S. Makieva, M. Sachs, Min Xie, Ana Velasco, Samia El-Hadad, D. R. Kalaitzopoulos, Ioannis Dedes, R. Stiller, B. Leeners
{"title":"Reply: Double vitrification and warming does not compromise the chance of live birth—a potential invalid conclusion","authors":"S. Makieva, M. Sachs, Min Xie, Ana Velasco, Samia El-Hadad, D. R. Kalaitzopoulos, Ioannis Dedes, R. Stiller, B. Leeners","doi":"10.1093/hropen/hoad050","DOIUrl":"https://doi.org/10.1093/hropen/hoad050","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"20 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Grubliauskaitė, H. Vlieghe, S. Moghassemi, A. Dadashzadeh, A. Camboni, Ž. Gudlevičienė, C. Amorim
Do ovarian stromal cells (OSCs) influence the viability and growth of human pre-antral follicles in vitro? A feeder layer of oSCs promotes the growth and transition of low developmental stage follicles to the primary/secondary stage while maintaining a high proportion of viable follicles. In the ovary, follicles rely on the support of ovarian cells, which secrete essential factors for their survival and development. This phenomenon has also been demonstrated in vitro through the 3D culture of isolated mouse primary and secondary follicles on a feeder layer of ovarian stromal cells. This co-culture notably enhances follicle survival and growth. Pre-antral follicles were isolated from human frozen-thawed ovarian tissue (OT) biopsies and then encapsulated in 1% alginate scaffolds. These embedded pre-antral follicles were either placed directly on the OSCs feeder layer or at the bottom of a culture dish for a 7-day in vitro culture (control). The study compared follicle viability, growth and hormone production between the different groups. Primordial/intermediate and primary follicles were isolated from frozen-thawed OT of cancer patients (n = 6). Ovarian stromal cells were then isolated from OT of post-menopausal women and cultured as a feeder layer. Follicle diameter was measured on days 0 and 7 using an inverted microscope to assess their development based on the increase in diameter. Viability was evaluated by staining a subset of follicles (n = 87) with calcein AM and ethidium homodimer-I, followed by classification into healthy/minimally damaged and damaged/dead follicles using confocal fluorescence microscopy. Additionally, estradiol levels were measured using ELISA. A total of 382 human preantral follicles (370 primordial/intermediate and 12 primary) with a mean diameter of 40.8 ± 9.9 µm (mean±SD) were isolated, embedded in 1% alginate hydrogel, and placed either on a monolayer of oSCs or directly on the plastic. By Day 7, the preantral follicles showed a significant size increase under both culture conditions (p < 0.0001 for D0 vs D7). The mean diameter of follicles (quiescent and growing) cultured on the feeder layer was 80.6 ± 11.0 μm compared to 67.3 ± 7.2 μm without it (p = 0.07). During the 7-day in vitro culture, the viability of the follicles significantly decreased only in the group without an OSCs monolayer compared to the D0 viability (p < 0.05). Additionally, more follicles transitioned to a higher developmental stage in the presence of OSCs (D0 primordial/intermediate: 184, primary: 7 vs D7 primordial/intermediate: 51, primary/secondary: 93) compared to those cultured without OSCs (D0 primordial/intermediate: 186, primary: 5 vs D7 primordial/intermediate: 84, primary/secondary: 65; p < 0.001). Specifically, 66 and 44 follicles reached the secondary stage (75 < x < 200 μm) in the presence and absence of OSCs, respectively. Moreover, the estradiol level was significantly higher (p = 0.006) i
{"title":"Influence of ovarian stromal cells on human ovarian follicle growth in a 3D environment","authors":"M. Grubliauskaitė, H. Vlieghe, S. Moghassemi, A. Dadashzadeh, A. Camboni, Ž. Gudlevičienė, C. Amorim","doi":"10.1093/hropen/hoad052","DOIUrl":"https://doi.org/10.1093/hropen/hoad052","url":null,"abstract":"\u0000 \u0000 \u0000 Do ovarian stromal cells (OSCs) influence the viability and growth of human pre-antral follicles in vitro?\u0000 \u0000 \u0000 \u0000 A feeder layer of oSCs promotes the growth and transition of low developmental stage follicles to the primary/secondary stage while maintaining a high proportion of viable follicles.\u0000 \u0000 \u0000 \u0000 In the ovary, follicles rely on the support of ovarian cells, which secrete essential factors for their survival and development. This phenomenon has also been demonstrated in vitro through the 3D culture of isolated mouse primary and secondary follicles on a feeder layer of ovarian stromal cells. This co-culture notably enhances follicle survival and growth.\u0000 \u0000 \u0000 \u0000 Pre-antral follicles were isolated from human frozen-thawed ovarian tissue (OT) biopsies and then encapsulated in 1% alginate scaffolds. These embedded pre-antral follicles were either placed directly on the OSCs feeder layer or at the bottom of a culture dish for a 7-day in vitro culture (control). The study compared follicle viability, growth and hormone production between the different groups.\u0000 \u0000 \u0000 \u0000 Primordial/intermediate and primary follicles were isolated from frozen-thawed OT of cancer patients (n = 6). Ovarian stromal cells were then isolated from OT of post-menopausal women and cultured as a feeder layer. Follicle diameter was measured on days 0 and 7 using an inverted microscope to assess their development based on the increase in diameter. Viability was evaluated by staining a subset of follicles (n = 87) with calcein AM and ethidium homodimer-I, followed by classification into healthy/minimally damaged and damaged/dead follicles using confocal fluorescence microscopy. Additionally, estradiol levels were measured using ELISA.\u0000 \u0000 \u0000 \u0000 A total of 382 human preantral follicles (370 primordial/intermediate and 12 primary) with a mean diameter of 40.8 ± 9.9 µm (mean±SD) were isolated, embedded in 1% alginate hydrogel, and placed either on a monolayer of oSCs or directly on the plastic. By Day 7, the preantral follicles showed a significant size increase under both culture conditions (p < 0.0001 for D0 vs D7). The mean diameter of follicles (quiescent and growing) cultured on the feeder layer was 80.6 ± 11.0 μm compared to 67.3 ± 7.2 μm without it (p = 0.07). During the 7-day in vitro culture, the viability of the follicles significantly decreased only in the group without an OSCs monolayer compared to the D0 viability (p < 0.05). Additionally, more follicles transitioned to a higher developmental stage in the presence of OSCs (D0 primordial/intermediate: 184, primary: 7 vs D7 primordial/intermediate: 51, primary/secondary: 93) compared to those cultured without OSCs (D0 primordial/intermediate: 186, primary: 5 vs D7 primordial/intermediate: 84, primary/secondary: 65; p < 0.001). Specifically, 66 and 44 follicles reached the secondary stage (75 < x < 200 μm) in the presence and absence of OSCs, respectively. Moreover, the estradiol level was significantly higher (p = 0.006) i","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138951660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yunhan Nie, Wenya Guo, Xi Shen, Yating Xie, Yuqi Zeng, Hongyuan Gao, Yali Liu, Li Wang
What are the odds of achieving pregnancy when adopting progestin-primed ovarian stimulation (PPOS)-related protocols combined with repetitive frozen–thawed transfer (FET) cycles in patients with different clinical characteristics? The cumulative live birth rates (CLBRs) of women undergoing different PPOS-related protocols can be significantly and consistently enhanced within six FET cycles when the female age is < 40 years (or even <45 years) and when >5 oocytes are retrieved, regardless of antral follicle count (AFC). There have been numerous studies on the live birth rate of the first FET cycle in patients with PPOS-related protocols. These studies have focused mainly on comparing pregnancy outcomes with those of other stimulation protocols. However, owing to the unique features of the PPOS-related strategy, such as its flexible timing of oocyte retrieval and repeated transfer of frozen embryos, studies using the CLBR as an overall indicator of success and investigating which types of patients would benefit from this protocol are lacking. This retrospective cohort study included 18,593 women who underwent PPOS-related protocols (dydrogesterone + hMG, medroxyprogesterone acetate + hMG, micronized progesterone + hMG treatment, and luteal-phase ovarian stimulation protocol) from 1 March 2011 to 31 September 2022 in our centre. The population was categorized by female age, number of oocytes retrieved, and AFC in the analysis of CLBR within six FET cycles. The age groups (groups 1-5, respectively) were <30, 30-34, 35-39, 40-44, and ≥45 years. The number of oocytes retrieved was grouped as 1-5, 6-10, 11-15, 16-20, and >20. AFC was grouped as < 5, 5-10, 11-15, and >15. The Kaplan–Meier analysis (optimistic method), which hypothesized that patients who did not continue treatment had the same chance of achieving a live birth as those who continued, and the competing risk method (conservative method) which hypothesized they had no chance of achieving a live birth, were applied. In further analyses, the Cox model and Fine–Gray model were adopted: the former corresponds to the optimistic scenario, and the latter corresponds to the pessimistic scenario. CLBR had a declining trend with female age over six FET cycles (groups 1-5, respectively: optimistic: 96.9%, 96.6%, 91.4%, 67.3%, and 11.7%; conservative: 87.3%, 85.0%, 74.0%, 41.3%, and 7.5%), requiring more FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 4 and >6 cycles; conservative: 2, 2, 2, > 6 and > 6 cycles). CLBR showed an increasing trend with the number of oocytes retrieved (groups 1-5, respectively: optimistic: 93.8%, 94.3%, 95.8%, 96.0%, and 95.6%; conservative: 66.2%, 78.3%, 85.6%, 88.9%, and 91.0%). All groups needed the same number of FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 2 and 2 cycles; conservative: 2, 2, 2, 2 and 2 cycles). Furthermore,
不同临床特征的患者在采用孕激素促排卵(PPOS)相关方案结合重复冻融移植(FET)周期时,怀孕的几率有多大? 当女性年龄达到 5 个卵母细胞时,无论前卵泡数(AFC)如何,接受不同 PPOS 相关方案的女性在 6 个 FET 周期内的累积活产率(CLBR)均可显著且持续地提高。 关于采用 PPOS 相关方案的患者在第一个 FET 周期的活产率,已有许多研究。这些研究主要集中于比较与其他刺激方案的妊娠结果。然而,由于 PPOS 相关策略的独特性,如取回卵母细胞的时间灵活、重复移植冷冻胚胎等,将 CLBR 作为成功率的总体指标,并调查哪些类型的患者可从该方案中获益的研究还很缺乏。 这项回顾性队列研究纳入了本中心2011年3月1日至2022年9月31日期间接受PPOS相关方案(地屈孕酮+hMG、醋酸甲羟孕酮+hMG、微粒化孕酮+hMG治疗和黄体期卵巢刺激方案)的18593名女性。 研究对象按女性年龄、取卵数量和六个 FET 周期内 CLBR 分析中的 AFC 进行分类。年龄组(1-5 组)分别为 20 人。AFC分为15组。采用卡普兰-梅耶分析法(乐观法)和竞争风险法(保守法)进行分析,前者假设不继续治疗的患者与继续治疗的患者获得活产的机会相同,后者假设他们没有机会获得活产。在进一步分析中,采用了 Cox 模型和 Fine-Gray 模型:前者对应于乐观方案,后者对应于悲观方案。 在六个 FET 周期中,CLBR 随女性年龄呈下降趋势(1-5 组分别为:乐观组:96.9%、96.6%、91.4%、67.3% 和 11.7%;保守组:87.3%、85.0%、74.0%、41.3% 和 7.5%),需要更多的 FET 周期才能达到至少 50%的成功率(1-5 组分别为:乐观组:2、2、2、4 和 >6 个周期;保守组:2、2、2、>6 和 >6 个周期)。CLBR 随取回卵母细胞数量的增加而呈上升趋势(1-5 组分别为:乐观组:93.8%、94.3%、95.8%、96.0% 和 95.6%;保守组:66.2%、78.3%、85.6%、88.9% 和 91.0%)。所有组别都需要相同数量的 FET 周期才能达到至少 50%的成功率(1-5 组分别为:乐观组:2、2、2、2 和 2 个周期;保守组:2、2、2、2 和 2 个周期)。此外,6 个 FET 周期内的 CLBR 随 AFC 数量的增加而呈上升趋势(1-4 组分别为:乐观组:89.2%、94.8%、95.9% 和 96.3%;保守组:67.4%、78.2%、83.9% 和 88.1%),到第二个 FET 周期时,所有 4 组的成功率均达到至少 50%。 目前的研究因其回顾性设计和单中心性质而受到限制,这可能会限制我们研究结果的推广性。 本研究介绍了两个模型(卡普兰-梅耶分析法和竞争风险法),用于评估使用 PPOS 相关方案的患者的临床结果,这两个模型对高龄患者或卵巢储备功能减退的患者尤其有用。我们的研究结果鼓励 45 岁以下的患者,尤其是 40 岁以下的患者,以及 AFC 较低和取卵较少的患者尝试这种新方案。此外,本研究还证明了不同临床特征的患者在六个 FET 周期内 CLBR 的改善程度,为决定移植失败后是否继续进行 ART 提供了有价值的参考。 本研究得到了国家自然科学基金的资助(L.W.的基金号为 82071603,刘宇的基金号为 82001502)。无利益冲突需要声明。 不适用。
{"title":"The cumulative live birth rates of 18,593 women with progestin-primed ovarian stimulation-related protocols and frozen–thawed transfer cycles","authors":"Yunhan Nie, Wenya Guo, Xi Shen, Yating Xie, Yuqi Zeng, Hongyuan Gao, Yali Liu, Li Wang","doi":"10.1093/hropen/hoad051","DOIUrl":"https://doi.org/10.1093/hropen/hoad051","url":null,"abstract":"\u0000 \u0000 \u0000 What are the odds of achieving pregnancy when adopting progestin-primed ovarian stimulation (PPOS)-related protocols combined with repetitive frozen–thawed transfer (FET) cycles in patients with different clinical characteristics?\u0000 \u0000 \u0000 \u0000 The cumulative live birth rates (CLBRs) of women undergoing different PPOS-related protocols can be significantly and consistently enhanced within six FET cycles when the female age is < 40 years (or even <45 years) and when >5 oocytes are retrieved, regardless of antral follicle count (AFC).\u0000 \u0000 \u0000 \u0000 There have been numerous studies on the live birth rate of the first FET cycle in patients with PPOS-related protocols. These studies have focused mainly on comparing pregnancy outcomes with those of other stimulation protocols. However, owing to the unique features of the PPOS-related strategy, such as its flexible timing of oocyte retrieval and repeated transfer of frozen embryos, studies using the CLBR as an overall indicator of success and investigating which types of patients would benefit from this protocol are lacking.\u0000 \u0000 \u0000 \u0000 This retrospective cohort study included 18,593 women who underwent PPOS-related protocols (dydrogesterone + hMG, medroxyprogesterone acetate + hMG, micronized progesterone + hMG treatment, and luteal-phase ovarian stimulation protocol) from 1 March 2011 to 31 September 2022 in our centre.\u0000 \u0000 \u0000 \u0000 The population was categorized by female age, number of oocytes retrieved, and AFC in the analysis of CLBR within six FET cycles. The age groups (groups 1-5, respectively) were <30, 30-34, 35-39, 40-44, and ≥45 years. The number of oocytes retrieved was grouped as 1-5, 6-10, 11-15, 16-20, and >20. AFC was grouped as < 5, 5-10, 11-15, and >15. The Kaplan–Meier analysis (optimistic method), which hypothesized that patients who did not continue treatment had the same chance of achieving a live birth as those who continued, and the competing risk method (conservative method) which hypothesized they had no chance of achieving a live birth, were applied. In further analyses, the Cox model and Fine–Gray model were adopted: the former corresponds to the optimistic scenario, and the latter corresponds to the pessimistic scenario.\u0000 \u0000 \u0000 \u0000 CLBR had a declining trend with female age over six FET cycles (groups 1-5, respectively: optimistic: 96.9%, 96.6%, 91.4%, 67.3%, and 11.7%; conservative: 87.3%, 85.0%, 74.0%, 41.3%, and 7.5%), requiring more FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 4 and >6 cycles; conservative: 2, 2, 2, > 6 and > 6 cycles). CLBR showed an increasing trend with the number of oocytes retrieved (groups 1-5, respectively: optimistic: 93.8%, 94.3%, 95.8%, 96.0%, and 95.6%; conservative: 66.2%, 78.3%, 85.6%, 88.9%, and 91.0%). All groups needed the same number of FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 2 and 2 cycles; conservative: 2, 2, 2, 2 and 2 cycles). Furthermore,","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"139 39","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138953328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Is PCOS associated with higher risks of extreme birth size and/or preterm birth in mothers with different hypertension types? PCOS was associated with additional risks of preterm birth in mothers with chronic hypertension and in singleton pregnancies of mothers with pre-eclampsia, and with increased risks of offspring being large for gestational age (LGA) in mothers with gestational hypertension. Women with PCOS are more likely to develop gestational hypertension, preeclampsia, and chronic hypertension. Although adverse birth outcomes have been frequently reported in mothers with PCOS, such associations in the setting of a hypertensive disorder remain unknown. This is a population-based cohort study including all live births 2004-2014 in Finland (n = 652 732), excluding mothers with diagnoses that could cause signs and symptoms like PCOS to ensure diagnosis specificity. Maternal diagnoses of PCOS, gestational hypertension, chronic hypertension, and pre-eclampsia were identified from the Finnish national registries. Generalized estimating equation and multivariable logistic regression were used to assess the adjusted odds ratio (aOR) and 95% CIs of preterm birth, very preterm birth and offspring being small (SGA) or large (LGA) for gestational age in hypertensive mothers with or without PCOS, using normotensive mothers without PCOS as reference. Of 43 902 (6.7%) mothers with hypertensive disorders, 1709 (3.9%) had PCOS. Significant interactions were detected for PCOS with hypertension on preterm birth, very preterm birth, offspring being SGA and LGA (F = 504.1, pinteraction <0.001; F = 124.2, pinteraction <0.001; F = 99.5, pinteraction <0.001; F = 2.7, pinteraction =0.012, respectively). Using mothers with no hypertensive disorder and no PCOS as reference, the risks of preterm and very preterm birth were overrepresented in mothers with chronic hypertension and pre-eclampsia without PCOS. PCOS was associated with higher risks of preterm birth (aOR PCOS 4.02, 3.14–5.15 vs. aOR non-PCOS 2.51, 2.32–2.71) in mothers with chronic hypertension, with significant interaction between the exposures (F = 32.7, pinteraction <0.001). Comorbid PCOS was also associated with a higher risk of preterm birth in singleton pregnancies of mothers with pre-eclampsia (aOR PCOS 7.33, 5.92–9.06 vs. aOR non-PCOS 5.72, 5.43–6.03; F = 50.0, pinteraction<0.001). Furthermore, the combined associations of PCOS with chronic hypertension or pre-eclampsia persisted for spontaneous births. Moreover, the risk of offspring LGA was increased in mothers with PCOS and gestational hypertension although decreased in those with gestational hypertension alone (aOR PCOS 2.04, 1.48–2.80 vs. aOR non-PCOS 0.80, 0.72–0.89; F = 9.7, pinteraction=0.002), whereas for offspring SGA the risks were comparable between hypertensive mothers with and those without PCOS. Information on medication treatment, gestational weeks of onset for pre-eclampsia and gesta
多囊卵巢综合征与不同高血压类型母亲的极端出生尺寸和/或早产风险是否相关?多囊卵巢综合征与慢性高血压母亲的早产风险增加有关,与子痫前期母亲的单胎妊娠有关,与妊娠高血压母亲的后代大胎龄(LGA)风险增加有关。患有多囊卵巢综合征的妇女更容易发生妊娠期高血压、先兆子痫和慢性高血压。尽管PCOS母亲的不良分娩结果经常被报道,但在高血压疾病的背景下,这种关联仍然未知。这是一项基于人群的队列研究,包括2004-2014年在芬兰出生的所有活产婴儿(n = 652 732),排除了诊断可能导致多囊卵巢综合征等体征和症状的母亲,以确保诊断的特异性。从芬兰国家登记处确定了多囊卵巢综合征、妊娠期高血压、慢性高血压和先兆子痫的母亲诊断。采用广义估计方程和多变量logistic回归方法,以无PCOS的正常血压母亲为参照,评估有PCOS或无PCOS的高血压母亲早产、极早产和胎龄小(SGA)或大(LGA)的调整优势比(aOR)和95% ci。43 902例(6.7%)患有高血压疾病的母亲中,1709例(3.9%)患有多囊卵巢综合征。PCOS合并高血压与早产、非常早产、子代SGA和LGA存在显著相互作用(F = 504.1, p相互作用<0.001;F = 124.2, p交互作用<0.001;F = 99.5, p交互作用<0.001;F = 2.7, p - interaction =0.012)。以无高血压疾病和无PCOS的母亲为对照,慢性高血压和先兆子痫无PCOS的母亲早产和非常早产的风险过高。PCOS与慢性高血压母亲的早产风险较高相关(aOR PCOS为4.02,3.14-5.15,aOR非PCOS为2.51,2.32-2.71),暴露之间存在显著交互作用(F = 32.7, p交互作用<0.001)。合并多囊卵巢综合征(PCOS)与子痫前期母亲的单胎妊娠早产风险较高相关(aOR PCOS为7.33,5.92-9.06,aOR非PCOS为5.72,5.43-6.03;F = 50.0, p交互作用<0.001)。此外,PCOS与慢性高血压或先兆子痫的联合关联在自然分娩中持续存在。此外,PCOS合并妊娠高血压的母亲的后代LGA风险增加,而单独妊娠高血压的母亲的后代LGA风险降低(aOR PCOS为2.04,1.48-2.80,aOR非PCOS为0.80,0.72-0.89;F = 9.7, p相互作用=0.002),而对于后代SGA的风险,高血压母亲与未患PCOS的母亲之间是相当的。没有关于药物治疗、子痫前期和妊娠期高血压发病的妊娠周数、孕期体重增加和多囊卵巢综合征表型的信息。所有诊断都是从登记处检索的,仅代表那些因其症状而寻求医疗护理的人。众所周知,1996年以前用于识别多囊卵巢综合征的ICD-9代码低估了多囊卵巢综合征的患病率,而将无排卵性不孕症纳入多囊卵巢综合征可能会引入过度代表偏差,尽管多囊卵巢综合征占无排卵性不孕症的80%。由于样本量有限,应谨慎解释与母体多囊卵巢综合征和高血压疾病相关的极早产风险。母体多囊卵巢综合征的多胎妊娠太少,无法进行亚组分析。此外,ART仅包括IVF/ICSI。其他治疗的潜在影响,如促排卵,没有被检查。多囊卵巢综合征与高血压母亲早产或后代LGA的额外风险相关,高血压类型之间存在差异。这些加剧的风险突出了妊娠咨询和高血压疾病妇女管理中多囊卵巢综合征的考虑。本研究得到山东省自然科学基金[ZR2020MH064 to X.C],山东大学和卡罗林斯卡研究所联合研究基金[SDU-KI-2019-08 to X.C and c.l],芬兰卫生与福利研究所:药物与妊娠项目[M.G.]、瑞典研究理事会[2022-01188 to C.L.]、斯德哥尔摩郡议会和卡罗林斯卡研究所之间的医学培训和临床研究区域协议(ALF)斯德哥尔摩郡议会[SLL20190589 to C.L.]、瑞典大脑基金会[FO2021-0412 to C.L.]。资助者在研究设计、数据收集、分析和解释、撰写报告或决定是否提交发表方面没有任何作用。作者报告没有利益冲突。不适用。
{"title":"Birth outcomes in mothers with hypertensive disorders and polycystic ovary syndrome: a population-based cohort study","authors":"Xinxia Chen, Mika Gissler, C. Lavebratt","doi":"10.1093/hropen/hoad048","DOIUrl":"https://doi.org/10.1093/hropen/hoad048","url":null,"abstract":"\u0000 \u0000 \u0000 Is PCOS associated with higher risks of extreme birth size and/or preterm birth in mothers with different hypertension types?\u0000 \u0000 \u0000 \u0000 PCOS was associated with additional risks of preterm birth in mothers with chronic hypertension and in singleton pregnancies of mothers with pre-eclampsia, and with increased risks of offspring being large for gestational age (LGA) in mothers with gestational hypertension.\u0000 \u0000 \u0000 \u0000 Women with PCOS are more likely to develop gestational hypertension, preeclampsia, and chronic hypertension. Although adverse birth outcomes have been frequently reported in mothers with PCOS, such associations in the setting of a hypertensive disorder remain unknown.\u0000 \u0000 \u0000 \u0000 This is a population-based cohort study including all live births 2004-2014 in Finland (n = 652 732), excluding mothers with diagnoses that could cause signs and symptoms like PCOS to ensure diagnosis specificity.\u0000 \u0000 \u0000 \u0000 Maternal diagnoses of PCOS, gestational hypertension, chronic hypertension, and pre-eclampsia were identified from the Finnish national registries. Generalized estimating equation and multivariable logistic regression were used to assess the adjusted odds ratio (aOR) and 95% CIs of preterm birth, very preterm birth and offspring being small (SGA) or large (LGA) for gestational age in hypertensive mothers with or without PCOS, using normotensive mothers without PCOS as reference.\u0000 \u0000 \u0000 \u0000 Of 43 902 (6.7%) mothers with hypertensive disorders, 1709 (3.9%) had PCOS. Significant interactions were detected for PCOS with hypertension on preterm birth, very preterm birth, offspring being SGA and LGA (F = 504.1, pinteraction <0.001; F = 124.2, pinteraction <0.001; F = 99.5, pinteraction <0.001; F = 2.7, pinteraction =0.012, respectively). Using mothers with no hypertensive disorder and no PCOS as reference, the risks of preterm and very preterm birth were overrepresented in mothers with chronic hypertension and pre-eclampsia without PCOS. PCOS was associated with higher risks of preterm birth (aOR PCOS 4.02, 3.14–5.15 vs. aOR non-PCOS 2.51, 2.32–2.71) in mothers with chronic hypertension, with significant interaction between the exposures (F = 32.7, pinteraction <0.001). Comorbid PCOS was also associated with a higher risk of preterm birth in singleton pregnancies of mothers with pre-eclampsia (aOR PCOS 7.33, 5.92–9.06 vs. aOR non-PCOS 5.72, 5.43–6.03; F = 50.0, pinteraction<0.001). Furthermore, the combined associations of PCOS with chronic hypertension or pre-eclampsia persisted for spontaneous births. Moreover, the risk of offspring LGA was increased in mothers with PCOS and gestational hypertension although decreased in those with gestational hypertension alone (aOR PCOS 2.04, 1.48–2.80 vs. aOR non-PCOS 0.80, 0.72–0.89; F = 9.7, pinteraction=0.002), whereas for offspring SGA the risks were comparable between hypertensive mothers with and those without PCOS.\u0000 \u0000 \u0000 \u0000 Information on medication treatment, gestational weeks of onset for pre-eclampsia and gesta","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"58 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138604961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. J. W. Tack, C. Brachet, V. Beauloye, C. Heinrichs, E. Boros, K. De Waele, S. van der Straaten, S. Van Aken, M. Craen, A. Lemay, A. Rochtus, K. Casteels, D. Beckers, T. Mouraux, K. Logghe, M. Van Loocke, G. Massa, K. Van de Vijver, H. Syryn, J. Van de Velde, E. De Baere, H. Verdin, M. Cools
What is the long-term outcome of individuals born with bilateral testicular regression (BTR) in relation to its underlying etiology? Statural growth and pubertal development are adequate with incremental doses of testosterone replacement therapy, however penile growth is often suboptimal, especially in those with a suspected genetic etiology (i.e. heterozygous DHX37 variants) or a micropenis at birth. BTR is a rare and poorly understood condition. Although a vascular origin has been postulated, heterozygous missense variants in DHX37 have been attributed to the phenotype as well. How these various etiologies impact the clinical phenotype, gonadal histology and outcome of BTR remains unclear. For this cross-sectional study, individuals with BTR were recruited in eight Belgian pediatric endocrinology departments, between December 2019 and December 2022. A physical exam was performed cross-sectionally in all 17 end-pubertal participants and a quality of care questionnaire was completed by 11 of them. Exome-based panel testing of 241 genes involved in gonadal development and spermatogenesis was performed along with a retrospective analysis of presentation and management. A centralized histological review of gonadal rests was done for 10 participants. A total of 35 participants (33 with male, one with female and one with non-binary gender identity), were recruited at a mean age of 15.0±5.7 years. The median age at presentation was 1.2 years [0-14 years]. Maternal gestational complications were common (38.2%), with a notably high incidence of monozygotic twin pregnancies (8.8%). Heterozygous (likely) pathogenic missense variants in DHX37 (p.Arg334Trp and p.Arg308Gln) were found in three participants. No other (likely) pathogenic variants were found. All three participants with a DHX37 variant had a microphallus at birth (leading to female sex assignment in one), while only six of the remaining 31 participants without a DHX37 variant (19.4%) had a microphallus at birth (information regarding one participant was missing). Testosterone therapy during infancy to increase penile growth was more effective in those without versus those with a DHX37 variant. The three participants with a DHX37 variant developed a male, female and non-binary gender identity, respectively; all other participants identified as males. Testosterone replacement therapy (TRT) in incremental doses had been initiated in 25 participants (median age at start 12.4 years). Final height was within the target height range in all end-pubertal participants, however, five out of 11 participants (45.5%), for whom stretched penile length (SPL) was measured, had a micropenis (mean adult SPL: 9.6 ± 2.5). Of the 11 participants who completed the questionnaire, five (45.5%) reported suboptimal understanding of the goals and effects of TRT at the time of puberty induction. Furthermore, only six (54.5%) and five (45.5%) of these 11 participants indicated they we
{"title":"Etiology, histology and long-term outcome of bilateral testicular regression: a large Belgian series","authors":"L. J. W. Tack, C. Brachet, V. Beauloye, C. Heinrichs, E. Boros, K. De Waele, S. van der Straaten, S. Van Aken, M. Craen, A. Lemay, A. Rochtus, K. Casteels, D. Beckers, T. Mouraux, K. Logghe, M. Van Loocke, G. Massa, K. Van de Vijver, H. Syryn, J. Van de Velde, E. De Baere, H. Verdin, M. Cools","doi":"10.1093/hropen/hoad047","DOIUrl":"https://doi.org/10.1093/hropen/hoad047","url":null,"abstract":"\u0000 \u0000 \u0000 What is the long-term outcome of individuals born with bilateral testicular regression (BTR) in relation to its underlying etiology?\u0000 \u0000 \u0000 \u0000 Statural growth and pubertal development are adequate with incremental doses of testosterone replacement therapy, however penile growth is often suboptimal, especially in those with a suspected genetic etiology (i.e. heterozygous DHX37 variants) or a micropenis at birth.\u0000 \u0000 \u0000 \u0000 BTR is a rare and poorly understood condition. Although a vascular origin has been postulated, heterozygous missense variants in DHX37 have been attributed to the phenotype as well. How these various etiologies impact the clinical phenotype, gonadal histology and outcome of BTR remains unclear.\u0000 \u0000 \u0000 \u0000 For this cross-sectional study, individuals with BTR were recruited in eight Belgian pediatric endocrinology departments, between December 2019 and December 2022. A physical exam was performed cross-sectionally in all 17 end-pubertal participants and a quality of care questionnaire was completed by 11 of them. Exome-based panel testing of 241 genes involved in gonadal development and spermatogenesis was performed along with a retrospective analysis of presentation and management. A centralized histological review of gonadal rests was done for 10 participants.\u0000 \u0000 \u0000 \u0000 A total of 35 participants (33 with male, one with female and one with non-binary gender identity), were recruited at a mean age of 15.0±5.7 years.\u0000 \u0000 \u0000 \u0000 The median age at presentation was 1.2 years [0-14 years]. Maternal gestational complications were common (38.2%), with a notably high incidence of monozygotic twin pregnancies (8.8%). Heterozygous (likely) pathogenic missense variants in DHX37 (p.Arg334Trp and p.Arg308Gln) were found in three participants. No other (likely) pathogenic variants were found. All three participants with a DHX37 variant had a microphallus at birth (leading to female sex assignment in one), while only six of the remaining 31 participants without a DHX37 variant (19.4%) had a microphallus at birth (information regarding one participant was missing). Testosterone therapy during infancy to increase penile growth was more effective in those without versus those with a DHX37 variant. The three participants with a DHX37 variant developed a male, female and non-binary gender identity, respectively; all other participants identified as males. Testosterone replacement therapy (TRT) in incremental doses had been initiated in 25 participants (median age at start 12.4 years). Final height was within the target height range in all end-pubertal participants, however, five out of 11 participants (45.5%), for whom stretched penile length (SPL) was measured, had a micropenis (mean adult SPL: 9.6 ± 2.5). Of the 11 participants who completed the questionnaire, five (45.5%) reported suboptimal understanding of the goals and effects of TRT at the time of puberty induction. Furthermore, only six (54.5%) and five (45.5%) of these 11 participants indicated they we","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":" 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138616004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-25eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad045
F Horta, M Salih, C Austin, R Warty, V Smith, D L Rolnik, S Reddy, H Rezatofighi, B Vollenhoven
{"title":"Reply: Artificial intelligence as a door opener for a new era of human reproduction.","authors":"F Horta, M Salih, C Austin, R Warty, V Smith, D L Rolnik, S Reddy, H Rezatofighi, B Vollenhoven","doi":"10.1093/hropen/hoad045","DOIUrl":"10.1093/hropen/hoad045","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad045"},"PeriodicalIF":8.3,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464786","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 : 2023-11-25eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad043
Markus Hengstschläger
{"title":"Artificial intelligence as a door opener for a new era of human reproduction.","authors":"Markus Hengstschläger","doi":"10.1093/hropen/hoad043","DOIUrl":"10.1093/hropen/hoad043","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad043"},"PeriodicalIF":0.0,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464784","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 : 2023-11-23eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad046
Yaping Jiang, Lei Jin, Bo Huang, Li Wu, Xinling Ren, Hui He
<p><strong>Study question: </strong>Is early rescue ICSI (E-RICSI) an effective and safe technique compared to conventional ICSI?</p><p><strong>Summary answer: </strong>Despite the higher multi-pronucleus (PN) rate compared to conventional ICSI, E-RICSI did not add extra risks to clinical and neonatal outcomes.</p><p><strong>What is known already: </strong>Based on the finding that the second polar body was released in 80% of fertilized oocytes by 4 h after exposure to spermatozoa and in ∼90% of fertilized oocytes by 6 h, E-RICSI brings forward the timing of rescue ICSI to 6 h after initial insemination, and effectively prevents oocyte aging and embryo-uterus asynchrony. However, some researchers still voice concerns about the efficacy and safety of E-RICSI, and comparative studies are limited.</p><p><strong>Study design size duration: </strong>A retrospective cohort study was conducted on patients who underwent conventional ICSI or E-RICSI treatment between January 2015 and December 2020 at a university-affiliated hospital. Using 1:1 propensity score matching, 1496 cases entered each group.</p><p><strong>Participants/materials setting methods: </strong>In total, 1496 couples undergoing conventional ICSI oocyte retrieval cycles and 1496 undergoing E-RICSI oocyte retrieval cycles were enrolled in this study, and basic clinical characteristics, embryologic data, clinical outcomes and neonatal data were compared between groups. The embryos in the E-RICSI group were divided into two subgroups: those fertilized by iIVF (IVF subgroup) and those fertilized by E-RICSI (E-RICSI subgroup); the embryologic data, clinical outcomes, and neonatal data for these subgroups were also compared with the conventional ICSI group. Logistic regression was used for statistical analysis with potential confounder adjustment.</p><p><strong>Main results and the role of chance: </strong>The 2PN rate, blastocyst formation rate, and viable blastocyst formation rate of the E-RICSI group were significantly lower compared to the conventional ICSI group (2PN rate: <i>P</i> < 0.001; blastocyst formation rate: <i>P</i> < 0.001; viable blastocyst formation rate: <i>P</i> = 0.004), and the multi-PN rate in the E-RICSI group was significantly higher than the conventional ICSI group (<i>P</i> < 0.001). However, the number of 2PN embryos, normal cleavage embryo rate, Day 3 high-quality cleavage embryo rate, and high-quality blastocyst rate were similar between groups. When considering the IVF embryos and E-RCSI embryos in the E-RICSI group independently, the 2PN rate of the conventional ICSI group was significantly lower than E-RICSI subgroup but higher than the IVF subgroup, whereas the blastocyst formation rate and viable blastocyst formation rate were higher than E-RICSI embryos but comparable to IVF embryos. As for the clinical and neonatal outcomes, the implantation rate of the E-RICSI subgroup was significantly lower than the IVF subgroup but comparable to the conventional ICSI gro
{"title":"Cumulative live birth rate and neonatal outcomes after early rescue ICSI: a propensity score matching analysis.","authors":"Yaping Jiang, Lei Jin, Bo Huang, Li Wu, Xinling Ren, Hui He","doi":"10.1093/hropen/hoad046","DOIUrl":"https://doi.org/10.1093/hropen/hoad046","url":null,"abstract":"<p><strong>Study question: </strong>Is early rescue ICSI (E-RICSI) an effective and safe technique compared to conventional ICSI?</p><p><strong>Summary answer: </strong>Despite the higher multi-pronucleus (PN) rate compared to conventional ICSI, E-RICSI did not add extra risks to clinical and neonatal outcomes.</p><p><strong>What is known already: </strong>Based on the finding that the second polar body was released in 80% of fertilized oocytes by 4 h after exposure to spermatozoa and in ∼90% of fertilized oocytes by 6 h, E-RICSI brings forward the timing of rescue ICSI to 6 h after initial insemination, and effectively prevents oocyte aging and embryo-uterus asynchrony. However, some researchers still voice concerns about the efficacy and safety of E-RICSI, and comparative studies are limited.</p><p><strong>Study design size duration: </strong>A retrospective cohort study was conducted on patients who underwent conventional ICSI or E-RICSI treatment between January 2015 and December 2020 at a university-affiliated hospital. Using 1:1 propensity score matching, 1496 cases entered each group.</p><p><strong>Participants/materials setting methods: </strong>In total, 1496 couples undergoing conventional ICSI oocyte retrieval cycles and 1496 undergoing E-RICSI oocyte retrieval cycles were enrolled in this study, and basic clinical characteristics, embryologic data, clinical outcomes and neonatal data were compared between groups. The embryos in the E-RICSI group were divided into two subgroups: those fertilized by iIVF (IVF subgroup) and those fertilized by E-RICSI (E-RICSI subgroup); the embryologic data, clinical outcomes, and neonatal data for these subgroups were also compared with the conventional ICSI group. Logistic regression was used for statistical analysis with potential confounder adjustment.</p><p><strong>Main results and the role of chance: </strong>The 2PN rate, blastocyst formation rate, and viable blastocyst formation rate of the E-RICSI group were significantly lower compared to the conventional ICSI group (2PN rate: <i>P</i> < 0.001; blastocyst formation rate: <i>P</i> < 0.001; viable blastocyst formation rate: <i>P</i> = 0.004), and the multi-PN rate in the E-RICSI group was significantly higher than the conventional ICSI group (<i>P</i> < 0.001). However, the number of 2PN embryos, normal cleavage embryo rate, Day 3 high-quality cleavage embryo rate, and high-quality blastocyst rate were similar between groups. When considering the IVF embryos and E-RCSI embryos in the E-RICSI group independently, the 2PN rate of the conventional ICSI group was significantly lower than E-RICSI subgroup but higher than the IVF subgroup, whereas the blastocyst formation rate and viable blastocyst formation rate were higher than E-RICSI embryos but comparable to IVF embryos. As for the clinical and neonatal outcomes, the implantation rate of the E-RICSI subgroup was significantly lower than the IVF subgroup but comparable to the conventional ICSI gro","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad046"},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814661","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 : 2023-11-15eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad044
Do-Yeal Ryu, Won-Ki Pang, Elikanah Olusayo Adegoke, Md Saidur Rahman, Yoo-Jin Park, Myung-Geol Pang
<p><strong>Study question: </strong>How does bisphenol-A (BPA) influence male fertility, and which mechanisms are activated following BPA exposure?</p><p><strong>Summary answer: </strong>BPA exposure causes hormonal disruption and alters mitochondrial dynamics and activity, ultimately leading to decreased male fertility.</p><p><strong>What is known already: </strong>As public health concerns following BPA exposure are rising globally, there is a need to understand the exact mechanisms of BPA on various diseases. BPA exposure causes hormonal imbalances and affects male fertility by binding the estrogen receptors (ERs), but the mechanism of how it mediates the hormonal dysregulation is yet to be studied.</p><p><strong>Study design size duration: </strong>This study consisted of a comparative study using mice that were separated into a control group and a group exposed to the lowest observed adverse effect level (LOAEL) (n = 20 mice/group) after a week of acclimatization to the environment. For this study, the LOAEL established by the US Environmental Protection Agency of 50 mg/kg body weight (BW)/day of BPA was used. The control mice were given corn oil orally. Based on the daily variations in BW, both groups were gavaged every day from 6 to 11 weeks (6-week exposure). Before sampling, mice were stabilized for a week. Then, the testes and spermatozoa of each mouse were collected to investigate the effects of BPA on male fertility. IVF was carried out using the cumulus-oocyte complexes from female hybrid B6D2F1/CrljOri mice (n = 3) between the ages of eight and twelve weeks.</p><p><strong>Participants/materials setting methods: </strong>Signaling pathways, apoptosis, and mitochondrial activity/dynamics-related proteins were evaluated by western blotting. ELISA was performed to determine the levels of sex hormones (FSH, LH, and testosterone) in serum. Hematoxylin and eosin staining was used to determine the effects of BPA on histological morphology and stage VII/VIII testicular seminiferous epithelium. Blastocyst formation and cleavage development rate were evaluated using IVF.</p><p><strong>Main results and the role of chance: </strong>BPA acted by binding to ERs and G protein-coupled receptors and activating the protein kinase A and mitogen-activated protein kinase signaling pathways, leading to aberrant hormone levels and effects on the respiratory chain complex, ATP synthase and protein-related apoptotic pathways in testis mitochondria (<i>P </i><<i> </i>0.05). Subsequently, embryo cleavage and blastocyst formation were reduced after the use of affected sperm, and abnormal morphology of seminiferous tubules and stage VII and VIII seminiferous epithelial cells (<i>P </i><<i> </i>0.05) was observed. It is noteworthy that histopathological lesions were detected in the testes at the LOAEL dose, even though the mice remained generally healthy and did not exhibit significant changes in BW following BPA exposure. These observations suggest that testicul
{"title":"Bisphenol-A disturbs hormonal levels and testis mitochondrial activity, reducing male fertility.","authors":"Do-Yeal Ryu, Won-Ki Pang, Elikanah Olusayo Adegoke, Md Saidur Rahman, Yoo-Jin Park, Myung-Geol Pang","doi":"10.1093/hropen/hoad044","DOIUrl":"https://doi.org/10.1093/hropen/hoad044","url":null,"abstract":"<p><strong>Study question: </strong>How does bisphenol-A (BPA) influence male fertility, and which mechanisms are activated following BPA exposure?</p><p><strong>Summary answer: </strong>BPA exposure causes hormonal disruption and alters mitochondrial dynamics and activity, ultimately leading to decreased male fertility.</p><p><strong>What is known already: </strong>As public health concerns following BPA exposure are rising globally, there is a need to understand the exact mechanisms of BPA on various diseases. BPA exposure causes hormonal imbalances and affects male fertility by binding the estrogen receptors (ERs), but the mechanism of how it mediates the hormonal dysregulation is yet to be studied.</p><p><strong>Study design size duration: </strong>This study consisted of a comparative study using mice that were separated into a control group and a group exposed to the lowest observed adverse effect level (LOAEL) (n = 20 mice/group) after a week of acclimatization to the environment. For this study, the LOAEL established by the US Environmental Protection Agency of 50 mg/kg body weight (BW)/day of BPA was used. The control mice were given corn oil orally. Based on the daily variations in BW, both groups were gavaged every day from 6 to 11 weeks (6-week exposure). Before sampling, mice were stabilized for a week. Then, the testes and spermatozoa of each mouse were collected to investigate the effects of BPA on male fertility. IVF was carried out using the cumulus-oocyte complexes from female hybrid B6D2F1/CrljOri mice (n = 3) between the ages of eight and twelve weeks.</p><p><strong>Participants/materials setting methods: </strong>Signaling pathways, apoptosis, and mitochondrial activity/dynamics-related proteins were evaluated by western blotting. ELISA was performed to determine the levels of sex hormones (FSH, LH, and testosterone) in serum. Hematoxylin and eosin staining was used to determine the effects of BPA on histological morphology and stage VII/VIII testicular seminiferous epithelium. Blastocyst formation and cleavage development rate were evaluated using IVF.</p><p><strong>Main results and the role of chance: </strong>BPA acted by binding to ERs and G protein-coupled receptors and activating the protein kinase A and mitogen-activated protein kinase signaling pathways, leading to aberrant hormone levels and effects on the respiratory chain complex, ATP synthase and protein-related apoptotic pathways in testis mitochondria (<i>P </i><<i> </i>0.05). Subsequently, embryo cleavage and blastocyst formation were reduced after the use of affected sperm, and abnormal morphology of seminiferous tubules and stage VII and VIII seminiferous epithelial cells (<i>P </i><<i> </i>0.05) was observed. It is noteworthy that histopathological lesions were detected in the testes at the LOAEL dose, even though the mice remained generally healthy and did not exhibit significant changes in BW following BPA exposure. These observations suggest that testicul","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad044"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464785","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 : 2023-11-15eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad042
Nathalie B Neeser, Andrea Martani, Eva De Clercq, Christian De Geyter, Nicolas Vulliemoz, Bernice S Elger, Tenzin Wangmo
<p><strong>Study question: </strong>What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as 40 years onwards?</p><p><strong>Summary answer: </strong>Although the studies show discrepancies in defining who is an APA parent and an imbalance in the empirical evidence for offspring, mothers, and fathers, there is a drive towards finding psychotic disorders and (neuro-)developmental disorders among the offspring; overall, the observed advantages and disadvantages are difficult to compare.</p><p><strong>What is known already: </strong>In many societies, children are born to parents at advanced ages and there is rising attention in the literature towards the consequences of this trend.</p><p><strong>Study design size duration: </strong>The systematic search was conducted in six electronic databases (PubMed including Medline, Embase, Scopus, PsycInfo, CINAHL, and SocINDEX) and was limited to papers published between 2000 and 2021 and to English-language articles. Search terms used across all six electronic databases were: ('advanced parental age' OR 'advanced maternal age' OR 'advanced paternal age' OR 'advanced reproductive age' OR 'late parent*' OR 'late motherhood' OR 'late fatherhood') AND ('IVF' OR 'in vitro fertilization' OR 'in-vitro-fertilization' OR 'fertilization in vitro' OR 'ICSI' OR 'intracytoplasmic sperm injection' OR 'reproductive techn*' OR 'assisted reproductive technolog*' OR 'assisted reproduction' OR 'assisted conception' OR 'reproduction' OR 'conception' OR 'birth*' OR 'pregnan*') AND ('wellbeing' OR 'well-being' OR 'psycho-social' OR 'social' OR 'ethical' OR 'right to reproduce' OR 'justice' OR 'family functioning' OR 'parental competenc*' OR 'ageism' OR 'reproductive autonomy' OR 'outcome' OR 'risk*' OR 'benefit*').</p><p><strong>Participants/materials setting methods: </strong>The included papers were empirical studies in English published between 2000 and 2021, where the study either examined the wellbeing and psychosocial health of parents and/or their children, or focused on parental competences of APA parents or on the functioning of families with APA parents. A quality assessment of the identified studies was performed with the QATSDD tool. Additionally, 20% of studies were double-checked at the data extraction and quality assessment stage to avoid bias. The variables sought were: the geographical location, the year of publication, the methodological approach, the definitions of APA used, what study group was at the centre of the research, what research topic was studied, and what advantages and disadvantages of APA were found.</p><p><strong>Main results and the role of chance: </strong>A total number of 5403 articles were identified, leading to 2543 articles being included for title and abstract screening after removal of duplicates. This resulted in 98 articles included for a full-text reading by four researchers. Ult
{"title":"Building a family at advanced parental age: a systematic review on the risks and opportunities for parents and their offspring.","authors":"Nathalie B Neeser, Andrea Martani, Eva De Clercq, Christian De Geyter, Nicolas Vulliemoz, Bernice S Elger, Tenzin Wangmo","doi":"10.1093/hropen/hoad042","DOIUrl":"10.1093/hropen/hoad042","url":null,"abstract":"<p><strong>Study question: </strong>What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as 40 years onwards?</p><p><strong>Summary answer: </strong>Although the studies show discrepancies in defining who is an APA parent and an imbalance in the empirical evidence for offspring, mothers, and fathers, there is a drive towards finding psychotic disorders and (neuro-)developmental disorders among the offspring; overall, the observed advantages and disadvantages are difficult to compare.</p><p><strong>What is known already: </strong>In many societies, children are born to parents at advanced ages and there is rising attention in the literature towards the consequences of this trend.</p><p><strong>Study design size duration: </strong>The systematic search was conducted in six electronic databases (PubMed including Medline, Embase, Scopus, PsycInfo, CINAHL, and SocINDEX) and was limited to papers published between 2000 and 2021 and to English-language articles. Search terms used across all six electronic databases were: ('advanced parental age' OR 'advanced maternal age' OR 'advanced paternal age' OR 'advanced reproductive age' OR 'late parent*' OR 'late motherhood' OR 'late fatherhood') AND ('IVF' OR 'in vitro fertilization' OR 'in-vitro-fertilization' OR 'fertilization in vitro' OR 'ICSI' OR 'intracytoplasmic sperm injection' OR 'reproductive techn*' OR 'assisted reproductive technolog*' OR 'assisted reproduction' OR 'assisted conception' OR 'reproduction' OR 'conception' OR 'birth*' OR 'pregnan*') AND ('wellbeing' OR 'well-being' OR 'psycho-social' OR 'social' OR 'ethical' OR 'right to reproduce' OR 'justice' OR 'family functioning' OR 'parental competenc*' OR 'ageism' OR 'reproductive autonomy' OR 'outcome' OR 'risk*' OR 'benefit*').</p><p><strong>Participants/materials setting methods: </strong>The included papers were empirical studies in English published between 2000 and 2021, where the study either examined the wellbeing and psychosocial health of parents and/or their children, or focused on parental competences of APA parents or on the functioning of families with APA parents. A quality assessment of the identified studies was performed with the QATSDD tool. Additionally, 20% of studies were double-checked at the data extraction and quality assessment stage to avoid bias. The variables sought were: the geographical location, the year of publication, the methodological approach, the definitions of APA used, what study group was at the centre of the research, what research topic was studied, and what advantages and disadvantages of APA were found.</p><p><strong>Main results and the role of chance: </strong>A total number of 5403 articles were identified, leading to 2543 articles being included for title and abstract screening after removal of duplicates. This resulted in 98 articles included for a full-text reading by four researchers. Ult","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad042"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479675","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}