Pub Date : 2024-06-20eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae040
Hannan Al-Lamee, Katie Stone, Simon G Powell, James Wyatt, Andrew J Drakeley, Dharani K Hapangama, Nicola Tempest
<p><strong>Study question: </strong>Does endometrial compaction (EC) help predict pregnancy outcomes in those undergoing ART?</p><p><strong>Summary answer: </strong>EC is associated with a significantly higher clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR), but this does not translate to live birth rate (LBR).</p><p><strong>What is known already: </strong>EC describes the progesterone-induced decrease in endometrial thickness, which may be observed following the end of the proliferative phase, prior to embryo transfer. EC is proposed as a non-invasive tool to help predict pregnancy outcome in those undergoing ART, however, published data is conflicting.</p><p><strong>Study design size duration: </strong>A literature search was carried out by two independent authors using PubMed, Cochrane Library, MEDLINE, Embase, Science Direct, Scopus, and Web of Science from inception of databases to May 2023. All peer-reviewed studies reporting EC and pregnancy outcomes in patients undergoing IVF/ICSI treatment were included.</p><p><strong>Participants/materials setting methods: </strong>The primary outcome is LBR. Secondary outcomes included other pregnancy metrics (positive pregnancy test (PPT), CPR, OPR, miscarriage rate (MR)) and rate of EC. Comparative meta-analyses comparing EC and no EC were conducted for each outcome using a random-effects model if <i>I</i> <sup>2</sup> > 50%. The Mantel-Haenszel method was applied for pooling dichotomous data. Results are presented as odds ratios (OR) with 95% CI.</p><p><strong>Main results and the role of chance: </strong>Out of 4030 screened articles, 21 cohort studies were included in the final analysis (n = 27 857). No significant difference was found between LBR in the EC versus the no EC group (OR 0.95; 95% CI 0.87-1.04). OPR was significantly higher within the EC group (OR 1.61; 95% CI 1.09-2.38), particularly when EC ≥ 15% compared to no EC (OR 3.52; 95% CI 2.36-5.23). CPR was inconsistently defined across the studies, affecting the findings. When defined as a viable intrauterine pregnancy <12 weeks, the EC group had significantly higher CPR than no EC (OR 1.83; 95% CI 1.15-2.92). No significant differences were found between EC and no EC for PPT (OR 1.54; 95% CI 0.97-2.45) or MR (OR 1.06; 95% CI 0.92-1.56). The pooled weighted incidence of EC across all studies was 32% (95% CI 26-38%).</p><p><strong>Limitations reasons for caution: </strong>Heterogeneity due to differences between reported pregnancy outcomes, definition of EC, method of ultrasound, and cycle protocol may account for the lack of translation between CPR/OPR and LBR findings; thus, all pooled data should be viewed with an element of caution.</p><p><strong>Wider implications of the findings: </strong>In this dataset, the significantly higher CPR/OPR with EC does not translate to LBR. Although stratification of women according to EC cannot currently be recommended in clinical practice, a large and well-designed clinical trial to ri
研究问题：子宫内膜压实度（EC）是否有助于预测接受抗逆转录病毒疗法者的妊娠结局？EC与较高的临床妊娠率（CPR）和持续妊娠率（OPR）有关，但这并不意味着活产率（LBR）：EC是指在胚胎移植前的增殖期结束后，可观察到由孕激素引起的子宫内膜厚度的减少。EC被认为是一种非侵入性工具，有助于预测接受抗逆转录病毒疗法者的妊娠结局，但已发表的数据却相互矛盾：由两位独立作者使用 PubMed、Cochrane Library、MEDLINE、Embase、Science Direct、Scopus 和 Web of Science 进行文献检索，检索时间从数据库建立之初至 2023 年 5 月。所有报道接受体外受精（IVF）/卵胞浆内单精子显微注射（ICSI）治疗的患者的EC和妊娠结局的同行评审研究均被纳入其中：主要结果为LBR。次要结果包括其他妊娠指标（妊娠试验阳性（PPT）、CPR、OPR、流产率（MR））和EC率。如果 I 2 > 50%，则采用随机效应模型对每项结果进行 EC 与无 EC 的比较荟萃分析。曼特尔-汉斯泽尔法（Mantel-Haenszel）用于汇总二分法数据。结果以几率比（OR）和 95% CI 表示：在筛选出的 4030 篇文章中，有 21 项队列研究被纳入最终分析（n = 27 857）。EC组与无EC组的LBR无明显差异（OR 0.95; 95% CI 0.87-1.04）。EC组的OPR明显更高（OR 1.61；95% CI 1.09-2.38），尤其是当EC≥15%时与无EC组相比（OR 3.52；95% CI 2.36-5.23）。各研究对 CPR 的定义不一致，影响了研究结果。当定义为可行宫内妊娠时，需要谨慎：由于报告的妊娠结果、EC定义、超声检查方法和周期方案的不同而导致的异质性可能是CPR/OPR和LBR结果之间缺乏转化的原因；因此，所有汇总数据都应谨慎看待：在该数据集中，EC 的 CPR/OPR 明显高于 LBR。虽然目前还不能建议在临床实践中根据 EC 对妇女进行分层，但有必要进行一项大型、设计良好的临床试验，以严格评估 EC 作为成功妊娠的无创预测指标的作用。我们敦促在抗逆转录病毒疗法试验中强制执行一致的结果报告，以便对数据进行汇总、比较和总结：H.A.得到了休伊特生育中心的支持。S.G.P.和J.W.得到了利物浦大学医院NHS基金会的支持。D.K.H.获得了Wellbeing of Women项目基金（RG2137）和MRC临床研究培训奖学金（MR/V007238/1）的支持。N.T.得到了国家健康与护理研究所的支持。D.K.H.获得了Theramex公司的顾问酬金，并从Theramex公司和Gideon Richter公司获得了演讲报酬。其余作者没有需要报告的利益冲突：ProCORMBERCO CRD42022378464.
{"title":"Endometrial compaction to predict pregnancy outcomes in patients undergoing assisted reproductive technologies: a systematic review and meta-analysis.","authors":"Hannan Al-Lamee, Katie Stone, Simon G Powell, James Wyatt, Andrew J Drakeley, Dharani K Hapangama, Nicola Tempest","doi":"10.1093/hropen/hoae040","DOIUrl":"10.1093/hropen/hoae040","url":null,"abstract":"<p><strong>Study question: </strong>Does endometrial compaction (EC) help predict pregnancy outcomes in those undergoing ART?</p><p><strong>Summary answer: </strong>EC is associated with a significantly higher clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR), but this does not translate to live birth rate (LBR).</p><p><strong>What is known already: </strong>EC describes the progesterone-induced decrease in endometrial thickness, which may be observed following the end of the proliferative phase, prior to embryo transfer. EC is proposed as a non-invasive tool to help predict pregnancy outcome in those undergoing ART, however, published data is conflicting.</p><p><strong>Study design size duration: </strong>A literature search was carried out by two independent authors using PubMed, Cochrane Library, MEDLINE, Embase, Science Direct, Scopus, and Web of Science from inception of databases to May 2023. All peer-reviewed studies reporting EC and pregnancy outcomes in patients undergoing IVF/ICSI treatment were included.</p><p><strong>Participants/materials setting methods: </strong>The primary outcome is LBR. Secondary outcomes included other pregnancy metrics (positive pregnancy test (PPT), CPR, OPR, miscarriage rate (MR)) and rate of EC. Comparative meta-analyses comparing EC and no EC were conducted for each outcome using a random-effects model if <i>I</i> <sup>2</sup> > 50%. The Mantel-Haenszel method was applied for pooling dichotomous data. Results are presented as odds ratios (OR) with 95% CI.</p><p><strong>Main results and the role of chance: </strong>Out of 4030 screened articles, 21 cohort studies were included in the final analysis (n = 27 857). No significant difference was found between LBR in the EC versus the no EC group (OR 0.95; 95% CI 0.87-1.04). OPR was significantly higher within the EC group (OR 1.61; 95% CI 1.09-2.38), particularly when EC ≥ 15% compared to no EC (OR 3.52; 95% CI 2.36-5.23). CPR was inconsistently defined across the studies, affecting the findings. When defined as a viable intrauterine pregnancy <12 weeks, the EC group had significantly higher CPR than no EC (OR 1.83; 95% CI 1.15-2.92). No significant differences were found between EC and no EC for PPT (OR 1.54; 95% CI 0.97-2.45) or MR (OR 1.06; 95% CI 0.92-1.56). The pooled weighted incidence of EC across all studies was 32% (95% CI 26-38%).</p><p><strong>Limitations reasons for caution: </strong>Heterogeneity due to differences between reported pregnancy outcomes, definition of EC, method of ultrasound, and cycle protocol may account for the lack of translation between CPR/OPR and LBR findings; thus, all pooled data should be viewed with an element of caution.</p><p><strong>Wider implications of the findings: </strong>In this dataset, the significantly higher CPR/OPR with EC does not translate to LBR. Although stratification of women according to EC cannot currently be recommended in clinical practice, a large and well-designed clinical trial to ri","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae040"},"PeriodicalIF":8.3,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592292","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 : 2024-06-20eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae042
Jiao Tian, Zhe Zhang, Jie Mei, Na Kong, Yuan Yan, Xiaoyue Shen, Jidong Zhou, Yang Zhang, Nannan Kang, Xin Zhen, Lijun Ding, Guijun Yan, Haixiang Sun, Xiaoqiang Sheng
<p><strong>Study question: </strong>Does abnormal serotonin homeostasis contribute to impaired endometrial decidualization in patients with recurrent implantation failure (RIF)?</p><p><strong>Summary answer: </strong>Abnormal serotonin homeostasis in patients with RIF, which is accompanied by decreased monoamine oxidase (MAO) expression, affects the decidualization of endometrial stromal cells and leads to embryo implantation failure.</p><p><strong>What is known already: </strong>Previous studies have indicated that the expression of MAO, which metabolizes serotonin, is reduced in the endometrium of patients with RIF, and serotonin can induce disruption of implantation in rats. However, whether abnormal serotonin homeostasis leads to impaired decidualization in patients with RIF and, if so, the mechanism involved, remains unclear.</p><p><strong>Study design size duration: </strong>Endometrial samples from 25 patients with RIF and 25 fertile patients were used to investigate the expression levels of monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), and serotonin. We isolated human endometrial stromal cells to investigate the role of MAOA, MAOB, and serotonin in inducing decidualization <i>in vitro</i> and further explored the underlying mechanism using RNA-sequencing (RNA-seq) and liquid chromatography-mass spectrometry (LC/MS) analyses.</p><p><strong>Participants/materials setting methods: </strong>The levels of serotonin in the endometrium of patients with RIF were detected by ELISA and immunohistofluorescence, and the key genes involved in abnormal serotonin metabolism were analyzed via combination with single-cell sequencing data. The effects of MAOA or MAOB on the decidualization of stromal cells were investigated using an <i>in vitro</i> human endometrial stromal cell-induced decidualization model and a mouse artificially induced decidualization model. The potential mechanisms by which MAOA and MAOB regulate decidualization were explored by RNA-seq and LC/MS analysis.</p><p><strong>Main results and the role of chance: </strong>We found that women with RIF have abnormal serotonin metabolism in the endometrium and attenuated MAO in endometrial stromal cells. Endometrial decidualization was accompanied by increased MAO <i>in vivo</i> and <i>in vitro</i>. However attenuated MAO caused an increased local serotonin content in the endometrium, impairing stromal cell decidualization. RNA-seq and LC/MS analyses showed that abnormal lipid metabolism, especially phosphatidylcholine metabolism, was involved in the defective decidualization caused by MAO deficiency. Furthermore, decidualization defects were rescued by phosphatidylcholine supplementation.</p><p><strong>Large scale data: </strong>RNA-seq information and raw data can be found at NCBI Bioproject number PRJNA892255.</p><p><strong>Limitations reasons for caution: </strong>This study revealed that impaired serotonin metabolic homeostasis and abnormally reduced MAO expression were among th
研究问题：5-羟色胺稳态异常是否会导致复发性着床失败（RIF）患者的子宫内膜蜕膜化受损？RIF患者的血清素平衡异常伴随着单胺氧化酶（MAO）表达的降低，会影响子宫内膜基质细胞的蜕膜化，导致胚胎植入失败：既往研究表明，RIF 患者子宫内膜中代谢羟色胺的 MAO 表达减少，羟色胺可诱导大鼠着床障碍。然而，血清素平衡异常是否会导致RIF患者的蜕膜形成受损，如果是，其机制是什么，目前仍不清楚：研究使用了 25 名 RIF 患者和 25 名育龄患者的子宫内膜样本，以调查单胺氧化酶 A（MAOA）、单胺氧化酶 B（MAOB）和血清素的表达水平。我们分离了人类子宫内膜基质细胞，以研究 MAOA、MAOB 和血清素在体外诱导蜕膜化中的作用，并使用 RNA 序列（RNA-seq）和液相色谱-质谱（LC/MS）分析进一步探索其潜在机制：通过ELISA和免疫组化荧光法检测RIF患者子宫内膜中5-羟色胺的水平，并结合单细胞测序数据分析参与5-羟色胺代谢异常的关键基因。通过体外人类子宫内膜基质细胞诱导蜕膜化模型和小鼠人工诱导蜕膜化模型，研究了MAOA或MAOB对基质细胞蜕膜化的影响。通过RNA-seq和LC/MS分析探讨了MAOA和MAOB调控蜕膜化的潜在机制：我们发现，患有 RIF 的妇女子宫内膜中的血清素代谢异常，子宫内膜基质细胞中的 MAO 功能减弱。子宫内膜蜕膜化伴随着体内和体外 MAO 的增加。然而，MAO的减弱会导致子宫内膜局部血清素含量增加，从而影响基质细胞的蜕膜化。RNA-seq和LC/MS分析表明，脂质代谢异常，尤其是磷脂酰胆碱代谢异常，与MAO缺乏导致的蜕膜化缺陷有关。此外，补充磷脂酰胆碱可挽救蜕皮缺陷：RNA-seq信息和原始数据可在NCBI生物项目编号PRJNA892255中找到：本研究发现，血清素代谢平衡受损和 MAO 表达异常减少是导致 RIF 的原因之一。然而，血清素在子宫内膜中的来源和其他潜在功能仍有待进一步探索：这项研究为人类子宫内膜蜕膜化过程中血清素的平衡机制提供了新的见解，也为治疗RIF患者提供了新的生物标志物或靶点：X.Sheng受到国家自然科学基金（82001629）、温州市基础公益研究项目（Y20240030）、江苏省自然科学基金青年项目（BK20200116）和江苏省博士后科研基金（2021K277B）的资助。H.S. 受国家自然科学基金资助（82030040）。G.Y. 受国家自然科学基金资助（82171653）。作者声明无利益冲突。
{"title":"Dysregulation of endometrial stromal serotonin homeostasis leading to abnormal phosphatidylcholine metabolism impairs decidualization in patients with recurrent implantation failure.","authors":"Jiao Tian, Zhe Zhang, Jie Mei, Na Kong, Yuan Yan, Xiaoyue Shen, Jidong Zhou, Yang Zhang, Nannan Kang, Xin Zhen, Lijun Ding, Guijun Yan, Haixiang Sun, Xiaoqiang Sheng","doi":"10.1093/hropen/hoae042","DOIUrl":"10.1093/hropen/hoae042","url":null,"abstract":"<p><strong>Study question: </strong>Does abnormal serotonin homeostasis contribute to impaired endometrial decidualization in patients with recurrent implantation failure (RIF)?</p><p><strong>Summary answer: </strong>Abnormal serotonin homeostasis in patients with RIF, which is accompanied by decreased monoamine oxidase (MAO) expression, affects the decidualization of endometrial stromal cells and leads to embryo implantation failure.</p><p><strong>What is known already: </strong>Previous studies have indicated that the expression of MAO, which metabolizes serotonin, is reduced in the endometrium of patients with RIF, and serotonin can induce disruption of implantation in rats. However, whether abnormal serotonin homeostasis leads to impaired decidualization in patients with RIF and, if so, the mechanism involved, remains unclear.</p><p><strong>Study design size duration: </strong>Endometrial samples from 25 patients with RIF and 25 fertile patients were used to investigate the expression levels of monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), and serotonin. We isolated human endometrial stromal cells to investigate the role of MAOA, MAOB, and serotonin in inducing decidualization <i>in vitro</i> and further explored the underlying mechanism using RNA-sequencing (RNA-seq) and liquid chromatography-mass spectrometry (LC/MS) analyses.</p><p><strong>Participants/materials setting methods: </strong>The levels of serotonin in the endometrium of patients with RIF were detected by ELISA and immunohistofluorescence, and the key genes involved in abnormal serotonin metabolism were analyzed via combination with single-cell sequencing data. The effects of MAOA or MAOB on the decidualization of stromal cells were investigated using an <i>in vitro</i> human endometrial stromal cell-induced decidualization model and a mouse artificially induced decidualization model. The potential mechanisms by which MAOA and MAOB regulate decidualization were explored by RNA-seq and LC/MS analysis.</p><p><strong>Main results and the role of chance: </strong>We found that women with RIF have abnormal serotonin metabolism in the endometrium and attenuated MAO in endometrial stromal cells. Endometrial decidualization was accompanied by increased MAO <i>in vivo</i> and <i>in vitro</i>. However attenuated MAO caused an increased local serotonin content in the endometrium, impairing stromal cell decidualization. RNA-seq and LC/MS analyses showed that abnormal lipid metabolism, especially phosphatidylcholine metabolism, was involved in the defective decidualization caused by MAO deficiency. Furthermore, decidualization defects were rescued by phosphatidylcholine supplementation.</p><p><strong>Large scale data: </strong>RNA-seq information and raw data can be found at NCBI Bioproject number PRJNA892255.</p><p><strong>Limitations reasons for caution: </strong>This study revealed that impaired serotonin metabolic homeostasis and abnormally reduced MAO expression were among th","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae042"},"PeriodicalIF":8.3,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876886","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}
<p><strong>Study question: </strong>Do singleton children conceived by ART have a higher asthma risk than naturally conceived (NC) singletons?</p><p><strong>Summary answer: </strong>The asthma risk was similar for ART-conceived singletons and NC singletons, and there were no clear differences between the various types of ART.</p><p><strong>What is known already: </strong>Whether ART increases asthma risk in offspring is questionable. The evidence is inconsistent and limited by ethnicity, geographic distribution, inadequate confounder adjustment, unsatisfactory control groups, and specific methods of ART. Furthermore, the mediating effects of obstetric and neonatal outcomes on the association between ART and asthma remain unclear.</p><p><strong>Study design size duration: </strong>This observational, single-centre study was conducted at a reproductive centre of an affiliated university hospital between September 2009 and April 2023. A total of 3227 singletons aged 3-6 years conceived by IVF versus ICSI or fresh versus frozen embryo transfer were retrospectively enrolled, and a total of 1206 NC singletons of the same age were subsequently recruited.</p><p><strong>Participants/materials setting methods: </strong>Asthma was defined as a self-reported physician diagnosis or wheezing in the past 12 months. We performed multivariable logistic regression analyses to examine associations between asthma in offspring and ART use, adjusting for parental characteristics (age, education level, occupation type, BMI, asthma), smoking exposure, residence type, child sex, child age, and year of follow-up. Mediating effects were explored using longitudinal mediation structural equation modelling.</p><p><strong>Main results and the role of chance: </strong>Asthma was reported for 51 (4.2%) of the 1206 NC singletons (median [interquartile range] age 5 [4-5] years; 48.1% females) and 169 (5.2%) of the 3227 ART-conceived singletons (5 [5-5] years; 47.6% females). We found that risks of childhood asthma in singletons conceived by ART were, overall, similar to those of NC singletons before (odds ratio [OR], 1.25 [95% CI, 0.92-1.74]; <i>P </i>=<i> </i>0.170) and after adjustment (adjusted OR [aOR], 0.66 [95% CI, 0.44-1.03]; <i>P </i>=<i> </i>0.126). The results were similar in multiple sensitivity analyses, and there were no clear differences in asthma risks according to the method of ART. Mediation analysis revealed a significant positive indirect effect of neonatal intensive care unit (NICU) admission (standard path coefficient, <i>b</i> = 0.025, <i>P </i><<i> </i>0.05) and a negative indirect effect of breastfeeding (<i>b </i>= -0.012, <i>P </i><<i> </i>0.05) on the association between ART and asthma in singleton offspring.</p><p><strong>Limitations reasons for caution: </strong>This study is limited to singletons only and cannot be generalized. The study is also limited by its retrospective observational single-centre nature and sample size. Mediation analyses were ex
{"title":"The risk of asthma in singletons conceived by ART: a retrospective cohort study.","authors":"Shuangying Liu, Xiaoqian Zhou, Wei Wang, Min Zhang, Yu Sun, Xiaoling Hu, Jiali You, Xiaofei Huang, Yingzhi Yang, Guofang Feng, Lanfeng Xing, Long Bai, Minyue Tang, Yimin Zhu","doi":"10.1093/hropen/hoae041","DOIUrl":"10.1093/hropen/hoae041","url":null,"abstract":"<p><strong>Study question: </strong>Do singleton children conceived by ART have a higher asthma risk than naturally conceived (NC) singletons?</p><p><strong>Summary answer: </strong>The asthma risk was similar for ART-conceived singletons and NC singletons, and there were no clear differences between the various types of ART.</p><p><strong>What is known already: </strong>Whether ART increases asthma risk in offspring is questionable. The evidence is inconsistent and limited by ethnicity, geographic distribution, inadequate confounder adjustment, unsatisfactory control groups, and specific methods of ART. Furthermore, the mediating effects of obstetric and neonatal outcomes on the association between ART and asthma remain unclear.</p><p><strong>Study design size duration: </strong>This observational, single-centre study was conducted at a reproductive centre of an affiliated university hospital between September 2009 and April 2023. A total of 3227 singletons aged 3-6 years conceived by IVF versus ICSI or fresh versus frozen embryo transfer were retrospectively enrolled, and a total of 1206 NC singletons of the same age were subsequently recruited.</p><p><strong>Participants/materials setting methods: </strong>Asthma was defined as a self-reported physician diagnosis or wheezing in the past 12 months. We performed multivariable logistic regression analyses to examine associations between asthma in offspring and ART use, adjusting for parental characteristics (age, education level, occupation type, BMI, asthma), smoking exposure, residence type, child sex, child age, and year of follow-up. Mediating effects were explored using longitudinal mediation structural equation modelling.</p><p><strong>Main results and the role of chance: </strong>Asthma was reported for 51 (4.2%) of the 1206 NC singletons (median [interquartile range] age 5 [4-5] years; 48.1% females) and 169 (5.2%) of the 3227 ART-conceived singletons (5 [5-5] years; 47.6% females). We found that risks of childhood asthma in singletons conceived by ART were, overall, similar to those of NC singletons before (odds ratio [OR], 1.25 [95% CI, 0.92-1.74]; <i>P </i>=<i> </i>0.170) and after adjustment (adjusted OR [aOR], 0.66 [95% CI, 0.44-1.03]; <i>P </i>=<i> </i>0.126). The results were similar in multiple sensitivity analyses, and there were no clear differences in asthma risks according to the method of ART. Mediation analysis revealed a significant positive indirect effect of neonatal intensive care unit (NICU) admission (standard path coefficient, <i>b</i> = 0.025, <i>P </i><<i> </i>0.05) and a negative indirect effect of breastfeeding (<i>b </i>= -0.012, <i>P </i><<i> </i>0.05) on the association between ART and asthma in singleton offspring.</p><p><strong>Limitations reasons for caution: </strong>This study is limited to singletons only and cannot be generalized. The study is also limited by its retrospective observational single-centre nature and sample size. Mediation analyses were ex","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae041"},"PeriodicalIF":8.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749914","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 : 2024-06-18eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae039
Leonie D Schreck, Eva S L Pedersen, Katie Dexter, Michele Manion, Nathalie Massin, Bernard Maitre, Myrofora Goutaki, Claudia E Kuehni
<p><strong>Study question: </strong>What is the prevalence of infertility and ectopic pregnancies among individuals with primary ciliary dyskinesia (PCD)?</p><p><strong>Summary answer: </strong>We found that 39 of 50 men (78%) and 72 of 118 women (61%) with PCD were infertile and that women with PCD had an increased risk of ectopic pregnancies (7.6 per 100 pregnancies, 95% CI 4.7-12.2).</p><p><strong>What is known already: </strong>PCD is a heterogeneous multiorgan disease caused by mutations in genes required for the function and structure of motile cilia. Previous studies identified a link between PCD and infertility, but original data on prevalence of infertility and risk of ectopic pregnancies, the use and efficacy of medically assisted reproduction (MAR), and the association of fertility with PCD genotype are extremely limited.</p><p><strong>Study design size duration: </strong>We performed a cross-sectional survey about fertility within the <i>Living with PCD</i> study (formerly COVID-PCD). <i>Living with PCD</i> is an international, online, participatory study that collects information directly from people with PCD. People with PCD of any age from anywhere in the world can participate in the study. At the time of the survey, 482 adults with PCD were registered within the <i>Living with PCD</i> study.</p><p><strong>Participants/materials setting methods: </strong>We sent a questionnaire on fertility on 12 July 2022, to all participants older than 18 years enrolled in the <i>Living with PCD</i> study. Responses were collected until 8 March 2023. The fertility questionnaire covered topics related to pregnancy attempts, use of MAR, and pregnancy outcomes. Data were collected via the Research Electronic Data Capture (REDCap) platform. We defined infertility as failure to achieve a clinical pregnancy after 12 months or use of MAR for at least one pregnancy.</p><p><strong>Main results and the role of chance: </strong>In total, 265 of 482 adult participants (55%) completed the fertility questionnaire. Among 168 adults who had tried to conceive, 39 of 50 men (78%) and 72 of 118 women (61%) were infertile. Of the infertile men, 28 had tried MAR, and 17 of them (61%) fathered a child with the help of MAR. Among infertile women, 59 had used MAR, and 41 of them (69%) became pregnant with the help of MAR. In our population, women with PCD showed a relatively high risk of ectopic pregnancies: 1 in 10 women who became pregnant had at least one ectopic pregnancy and 7.6% of pregnancies were ectopic (95% CI 4.7-12.2). We evaluated the association between fertility and affected PCD genes in 46 individuals (11 men, 35 women) with available genetic and fertility information, and found differences between genotypes, e.g. all five women with a mutation in <i>CCDC40</i> were infertile and all five with <i>DNAH11</i> were fertile.</p><p><strong>Limitations reasons for caution: </strong>The study has limitations, including potential selection bias as people experie
{"title":"Infertility and pregnancy outcomes among adults with primary ciliary dyskinesia.","authors":"Leonie D Schreck, Eva S L Pedersen, Katie Dexter, Michele Manion, Nathalie Massin, Bernard Maitre, Myrofora Goutaki, Claudia E Kuehni","doi":"10.1093/hropen/hoae039","DOIUrl":"10.1093/hropen/hoae039","url":null,"abstract":"<p><strong>Study question: </strong>What is the prevalence of infertility and ectopic pregnancies among individuals with primary ciliary dyskinesia (PCD)?</p><p><strong>Summary answer: </strong>We found that 39 of 50 men (78%) and 72 of 118 women (61%) with PCD were infertile and that women with PCD had an increased risk of ectopic pregnancies (7.6 per 100 pregnancies, 95% CI 4.7-12.2).</p><p><strong>What is known already: </strong>PCD is a heterogeneous multiorgan disease caused by mutations in genes required for the function and structure of motile cilia. Previous studies identified a link between PCD and infertility, but original data on prevalence of infertility and risk of ectopic pregnancies, the use and efficacy of medically assisted reproduction (MAR), and the association of fertility with PCD genotype are extremely limited.</p><p><strong>Study design size duration: </strong>We performed a cross-sectional survey about fertility within the <i>Living with PCD</i> study (formerly COVID-PCD). <i>Living with PCD</i> is an international, online, participatory study that collects information directly from people with PCD. People with PCD of any age from anywhere in the world can participate in the study. At the time of the survey, 482 adults with PCD were registered within the <i>Living with PCD</i> study.</p><p><strong>Participants/materials setting methods: </strong>We sent a questionnaire on fertility on 12 July 2022, to all participants older than 18 years enrolled in the <i>Living with PCD</i> study. Responses were collected until 8 March 2023. The fertility questionnaire covered topics related to pregnancy attempts, use of MAR, and pregnancy outcomes. Data were collected via the Research Electronic Data Capture (REDCap) platform. We defined infertility as failure to achieve a clinical pregnancy after 12 months or use of MAR for at least one pregnancy.</p><p><strong>Main results and the role of chance: </strong>In total, 265 of 482 adult participants (55%) completed the fertility questionnaire. Among 168 adults who had tried to conceive, 39 of 50 men (78%) and 72 of 118 women (61%) were infertile. Of the infertile men, 28 had tried MAR, and 17 of them (61%) fathered a child with the help of MAR. Among infertile women, 59 had used MAR, and 41 of them (69%) became pregnant with the help of MAR. In our population, women with PCD showed a relatively high risk of ectopic pregnancies: 1 in 10 women who became pregnant had at least one ectopic pregnancy and 7.6% of pregnancies were ectopic (95% CI 4.7-12.2). We evaluated the association between fertility and affected PCD genes in 46 individuals (11 men, 35 women) with available genetic and fertility information, and found differences between genotypes, e.g. all five women with a mutation in <i>CCDC40</i> were infertile and all five with <i>DNAH11</i> were fertile.</p><p><strong>Limitations reasons for caution: </strong>The study has limitations, including potential selection bias as people experie","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae039"},"PeriodicalIF":8.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499781","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}
<p><strong>Study question: </strong>Are women's reproductive factors associated with physical frailty and comprehensive frailty in middle-age and later life?</p><p><strong>Summary answer: </strong>Early menarche at <13 years, age at menopause <45 years, surgical menopause, experiencing miscarriage and a shorter reproductive period of <35 years were associated with increased odds of frailty, while having two or three children was related to decreased likelihood of frailty.</p><p><strong>What is known already: </strong>Evidence has shown that women are frailer than men in all age groups and across different populations, although women have longer lifespans. Female-specific reproductive factors may be related to risk of frailty in women.</p><p><strong>Study design size duration: </strong>A population-based cross-sectional study involved 189 898 women from the UK Biobank.</p><p><strong>Participants/materials setting methods: </strong>Frailty phenotype and frailty index were used to assess physical frailty and comprehensive frailty (assessed using 38 health indicators for physical and mental wellbeing), respectively. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% CI between reproductive factors and likelihood of physical frailty and comprehensive frailty. Restricted cubic spline models were used to test the non-linear associations between them. In addition, we examined the combined effect of categorized age at menopause and menopause hormone therapy (MHT) on frailty.</p><p><strong>Main results and the role of chance: </strong>There was a J-shape relationship between age at menarche, reproductive period, and frailty; age at menarche <13 years and >16 years, and reproductive period <35 years or >40 years were all associated with increased odds of frailty. There was a negative linear relationship between menopausal age (either natural or surgical) and odds of frailty. Surgical menopause was associated with 30% higher odds of physical frailty (1.34, 1.27-1.43) and 30% higher odds of comprehensive frailty (1.30, 1.25-1.35). Having two or three children was linked to the lowest likelihood of physical frailty (0.48, 0.38-0.59) and comprehensive frailty (0.72, 0.64-0.81). Experiencing a miscarriage increased the odds of frailty. MHT use was linked to increased odds of physical frailty in women with normal age at natural menopause (after 45 years), while no elevated likelihood was observed in women with early natural menopause taking MHT.</p><p><strong>Limitations reasons for caution: </strong>The reproductive factors were self-reported and the data might be subject to recall bias. We lacked information on the types and initiation time of MHT, could not identify infertile women who later became pregnant, and the number of infertile women may be underestimated. Individuals participating in the UK Biobank are not representative of the general UK population, limiting the generalization of our findings.</p><p><strong>Wider
{"title":"Reproductive factors and their association with physical and comprehensive frailty in middle-aged and older women: a large-scale population-based study.","authors":"Wenting Hao, Qi Wang, Ruihong Yu, Shiva Raj Mishra, Salim S Virani, Nipun Shrestha, Chunying Fu, Dongshan Zhu","doi":"10.1093/hropen/hoae038","DOIUrl":"10.1093/hropen/hoae038","url":null,"abstract":"<p><strong>Study question: </strong>Are women's reproductive factors associated with physical frailty and comprehensive frailty in middle-age and later life?</p><p><strong>Summary answer: </strong>Early menarche at <13 years, age at menopause <45 years, surgical menopause, experiencing miscarriage and a shorter reproductive period of <35 years were associated with increased odds of frailty, while having two or three children was related to decreased likelihood of frailty.</p><p><strong>What is known already: </strong>Evidence has shown that women are frailer than men in all age groups and across different populations, although women have longer lifespans. Female-specific reproductive factors may be related to risk of frailty in women.</p><p><strong>Study design size duration: </strong>A population-based cross-sectional study involved 189 898 women from the UK Biobank.</p><p><strong>Participants/materials setting methods: </strong>Frailty phenotype and frailty index were used to assess physical frailty and comprehensive frailty (assessed using 38 health indicators for physical and mental wellbeing), respectively. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% CI between reproductive factors and likelihood of physical frailty and comprehensive frailty. Restricted cubic spline models were used to test the non-linear associations between them. In addition, we examined the combined effect of categorized age at menopause and menopause hormone therapy (MHT) on frailty.</p><p><strong>Main results and the role of chance: </strong>There was a J-shape relationship between age at menarche, reproductive period, and frailty; age at menarche <13 years and >16 years, and reproductive period <35 years or >40 years were all associated with increased odds of frailty. There was a negative linear relationship between menopausal age (either natural or surgical) and odds of frailty. Surgical menopause was associated with 30% higher odds of physical frailty (1.34, 1.27-1.43) and 30% higher odds of comprehensive frailty (1.30, 1.25-1.35). Having two or three children was linked to the lowest likelihood of physical frailty (0.48, 0.38-0.59) and comprehensive frailty (0.72, 0.64-0.81). Experiencing a miscarriage increased the odds of frailty. MHT use was linked to increased odds of physical frailty in women with normal age at natural menopause (after 45 years), while no elevated likelihood was observed in women with early natural menopause taking MHT.</p><p><strong>Limitations reasons for caution: </strong>The reproductive factors were self-reported and the data might be subject to recall bias. We lacked information on the types and initiation time of MHT, could not identify infertile women who later became pregnant, and the number of infertile women may be underestimated. Individuals participating in the UK Biobank are not representative of the general UK population, limiting the generalization of our findings.</p><p><strong>Wider","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae038"},"PeriodicalIF":8.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473256","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 : 2024-05-30eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae034
Jacques Donnez, Marie-Madeleine Dolmans
{"title":"Endometriosis: from iron and macrophages to exosomes. Is the sky clearing?","authors":"Jacques Donnez, Marie-Madeleine Dolmans","doi":"10.1093/hropen/hoae034","DOIUrl":"10.1093/hropen/hoae034","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae034"},"PeriodicalIF":8.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437889","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 : 2024-05-29eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae035
Paolo Vercellini, Camilla Erminia Maria Merli, Paola Viganò
{"title":"'There will be blood'<sup>†</sup> A proof of concept for the role of haemorrhagic corpora lutea in the pathogenesis of endometriosis.","authors":"Paolo Vercellini, Camilla Erminia Maria Merli, Paola Viganò","doi":"10.1093/hropen/hoae035","DOIUrl":"10.1093/hropen/hoae035","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae035"},"PeriodicalIF":8.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437890","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 : 2024-05-29eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae029
G Condous, B Gerges, I Thomassin-Naggara, C Becker, C Tomassetti, H Krentel, B J van Herendael, M Malzoni, M S Abrao, E Saridogan, J Keckstein, G Hudelist
The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and International Deep Endometriosis Analysis (IDEA) group, the European Endometriosis League (EEL), the European Society for Gynaecological Endoscopy (ESGE), ESHRE, the International Society for Gynecologic Endoscopy (ISGE), the American Association of Gynecologic Laparoscopists (AAGL) and the European Society of Urogenital Radiology (ESUR) elected an international, multidisciplinary panel of gynecological surgeons, sonographers, and radiologists, including a steering committee, which searched the literature for relevant articles in order to review the literature and provide evidence-based and clinically relevant statements on the use of imaging techniques for non-invasive diagnosis and classification of pelvic deep endometriosis. Preliminary statements were drafted based on review of the relevant literature. Following two rounds of revisions and voting orchestrated by chairs of the participating societies, consensus statements were finalized. A final version of the document was then resubmitted to the society chairs for approval. Twenty statements were drafted, of which 14 reached strong and three moderate agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and society chairs and rephrased, followed by an additional round of voting. At the conclusion of the process, 14 statements had strong and five statements moderate agreement, with one statement left in equipoise. This consensus work aims to guide clinicians involved in treating women with suspected endometriosis during patient assessment, counselling, and planning of surgical treatment strategies.
{"title":"Non-invasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems: an International Consensus Statement<sup />.","authors":"G Condous, B Gerges, I Thomassin-Naggara, C Becker, C Tomassetti, H Krentel, B J van Herendael, M Malzoni, M S Abrao, E Saridogan, J Keckstein, G Hudelist","doi":"10.1093/hropen/hoae029","DOIUrl":"10.1093/hropen/hoae029","url":null,"abstract":"<p><p>The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and International Deep Endometriosis Analysis (IDEA) group, the European Endometriosis League (EEL), the European Society for Gynaecological Endoscopy (ESGE), ESHRE, the International Society for Gynecologic Endoscopy (ISGE), the American Association of Gynecologic Laparoscopists (AAGL) and the European Society of Urogenital Radiology (ESUR) elected an international, multidisciplinary panel of gynecological surgeons, sonographers, and radiologists, including a steering committee, which searched the literature for relevant articles in order to review the literature and provide evidence-based and clinically relevant statements on the use of imaging techniques for non-invasive diagnosis and classification of pelvic deep endometriosis. Preliminary statements were drafted based on review of the relevant literature. Following two rounds of revisions and voting orchestrated by chairs of the participating societies, consensus statements were finalized. A final version of the document was then resubmitted to the society chairs for approval. Twenty statements were drafted, of which 14 reached strong and three moderate agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and society chairs and rephrased, followed by an additional round of voting. At the conclusion of the process, 14 statements had strong and five statements moderate agreement, with one statement left in equipoise. This consensus work aims to guide clinicians involved in treating women with suspected endometriosis during patient assessment, counselling, and planning of surgical treatment strategies.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae029"},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176476","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 : 2024-05-29eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae036
Prubpreet Chaggar, Tina Tellum, Lucrezia Viola De Braud, Sarah Annie Solangon, Thulasi Setty, Davor Jurkovic
<p><strong>Study question: </strong>Is acute haemoperitoneum that is managed conservatively a precursor of deep endometriosis?</p><p><strong>Summary answer: </strong>Our study provides evidence to suggest that acute haemoperitoneum may lead to the development of deep endometriosis in a significant proportion of cases.</p><p><strong>What is known already: </strong>A recent pilot study was the first to suggest that acute haemoperitoneum could be a precursor of deep endometriosis. However, the sample size was small, and the follow-up was not standardized owing to unknown rates of clot absorption and development of endometriosis.</p><p><strong>Study design size duration: </strong>This was a prospective observational cohort study conducted at a single centre over a 31-month period. A required sample size of 30 was calculated using results from a previous study, with a minimum of 15 women each in the groups with and without significant haemoperitoneum (study and control groups, respectively). A total of 59 women were recruited to the study and eight were lost to follow-up. The final sample comprised 51 women, 15 in the study group and 36 in the control group.</p><p><strong>Participants/materials setting methods: </strong>All non-pregnant, premenopausal women aged 18-50 years who consecutively presented to our dedicated gynaecological diagnostic unit with severe acute lower abdominal pain were eligible for this study. We only included women who were clinically stable and were suitable for conservative management. Those with prior history or evidence of endometriosis on their initial ultrasound scan, previous hysterectomy, or bilateral oophorectomy were excluded. Participants had standardized follow-up visits for 6 months, with pelvic ultrasound scans and the British Society of Gynaecological Endoscopy pelvic pain questionnaires completed at each visit. The primary outcome was the sonographically confirmed presence of newly formed endometriosis. Secondary outcomes were the presence and change of pelvic pain symptoms and health-related quality of life (HR-QOL).</p><p><strong>Main results and the role of chance: </strong>After completion of follow-up, 7/15 (47%; 95% CI 21.3-71.4%) women presenting with acute haemoperitoneum (study group) developed sonographic evidence of deep endometriosis, compared to 0/36 (0%; 97.5% CI 0.0-9.7%) women in the control group. A ruptured functional haemorrhagic cyst was the most common cause of haemoperitoneum, occurring in 13/15 cases (87%). The time from the initial event to sonographic evidence of endometriosis varied from 2 to 6 months. The EuroQol visual analogue scores were not significantly different at baseline between the groups that developed and did not develop endometriosis [28 (interquartile range (IQR) 15-40, n = 6) vs 56 (IQR 35-75, n = 44), <i>P </i>=<i> </i>0.09], while the EuroQol-5D values were lower in the endometriosis group [-0.01 (IQR -0.07 to 0.19, n = 6) vs 0.62 (IQR 0.24-0.73, n = 44), <i>P </i>=<i>
{"title":"Development of deep pelvic endometriosis following acute haemoperitoneum: a prospective ultrasound study.","authors":"Prubpreet Chaggar, Tina Tellum, Lucrezia Viola De Braud, Sarah Annie Solangon, Thulasi Setty, Davor Jurkovic","doi":"10.1093/hropen/hoae036","DOIUrl":"10.1093/hropen/hoae036","url":null,"abstract":"<p><strong>Study question: </strong>Is acute haemoperitoneum that is managed conservatively a precursor of deep endometriosis?</p><p><strong>Summary answer: </strong>Our study provides evidence to suggest that acute haemoperitoneum may lead to the development of deep endometriosis in a significant proportion of cases.</p><p><strong>What is known already: </strong>A recent pilot study was the first to suggest that acute haemoperitoneum could be a precursor of deep endometriosis. However, the sample size was small, and the follow-up was not standardized owing to unknown rates of clot absorption and development of endometriosis.</p><p><strong>Study design size duration: </strong>This was a prospective observational cohort study conducted at a single centre over a 31-month period. A required sample size of 30 was calculated using results from a previous study, with a minimum of 15 women each in the groups with and without significant haemoperitoneum (study and control groups, respectively). A total of 59 women were recruited to the study and eight were lost to follow-up. The final sample comprised 51 women, 15 in the study group and 36 in the control group.</p><p><strong>Participants/materials setting methods: </strong>All non-pregnant, premenopausal women aged 18-50 years who consecutively presented to our dedicated gynaecological diagnostic unit with severe acute lower abdominal pain were eligible for this study. We only included women who were clinically stable and were suitable for conservative management. Those with prior history or evidence of endometriosis on their initial ultrasound scan, previous hysterectomy, or bilateral oophorectomy were excluded. Participants had standardized follow-up visits for 6 months, with pelvic ultrasound scans and the British Society of Gynaecological Endoscopy pelvic pain questionnaires completed at each visit. The primary outcome was the sonographically confirmed presence of newly formed endometriosis. Secondary outcomes were the presence and change of pelvic pain symptoms and health-related quality of life (HR-QOL).</p><p><strong>Main results and the role of chance: </strong>After completion of follow-up, 7/15 (47%; 95% CI 21.3-71.4%) women presenting with acute haemoperitoneum (study group) developed sonographic evidence of deep endometriosis, compared to 0/36 (0%; 97.5% CI 0.0-9.7%) women in the control group. A ruptured functional haemorrhagic cyst was the most common cause of haemoperitoneum, occurring in 13/15 cases (87%). The time from the initial event to sonographic evidence of endometriosis varied from 2 to 6 months. The EuroQol visual analogue scores were not significantly different at baseline between the groups that developed and did not develop endometriosis [28 (interquartile range (IQR) 15-40, n = 6) vs 56 (IQR 35-75, n = 44), <i>P </i>=<i> </i>0.09], while the EuroQol-5D values were lower in the endometriosis group [-0.01 (IQR -0.07 to 0.19, n = 6) vs 0.62 (IQR 0.24-0.73, n = 44), <i>P </i>=<i>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae036"},"PeriodicalIF":8.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437888","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 : 2024-05-22eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae028
Jie Hao, Tianyi Li, Manuel Heinzelmann, Elisabeth Moussaud-Lamodière, Filipa Lebre, Kaarel Krjutškov, Anastasios Damdimopoulos, Catarina Arnelo, Karin Pettersson, Ernesto Alfaro-Moreno, Cecilia Lindskog, Majorie van Duursen, Pauliina Damdimopoulou
<p><strong>Study question: </strong>What is the effect of the chemical <i>in vitro</i> activation (cIVA) protocol compared with fragmentation only (Frag, also known as mechanical IVA) on gene expression, follicle activation and growth in human ovarian tissue <i>in vitro</i>?</p><p><strong>Summary answer: </strong>Although histological assessment shows that cIVA significantly increases follicle survival and growth compared to Frag, both protocols stimulate extensive and nearly identical transcriptomic changes in cultured tissue compared to freshly collected ovarian tissue, including marked changes in energy metabolism and inflammatory responses.</p><p><strong>What is known already: </strong>Treatments based on cIVA of the phosphatase and tensin homolog (PTEN)-phosphatidylinositol 3-kinase (PI3K) pathway in ovarian tissue followed by auto-transplantation have been administered to patients with refractory premature ovarian insufficiency (POI) and resulted in live births. However, comparable effects with mere tissue fragmentation have been shown, questioning the added value of chemical stimulation that could potentially activate oncogenic responses.</p><p><strong>Study design size duration: </strong>Fifty-nine ovarian cortical biopsies were obtained from consenting women undergoing elective caesarean section (C-section). The samples were fragmented for culture studies. Half of the fragments were exposed to bpV (HOpic)+740Y-P (Frag+cIVA group) during the first 24 h of culture, while the other half were cultured with medium only (Frag group). Subsequently, both groups were cultured with medium only for an additional 6 days. Tissue and media samples were collected for histological, transcriptomic, steroid hormone, and cytokine/chemokine analyses at various time points.</p><p><strong>Participants/materials setting methods: </strong>Effects on follicles were evaluated by counting and scoring serial sections stained with hematoxylin and eosin before and after the 7-day culture. Follicle function was assessed by quantification of steroids by ultra-performance liquid chromatography tandem-mass spectrometry at different time points. Cytokines and chemokines were measured by multiplex assay. Transcriptomic effects were measured by RNA-sequencing (RNA-seq) of the tissue after the initial 24-h culture. Selected differentially expressed genes (DEGs) were validated by quantitative PCR and immunofluorescence in cultured ovarian tissue as well as in KGN cell (human ovarian granulosa-like tumor cell line) culture experiments.</p><p><strong>Main results and the role of chance: </strong>Compared to the Frag group, the Frag+cIVA group exhibited a significantly higher follicle survival rate, increased numbers of secondary follicles, and larger follicle sizes. Additionally, the tissue in the Frag+cIVA group produced less dehydroepiandrosterone compared to Frag. Cytokine measurement showed a strong inflammatory response at the start of the culture in both groups. The RNA-s
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