Human reproduction open最新文献

{"title":"Prior exposure to alkylating agents negatively impacts testicular organoid formation in cells obtained from childhood cancer patients.","authors":"Yanhua Cui, Femke Harteveld, Hajar Ali Mohammed Ba Omar, Yifan Yang, Ragnar Bjarnason, Patrik Romerius, Mikael Sundin, Ulrika Norén Nyström, Cecilia Langenskiöld, Hartmut Vogt, Lars Henningsohn, Per Frisk, Kaisa Vepsäläinen, Cecilia Petersen, Rod T Mitchell, Jingtao Guo, João Pedro Alves-Lopes, Kirsi Jahnukainen, Jan-Bernd Stukenborg","doi":"10.1093/hropen/hoae049","DOIUrl":"10.1093/hropen/hoae049","url":null,"abstract":"<p><strong>Study question: </strong>Can human pre- and peri-pubertal testicular cells obtained from childhood cancer patients, previously treated with chemotherapy, form testicular organoids (TOs)?</p><p><strong>Summary answer: </strong>Organoid formation from testicular tissue collected from childhood cancer patients positively correlates with SRY-Box transcription factor 9 (SOX9) expression in Sertoli cells, which in turn negatively correlates with previous exposure to alkylating chemotherapy.</p><p><strong>What is known already: </strong>Pre- and peri-pubertal boys exposed to highly gonadotoxic therapies can only safeguard their fertility potential through testicular tissue cryopreservation. Today, there is no established clinical tool to restore fertility using these testicular samples. Organoids hold promise in providing fundamental early insights in creating such platforms. However, the generation of TOs that closely resemble the innate testis, to enable a thorough monitoring of the necessary steps for germ cell differentiation and somatic functionalities, remains a challenge.</p><p><strong>Study design size duration: </strong>We used a Matrigel-based three-layer gradient culture system to generate human TOs and to reveal whether chemotherapy exposure affects TO formation capacity and the functionality of pre- and peri-pubertal testicular somatic cells. Testicular cells of 11 boys (aged 7.7 ± 4.1 (mean ± SD) years) were assessed for TO formation in relation to previous chemotherapy exposure and SOX9 expression in histological sections of paraffin-embedded testicular tissue samples collected on the day of biopsy and compared with testicular tissue samples obtained from 28 consecutive patients (aged 6.9 ± 3.8 (mean ± SD) years). All 39 patients were part of the fertility preservation project NORDFERTIL; an additional 10 samples (from boys aged 5.5 ± 3.5 (mean ± SD) years, without an underlying pathology) in an internal biobank collection were used as controls.</p><p><strong>Participants/materials setting methods: </strong>We obtained 49 testicular tissue samples from boys aged 0.8-13.4 years. Fresh samples (n = 11) were dissociated into single-cell suspensions and applied to a three-layer gradient culture system for organoid formation. Histological sections of another 28 samples obtained as part of the fertility preservation project NORDFERTIL, and 10 samples from a sample collection of a pathology biobank were used to evaluate the effects of prior exposure to alkylating agents on testicular samples. Testicular organoid formation was defined based on morphological features, such as compartmentalized structures showing cord formation, and protein expression of testicular cell-specific markers for germ and somatic cells was evaluated via immunohistochemical staining. Hormone secretion was analysed by specific enzyme-linked immunosorbent assays for testosterone and anti-Müllerian hormone (AMH) production.</p><p><strong>Main results and the role ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074678","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}

{"title":"Aging promotes accumulation of senescent and multiciliated cells in human endometrial epithelium.","authors":"Marina Loid, Darina Obukhova, Keiu Kask, Apostol Apostolov, Alvin Meltsov, Demis Tserpelis, Arthur van den Wijngaard, Signe Altmäe, Galina Yahubyan, Vesselin Baev, Merli Saare, Maire Peters, Ave Minajeva, Priit Adler, Ganesh Acharya, Kaarel Krjutškov, Maria Nikolova, Felipe Vilella, Carlos Simon, Masoud Zamani Esteki, Andres Salumets","doi":"10.1093/hropen/hoae048","DOIUrl":"10.1093/hropen/hoae048","url":null,"abstract":"<p><strong>Study question: </strong>What changes occur in the endometrium during aging, and do they impact fertility?</p><p><strong>Summary answer: </strong>Both the transcriptome and cellular composition of endometrial samples from women of advanced maternal age (AMA) are significantly different from that of samples from young women, suggesting specific changes in epithelial cells that may affect endometrial receptivity.</p><p><strong>What is known already: </strong>Aging is associated with the accumulation of senescent cells in aging tissues. Reproductive aging is mostly attributed to the decline in ovarian reserve and oocyte quality, whereas the endometrium is a unique complex tissue that is monthly renewed under hormonal regulation. Several clinical studies have reported lower implantation and pregnancy rates in oocyte recipients of AMA during IVF. Molecular studies have indicated the presence of specific mutations within the epithelial cells of AMA endometrium, along with altered gene expression of bulk endometrial tissue.</p><p><strong>Study design size duration: </strong>Endometrial transcriptome profiling was performed for 44 women undergoing HRT during the assessment of endometrial receptivity before IVF. Patients younger than 28 years were considered as the young maternal age (YMA) group (age 23-27 years) and women older than 45 years were considered as the AMA group (age 47-50 years). Endometrial biopsies were obtained on Day 5 of progesterone treatment and RNA was extracted. All endometrial samples were evaluated as being receptive based on the expression of 68 common endometrial receptivity markers. Endometrial samples from another 24 women classified into four age groups (YMA, intermediate age group 1 (IMA1, age 29-35), intermediate age group 2 (IMA2, age 36-44), and AMA) were obtained in the mid-secretory stage of a natural cycle (NC) and used for validation studies across the reproductive lifespan.</p><p><strong>Participants/materials setting methods: </strong>A total of 24 HRT samples (12 YMA and 12 AMA) were subject to RNA sequencing (RNA-seq) and differential gene expression analysis, 20 samples (10 YMA and 10 AMA) were used for qPCR validation, and 24 NC samples (6 YMA, 6 IMA1, 6 IMA2 and 6AMA) were used for RNA-seq validation of AMA genes across the woman's reproductive lifespan. Immunohistochemistry (IHC) was used to confirm some expression changes at the protein level. Computational deconvolution using six endometrial cell type-specific transcriptomic profiles was conducted to compare the cellular composition between the groups.</p><p><strong>Main results and the role of chance: </strong>Comparisons between YMA and AMA samples identified a lower proportion of receptive endometria in the AMA group (<i>P</i> = 0.007). Gene expression profiling identified 491 differentially expressed age-sensitive genes (<i>P</i> adj < 0.05) that revealed the effects of age on endometrial epithelial growth and receptivity, likely contributing ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057496","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}

{"title":"The oocyte microenvironment is altered in adolescents compared to oocyte donors.","authors":"Dilan Gokyer, Sophia Akinboro, Luhan T Zhou, Anna Kleinhans, Monica M Laronda, Francesca E Duncan, Joan K Riley, Kara N Goldman, Elnur Babayev","doi":"10.1093/hropen/hoae047","DOIUrl":"10.1093/hropen/hoae047","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of oocyte donors?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Adolescents experience a period of subfecundity following menarche. Recent evidence suggests that this may be at least partially due to increased oocyte aneuploidy. Reproductive juvenescence in mammals is associated with suboptimal oocyte quality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This was a prospective cohort study. Adolescents (10-19 years old, n = 23) and oocyte donors (22-30 years old, n = 31) undergoing ovarian stimulation and oocyte retrieval at a single center between 1 November 2020 and 1 May 2023 were enrolled in this study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Patient demographics, ovarian stimulation, and oocyte retrieval outcomes were collected for all participants. The transcriptome of CCs associated with mature oocytes was compared between adolescents (10-19 years old, n = 19) and oocyte donors (22-30 years old, n = 19) using bulk RNA-sequencing. FF cytokine profiles (10-19 years old, n = 18 vs 25-30 years old, n = 16) were compared using cytokine arrays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;RNA-seq analysis revealed 581 differentially expressed genes in CCs of adolescents relative to oocyte donors, with 361 genes downregulated and 220 upregulated. Genes enriched in pathways involved in cell cycle and cell division (e.g. GO: 1903047, &lt;i&gt;P&lt;/i&gt; = 3.5 × 10&lt;sup&gt;-43&lt;/sup&gt;; GO: 0051983, &lt;i&gt;P&lt;/i&gt; = 4.1 × 10&lt;sup&gt;-30&lt;/sup&gt;; GO: 0000281, &lt;i&gt;P&lt;/i&gt; = 7.7 × 10&lt;sup&gt;-15&lt;/sup&gt;; GO: 0044839, &lt;i&gt;P&lt;/i&gt; = 5.3 × 10&lt;sup&gt;-13&lt;/sup&gt;) were significantly downregulated, while genes enriched in several pathways involved in cellular and vesicle organization (e.g. GO: 0010256, &lt;i&gt;P&lt;/i&gt; = 1.2 × 10&lt;sup&gt;-8&lt;/sup&gt;; GO: 0051129, &lt;i&gt;P&lt;/i&gt; = 6.8 × 10&lt;sup&gt;-7&lt;/sup&gt;; GO: 0016050, &lt;i&gt;P&lt;/i&gt; = 7.4 × 10&lt;sup&gt;-7&lt;/sup&gt;; GO: 0051640, &lt;i&gt;P&lt;/i&gt; = 8.1 × 10&lt;sup&gt;-7&lt;/sup&gt;) were upregulated in CCs of adolescents compared to oocyte donors. The levels of nine cytokines were significantly increased in FF of adolescents compared to oocyte donors: IL-1 alpha (2-fold), IL-1 beta (1.7-fold), I-309 (2-fold), IL-15 (1.6-fold), TARC (1.9-fold), TPO (2.1-fold), IGFBP-4 (2-fold), IL-12-p40 (1.7-fold), and ENA-78 (1.4-fold). Interestingly, seven of these cytokines have known pro-inflammatory roles. Importantly, neither the CC transcriptomes nor FF cytokine profiles were different in adolescents with or without cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;Original high-throughput sequencing data have been deposited in Gene Expression Omnibus (GEO) database with the accession number GSE26599","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115696","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}

{"title":"Extended versus conventional letrozole regimen in patients with polycystic ovary syndrome undergoing their first ovulation induction cycle: a prospective randomized controlled trial","authors":"Xiuxian Zhu, Jingwen Lang, Qiaoling Wang, Yonglun Fu","doi":"10.1093/hropen/hoae046","DOIUrl":"https://doi.org/10.1093/hropen/hoae046","url":null,"abstract":"\u0000 \u0000 \u0000 Can an extended letrozole regimen result in a higher ovulatory rate than a conventional regimen in patients with polycystic ovary syndrome (PCOS) undergoing their first ovulation induction cycle?\u0000 \u0000 \u0000 \u0000 There was no statistical difference in ovulation rate between patients with PCOS using the extended letrozole regimen and those using the conventional letrozole regimen.\u0000 \u0000 \u0000 \u0000 Letrozole has become the first-line agent for ovulation induction. However, there is still a proportion of non-responsive cycles in patients with PCOS undergoing ovulation induction therapy with letrozole alone, and the extended letrozole regimen has been demonstrated to be a feasible method for inducing ovulation in these non-responders. Nevertheless, whether the extended regimen could be applied to all patients with PCOS as a first choice for the induction of ovulation remains to be explored.\u0000 \u0000 \u0000 \u0000 This was a prospective randomized controlled trial that included 148 female patients with PCOS who underwent their first ovulation induction cycle with letrozole from January 2021 to October 2022.\u0000 \u0000 \u0000 \u0000 Participants were randomly assigned to receive an extended (5 mg letrozole daily for 7 days) or conventional regimen (5 mg letrozole daily for 5 days) for one treatment cycle. The ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, and the rate of multiple pregnancies.\u0000 \u0000 \u0000 \u0000 The ovulation rate among patients receiving an extended letrozole regimen was slightly higher than the rate with a conventional letrozole regimen, but the difference did not reach statistical significance in either the intention-to-treat analysis (90.54% [67/74] vs 79.73% [59/74], P = 0.065; relative risk [95% confidence interval]: 0.881 [0.768-1.009]) or per-protocol analysis (90.54% [67/74] vs 84.29% [59/70], P = 0.257; relative risk [95% confidence interval]: 0.931 [0.821-1.055]). The number of preovulatory follicles was nearly identical in the two groups (1.39±0.62 vs 1.37±0.59, P = 0.956), and no cases of ovarian hyperstimulation syndrome were observed. With regards to the endometrial parameters, the mean endometrium thickness was slightly thicker with the conventional LE regimen compared to that with the extended LE regimen, though with no statistical difference (9.27±1.72mm vs 9.57±2.28mm, P = 0.792). In the per-protocol analysis, the rates of clinical pregnancy (20.27% [15/74] vs 14.29% [10/70], P = 0.343; relative risk [95% confidence interval]: 0.705 [0.34-1.463]) and live birth (13.51% [10/74] vs 11.43% [8/70], P = 0.705; relative risk [95% confidence interval]: 0.846 [0.354-2.019]) did not differ significantly between treatment groups. Moreover, all conceptions were singletons without neonatal defects.\u0000 \u0000 \u0000 \u0000 The major concerns regarding this study are its single-centre and open-label nature. Additionally, the limited number of lean patients with PCOS with a mean body mass index of 23-25 kg/m2 enrolled in ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141826533","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}

{"title":"Is retrograde menstruation a universal, recurrent, physiological phenomenon? A systematic review of the evidence in humans and non-human primates","authors":"P. Vigano', Francesca Caprara, F. Giola, G. Di Stefano, E. Somigliana, P. Vercellini","doi":"10.1093/hropen/hoae045","DOIUrl":"https://doi.org/10.1093/hropen/hoae045","url":null,"abstract":"\u0000 \u0000 \u0000 What are the quantitative, qualitative and temporal patterns of retrograde mentruation?\u0000 \u0000 \u0000 \u0000 The extreme quantitative and qualitative heterogeneity of the available studies prevents the definitive conclusion that retrograde menstruation is a universal and consistent phenomenon during the reproductive period.\u0000 \u0000 \u0000 \u0000 Retrograde menstruation has been defined as a universal, physiological phenomenon that occurs similarly in about 90% of menstruators during the reproductive period. However, uncertainties still exists in terms of the event frequency, total amount and cellular composition of retrograde menstruation and the differences between individuals with versus those without endometriosis.\u0000 \u0000 \u0000 \u0000 Two systematic reviews were performed, one for human studies and one for non-human primate studies. We retrieved studies from the PubMed and Embase databases published between January 1, 1980 and November 1, 2023. Studies published in the English language were included and identified using a combination of MeSH terms. References from relevant publications were systematically screened and further articles were identified using PubMed’s “similar articles” and “cited by” functions.\u0000 \u0000 \u0000 \u0000 Results were reported in accordance with the PRISMA guidelines. Studies that did not report original data or provided a review of the field were excluded. Bias analysis was completed for each included human study by using the Newcastle-Ottawa scoring system.\u0000 \u0000 \u0000 \u0000 Fifteen studies were finally included in the human systematic review, mostly with limited sample sizes. The macroscopic visualization of blood in PF during menses was reported with a frequency ranging from 9% to 100%. A prevalence of endometrial cells detected in peritoneal fluid ranging from 8% to 75% was reported in the various studies. Controversial findings were reported in relation to patients with endometriosis. Retrograde menstruation has been evaluated cross-sectionally on single occasions, and no information is available on the course of the phenomenon within an entire cycle and between subsequent cycles. Two studies were included in the non-human primate systematic review; one of them showed that retrograde menstruation was observed more frequently in baboons with naturally occurring endometriosis (83%) than in those with a normal pelvis (51%).\u0000 \u0000 \u0000 \u0000 In humans, peritoneal fluid has often been collected at different cycle phases and not systematically during menstruation. The indication for laparoscopy was not always clear for all participants. A wide variety of methods were used to detect endometrial cells, including cytological staining, cell block analysis, immunocytochemistry and various methods of cell culture.\u0000 \u0000 \u0000 \u0000 The idea that almost all women experience retrograde menstruation regularly and similarly during their reproductive life is currently unsubstantiated. It is an academic notion accepted with criticism. Development of endometriosis may derive from differences in the frequency or ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141654601","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}

{"title":"Correction to: Fresh and cumulative live birth rates in mild versus conventional stimulation for IVF cycles in poor ovarian responders: a systematic review and meta-analysis.","authors":"","doi":"10.1093/hropen/hoae044","DOIUrl":"https://doi.org/10.1093/hropen/hoae044","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoaa066.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556056","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}

{"title":"Association between uterine artery embolization for postpartum hemorrhage and second delivery on maternal and offspring outcomes: a nationwide cohort study.","authors":"Woo Jin Yang, Danbee Kang, Ji-Hee Sung, Myung Gyu Song, Hyejeong Park, Taegyun Park, Juhee Cho, Tae-Seok Seo, Soo-Young Oh","doi":"10.1093/hropen/hoae043","DOIUrl":"10.1093/hropen/hoae043","url":null,"abstract":"<p><strong>Study question: </strong>What are the maternal and neonatal outcomes of second delivery in women who underwent uterine artery embolization (UAE) during their first delivery?</p><p><strong>Summary answer: </strong>Women who underwent UAE during their first delivery exhibited higher risks of placental problems, preterm births, and postpartum hemorrhage (PPH) in second delivery and the second offspring also showed increased risk of major congenital malformations, admission to the neonatal intensive care units (NICU), necrotizing enterocolitis, intraventricular hemorrhage, and bronchopulmonary dysplasia.</p><p><strong>What is known already: </strong>UAE is a minimally invasive procedure used as an alternative to hysterectomy for managing severe PPH. However, recent studies have raised concerns about potential obstetric complications, including recurrent PPH, placenta accreta spectrum (PAS), and fetal growth restriction in subsequent delivery following UAE.</p><p><strong>Study design size duration: </strong>This was a nationwide retrospective cohort study using the Korean National Health Insurance Service (K-NHIS) database, covering 50 million individuals from 2004 to 2020. The cohort included 3 616 923 women with live births between 1 January 2005 and 31 December 2019 with follow-up data extending to 31 December 2020.</p><p><strong>Participants/materials setting methods: </strong>The study included women who had their first live birth between 2005 and 2019, excluding those who underwent hysterectomy (without UAE = 3 612 389, UAE = 4534). Among them, we selected women who had single gestation secondary delivery (without UAE = 1 694 600, UAE = 1146). Propensity score matching was used to control for confounding factors, resulting in 11 184 women without UAE and 1119 women with UAE for subsequent analysis.</p><p><strong>Main results and the role of chance: </strong>Women in the UAE group had significantly higher risks of PAS (odds ratio (OR) = 38.91, 95% CI = 18.61-81.34), placenta previa (OR = 6.98, 95% CI = 5.57-8.75), and preterm birth (OR = 2.23, 95% CI = 1.71-2.90) during their second delivery. The risk of recurrent PPH was also significantly higher (OR = 8.94, 95% CI = 7.19-11.12). Their second offspring were more likely to have major congenital malformations (OR = 1.62, 95% CI = 1.25-2.11) and adverse neonatal outcomes, including NICU admissions (OR = 1.83, 95% CI = 1.48-2.25). Long-term outcomes showed a higher risk of attention-deficit/hyperactivity disorder (hazard ratio = 1.64, 95% CI = 1.03-2.63) but were otherwise comparable to those in the without UAE group.</p><p><strong>Limitations reasons for caution: </strong>Retrospective nature of the study may have introduced exposure and outcome misclassifications, despite the reliability of the K-NHIS database. Unmeasured confounders and selection bias due to only including live births could also have influenced the results.</p><p><strong>Wider implications of the findings: </strong>Wom","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735870","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}

{"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> ² > 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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}