Pub Date : 2024-09-17eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae055
Wen-Hong Dong, Xia Wang, Fan Yuan, Lei Wang, Tian-Miao Gu, Bing-Quan Zhu, Jie Shao
<p><strong>Study question: </strong>How many couples with at least one child under 3 years would like to have another one or more child(ren) in Eastern China and will an in-cash subsidy be conducive to couple's fertility intentions?</p><p><strong>Summary answer: </strong>In sum, only 15.1% of respondents had further fertility intentions (FFI) before learning about the subsidy, and the planned in-cash subsidy policy increased respondents' overall FFI by 8.5%.</p><p><strong>What is known already: </strong>Fertility has been declining globally and has reached a new low in China. The reasons why the Chinese three-child policy was under-realized, and how couples will react to a planned monthly ¥1000 (€141.2) subsidy policy, are not fully understood.</p><p><strong>Study design size duration: </strong>During January and February 2022, a cross-sectional online survey aiming to understand families' expenses of raising a child under 3 years old, and couples' FFI, was conducted. During the survey period, 272 510 respondents scanned the QR code. This study reports the findings pertaining to questions on respondents' sociodemographic characteristics, household factors, FFI, and changes in intention from negative to positive after learning about the planned in-cash subsidy. After exclusion, 144 893 eligible responses were included.</p><p><strong>Participants/materials setting methods: </strong>Respondents' FFI, the effect of a planned ¥1000/month*36 months' in-cash subsidy (€5083.2 in total) on people with a negative FFI before the subsidy, and potential reasons for persistent negative FFI after learning about the subsidy were collected through an anonymous online survey. Stepwise binary logistic regression models were used to select associated factors. The potential fertility rate change and government costs were estimated. A stratified analysis by current child number and sensitivity analysis were also conducted.</p><p><strong>Main results and the role of chance: </strong>In sum, 15.7% (22 804/144 893) of respondents were male, 15.1% of respondents reported a positive FFI, and 10.0% (12 288/123 051) without an FFI at first changed their intention after learning about the planned in-cash subsidy policy. For those who still said 'no FFI', 46.5%, 20.6%, and 14.7% chose pressure on housing status, expenses on children's education, and lack of time or energy for caring for another child as their first reasons. FFI was strongest in participants receiving the most financial support from their parents, i.e. grandparents (OR = 1.73, 95% CI = 1.63-1.84 for the >¥100 000/year group), and weakest in those already having two children (OR = 0.23, 95% CI = 0.22-0.24). For those with no FFI before learning about the subsidy policy, respondents with the highest house loan/rent (>¥120 000/year, OR = 1.27, 95% CI = 1.18-1.36) were more likely to change their FFI from 'No' to 'Yes', and those with the highest household income (>¥300 000/year, OR = 0.65, 95% CI = 0.60-0.71) were
{"title":"Will a government subsidy increase couples' further fertility intentions? A real-world study from a large-scale online survey in Eastern China.","authors":"Wen-Hong Dong, Xia Wang, Fan Yuan, Lei Wang, Tian-Miao Gu, Bing-Quan Zhu, Jie Shao","doi":"10.1093/hropen/hoae055","DOIUrl":"https://doi.org/10.1093/hropen/hoae055","url":null,"abstract":"<p><strong>Study question: </strong>How many couples with at least one child under 3 years would like to have another one or more child(ren) in Eastern China and will an in-cash subsidy be conducive to couple's fertility intentions?</p><p><strong>Summary answer: </strong>In sum, only 15.1% of respondents had further fertility intentions (FFI) before learning about the subsidy, and the planned in-cash subsidy policy increased respondents' overall FFI by 8.5%.</p><p><strong>What is known already: </strong>Fertility has been declining globally and has reached a new low in China. The reasons why the Chinese three-child policy was under-realized, and how couples will react to a planned monthly ¥1000 (€141.2) subsidy policy, are not fully understood.</p><p><strong>Study design size duration: </strong>During January and February 2022, a cross-sectional online survey aiming to understand families' expenses of raising a child under 3 years old, and couples' FFI, was conducted. During the survey period, 272 510 respondents scanned the QR code. This study reports the findings pertaining to questions on respondents' sociodemographic characteristics, household factors, FFI, and changes in intention from negative to positive after learning about the planned in-cash subsidy. After exclusion, 144 893 eligible responses were included.</p><p><strong>Participants/materials setting methods: </strong>Respondents' FFI, the effect of a planned ¥1000/month*36 months' in-cash subsidy (€5083.2 in total) on people with a negative FFI before the subsidy, and potential reasons for persistent negative FFI after learning about the subsidy were collected through an anonymous online survey. Stepwise binary logistic regression models were used to select associated factors. The potential fertility rate change and government costs were estimated. A stratified analysis by current child number and sensitivity analysis were also conducted.</p><p><strong>Main results and the role of chance: </strong>In sum, 15.7% (22 804/144 893) of respondents were male, 15.1% of respondents reported a positive FFI, and 10.0% (12 288/123 051) without an FFI at first changed their intention after learning about the planned in-cash subsidy policy. For those who still said 'no FFI', 46.5%, 20.6%, and 14.7% chose pressure on housing status, expenses on children's education, and lack of time or energy for caring for another child as their first reasons. FFI was strongest in participants receiving the most financial support from their parents, i.e. grandparents (OR = 1.73, 95% CI = 1.63-1.84 for the >¥100 000/year group), and weakest in those already having two children (OR = 0.23, 95% CI = 0.22-0.24). For those with no FFI before learning about the subsidy policy, respondents with the highest house loan/rent (>¥120 000/year, OR = 1.27, 95% CI = 1.18-1.36) were more likely to change their FFI from 'No' to 'Yes', and those with the highest household income (>¥300 000/year, OR = 0.65, 95% CI = 0.60-0.71) were","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae055"},"PeriodicalIF":8.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae053
Josianne Nunes Carriço, Catarina Inês Gonçalves, Asma Al-Naama, Najeeb Syed, José Maria Aragüés, Margarida Bastos, Fernando Fonseca, Teresa Borges, Bernardo Dias Pereira, Duarte Pignatelli, Davide Carvalho, Filipe Cunha, Ana Saavedra, Elisabete Rodrigues, Joana Saraiva, Luisa Ruas, Nuno Vicente, João Martin Martins, Adriana De Sousa Lages, Maria João Oliveira, Cíntia Castro-Correia, Miguel Melo, Raquel Gomes Martins, Joana Couto, Carolina Moreno, Diana Martins, Patrícia Oliveira, Teresa Martins, Sofia Almeida Martins, Olinda Marques, Carla Meireles, António Garrão, Cláudia Nogueira, Carla Baptista, Susana Gama-de-Sousa, Cláudia Amaral, Mariana Martinho, Catarina Limbert, Luisa Barros, Inês Henriques Vieira, Teresa Sabino, Luís R Saraiva, Manuel Carlos Lemos
<p><strong>Study question: </strong>What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)?</p><p><strong>Summary answer: </strong>Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included.</p><p><strong>What is known already: </strong>CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility.</p><p><strong>Study design size duration: </strong>Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls.</p><p><strong>Participants/materials setting methods: </strong>The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS).</p><p><strong>Main results and the role of chance: </strong>A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were <i>GNRHR</i>, <i>FGFR1</i>, <i>ANOS1</i>, and <i>CHD7</i>. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken.</p><p><strong>Wider implications of the findings: </strong>This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH.</p><p><strong>Study funding/competing interests: </strong>This research was fun
{"title":"Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort.","authors":"Josianne Nunes Carriço, Catarina Inês Gonçalves, Asma Al-Naama, Najeeb Syed, José Maria Aragüés, Margarida Bastos, Fernando Fonseca, Teresa Borges, Bernardo Dias Pereira, Duarte Pignatelli, Davide Carvalho, Filipe Cunha, Ana Saavedra, Elisabete Rodrigues, Joana Saraiva, Luisa Ruas, Nuno Vicente, João Martin Martins, Adriana De Sousa Lages, Maria João Oliveira, Cíntia Castro-Correia, Miguel Melo, Raquel Gomes Martins, Joana Couto, Carolina Moreno, Diana Martins, Patrícia Oliveira, Teresa Martins, Sofia Almeida Martins, Olinda Marques, Carla Meireles, António Garrão, Cláudia Nogueira, Carla Baptista, Susana Gama-de-Sousa, Cláudia Amaral, Mariana Martinho, Catarina Limbert, Luisa Barros, Inês Henriques Vieira, Teresa Sabino, Luís R Saraiva, Manuel Carlos Lemos","doi":"10.1093/hropen/hoae053","DOIUrl":"10.1093/hropen/hoae053","url":null,"abstract":"<p><strong>Study question: </strong>What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)?</p><p><strong>Summary answer: </strong>Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included.</p><p><strong>What is known already: </strong>CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility.</p><p><strong>Study design size duration: </strong>Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls.</p><p><strong>Participants/materials setting methods: </strong>The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS).</p><p><strong>Main results and the role of chance: </strong>A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were <i>GNRHR</i>, <i>FGFR1</i>, <i>ANOS1</i>, and <i>CHD7</i>. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken.</p><p><strong>Wider implications of the findings: </strong>This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH.</p><p><strong>Study funding/competing interests: </strong>This research was fun","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae053"},"PeriodicalIF":8.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae052
Maria Winkler-Dworak, Kryštof Zeman, Tomáš Sobotka
<p><strong>Study question: </strong>What are the factors influencing the decline in the birth rates observed in higher-income countries in the later phase of the COVID-19 pandemic?</p><p><strong>Summary answer: </strong>Our results suggest that economic uncertainty, non-pharmaceutical policy interventions, and the first wave of the population-wide vaccination campaign were associated with the decline in birth rates during 2022.</p><p><strong>What is known already: </strong>During the COVID-19 pandemic, birth rates in most higher-income countries first briefly declined and then shortly recovered, showing no common trends afterwards until early 2022, when they unexpectedly dropped.</p><p><strong>Study design size duration: </strong>This study uses population-wide data on monthly total fertility rates (TFRs) adjusted for seasonality and calendar effects provided in the Human Fertility Database (HFD). Births taking place between November 2020 and October 2022 correspond to conceptions occurring between February 2020 and January 2022, i.e. after the onset of the pandemic but prior to the Russian invasion of Ukraine. The data cover 26 countries, including 21 countries in Europe, the USA, Canada, Israel, Japan, and the Republic of Korea.</p><p><strong>Participants/materials setting methods: </strong>First, we provided a descriptive analysis of the monthly changes in the TFR. Second, we employed linear fixed effects regression models to estimate the association of explanatory factors with the observed seasonally adjusted TFRs. Our analysis considered three broader sets of explanatory factors: economic uncertainty, policy interventions restricting mobility and social activities outside the home, and the progression of vaccination programmes.</p><p><strong>Main results and the role of chance: </strong>We found that birth trends during the COVID-19 pandemic were associated with economic uncertainty, as measured by increased inflation (<i>P</i> < 0.001), whereas unemployment did not show any link to births during the pandemic (<i>P</i> = 0.677). The stringency of pandemic policy interventions was linked to a postponement of births, but only in countries with lower institutional trust and only in the early phase of the pandemic (<i>P</i> = 0.003). In countries with higher trust, stricter containment measures were positively associated with birth rates, both for conceptions in the first year of the pandemic (<i>P</i> = 0.019) and, albeit only weakly significant, for conceptions later in the pandemic (<i>P</i> = 0.057). Furthermore, we found a negative association between the share of the population having received the first dose of the COVID-19 vaccination and TFRs (<i>P</i> < 0.001), whereas the share of the population having completed the primary vaccination course (usually consisting of two doses) was linked to a recovery of birth rates (<i>P</i> < 0.001).</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>
{"title":"Birth rate decline in the later phase of the COVID-19 pandemic: the role of policy interventions, vaccination programmes, and economic uncertainty.","authors":"Maria Winkler-Dworak, Kryštof Zeman, Tomáš Sobotka","doi":"10.1093/hropen/hoae052","DOIUrl":"https://doi.org/10.1093/hropen/hoae052","url":null,"abstract":"<p><strong>Study question: </strong>What are the factors influencing the decline in the birth rates observed in higher-income countries in the later phase of the COVID-19 pandemic?</p><p><strong>Summary answer: </strong>Our results suggest that economic uncertainty, non-pharmaceutical policy interventions, and the first wave of the population-wide vaccination campaign were associated with the decline in birth rates during 2022.</p><p><strong>What is known already: </strong>During the COVID-19 pandemic, birth rates in most higher-income countries first briefly declined and then shortly recovered, showing no common trends afterwards until early 2022, when they unexpectedly dropped.</p><p><strong>Study design size duration: </strong>This study uses population-wide data on monthly total fertility rates (TFRs) adjusted for seasonality and calendar effects provided in the Human Fertility Database (HFD). Births taking place between November 2020 and October 2022 correspond to conceptions occurring between February 2020 and January 2022, i.e. after the onset of the pandemic but prior to the Russian invasion of Ukraine. The data cover 26 countries, including 21 countries in Europe, the USA, Canada, Israel, Japan, and the Republic of Korea.</p><p><strong>Participants/materials setting methods: </strong>First, we provided a descriptive analysis of the monthly changes in the TFR. Second, we employed linear fixed effects regression models to estimate the association of explanatory factors with the observed seasonally adjusted TFRs. Our analysis considered three broader sets of explanatory factors: economic uncertainty, policy interventions restricting mobility and social activities outside the home, and the progression of vaccination programmes.</p><p><strong>Main results and the role of chance: </strong>We found that birth trends during the COVID-19 pandemic were associated with economic uncertainty, as measured by increased inflation (<i>P</i> < 0.001), whereas unemployment did not show any link to births during the pandemic (<i>P</i> = 0.677). The stringency of pandemic policy interventions was linked to a postponement of births, but only in countries with lower institutional trust and only in the early phase of the pandemic (<i>P</i> = 0.003). In countries with higher trust, stricter containment measures were positively associated with birth rates, both for conceptions in the first year of the pandemic (<i>P</i> = 0.019) and, albeit only weakly significant, for conceptions later in the pandemic (<i>P</i> = 0.057). Furthermore, we found a negative association between the share of the population having received the first dose of the COVID-19 vaccination and TFRs (<i>P</i> < 0.001), whereas the share of the population having completed the primary vaccination course (usually consisting of two doses) was linked to a recovery of birth rates (<i>P</i> < 0.001).</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae052"},"PeriodicalIF":8.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae050
Sarah Munk Andreasen, Lise Gehrt, Casper P Hagen, Anders Juul, Gylli Mola, Margit Bistrup Fischer, Marianne Skovsager Andersen, David Møbjerg Kristensen, Tina Kold Jensen
<p><strong>Study question: </strong>Does anogenital distance (AGD) - distance from the anus to the genitals - correlate from infancy (3 months) to the age of 9 years in boys and girls?</p><p><strong>Summary answer: </strong>In boys, AGD correlated from infancy to 9 years of age, whereas in girls, correlations were weaker, especially between infancy and later childhood.</p><p><strong>What is known already: </strong>AGD is considered a marker for prenatal androgen action. In males, reduced AGD is associated with testicular cancer, infertility, and lower sperm count. In females, AGD is associated with endometriosis and polycystic ovary syndrome.</p><p><strong>Study design size duration: </strong>In the Odense Child Cohort, a prospective population-based birth cohort, pregnant women were enrolled in early pregnancy. AGD and BMI were measured repeatedly in children at ages 3 and 18 months, as well as at 3, 5, 7, and 9 years.</p><p><strong>Participants/materials setting methods: </strong>AGD was measured from the anus to the scrotum (AGDas) and to the penis (AGDap) in 1022 boys, and to the posterior fourchette and the clitoris in 887 girls repeatedly between the age of 3 months to 9 years. In total, 7706 assessments were made. AGD was adjusted for body weight, and <i>SD scores</i> (the difference between individual AGD and the mean of AGD in the population divided by SD of AGD) were calculated for each child. Pearson correlation coefficient (<i>r</i>) of each measurement was performed to investigate whether individual AGD was stable during childhood. Short predictive values at 3 months (20th percentile) to 9 years were investigated using the AUC produced by the receiver operating characteristic curve.</p><p><strong>Main results and the role of chance: </strong>In boys, AGD/body size-index <i>SD score</i> correlated significantly between infancy and 9 years, strongest for AGDas (<i>r</i> = 0.540 <i>P</i> > 0.001). In girls, weaker significant correlation coefficients were found between AGD at infancy and 9 years; higher correlation coefficients were found between AGD from 3 to 9 years (<i>P</i> > 0.001). Short AGDas in infancy predicted short AGDas in boys aged 9 years (AUC: 0.767, sensitivity 0.71, specificity 0.71). The predictive values of short infant AGDap, penile width (in boys), and AGD (in girls) concerning short outcomes at 9 years were low.</p><p><strong>Limitations reasons for caution: </strong>The AGD measurements are less precisely measurable in girls compared to boys, especially in infancy, resulting in less reproducible measurements. Additionally, because AGD is shorter in girls, the same absolute measurement error is relatively more significant, potentially contributing to greater variability and lower reproducibility in girls. This may contribute to the weaker correlations in girls compared to boys.</p><p><strong>Wider implications of the findings: </strong>In boys, AGDas, relative to body size, correlated from infancy to 9 years, sugge
{"title":"Correlation of anogenital distance from childhood to age 9 years-a prospective population-based birth cohort-the Odense Child Cohort.","authors":"Sarah Munk Andreasen, Lise Gehrt, Casper P Hagen, Anders Juul, Gylli Mola, Margit Bistrup Fischer, Marianne Skovsager Andersen, David Møbjerg Kristensen, Tina Kold Jensen","doi":"10.1093/hropen/hoae050","DOIUrl":"10.1093/hropen/hoae050","url":null,"abstract":"<p><strong>Study question: </strong>Does anogenital distance (AGD) - distance from the anus to the genitals - correlate from infancy (3 months) to the age of 9 years in boys and girls?</p><p><strong>Summary answer: </strong>In boys, AGD correlated from infancy to 9 years of age, whereas in girls, correlations were weaker, especially between infancy and later childhood.</p><p><strong>What is known already: </strong>AGD is considered a marker for prenatal androgen action. In males, reduced AGD is associated with testicular cancer, infertility, and lower sperm count. In females, AGD is associated with endometriosis and polycystic ovary syndrome.</p><p><strong>Study design size duration: </strong>In the Odense Child Cohort, a prospective population-based birth cohort, pregnant women were enrolled in early pregnancy. AGD and BMI were measured repeatedly in children at ages 3 and 18 months, as well as at 3, 5, 7, and 9 years.</p><p><strong>Participants/materials setting methods: </strong>AGD was measured from the anus to the scrotum (AGDas) and to the penis (AGDap) in 1022 boys, and to the posterior fourchette and the clitoris in 887 girls repeatedly between the age of 3 months to 9 years. In total, 7706 assessments were made. AGD was adjusted for body weight, and <i>SD scores</i> (the difference between individual AGD and the mean of AGD in the population divided by SD of AGD) were calculated for each child. Pearson correlation coefficient (<i>r</i>) of each measurement was performed to investigate whether individual AGD was stable during childhood. Short predictive values at 3 months (20th percentile) to 9 years were investigated using the AUC produced by the receiver operating characteristic curve.</p><p><strong>Main results and the role of chance: </strong>In boys, AGD/body size-index <i>SD score</i> correlated significantly between infancy and 9 years, strongest for AGDas (<i>r</i> = 0.540 <i>P</i> > 0.001). In girls, weaker significant correlation coefficients were found between AGD at infancy and 9 years; higher correlation coefficients were found between AGD from 3 to 9 years (<i>P</i> > 0.001). Short AGDas in infancy predicted short AGDas in boys aged 9 years (AUC: 0.767, sensitivity 0.71, specificity 0.71). The predictive values of short infant AGDap, penile width (in boys), and AGD (in girls) concerning short outcomes at 9 years were low.</p><p><strong>Limitations reasons for caution: </strong>The AGD measurements are less precisely measurable in girls compared to boys, especially in infancy, resulting in less reproducible measurements. Additionally, because AGD is shorter in girls, the same absolute measurement error is relatively more significant, potentially contributing to greater variability and lower reproducibility in girls. This may contribute to the weaker correlations in girls compared to boys.</p><p><strong>Wider implications of the findings: </strong>In boys, AGDas, relative to body size, correlated from infancy to 9 years, sugge","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae050"},"PeriodicalIF":8.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Study question: </strong>Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles?</p><p><strong>Summary answer: </strong>The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO<sub>2</sub>) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy.</p><p><strong>What is known already: </strong>Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods.</p><p><strong>Study design size duration: </strong>This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study.</p><p><strong>Participants/materials setting methods: </strong>Daily average levels of six air pollutants (fine particulate matter (PM<sub>2.5</sub>), inhalable particulate matter (PM<sub>10</sub>), SO<sub>2</sub>, nitrogen dioxide (NO<sub>2</sub>), carbon monoxide (CO), and ozone (O<sub>3</sub>)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations.</p><p><strong>Main results and the role of chance: </strong>The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM<sub>2.5</sub> during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO<sub>2</sub> in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were obs
{"title":"Association of ambient air pollutant mixtures with IVF/ICSI-ET clinical pregnancy rates during critical exposure periods.","authors":"Rui-Ling Liu, Tong Wang, Ying-Ling Yao, Xing-Yu Lv, Yu-Ling Hu, Xin-Zhen Chen, Xiao-Jun Tang, Zhao-Hui Zhong, Li-Juan Fu, Xin Luo, Li-Hong Geng, Shao-Min Yu, Yu-Bin Ding","doi":"10.1093/hropen/hoae051","DOIUrl":"https://doi.org/10.1093/hropen/hoae051","url":null,"abstract":"<p><strong>Study question: </strong>Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles?</p><p><strong>Summary answer: </strong>The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO<sub>2</sub>) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy.</p><p><strong>What is known already: </strong>Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods.</p><p><strong>Study design size duration: </strong>This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study.</p><p><strong>Participants/materials setting methods: </strong>Daily average levels of six air pollutants (fine particulate matter (PM<sub>2.5</sub>), inhalable particulate matter (PM<sub>10</sub>), SO<sub>2</sub>, nitrogen dioxide (NO<sub>2</sub>), carbon monoxide (CO), and ozone (O<sub>3</sub>)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations.</p><p><strong>Main results and the role of chance: </strong>The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM<sub>2.5</sub> during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO<sub>2</sub> in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were obs","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae051"},"PeriodicalIF":8.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae049
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
<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
{"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":"2024 3","pages":"hoae049"},"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}
Pub Date : 2024-08-12eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae048
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
<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
{"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":"2024 3","pages":"hoae048"},"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}
Pub Date : 2024-08-06eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae047
Dilan Gokyer, Sophia Akinboro, Luhan T Zhou, Anna Kleinhans, Monica M Laronda, Francesca E Duncan, Joan K Riley, Kara N Goldman, Elnur Babayev
<p><strong>Study question: </strong>Do the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of oocyte donors?</p><p><strong>Summary answer: </strong>The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors.</p><p><strong>What is known already: </strong>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.</p><p><strong>Study design size duration: </strong>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.</p><p><strong>Participants/materials setting methods: </strong>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.</p><p><strong>Main results and the role of chance: </strong>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, <i>P</i> = 3.5 × 10<sup>-43</sup>; GO: 0051983, <i>P</i> = 4.1 × 10<sup>-30</sup>; GO: 0000281, <i>P</i> = 7.7 × 10<sup>-15</sup>; GO: 0044839, <i>P</i> = 5.3 × 10<sup>-13</sup>) were significantly downregulated, while genes enriched in several pathways involved in cellular and vesicle organization (e.g. GO: 0010256, <i>P</i> = 1.2 × 10<sup>-8</sup>; GO: 0051129, <i>P</i> = 6.8 × 10<sup>-7</sup>; GO: 0016050, <i>P</i> = 7.4 × 10<sup>-7</sup>; GO: 0051640, <i>P</i> = 8.1 × 10<sup>-7</sup>) 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.</p><p><strong>Large scale data: </strong>Original high-throughput sequencing data have been deposited in Gene Expression Omnibus (GEO) database with the accession number GSE26599
{"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":"<p><strong>Study question: </strong>Do the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of oocyte donors?</p><p><strong>Summary answer: </strong>The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors.</p><p><strong>What is known already: </strong>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.</p><p><strong>Study design size duration: </strong>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.</p><p><strong>Participants/materials setting methods: </strong>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.</p><p><strong>Main results and the role of chance: </strong>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, <i>P</i> = 3.5 × 10<sup>-43</sup>; GO: 0051983, <i>P</i> = 4.1 × 10<sup>-30</sup>; GO: 0000281, <i>P</i> = 7.7 × 10<sup>-15</sup>; GO: 0044839, <i>P</i> = 5.3 × 10<sup>-13</sup>) were significantly downregulated, while genes enriched in several pathways involved in cellular and vesicle organization (e.g. GO: 0010256, <i>P</i> = 1.2 × 10<sup>-8</sup>; GO: 0051129, <i>P</i> = 6.8 × 10<sup>-7</sup>; GO: 0016050, <i>P</i> = 7.4 × 10<sup>-7</sup>; GO: 0051640, <i>P</i> = 8.1 × 10<sup>-7</sup>) 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.</p><p><strong>Large scale data: </strong>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":"2024 3","pages":"hoae047"},"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}
Pub Date : 2024-07-03eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae044
[This corrects the article DOI: 10.1093/hropen/hoaa066.].
[此处更正了文章 DOI：10.1093/hropen/hoaa066]。
{"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":"2024 3","pages":"hoae044"},"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}
Pub Date : 2024-06-26eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae043
Woo Jin Yang, Danbee Kang, Ji-Hee Sung, Myung Gyu Song, Hyejeong Park, Taegyun Park, Juhee Cho, Tae-Seok Seo, Soo-Young Oh
<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
{"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":"2024 3","pages":"hoae043"},"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}
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