA fragmentation was associated with lower fertilization and embryo cleavage rates. Notably, high sperm DNA fragmentation levels did not affect the clinical pregnancy, implantation, miscarriage, or live birth outcomes. Sub-analysis revealed lower fertilization, embryo cleavage, clinical pregnancy, live birth rates, and higher miscarriage rates in the intracytoplasmic sperm injection subgroup only. Conclusions: The sperm chromatin dispersion assay did not show significant differences in pregnancy or live birth rates between the high- and low-sperm DNA fragmentation groups. Noteworthy, hig

关键词： assisted reproductive technology Halosperm male infertility sperm chromatin dispersion sperm chromatin dispersion assay sperm DNA fragmentation

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Interacting and joint effects of assisted reproductive technology and gestational diabetes mellitus on preterm birth and the mediating role of gestational diabetes mellitus: a cohort study using a propensity score

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JOURNAL OF assisted REPRODUCTION AND GENETICS 2025年第2期42卷 489-498页

作者： Xiang, Yan-Xiao Xu, Zhou Xiao, Rui Yao, Ying-Ling Tang, Xiao-Jun Fu, Li-Juan Geng, Li-Hong Zhong, Zhao-Hui Ding, Yu-Bin Chongqing Med Univ Dept Obstet & Gynecol Women & Childrens Hosp Chongqing 401147 Peoples R China Chongqing Med Univ Sch Publ Hlth Dept Epidemil Joint Int Res Lab Reprod & DevMinist Educ China Chongqing 400016 Peoples R China Sichuan Jinxin Xinan Women & Childrens Hosp Dept Obstet Chengdu 610011 Sichuan Peoples R China Changsha Med Univ Dept Pharmacol Academician Workstat Changsha 410219 Peoples R China

ObjectiveTo investigate whether gestational diabetes mellitus (GDM) mediates the association between assisted reproductive technology (ART) and preterm birth (PTB), and to examine the interaction and joint effects of ART and GDM on *** retrospective cohort study utilized data from 20,721 mothers with singleton live births at Sichuan Jinxin Xinan Women and Children's Hospital from January 2020 to December 2023. The exposures were ART and GDM, and the outcome was PTB. Multivariate logistic regression assessed the separate associations of ART and GDM with PTB. Mediation, interaction, and joint effects were analyzed using R ***1,053 (5.08%) women experienced PTB. ART (OR 1.60;95% CI 1.27-2.03) and GDM (OR 1.51;95% CI 1.19-1.92) were both associated with increased PTB risk. GDM partially mediated the ART-PTB relationship (PM 2.72%;95%CI 0.47%-8.86%). No additive interaction was found between GDM and ART for PTB in the general population. However, a significant additive interaction was observed in women aged >= 35 years (RERI 1.22;95%CI 0.27-2.39). Compared to the spontaneous conception (SC)-non-GDM group, the SC-GDM (OR 1.56;95%CI 1.07-2.29), ART-non-GDM (OR 1.63;95%CI 1.22-2.18), and ART-GDM (OR 2.42;95%CI 1.74-3.37) groups had higher PTB *** was associated with higher PTB risk, partially mediated by GDM. Women undergoing ART who develop GDM may face greater PTB risk than those exposed to only one factor, with a synergistic effect in older pregnancies.

关键词： assisted reproductive technology Gestational diabetes Mellitus Preterm birth Mediating effect Interaction

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Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles

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SCIENTIFIC REPORTS 2025年第1期15卷 1-8页

作者： Ito, Ayumu Katagiri, Yukiko Nakaoka, Kentaro Unagami, Mami Ichizawa, Koichiro Amano, Kenji Tokuda, Yukiko Oigawa, Satoko Yoneyama, Masato Tsuchiya, Takahiro Sekiguchi, Mami Furui, Mayuko Umemura, Nahomi Tamaki, Yuko Nagao, Koichi Nakata, Masahiko Toho Univ Fac Med Dept Obstet & Gynecol Tokyo Japan Toho Univ Omori Med Ctr Dept Obstet & Gynecol 6-11-1 OmorinishiOta Ku Tokyo Japan Toho Univ Omori Med Ctr Reprod Ctr Tokyo Japan Toho Univ Omori Med Ctr Dept Urol Tokyo Japan

We assessed the effects of endometrial injection of embryo culture supernatants on assisted reproductive technology (ART) outcomes in frozen-thawed embryo transfer (FET) cycles. Hormone replacement therapy cycles with blastocyst transfer on day 5 after fertilization were included, excluding cycles potentially affecting implantation. The stimulation of endometrial embryo transfer (SEET) group (118 cycles) received endometrial injections of the embryo culture supernatant, while the blastocyst transfer (BT) group (878 cycles) did not. Maternal age was significantly higher in the SEET than in the BT group (p < 0.05). The implantation, ongoing pregnancy, and live birth rates were significantly lower (all p < 0.05) in the SEET than in the BT group. Clinical pregnancy and miscarriage rates were not significantly different between the groups. Age-adjusted odds ratios (ORs) (95% confidence interval [CI]) for implantation and miscarriage were 1.02(0.69-1.52) and 1.97 (1.04-3.72), respectively, in the SEET group. Multivariate analysis was performed, including female age, BMI, AMH, and other potential factors influencing ART outcomes. The adjusted odds ratios (95% CI) for clinical pregnancy and miscarriage in the SEET group were 1.00 (0.63-1.58) and 2.08 (1.02-4.24), respectively. Additionally, the adjusted odds ratio for miscarriage was 0.732 (0.22-2.47) in patients aged < 37 years and 4.63 (1.61-13.3) in those aged >= 37 years. In conclusion, endometrial injection of the embryo culture supernatant may adversely affect ART outcomes in FET cycles, especially in maternal age >= 37 years.

关键词： Repeated implantation failure Stimulation of endometrium embryo transfer Endometrial injection Embryo culture supernatant Frozen-thawed embryo transfer assisted reproductive technology

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Comprehensive Health Assessment of School-Age Children Conceived by assisted reproductive technology: A Prospective Cohort Follow-Up Study

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BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY 2025年第0期132卷 8-17页

作者： Wang, Jing Chen, Lingling Yong, Yonghong Yu, Xiang Chen, Yin Zhang, Jie Xia, Xinru Cui, Yugui Diao, Feiyang Liu, Jiayin Meng, Yan Nanjing Med Univ Affiliated Hosp 1 Clin Ctr Reprod Med State Key Lab Reprod Med & Offspring Hlth Nanjing Peoples R China Nanjing Med Univ Affiliated Hosp 1 Dept Cardiol Nanjing Peoples R China Nanjing Med Univ Affiliated Hosp 1 Dept Pediat Nanjing Peoples R China

ObjectiveTo assess the comprehensive health status of school-age children conceived through assisted reproductive technology (ART) compared to that of those conceived *** prospective cohort study of children conceived through *** Affiliated Hospital of Nanjing Medical University, *** SampleOne hundred school-age children were enrolled and followed up (51 conceived via ART and 49 naturally conceived (controls)).MethodsA comprehensive health status assessment was performed in children aged 6-12 years, including anthropometric measurements, glucose-lipid metabolism, echocardiography, intelligence, behaviour, vision and hearing. Multivariate regression models were used to adjust for sociodemographic and perinatal *** Outcome MeasuresComprehensive health status of children conceived via *** conceived by ART had similar height, weight, blood pressure, blood glucose and lipid profiles compared to the controls. Echocardiography showed similar cardiac geometric morphology and left/right ventricular diastolic-systolic function between the two groups. ART children had lower carotid intima-media thickness than controls (0.52 +/- 0.11 vs. 0.58 +/- 0.11). Visual acuity, hearing and intellectual and behavioural assessments were similar. An alternating covering test for the eyes showed a higher incidence of abnormal eye movement in the ART group than in the control group (87.76% vs. 68.89%).ConclusionsThe similar overall health status of ART- and naturally conceived children is reassuring for those receiving ART. However, our study shows a possible increase in the incidence of latent exotropia among ART children. Long-term follow-up is warranted to assess the overall health status associated with ART throughout the lifespan.

关键词： assisted reproductive technology children echocardiography glucose and lipid metabolism health heart intelligence psychology and personality vision and hearing

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The effects of e-health care on health outcomes and psychological distress in patients undergoing assisted reproductive technology: A systematic review and meta-analysis of randomized controlled trials

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EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND reproductive BIOLOGY 2025年 305卷 394-403页

作者： Wang, Yan Zhao, Xiaoyan Wang, Yuyang Pu, Yan Sichuan Univ West China Univ Hosp 2 Dept Reprod Med Nursing Chengdu Peoples R China Sichuan Univ Minist Educ Key Lab Birth Defects & Related Dis Women & Childr Chengdu Peoples R China

Background: Many studies have reported that electronic health (e-health) care helps health professionals manage patients undergoing assisted reproductive technology (ART) and improves their reproductive outcomes and psychological distress. However, little is known about the effectiveness of e-health care on the health outcomes of patients undergoing ART. Objectives: This study aimed to evaluate the effectiveness of e-health care on patient-centered health outcomes, such as live birth rate, pregnancy rate, time to pregnancy, etc. as well as psychological distress (i.e., infertility distress and anxiety) among individuals undergoing ART. Design: A systematic review with random-effects or fixed-effects meta-analysis was conducted to compare e-health interventions with usual care in patients undergoing ART. Method: Electronic database, including Medline, EMBASE, Web of Science, CINHAL, and CENTRAL, were systematically searched from the inception to December 01, 2023. The authors independently reviewed the articles based on inclusion and exclusion criteria, extracted data, and assessed risk of bias used the Cochrane Risk of Bias tool version 2.0. Heterogeneity was evaluated with I-2 and Chi-square. We pooled data from each study using fixed-effects meta-analysis if heterogeneity was low. Random-effects meta-analysis was used to pool data with high heterogeneity. Subgroup analysis (i.e., data collection time point) and sensitivity analysis was performed. Result: Data were synthesized from 21 articles covering a total of 6,749 participants (female:6,227;male:522). Pooled analysis showed that e-health care may not increase live birth rate (RR 1.44 95 %CI0.78-2.67, P = 0.25). The clinical pregnancy rate was increased to 1.57 times in the e-health care group compared with the control group (Z = 2.19, P = 0.03) and the e-health care group had an increase in time to pregnancy by 17.40 days than that of the control group (Z = 2.13, P = 0.03). Lower score of Fertility Problem Inv

关键词： Electronic health Infertility assisted reproductive technology Meta-analysis

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The role of granulocyte-macrophage colony-stimulating factor in female assisted reproductive technology treatment: a systematic review and meta-analysis

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JOURNAL OF assisted REPRODUCTION AND GENETICS 2025年第4期42卷 1067-1081页

作者： Yan, Jing Zheng, Lian-wen Xu, Ying Chu, Xiu-ming Zhang, Jing-shun Zhang, Xue-ying Liang, Yan Liu, Shan-shan Fu, Lu-lu Jilin Univ Hosp 2 Reprod Med Ctr Changchun 130000 Peoples R China Jilin Prov FAW Gen Hosp Changchun 130000 Peoples R China

The objective of this study is to explore the impact of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF) in female undergoing assisted reproductive technology (ART) on reproductive outcomes. A literature search was performed using electronic databases (PubMed, EMBASE, Web of Science, CNKI, Wanfang data, Geen Medical, and Cochrane Library). Risk ratio (RR), odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CI) for various outcomes were presented. The publication bias and heterogeneity were determined using funnel plot symmetry and I-2 test separately. The combined results of the RCT studies did not reveal statistical differences between the GM-CSF group and the control group for any outcome indicators. However, our pooling of results showed that after meta-analysis of non-RCT studies, GM-CSF had a positive effect on implantation rate (OR 1.90;95% CI 1.11-3.24), clinical pregnancy rate (OR 1.54;95% CI 1.21-1.95), live birth rate (OR 1.43;95% CI 1.04-1.98), and available embryo rate (OR 1.27;95% CI 1.10-1.46). In conclusion, these results suggest that for a subset of women undergoing ART, GM-CSF may favorably affect CPR, LBR, IR, and available embryo rate (AER).

关键词： Granulocyte-macrophage colony-stimulating factor assisted reproductive technology Intracytoplasmic sperm injection In vitro fertilization Clinical pregnancy rate Miscarriage rate Live birth rate

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Placental expression and methylation of angiogenic factors in assisted reproductive technology pregnancies from India

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EPIGENOMICS 2025年第1期17卷 21-31页

作者： Sundrani, Deepali Kapare, Aishwarya Yadav, Himanshi Randhir, Karuna Gupte, Sanjay Joshi, Sadhana Bharati Vidyapeeth Deemed Univ ICMR Collaborating Ctr Excellence CCoE Interact Res Sch Hlth Affairs Mother & Child Hlth Pune Maharashtra India Gupte Hosp & Res Ctr Dept Obstet & Gynecol Pune Maharashtra India

Aim: This study aims to examine the gene expression and DNA methylation patterns of angiogenic factors in the placentae of Indian women who underwent assisted reproductive technology (ART) procedures and their association with maternal one-carbon metabolites and birth outcome. Methods: Placental gene expression and DNA methylation of angiogenic factors (VEGF, PlGF, FLT-1, KDR) in Indian women who underwent ART procedures (n = 64) and women who conceived naturally (Non-ART) (n = 93) was investigated using RT-qPCR and Epitect Methyl-II PCR assay kits. Maternal plasma one-carbon metabolites were assessed by CMIA technology. Result: Gene expression of FLT-1 and KDR was higher (p < 0.05) in the ART placentae. Placental global DNA methylation levels were higher (p < 0.01) and DNA methylation levels of VEGF promoter were lower (p < 0.05) in ART compared to non-ART women. Maternal plasma folate and vitamin B-12 levels were higher (p < 0.01) in the ART group. Gene expression of PlGF was negatively associated with maternal plasma folate (p < 0.05) whereas KDR was positively associated with maternal plasma homocysteine (p < 0.05). Gene expression of KDR was positively associated with chest circumference of the baby (p < 0.05). Conclusion: Hypomethylation of VEGF and increased expression of FLT-1 and KDR was observed in the placentae of women who underwent ART procedure.

关键词： assisted reproductive technology angiogenic factors gene expression methylation placenta

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