Pub Date : 2025-11-25eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf074
Danbee Kang, Jihye Heo, Ki Hong Choi, Taegyun Park, Ji-Hee Sung, Taek Kyu Park, Joo Myung Lee, Juhee Cho, Jeong Hoon Yang, Young Bin Song, Joo-Yong Hahn, Seung-Hyuk Choi, Hyeon-Cheol Gwon, Soo-Young Oh
<p><strong>Study question: </strong>Is maternal pre-existing atherosclerotic cardiovascular disease (ASCVD) associated with neonatal and long-term offspring outcomes?</p><p><strong>Summary answer: </strong>Maternal pre-existing ASCVD is independently associated with consistent increases in neonatal and early childhood adverse outcomes.</p><p><strong>What is known already: </strong>Maternal cardiovascular health may influence offspring development through intrauterine and early-life mechanisms. However, the impact of maternal pre-existing ASCVD on neonatal and long-term offspring's neurodevelopmental outcomes remains poorly understood.</p><p><strong>Study design size duration: </strong>We conducted a nationwide cohort study linking maternal and child health data from the Korean National Health Insurance Service between 2005 and 2019.</p><p><strong>Participants/materials setting methods: </strong>Pre-existing ASCVD was defined by diagnostic codes for myocardial infarction, ischemic stroke, or angina prior to conception. Offspring outcomes included neonatal complications (congenital malformations, sepsis, neonatal intensive care unit admission) and neurodevelopmental disorders (developmental delay, seizure, or attention-deficit hyperactivity disorder), with follow-up through 2020. Among 5 461 222 live births (3 640 815 unique mothers), 145 315 (2.7%) were delivered by women with pre-existing ASCVD before pregnancy. Propensity score matching (1:4) was used to adjust for baseline maternal characteristics.</p><p><strong>Main results and the role of chance: </strong>Offspring of mothers with ASCVD had increased risk of congenital malformations (adjusted odds ratio [aOR] 1.09, 95% CI: 1.07-1.12), neonatal intensive care unit admission (aOR 1.19, 95% CI: 1.16-1.22), and neonatal sepsis (aOR 1.11, 95% CI: 1.07-1.15). The risk of neurodevelopmental disorders was also elevated (adjusted hazard ratio 1.08, 95% CI: 1.07-1.10). The absolute risk differences were consistent regardless of the presence of adverse pregnancy outcomes during pregnancy.</p><p><strong>Limitations reason for caution: </strong>As with all observational studies, residual confounding could not be ruled out. Only live births are included.</p><p><strong>Wider implications of the findings: </strong>Maternal pre-existing ASCVD was associated with modest but consistent increases in neonatal and early childhood adverse outcomes. These associations appeared to persist regardless of the presence of adverse pregnancy outcomes, suggesting a possible independent contribution of maternal ASCVD on offspring development. Our findings suggest the importance of identifying and monitoring pregnancies of women with cardiovascular disease and indicate that early neurodevelopmental surveillance may be considered in affected children.</p><p><strong>Study funding/competing interests: </strong>This study was supported by the Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of
{"title":"Association of maternal pre-existing atherosclerotic cardiovascular disease and neonatal and long-term offspring outcomes: a nationwide mother-child paired cohort.","authors":"Danbee Kang, Jihye Heo, Ki Hong Choi, Taegyun Park, Ji-Hee Sung, Taek Kyu Park, Joo Myung Lee, Juhee Cho, Jeong Hoon Yang, Young Bin Song, Joo-Yong Hahn, Seung-Hyuk Choi, Hyeon-Cheol Gwon, Soo-Young Oh","doi":"10.1093/hropen/hoaf074","DOIUrl":"10.1093/hropen/hoaf074","url":null,"abstract":"<p><strong>Study question: </strong>Is maternal pre-existing atherosclerotic cardiovascular disease (ASCVD) associated with neonatal and long-term offspring outcomes?</p><p><strong>Summary answer: </strong>Maternal pre-existing ASCVD is independently associated with consistent increases in neonatal and early childhood adverse outcomes.</p><p><strong>What is known already: </strong>Maternal cardiovascular health may influence offspring development through intrauterine and early-life mechanisms. However, the impact of maternal pre-existing ASCVD on neonatal and long-term offspring's neurodevelopmental outcomes remains poorly understood.</p><p><strong>Study design size duration: </strong>We conducted a nationwide cohort study linking maternal and child health data from the Korean National Health Insurance Service between 2005 and 2019.</p><p><strong>Participants/materials setting methods: </strong>Pre-existing ASCVD was defined by diagnostic codes for myocardial infarction, ischemic stroke, or angina prior to conception. Offspring outcomes included neonatal complications (congenital malformations, sepsis, neonatal intensive care unit admission) and neurodevelopmental disorders (developmental delay, seizure, or attention-deficit hyperactivity disorder), with follow-up through 2020. Among 5 461 222 live births (3 640 815 unique mothers), 145 315 (2.7%) were delivered by women with pre-existing ASCVD before pregnancy. Propensity score matching (1:4) was used to adjust for baseline maternal characteristics.</p><p><strong>Main results and the role of chance: </strong>Offspring of mothers with ASCVD had increased risk of congenital malformations (adjusted odds ratio [aOR] 1.09, 95% CI: 1.07-1.12), neonatal intensive care unit admission (aOR 1.19, 95% CI: 1.16-1.22), and neonatal sepsis (aOR 1.11, 95% CI: 1.07-1.15). The risk of neurodevelopmental disorders was also elevated (adjusted hazard ratio 1.08, 95% CI: 1.07-1.10). The absolute risk differences were consistent regardless of the presence of adverse pregnancy outcomes during pregnancy.</p><p><strong>Limitations reason for caution: </strong>As with all observational studies, residual confounding could not be ruled out. Only live births are included.</p><p><strong>Wider implications of the findings: </strong>Maternal pre-existing ASCVD was associated with modest but consistent increases in neonatal and early childhood adverse outcomes. These associations appeared to persist regardless of the presence of adverse pregnancy outcomes, suggesting a possible independent contribution of maternal ASCVD on offspring development. Our findings suggest the importance of identifying and monitoring pregnancies of women with cardiovascular disease and indicate that early neurodevelopmental surveillance may be considered in affected children.</p><p><strong>Study funding/competing interests: </strong>This study was supported by the Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf074"},"PeriodicalIF":11.1,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf073
Liu Jiang, Jiayin Zhou, Haoming Huang, Yan Li, Mingwei Lv, Yueping Zhou, Yuchen Gong, Xinyao Hu, Jie Li, Zhiqi Liao, Xiujuan Tan, Lei Jin, Kun Qian
<p><strong>Study question: </strong>What are the impacts of different male infertility factors on embryological, cumulative pregnancy and neonatal outcomes of IVF/ICSI cycles?</p><p><strong>Summary answer: </strong>Some severe male infertility factors, i.e. severe oligoasthenozoospermia (OAT-S) and non-obstructive azoospermia (NOA), may be negatively associated with fertilization, embryo development, and cumulative live birth rates, but not with neonatal outcomes.</p><p><strong>What is known already: </strong>Previous studies examining the effect of male infertility factors on IVF/ICSI clinical outcomes have drawn contradictory conclusions, largely because the semen quality of male partners could fluctuate due to many factors, and there are many confounding factors from female partners.</p><p><strong>Study design size duration: </strong>This retrospective cohort study involved 4714 males with various semen abnormalities and 10 283 males with normozoospermia whose partners underwent their first IVF/ICSI cycle between January 2018 and September 2022 in the reproductive medicine centre of a university hospital.</p><p><strong>Participants/materials setting methods: </strong>Only couples with infertility caused by fallopian tubal factors, male factors, or unknown reasons were included. The patients were divided into five different groups: normozoospermia (N), mild-moderate male factor (MMF), OAT-S, azoospermia-husband (Azoospermia-H), and azoospermia-donor (Azoospermia-D). The Azoospermia-H group was further divided into obstructive azoospermia (OA) and NOA. We compared rates of fertilization, embryo development, and cumulative pregnancy as well as neonatal outcomes. Reproductive and neonatal outcomes of men with various semen abnormalities were studied through propensity score matching (PSM) comparisons along with corresponding control groups (N) (with matching factors: female age, female BMI, male age, male BMI, ovarian stimulation protocol, number of oocytes obtained, and endometrial thickness). Fertilization outcomes were also compared and stratified by IVF or ICSI.</p><p><strong>Main results and the role of chance: </strong>The mean female ages in the azoospermia, OAT-S, MMF, and N groups were 28.9, 29.4, 31.0, and 31.0 years old, respectively, which were similar between groups after PSM. The normal fertilization rates were significantly reduced in the OAT-S and Azoospermia-H groups compared with the control group in ICSI cycles (68.1% vs 71.5%, <i>P </i>= 0.001; 65.3% vs 72.4%, <i>P </i>< 0.001). The embryo utilization rates were also significantly decreased in the OAT-S and Azoospermia-H groups compared with controls in IVF/ICSI cycles (48.8% vs 57.3%, <i>P </i>< 0.001; 53.9% vs 58.1%, <i>P </i>= 0.001). Regarding pregnancy outcomes, the cumulative live birth rate in the OAT-S group was decreased (66.3% vs 74.5%, OR 0.68, 95% CI: 0.56-0.81). Among azoospermia cases, the NOA group exhibited a lower live birth rate (66.4% vs 75.8%, OR 0.63, 95% C
研究问题：不同男性不育因素对IVF/ICSI周期的胚胎学、累积妊娠和新生儿结局有何影响？总结回答：一些严重的男性不育因素，如严重少弱精子症（OAT-S）和非阻塞性无精子症（NOA），可能与受精、胚胎发育和累计活产率负相关，但与新生儿结局无关。已知情况：先前关于男性不育因素对IVF/ICSI临床结果影响的研究得出了相互矛盾的结论，这主要是因为男性伴侣的精液质量可能因许多因素而波动，而女性伴侣也有许多混杂因素。研究设计规模持续时间：这项回顾性队列研究涉及4714名患有各种精液异常的男性和10283名患有正常精子症的男性，他们的伴侣在2018年1月至2022年9月期间在一所大学医院的生殖医学中心接受了第一次IVF/ICSI周期。受试者/材料设置方法：仅纳入因输卵管因素、男性因素或未知原因导致不孕的夫妇。患者分为5组：无精子症(N)、轻度-中度男性因素（MMF）、OAT-S、无精子-丈夫（Azoospermia-H）和无精子-供体（Azoospermia-D）。无精子症- h组进一步分为阻塞性无精子症（OA）和NOA。我们比较了受精率、胚胎发育、累积妊娠和新生儿结局。通过倾向评分匹配（PSM）与相应的对照组(N)（匹配因素：女性年龄、女性BMI、男性年龄、男性BMI、卵巢刺激方案、获得的卵母细胞数量、子宫内膜厚度）比较，研究各种精液异常男性的生殖和新生儿结局。受精结果也通过IVF或ICSI进行比较和分层。无精子症组、OAT-S组、MMF组、N组女性平均年龄分别为28.9岁、29.4岁、31.0岁、31.0岁，PSM后各组女性平均年龄基本一致。在ICSI周期中，OAT-S组和azoosperia - h组的正常受精率明显低于对照组（68.1% vs 71.5%, P = 0.001; 65.3% vs 72.4%, P P P = 0.001）。关于妊娠结局，OAT-S组的累计活产率下降（66.3% vs 74.5%, OR 0.68, 95% CI: 0.56-0.81）。在无精子症病例中，与对照组相比，NOA组的活产率较低（66.4% vs 75.8%, OR 0.63, 95% CI: 0.40-0.99），而流产率较高（18.2% vs 9.4%, OR 2.15, 95% CI: 1.20-3.85）。未观察到男性不育因素对产科/围产期结局的影响。在IVF/ICSI周期中，MMF组、无精子症- d组、OA组和对照组的生殖和新生儿结局相似。局限性：本研究的主要局限性在于观察性和回顾性设计本身。尽管协变量调整，残余偏倚仍然存在，并且单中心队列限制了其可推广性。研究结果的更广泛意义：这些发现为OAT-S和NOA群体提供了新的见解，他们可以在IVF/ICSI之前进行干预。令人放心的是，IVF/ICSI可能是MMF、无精子症- d和OA组患者有效和安全的方法，避免了额外的药物治疗和相关负担。研究经费利益竞争：本研究由国家重点研发计划基金（No. 2018YFA0108400）资助。资助者在研究设计、数据收集或分析、发表决定或手稿准备中没有任何作用。作者宣称他们没有竞争利益。试验注册号：无。
{"title":"Do different male infertility factors impact embryological, cumulative pregnancy and neonatal outcomes in IVF/ICSI cycles? A retrospective cohort study.","authors":"Liu Jiang, Jiayin Zhou, Haoming Huang, Yan Li, Mingwei Lv, Yueping Zhou, Yuchen Gong, Xinyao Hu, Jie Li, Zhiqi Liao, Xiujuan Tan, Lei Jin, Kun Qian","doi":"10.1093/hropen/hoaf073","DOIUrl":"10.1093/hropen/hoaf073","url":null,"abstract":"<p><strong>Study question: </strong>What are the impacts of different male infertility factors on embryological, cumulative pregnancy and neonatal outcomes of IVF/ICSI cycles?</p><p><strong>Summary answer: </strong>Some severe male infertility factors, i.e. severe oligoasthenozoospermia (OAT-S) and non-obstructive azoospermia (NOA), may be negatively associated with fertilization, embryo development, and cumulative live birth rates, but not with neonatal outcomes.</p><p><strong>What is known already: </strong>Previous studies examining the effect of male infertility factors on IVF/ICSI clinical outcomes have drawn contradictory conclusions, largely because the semen quality of male partners could fluctuate due to many factors, and there are many confounding factors from female partners.</p><p><strong>Study design size duration: </strong>This retrospective cohort study involved 4714 males with various semen abnormalities and 10 283 males with normozoospermia whose partners underwent their first IVF/ICSI cycle between January 2018 and September 2022 in the reproductive medicine centre of a university hospital.</p><p><strong>Participants/materials setting methods: </strong>Only couples with infertility caused by fallopian tubal factors, male factors, or unknown reasons were included. The patients were divided into five different groups: normozoospermia (N), mild-moderate male factor (MMF), OAT-S, azoospermia-husband (Azoospermia-H), and azoospermia-donor (Azoospermia-D). The Azoospermia-H group was further divided into obstructive azoospermia (OA) and NOA. We compared rates of fertilization, embryo development, and cumulative pregnancy as well as neonatal outcomes. Reproductive and neonatal outcomes of men with various semen abnormalities were studied through propensity score matching (PSM) comparisons along with corresponding control groups (N) (with matching factors: female age, female BMI, male age, male BMI, ovarian stimulation protocol, number of oocytes obtained, and endometrial thickness). Fertilization outcomes were also compared and stratified by IVF or ICSI.</p><p><strong>Main results and the role of chance: </strong>The mean female ages in the azoospermia, OAT-S, MMF, and N groups were 28.9, 29.4, 31.0, and 31.0 years old, respectively, which were similar between groups after PSM. The normal fertilization rates were significantly reduced in the OAT-S and Azoospermia-H groups compared with the control group in ICSI cycles (68.1% vs 71.5%, <i>P </i>= 0.001; 65.3% vs 72.4%, <i>P </i>< 0.001). The embryo utilization rates were also significantly decreased in the OAT-S and Azoospermia-H groups compared with controls in IVF/ICSI cycles (48.8% vs 57.3%, <i>P </i>< 0.001; 53.9% vs 58.1%, <i>P </i>= 0.001). Regarding pregnancy outcomes, the cumulative live birth rate in the OAT-S group was decreased (66.3% vs 74.5%, OR 0.68, 95% CI: 0.56-0.81). Among azoospermia cases, the NOA group exhibited a lower live birth rate (66.4% vs 75.8%, OR 0.63, 95% C","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf073"},"PeriodicalIF":11.1,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf070
Haris Imsirovic, Harriet Richardson, Jonas Shellenberger, Maria P Velez
<p><strong>Study question: </strong>Are different types of thyroid cancer treatment among young women associated with adverse reproductive outcomes?</p><p><strong>Summary answer: </strong>All types of thyroid cancer treatment were associated with infertility diagnosis and early menopause, but not associated with premature ovarian insufficiency (POI) or lower childbirth rates.</p><p><strong>What is known already: </strong>Thyroid cancer and/or its treatment may affect thyroid function, and thyroid hormone imbalances may affect reproduction.</p><p><strong>Study design size duration: </strong>Population-based matched cohort study included adolescent and young adult women (AYAs, 15-39 years) treated for thyroid cancer in Ontario, Canada between 1992 and 2019, after they had lived at least 3 years free of recurrence.</p><p><strong>Participants/materials setting methods: </strong>Each participant was matched to five cancer-free women based on age, census subdivision, parity, and year of cancer diagnosis. The study cohort consisted of 6474 women undergoing thyroid cancer treatment and 31 922 women without cancer. Exposure status was determined by thyroid cancer treatment, namely: (i) cancer-free (unexposed; referent), (ii) less than total thyroidectomy (LTT), (iii) total thyroidectomy (TOT), or (iv) total thyroidectomy in combination with radioactive iodine therapy (TOT+RAI). Among the exposed, 3396 (52.5%) received TOT, 1520 had (23.5%) LTT, and 1558 (24.1%) had TOT+RAI. Our main outcomes of interest were infertility diagnosis, POI (i.e. cessation of ovarian function before age 40 years), early menopause (menopause before age 45 years), and childbirth rates. Poisson regression models generated weighted relative risks (wRR) using inverse probability of treatment weighting to adjust for imbalances in baseline characteristics.</p><p><strong>Main results and the role of chance: </strong>Mean (SD) age at thyroid cancer diagnosis was 30.6 (6.1) years. The rate of infertility was 3186/31 922 (10.0%) among unexposed, 177/1520 (11.6%) after LTT, 414/3396 (12.2%) after TOT, and 213/1558 (13.7%) following TOT+RAI. The weighted relative risk (wRR) was 1.26 (1.12-1.39) for LTT, 1.22 (1.13-1.32) for TOT, and 1.34 (1.19-1.48) following TOT+RAI. The rate of early menopause was 713/31 922 (2.2%) among unexposed, 46/1520 (3.0%) after LTT, 78/3396 (2.3%) after TOT, and 54/1558 (3.5%) following TOT+RAI. The wRR was 1.42 (1.09-1.72) for LTT, 1.02 (0.83-1.20) for TOT, and 1.54 (1.21-1.89) following TOT+RAI. The rates of POI and childbirth were similar between the unexposed and treatment groups.</p><p><strong>Limitations reasons for caution: </strong>Misclassification is a possibility when using linkage of administrative databases. Absence of information about thyroid hormone supplementation and TSH levels in the study databases is another limitation. Since the unexposed group consisted of cancer-free women, we cannot distinguish whether the observed associations reflect the
{"title":"Thyroid cancer treatment among adolescents and young adult women and reproductive outcomes: a population-based cohort study.","authors":"Haris Imsirovic, Harriet Richardson, Jonas Shellenberger, Maria P Velez","doi":"10.1093/hropen/hoaf070","DOIUrl":"10.1093/hropen/hoaf070","url":null,"abstract":"<p><strong>Study question: </strong>Are different types of thyroid cancer treatment among young women associated with adverse reproductive outcomes?</p><p><strong>Summary answer: </strong>All types of thyroid cancer treatment were associated with infertility diagnosis and early menopause, but not associated with premature ovarian insufficiency (POI) or lower childbirth rates.</p><p><strong>What is known already: </strong>Thyroid cancer and/or its treatment may affect thyroid function, and thyroid hormone imbalances may affect reproduction.</p><p><strong>Study design size duration: </strong>Population-based matched cohort study included adolescent and young adult women (AYAs, 15-39 years) treated for thyroid cancer in Ontario, Canada between 1992 and 2019, after they had lived at least 3 years free of recurrence.</p><p><strong>Participants/materials setting methods: </strong>Each participant was matched to five cancer-free women based on age, census subdivision, parity, and year of cancer diagnosis. The study cohort consisted of 6474 women undergoing thyroid cancer treatment and 31 922 women without cancer. Exposure status was determined by thyroid cancer treatment, namely: (i) cancer-free (unexposed; referent), (ii) less than total thyroidectomy (LTT), (iii) total thyroidectomy (TOT), or (iv) total thyroidectomy in combination with radioactive iodine therapy (TOT+RAI). Among the exposed, 3396 (52.5%) received TOT, 1520 had (23.5%) LTT, and 1558 (24.1%) had TOT+RAI. Our main outcomes of interest were infertility diagnosis, POI (i.e. cessation of ovarian function before age 40 years), early menopause (menopause before age 45 years), and childbirth rates. Poisson regression models generated weighted relative risks (wRR) using inverse probability of treatment weighting to adjust for imbalances in baseline characteristics.</p><p><strong>Main results and the role of chance: </strong>Mean (SD) age at thyroid cancer diagnosis was 30.6 (6.1) years. The rate of infertility was 3186/31 922 (10.0%) among unexposed, 177/1520 (11.6%) after LTT, 414/3396 (12.2%) after TOT, and 213/1558 (13.7%) following TOT+RAI. The weighted relative risk (wRR) was 1.26 (1.12-1.39) for LTT, 1.22 (1.13-1.32) for TOT, and 1.34 (1.19-1.48) following TOT+RAI. The rate of early menopause was 713/31 922 (2.2%) among unexposed, 46/1520 (3.0%) after LTT, 78/3396 (2.3%) after TOT, and 54/1558 (3.5%) following TOT+RAI. The wRR was 1.42 (1.09-1.72) for LTT, 1.02 (0.83-1.20) for TOT, and 1.54 (1.21-1.89) following TOT+RAI. The rates of POI and childbirth were similar between the unexposed and treatment groups.</p><p><strong>Limitations reasons for caution: </strong>Misclassification is a possibility when using linkage of administrative databases. Absence of information about thyroid hormone supplementation and TSH levels in the study databases is another limitation. Since the unexposed group consisted of cancer-free women, we cannot distinguish whether the observed associations reflect the","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf070"},"PeriodicalIF":11.1,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12671970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145672929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf066
[This corrects the article DOI: 10.1093/hropen/hoaf047.].
[这更正了文章DOI: 10.1093/hropen/hoaf047.]。
{"title":"Correction to: Pregnancy and perinatal outcomes after modified natural cycle-frozen embryo transfers according to size of the dominant follicle on the hCG trigger day.","authors":"","doi":"10.1093/hropen/hoaf066","DOIUrl":"10.1093/hropen/hoaf066","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoaf047.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf066"},"PeriodicalIF":11.1,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12596473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-02eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf065
[This corrects the article DOI: 10.1093/hropen/hoac014.].
[更正文章DOI: 10.1093/hropen/hoac014.]。
{"title":"Correction to: Protocol for developing a core outcome set for male infertility research: an international consensus development study.","authors":"","doi":"10.1093/hropen/hoaf065","DOIUrl":"https://doi.org/10.1093/hropen/hoaf065","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoac014.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf065"},"PeriodicalIF":11.1,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12582369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf069
Di Song, Taoli Ding, Tuan Li, Peng Zhang, Yangyun Zou, Yuanbo Hu, Hong Ye, Yajun Xu, Shengnan Wang, Tuanping Zhou, Sijia Lu, Hongli Yan
<p><strong>Study question: </strong>Can third-generation sequencing (TGS)-based polar body (PB) analysis serve as a viable alternative to conventional trophectoderm (TE) biopsy for preimplantation genetic testing for aneuploidy (PGT-A)?</p><p><strong>Summary answer: </strong>This study demonstrates the feasibility of using TGS and PB biopsy for clinical PGT-A, particularly in advanced maternal age (AMA) patients.</p><p><strong>What is known already: </strong>TE biopsy, the current standard approach for PGT-A, is limited by embryonic mosaicism. Mosaicism potentially leads to false-positive aneuploidy diagnoses, resulting in the discard of genetically normal embryos and compromising the cumulative live birth rates (CLBRs).</p><p><strong>Study design size duration: </strong>A total of 125 oocytes were collected from 30 couples. First (PB1) and second (PB2) polar bodies from 89 oocytes were individually amplified and sequenced, while those from the remaining 36 oocytes were processed jointly (PB1 + PB2). Then, 74 oocytes were successfully fertilized and developed into blastocysts (59.2% blastulation rate), and from these, corresponding TE biopsies were obtained.</p><p><strong>Participants/materials setting methods: </strong>Both PB and TE samples underwent whole-genome amplification (WGA) using multiple annealing and looping-based amplification cycles (MALBAC), followed by next-generation sequencing (NGS; all samples) and TGS (PB samples only). Copy number variation (CNV) analysis was performed for aneuploidy screening. Single-nucleotide polymorphisms (SNPs) from TE samples and parental peripheral blood were analyzed to determine the origin of CNVs and investigate discrepancies between TE- and PB-based PGT-A results. Clinical information from patients was collected for inter-group statistical comparisons.</p><p><strong>Main results and the role of chance: </strong>The amplification success rate was 97.75% (87/89) for PB1 and 92.13% (82/89) for PB2, while the amplification success rate for PB1 + PB2 was 97.22% (35/36), comparable to that of TE-biopsied cells. The concordance rate of CNV results between NGS and TGS was 96.81%, with observed discrepancies primarily attributed to differences in the sizes of segmental imbalances and varying levels of intermediate copy numbers. However, when inferring oocyte ploidy status from PB analysis, the concordance rate with TE-biopsied CNV results (blastocyst formation rate 59.2%) was 75.68% (56/74). Among the 56 embryos with consistent results, the CNV profiles of 40 embryos were identical, while the remaining 16 were embryos with paternal meiotic or mitotic abnormalities. Our results demonstrated a higher euploidy rate with PB-based PGT-A (55.4%) compared to blastocyst-stage PGT-A (43.1%). Additionally, the euploidy rate in oocytes from AMA patients (>38 years) was 40%, which was lower than that in younger patients (≤38 years; 64%).</p><p><strong>Limitations reasons for caution: </strong>PGT-A via PB biopsy is su
{"title":"Rapid and minimally invasive preimplantation genetic testing for aneuploidies (PGT-A) based on polar body and nanopore sequencing: a viable alternative to conventional trophectoderm-based PGT-A?","authors":"Di Song, Taoli Ding, Tuan Li, Peng Zhang, Yangyun Zou, Yuanbo Hu, Hong Ye, Yajun Xu, Shengnan Wang, Tuanping Zhou, Sijia Lu, Hongli Yan","doi":"10.1093/hropen/hoaf069","DOIUrl":"10.1093/hropen/hoaf069","url":null,"abstract":"<p><strong>Study question: </strong>Can third-generation sequencing (TGS)-based polar body (PB) analysis serve as a viable alternative to conventional trophectoderm (TE) biopsy for preimplantation genetic testing for aneuploidy (PGT-A)?</p><p><strong>Summary answer: </strong>This study demonstrates the feasibility of using TGS and PB biopsy for clinical PGT-A, particularly in advanced maternal age (AMA) patients.</p><p><strong>What is known already: </strong>TE biopsy, the current standard approach for PGT-A, is limited by embryonic mosaicism. Mosaicism potentially leads to false-positive aneuploidy diagnoses, resulting in the discard of genetically normal embryos and compromising the cumulative live birth rates (CLBRs).</p><p><strong>Study design size duration: </strong>A total of 125 oocytes were collected from 30 couples. First (PB1) and second (PB2) polar bodies from 89 oocytes were individually amplified and sequenced, while those from the remaining 36 oocytes were processed jointly (PB1 + PB2). Then, 74 oocytes were successfully fertilized and developed into blastocysts (59.2% blastulation rate), and from these, corresponding TE biopsies were obtained.</p><p><strong>Participants/materials setting methods: </strong>Both PB and TE samples underwent whole-genome amplification (WGA) using multiple annealing and looping-based amplification cycles (MALBAC), followed by next-generation sequencing (NGS; all samples) and TGS (PB samples only). Copy number variation (CNV) analysis was performed for aneuploidy screening. Single-nucleotide polymorphisms (SNPs) from TE samples and parental peripheral blood were analyzed to determine the origin of CNVs and investigate discrepancies between TE- and PB-based PGT-A results. Clinical information from patients was collected for inter-group statistical comparisons.</p><p><strong>Main results and the role of chance: </strong>The amplification success rate was 97.75% (87/89) for PB1 and 92.13% (82/89) for PB2, while the amplification success rate for PB1 + PB2 was 97.22% (35/36), comparable to that of TE-biopsied cells. The concordance rate of CNV results between NGS and TGS was 96.81%, with observed discrepancies primarily attributed to differences in the sizes of segmental imbalances and varying levels of intermediate copy numbers. However, when inferring oocyte ploidy status from PB analysis, the concordance rate with TE-biopsied CNV results (blastocyst formation rate 59.2%) was 75.68% (56/74). Among the 56 embryos with consistent results, the CNV profiles of 40 embryos were identical, while the remaining 16 were embryos with paternal meiotic or mitotic abnormalities. Our results demonstrated a higher euploidy rate with PB-based PGT-A (55.4%) compared to blastocyst-stage PGT-A (43.1%). Additionally, the euploidy rate in oocytes from AMA patients (>38 years) was 40%, which was lower than that in younger patients (≤38 years; 64%).</p><p><strong>Limitations reasons for caution: </strong>PGT-A via PB biopsy is su","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf069"},"PeriodicalIF":11.1,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12627406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf068
Anna Mathilde Yde, Lotte Berdiin Colmorn, Amalie Somuncu Johansen, Elisabeth Clare Larsen, Anja Pinborg, Kirsten Tryde Macklon
<p><strong>Study question: </strong>What is the return rate for the use of ovarian tissue cryopreserved for fertility preservation prior to gonadotoxic treatment?</p><p><strong>Summary answer: </strong>The return rate for the use of ovarian tissue cryopreserved for fertility preservation prior to gonadotoxic treatment is modest, with most studies reporting rates of ≤5%.</p><p><strong>What is known already: </strong>A considerable number of years have passed since ovarian tissue cryopreservation (OTC) was first implemented for fertility preservation, and many studies now provide long-term follow-up data, including return rates. This allows for a more comprehensive evaluation of OTC as a fertility preservation option and of the characteristics of the population to whom it is offered.</p><p><strong>Study design size duration: </strong>We searched PubMed, EMBASE, and the Cochrane Library for MeSH words, Emtree terms, and text words related to return rates for the use of ovarian tissue cryopreserved prior to gonadotoxic treatment up to March 2025, in the English language. There were no limitations regarding the year of publication.</p><p><strong>Participants/materials setting methods: </strong>Each study was screened independently by two reviewers who were blinded to each other's choices. We included studies reporting the proportion of women who returned for autologous ovarian tissue transplantation (AOTT) among those who had undergone OTC. We excluded studies in languages other than English, abstracts without full text, letters to the editor, and case series involving fewer than 25 females undergoing OTC. Risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Cohort Studies. The overall certainty of evidence was assessed using GRADE (grading of recommendations, assessment, development, and evaluation).</p><p><strong>Main results and the role of chance: </strong>Out of 2748 studies, 25 were included in the review. All studies were cohort studies that included from 26 to 2475 participants. Of the 25 studies, 18 reported a return rate of ≤5%, 6 reported a return rate of >5 to ≤10% while only 1 study reported a return rate of 14%. The overall quality of the studies in reporting the return rate for the use of cryopreserved ovarian tissue, as assessed using GRADE, was moderate.</p><p><strong>Limitations reasons for caution: </strong>In most studies, follow-up occurred within the overall study period, and only one study reported a minimum follow-up duration. Since AOTT may occur several years after OTC, limited follow-up time may bias the results. Most studies included both pediatric patients and adults undergoing OTC, without accounting for participants who had not yet reached reproductive age or desired pregnancy when calculating return rates at the end of follow-up.</p><p><strong>Wider implications of the findings: </strong>The modest utilization rates found in this study emphasize the need for careful consider
{"title":"Return rates for the use of ovarian tissue cryopreserved prior to gonadotoxic treatment as fertility preservation: a systematic review.","authors":"Anna Mathilde Yde, Lotte Berdiin Colmorn, Amalie Somuncu Johansen, Elisabeth Clare Larsen, Anja Pinborg, Kirsten Tryde Macklon","doi":"10.1093/hropen/hoaf068","DOIUrl":"10.1093/hropen/hoaf068","url":null,"abstract":"<p><strong>Study question: </strong>What is the return rate for the use of ovarian tissue cryopreserved for fertility preservation prior to gonadotoxic treatment?</p><p><strong>Summary answer: </strong>The return rate for the use of ovarian tissue cryopreserved for fertility preservation prior to gonadotoxic treatment is modest, with most studies reporting rates of ≤5%.</p><p><strong>What is known already: </strong>A considerable number of years have passed since ovarian tissue cryopreservation (OTC) was first implemented for fertility preservation, and many studies now provide long-term follow-up data, including return rates. This allows for a more comprehensive evaluation of OTC as a fertility preservation option and of the characteristics of the population to whom it is offered.</p><p><strong>Study design size duration: </strong>We searched PubMed, EMBASE, and the Cochrane Library for MeSH words, Emtree terms, and text words related to return rates for the use of ovarian tissue cryopreserved prior to gonadotoxic treatment up to March 2025, in the English language. There were no limitations regarding the year of publication.</p><p><strong>Participants/materials setting methods: </strong>Each study was screened independently by two reviewers who were blinded to each other's choices. We included studies reporting the proportion of women who returned for autologous ovarian tissue transplantation (AOTT) among those who had undergone OTC. We excluded studies in languages other than English, abstracts without full text, letters to the editor, and case series involving fewer than 25 females undergoing OTC. Risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Cohort Studies. The overall certainty of evidence was assessed using GRADE (grading of recommendations, assessment, development, and evaluation).</p><p><strong>Main results and the role of chance: </strong>Out of 2748 studies, 25 were included in the review. All studies were cohort studies that included from 26 to 2475 participants. Of the 25 studies, 18 reported a return rate of ≤5%, 6 reported a return rate of >5 to ≤10% while only 1 study reported a return rate of 14%. The overall quality of the studies in reporting the return rate for the use of cryopreserved ovarian tissue, as assessed using GRADE, was moderate.</p><p><strong>Limitations reasons for caution: </strong>In most studies, follow-up occurred within the overall study period, and only one study reported a minimum follow-up duration. Since AOTT may occur several years after OTC, limited follow-up time may bias the results. Most studies included both pediatric patients and adults undergoing OTC, without accounting for participants who had not yet reached reproductive age or desired pregnancy when calculating return rates at the end of follow-up.</p><p><strong>Wider implications of the findings: </strong>The modest utilization rates found in this study emphasize the need for careful consider","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf068"},"PeriodicalIF":11.1,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12638063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145590030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-24eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoaf064
Veronica Bandini, Sonia Cipriani, Chiara Pillinini, Stefano Angioni, Ludovica Bartiromo, Anna Biasioli, Massimo Candiani, Valerio Carletti, Maurizio Nicola D'Alterio, Domenico Incandela, Lucia Lazzeri, Antonio Maiorana, Ludovico Muzii, Alessio Perandini, Federica Perelli, Maria Grazia Porpora, Diego Raimondo, Valentino Remorgida, Giulia Rovero, Federica Savasta, Stefano Scarperi, Matteo Schimberni, Renato Seracchioli, Eugenio Solima, Giuseppe Sorrenti, Roberta Venturella, Michele Vignali, Giuseppe Vizzielli, Veronica Yacoub, Fulvio Zullo, Errico Zupi, Paolo Vercellini
<p><strong>Study question: </strong>Are endometriotic lesions affecting bilateral organs or anatomical structures distributed symmetrically on both sides of the body?</p><p><strong>Summary answer: </strong>The left-sided preponderance of pelvic endometriotic lesions, and the right-sided dominance of thoracic and inguinal lesions, suggest that endometriotic lesions exhibit a non-random, asymmetric lateral distribution.</p><p><strong>What is known already: </strong>Evaluating the anatomical distribution of endometriotic lesions may elucidate the underlying pathogenic mechanism(s) of the disease. If the coelomic metaplasia or embryonic cell remnant theory is correct, a symmetrical right-left pattern would be expected. Conversely, retrograde menstruation would likely result in asymmetrical distribution, influenced by gravity, peritoneal fluid circulation, and anatomical niches.</p><p><strong>Study design size duration: </strong>This systematic review with meta-analysis included full-length, English-language articles published up to 10 June 2024. Literature searches were performed in PubMed/Medline and Embase databases with the keyword 'endometriosis', 'lateral', 'distribution', 'right', 'left', and 'asymmetry'.</p><p><strong>Participants/materials setting methods: </strong>The review focused on anatomical structures commonly affected by endometriosis with surgically defined right or left laterality: ovaries, uterosacral ligaments, colon, ureters, inguinal regions, and hemithorax (diaphragm, pleura, lungs). Case reports were excluded. Risk of bias was assessed using ROBINS-I for non-randomized studies and a dedicated tool for case series. Meta-analyses of proportions were conducted in R. Heterogeneity was quantified using the <i>I</i> <sup>2</sup> statistic. Funnel plots for publication bias and Egger tests were performed using Stata.</p><p><strong>Main results and the role of chance: </strong>Of 6356 articles screened, 154 met the inclusion criteria. A statistically significant left-sided preponderance was observed for ovarian (58%; 95% CI: 57-60%; <i>P < </i>0.001), uterosacral ligament (56%; 95% CI: 54-59%; <i>P < </i>0.001), ureteral (71%; 95% CI: 67-76%; <i>P < </i>0.001), and bowel (72%; 95% CI: 64-79%; <i>P < </i>0.001) lesions, whereas thoracic (98%; 95% CI: 96-100%; <i>P < </i>0.001) and inguinal (92%; 95% CI: 83-98%; <i>P < </i>0.001) lesions were predominantly right-sided. These findings were confirmed in the sensitivity analyses. Egger's test indicated a possible small study effect only for ovarian lesions (<i>P </i>= 0.012).</p><p><strong>Limitations reasons for caution: </strong>The preponderance of retrospective studies, the variability in surgical procedures, and the potential difficulties in accurately distinguishing unilateral from bilateral lesions may have influenced the magnitude of the estimated difference. However, the large patient cohorts, geographical diversity, and consistent asymmetry across lesion types strengthen the resu
研究问题：子宫内膜异位症病变是否影响双侧器官或解剖结构在身体两侧对称分布？总结回答：左侧占优势的盆腔子宫内膜异位症病变，右侧占优势的胸腔和腹股沟病变，提示子宫内膜异位症病变表现出非随机、不对称的外侧分布。已知情况：评估子宫内膜异位症病变的解剖分布可能阐明该疾病的潜在致病机制。如果体腔化生或胚胎细胞残体理论是正确的，一个对称的左右模式将是预期的。相反，月经逆行可能会导致不对称分布，受重力、腹膜液体循环和解剖壁龛的影响。研究设计规模持续时间：本系统综述采用荟萃分析，纳入截至2024年6月10日发表的完整英文文章。在PubMed/Medline和Embase数据库中进行文献检索，关键词为“子宫内膜异位症”、“横向”、“分布”、“右”、“左”和“不对称”。参与者/材料设置方法：本综述集中于手术确定的左右侧子宫内膜异位症常见的解剖结构：卵巢、子宫骶韧带、结肠、输尿管、腹股沟区域和半胸（隔膜、胸膜、肺）。病例报告被排除在外。对非随机研究使用ROBINS-I评估偏倚风险，对病例系列使用专用工具。在r中进行了比例的荟萃分析，异质性采用i2统计量进行量化。使用Stata进行发表偏倚和Egger检验的漏斗图。主要结果和偶然性的作用：筛选的6356篇文章中，154篇符合纳入标准。卵巢（58%;95% CI: 57-60%; P 0.001）、子宫骶韧带（56%;95% CI: 54-59%; P 0.001）、输尿管（71%;95% CI: 67-76%; P 0.001）和肠（72%;95% CI: 64-79%; P 0.001）病变以左侧为主，而胸部（98%;95% CI: 96-100%; P 0.001）和腹股沟（92%;95% CI: 83-98%; P 0.001）病变以右侧为主。这些发现在敏感性分析中得到证实。Egger’s检验表明，只有卵巢病变可能存在较小的研究效应（P = 0.012）。注意的局限性：回顾性研究的优势，手术方法的可变性，以及准确区分单侧和双侧病变的潜在困难可能影响了估计差异的大小。然而，庞大的患者队列、地理多样性和病变类型之间一致的不对称性加强了结果的有效性和普遍性。研究结果的更广泛意义：子宫内膜异位症病变的分布模式，包括在骨盆和上腹部/胸部观察到的相反的不对称，可以通过影响返流子宫内膜细胞播散和植入的因素来解释。然而，体腔化生理论或胚胎细胞残体理论也不能解释这一现象。这可能具有重要的临床意义，为二级预防策略提供致病基础。研究经费/竞争利益：本文的开放获取设施由意大利卫生部，当前研究IRCCS Ca' Granda Ospedale Maggiore Policlinico资助。P.V.是《人类生殖开放》、《加拿大妇产科杂志》和《斯堪的纳维亚妇产科学报》国际编辑委员会的成员；从威科集团（Wolters Kluwer）获得了《UpToDate》章节的版税。所有其他作者声明无利益冲突。注册号：CRD42024511356 （PROSPERO）。
{"title":"Lateral distribution of endometriotic lesions: the anatomical recesses hypothesis. A systematic review and meta-analysis.","authors":"Veronica Bandini, Sonia Cipriani, Chiara Pillinini, Stefano Angioni, Ludovica Bartiromo, Anna Biasioli, Massimo Candiani, Valerio Carletti, Maurizio Nicola D'Alterio, Domenico Incandela, Lucia Lazzeri, Antonio Maiorana, Ludovico Muzii, Alessio Perandini, Federica Perelli, Maria Grazia Porpora, Diego Raimondo, Valentino Remorgida, Giulia Rovero, Federica Savasta, Stefano Scarperi, Matteo Schimberni, Renato Seracchioli, Eugenio Solima, Giuseppe Sorrenti, Roberta Venturella, Michele Vignali, Giuseppe Vizzielli, Veronica Yacoub, Fulvio Zullo, Errico Zupi, Paolo Vercellini","doi":"10.1093/hropen/hoaf064","DOIUrl":"10.1093/hropen/hoaf064","url":null,"abstract":"<p><strong>Study question: </strong>Are endometriotic lesions affecting bilateral organs or anatomical structures distributed symmetrically on both sides of the body?</p><p><strong>Summary answer: </strong>The left-sided preponderance of pelvic endometriotic lesions, and the right-sided dominance of thoracic and inguinal lesions, suggest that endometriotic lesions exhibit a non-random, asymmetric lateral distribution.</p><p><strong>What is known already: </strong>Evaluating the anatomical distribution of endometriotic lesions may elucidate the underlying pathogenic mechanism(s) of the disease. If the coelomic metaplasia or embryonic cell remnant theory is correct, a symmetrical right-left pattern would be expected. Conversely, retrograde menstruation would likely result in asymmetrical distribution, influenced by gravity, peritoneal fluid circulation, and anatomical niches.</p><p><strong>Study design size duration: </strong>This systematic review with meta-analysis included full-length, English-language articles published up to 10 June 2024. Literature searches were performed in PubMed/Medline and Embase databases with the keyword 'endometriosis', 'lateral', 'distribution', 'right', 'left', and 'asymmetry'.</p><p><strong>Participants/materials setting methods: </strong>The review focused on anatomical structures commonly affected by endometriosis with surgically defined right or left laterality: ovaries, uterosacral ligaments, colon, ureters, inguinal regions, and hemithorax (diaphragm, pleura, lungs). Case reports were excluded. Risk of bias was assessed using ROBINS-I for non-randomized studies and a dedicated tool for case series. Meta-analyses of proportions were conducted in R. Heterogeneity was quantified using the <i>I</i> <sup>2</sup> statistic. Funnel plots for publication bias and Egger tests were performed using Stata.</p><p><strong>Main results and the role of chance: </strong>Of 6356 articles screened, 154 met the inclusion criteria. A statistically significant left-sided preponderance was observed for ovarian (58%; 95% CI: 57-60%; <i>P < </i>0.001), uterosacral ligament (56%; 95% CI: 54-59%; <i>P < </i>0.001), ureteral (71%; 95% CI: 67-76%; <i>P < </i>0.001), and bowel (72%; 95% CI: 64-79%; <i>P < </i>0.001) lesions, whereas thoracic (98%; 95% CI: 96-100%; <i>P < </i>0.001) and inguinal (92%; 95% CI: 83-98%; <i>P < </i>0.001) lesions were predominantly right-sided. These findings were confirmed in the sensitivity analyses. Egger's test indicated a possible small study effect only for ovarian lesions (<i>P </i>= 0.012).</p><p><strong>Limitations reasons for caution: </strong>The preponderance of retrospective studies, the variability in surgical procedures, and the potential difficulties in accurately distinguishing unilateral from bilateral lesions may have influenced the magnitude of the estimated difference. However, the large patient cohorts, geographical diversity, and consistent asymmetry across lesion types strengthen the resu","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoaf064"},"PeriodicalIF":11.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-22eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf067
Narumi Ogonuki, Toshiaki Hino, Yasuhiro Fujiwara, Yuki Osawa, Seiya Mizuno, Fumihiro Sugiyama, Tetsuo Kunieda, Junko Otsuki, Seiya Oura, Tamio Furuse, Yuki Okada, Masaru Tamura, Elena de la Casa-Esperon, Masahito Ikawa, Kimiko Inoue, Atsuo Ogura
<p><strong>Study question: </strong>At which arrest stage can spermatocytes be rescued by injection into meiotic oocytes?</p><p><strong>Summary answer: </strong>In mice, spermatocytes arrested at the diplotene stage, but not at the pachytene stage, can resume meiosis within immature oocytes and support full-term embryonic development.</p><p><strong>What is known already: </strong>In mice, at least some of the spermatocyte arrest mutations can be overcome by injecting spermatocytes into immature oocytes.</p><p><strong>Study design size duration: </strong>The study was carried out from October 2019 to April 2025. Adult azoospermic mice (at 4-26 weeks of age) from nine strains carrying spermatocyte arrest mutations were used as spermatocyte donors. Adult B6D2F1 females at 9-12 weeks of age were used as oocyte donors for spermatocyte injection. Adult ICR strain pseudopregnant females at 9-12 weeks of age were used as recipients for embryo transfer experiments.</p><p><strong>Participants/materials setting methods: </strong>The most advanced stage of spermatocytes from each mutant strain was assessed by chromosome spread analysis. These most advanced spermatocytes of each strain were injected into metaphase I (MI) oocytes. About half a volume of the ooplasm had been removed from the recipient oocytes to ensure more stable chromosome behaviours during meiosis. The spermatocyte-injected oocytes were allowed to mature <i>in vitro</i> to the metaphase II (MII) stage, and their ooplasm was refreshed with the ooplasm from intact MII oocytes. After activation with SrCl<sub>2</sub>, the reconstructed oocytes that reached the 2-cell stage were transferred into the oviducts of pseudopregnant females. On Day 19.5, recipient females were euthanized and their uteri were examined for live foetuses.</p><p><strong>Main results and the role of chance: </strong>Based on spermatocyte spread analysis, sperm mutants were categorized into three classes: Class 1, arrest at mid-diplotene or later stage; Class 2, arrest at early diplotene stage; and Class 3, arrest at pachytene stage. All four Class 1 mutants could resume normal meiosis following injection into MI oocytes, as evidenced by births of normal offspring. Similarly, one of two Class 2 mutants could be rescued, but the other could not. By contrast, three Class 3 mutants did not support embryo development to term because of complete implantation failure, indicating that reconstructed embryos carried severe chromosomal aberrations.</p><p><strong>Large-scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>The number of mutant strains examined was limited. Nevertheless, the findings were consistent: the more advanced the arrest stage of spermatocytes, the higher the likelihood of a successful rescue.</p><p><strong>Wider implications of the findings: </strong>In humans, a considerable proportion of spermatogenic arrest occurs at the primary spermatocyte stage. Spermatocyte injection might be an
研究问题：在哪个停滞阶段精子细胞可以被注射到减数分裂卵母细胞中抢救？在小鼠中，在二倍体期（而非粗倍体期）停滞的精母细胞可以在未成熟卵母细胞内恢复减数分裂并支持足月胚胎发育。已知情况：在小鼠中，通过将精母细胞注射到未成熟的卵母细胞中，至少可以克服一些精母细胞阻滞突变。研究设计规模持续时间：该研究于2019年10月至2025年4月进行。来自9株携带精子细胞阻滞突变的成年无精子小鼠（4-26周龄）被用作精子细胞供体。9-12周龄的成年B6D2F1雌性作为卵母细胞供体进行精母细胞注射。以9 ~ 12周龄的成年ICR株假孕雌鼠为受体进行胚胎移植实验。参与者/材料设置方法：通过染色体扩散分析评估每个突变株的最晚期精母细胞。每个菌株的这些最先进的精细胞被注射到中期I （MI）卵母细胞中。为了确保减数分裂过程中更稳定的染色体行为，从受体卵母细胞中取出了大约一半体积的卵浆。注射精母细胞的卵母细胞在体外成熟至中期II期（MII），其卵浆被完整的MII期卵母细胞的卵浆更新。经SrCl2激活后，重建的卵母细胞达到2细胞期，被转移到假妊娠雌性的输卵管中。在第19.5天，对雌性受体实施安乐死，并检查其子宫内是否有活胎。主要结果和偶然性的作用：根据精母细胞扩散分析，将精子突变体分为三类：1类，在双倍体中期或后期停止；第2类，在早期外交阶段逮捕；第三类，在粗化期停止。所有四种1类突变体在注射到MI卵母细胞后都能恢复正常的减数分裂，正常后代的出生证明了这一点。同样，两个2类突变体中的一个可以获救，而另一个则不能。相比之下，三个3类突变体由于完全着床失败而无法支持胚胎发育至足月，这表明重建的胚胎携带严重的染色体畸变。大规模数据：无。局限性：注意的原因：检测的突变株数量有限。然而，研究结果是一致的：精子细胞的阻滞阶段越晚，成功抢救的可能性就越高。研究结果的更广泛含义：在人类中，相当大比例的生精停止发生在初级精母细胞阶段。精母细胞注射可能是未来治疗人类男性因素性不孕的一种选择。然而，许多伦理和技术挑战仍有待解决，并且必须仔细考虑小鼠和人类之间的生殖生理差异。研究经费/竞争利益：本研究得到了日本科学促进会（Japan Society for Science Promotion to A.O.）（资助号：JP19H05758）、K.I.（资助号：23H04956）、M.I.（资助号：JP23K20043）和no .（资助号：25H01372）的科学研究援助基金（KAKENHI）的支持，以及Castilla-La Mancha大学2023年和2025年的资助，用于在外国大学和研究中心住宿到e.c.e。作者声明他们没有利益冲突。
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Pub Date : 2025-10-15eCollection Date: 2025-01-01DOI: 10.1093/hropen/hoaf063
Francesca Paola Luongo, Irene Ortega Baño, Giuseppe Belmonte, Mariangela Gentile, Eugenio Paccagnini, Andres Salumets, Paola Piomboni, Alice Luddi
Study question: Can menstrual blood-derived organoids (MB-organoids) and human endometrial stromal cells (MB-ESCs) serve as a physiologically relevant, non-invasive model for studying endometrial function and hormonal response?
Summary answer: MB-organoids and ESCs recapitulate key structural and functional features of the endometrium, responding to hormonal stimulation in a manner comparable to biopsy-derived models, supporting their use in reproductive research.
What is known already: Endometrial organoids derived from biopsy samples have provided valuable insights into endometrial physiology and implantation. However, their reliance on invasive tissue sampling limits their clinical and research applications. Menstrual blood contains viable endometrial cells, yet its potential for generating functional three-dimensional (3D) models remains underexplored.
Study design size duration: This cross-sectional, in vitro cell culture study established and characterized 3D-organoids and ESCs derived from menstrual blood, assessing their structural and functional properties as well as their response to hormonal stimulation over a culture period of several weeks. The work was carried out between October 2023 and December 2024, in two European University hospitals.
Participants/materials setting methods: Menstrual blood samples were collected from healthy fertile donors (n = 6). Isolated endometrial cells were cultured using a three-layer gradient system to generate MB-organoids or selected for deriving MB-ESCs. MB-organoids were characterized based on morphological features, including periodic acid-Schiff (PAS) staining for glycogen deposition, scanning electron microscopy (SEM) for pinopode analysis, and immunofluorescence for epithelial (CK8/18) and stromal (vimentin) markers. ESCs were assessed for decidualization by measuring IGFBP-1 and ZBTB16 expression after hormonal stimulation, with mifepristone used to terminate progesterone signaling.
Main results and the role of chance: MB-organoids demonstrated structural and functional characteristics similar to biopsy-derived endometrial organoids, including glycogen accumulation and pinopode formation, indicative of endometrial receptivity. Immunofluorescence confirmed the presence of both epithelial and stromal populations as well as glycodelin A production. MB-ESCs underwent decidualization in response to hormonal stimulation, with IGFBP-1 and ZBTB16 upregulation, which was suppressed by mifepristone, confirming their functional relevance.
Limitations reasons for caution: This in vitro culture system models key endometrial features but lacks the complexity of in vivo conditions. While menstrual blood derived organoids and ESCs respond to hormonal cues, donor variability and the absence of immune
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