A C Kiser, R Hemmert, R Myrer, B T Bucher, K Eilbeck, M Varner, J B Stanford, C M Peterson, A Z Pollack, L V Farland, K C Schliep
<p><strong>Study question: </strong>How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease?</p><p><strong>Summary answer: </strong>For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy.</p><p><strong>What is known already: </strong>Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high inter- and intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.</p><p><strong>Study design, size, duration: </strong>In this validation study, participants (n = 412) of the Utah operative cohort of the ENDO Study (2007-2009) were linked to medical records from the Utah Population Database (UPDB) to compare endometriosis diagnoses from each source. The UPDB is a unique database containing linked data on over 11 million individuals, including statewide ambulatory and inpatient records, state vital records, and University of Utah Health and Intermountain Healthcare electronic healthcare records, capturing most Utah residents.</p><p><strong>Participants/materials, setting, methods: </strong>The ENDO operative cohort consisted of individuals aged 18-44 years with no prior endometriosis diagnosis who underwent gynecologic laparoscopy or laparotomy for a variety of surgical indications. In total, 173 women were diagnosed with endometriosis based on surgical visualization of disease, 35% with superficial endometriosis, 9% with ovarian endometriomas, and 14% with deep infiltrating endometriosis. Contemporary administrative health data from the UPDB included ICD diagnostic codes from Utah Department of Health in-patient and ambulatory surgery records and University of Utah and Intermountain Health electronic health records.</p><p><strong>Main results and the role of chance: </strong>For endometriosis diagnosis, we found relatively high sensitivity (0.88) and specificity (0.87) and substantial agreement (Kappa [Κ] = 0.74). We found similarly high sensitivity, specificity, and agreement for superficial endometriosis (n = 143, 0.86, 0.83, Κ = 0.65) and ovarian endometriomas (n = 38, 0.82, 0.92, Κ = 0.58). However, deep infiltrating endometriosis (n = 58) had lower sensitivity (0.12) and agreement (Κ = 0.17), with high specificity (0.99).</p><p><strong>Limitations, reasons for caution: </strong>Medication prescription data and unstructured data, such as clinical notes, were not included in the UPDB data used for this study. These additional data types could aid in detection of endometriosis. Most participants were white or Asian with Hispanic ethnicity reported 11% of the time,
{"title":"Validation of administrative health data for the identification of endometriosis diagnosis.","authors":"A C Kiser, R Hemmert, R Myrer, B T Bucher, K Eilbeck, M Varner, J B Stanford, C M Peterson, A Z Pollack, L V Farland, K C Schliep","doi":"10.1093/humrep/deae281","DOIUrl":"10.1093/humrep/deae281","url":null,"abstract":"<p><strong>Study question: </strong>How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease?</p><p><strong>Summary answer: </strong>For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy.</p><p><strong>What is known already: </strong>Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high inter- and intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.</p><p><strong>Study design, size, duration: </strong>In this validation study, participants (n = 412) of the Utah operative cohort of the ENDO Study (2007-2009) were linked to medical records from the Utah Population Database (UPDB) to compare endometriosis diagnoses from each source. The UPDB is a unique database containing linked data on over 11 million individuals, including statewide ambulatory and inpatient records, state vital records, and University of Utah Health and Intermountain Healthcare electronic healthcare records, capturing most Utah residents.</p><p><strong>Participants/materials, setting, methods: </strong>The ENDO operative cohort consisted of individuals aged 18-44 years with no prior endometriosis diagnosis who underwent gynecologic laparoscopy or laparotomy for a variety of surgical indications. In total, 173 women were diagnosed with endometriosis based on surgical visualization of disease, 35% with superficial endometriosis, 9% with ovarian endometriomas, and 14% with deep infiltrating endometriosis. Contemporary administrative health data from the UPDB included ICD diagnostic codes from Utah Department of Health in-patient and ambulatory surgery records and University of Utah and Intermountain Health electronic health records.</p><p><strong>Main results and the role of chance: </strong>For endometriosis diagnosis, we found relatively high sensitivity (0.88) and specificity (0.87) and substantial agreement (Kappa [Κ] = 0.74). We found similarly high sensitivity, specificity, and agreement for superficial endometriosis (n = 143, 0.86, 0.83, Κ = 0.65) and ovarian endometriomas (n = 38, 0.82, 0.92, Κ = 0.58). However, deep infiltrating endometriosis (n = 58) had lower sensitivity (0.12) and agreement (Κ = 0.17), with high specificity (0.99).</p><p><strong>Limitations, reasons for caution: </strong>Medication prescription data and unstructured data, such as clinical notes, were not included in the UPDB data used for this study. These additional data types could aid in detection of endometriosis. Most participants were white or Asian with Hispanic ethnicity reported 11% of the time, ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"289-295"},"PeriodicalIF":6.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Study question: </strong>What role do sphingolipids have in mediating human sperm capacitation?</p><p><strong>Summary answer: </strong>Sphingosine 1-phosphate (S1P) mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1 and promoting production of reactive oxygen species such as nitric oxide and superoxide anion.</p><p><strong>What is known already: </strong>Bioactive sphingolipids, such as S1P, are fundamental for regulating numerous physiological domains and processes, such as cell membranes and signalling, cell death and proliferation, cell migration and invasiveness, inflammation, and central nervous system development.</p><p><strong>Study design, size, duration: </strong>Semen samples were obtained from a cohort of 10 healthy non-smoking volunteers (18-30 years old) to investigate the role of S1P in sperm.</p><p><strong>Participants/materials, setting, methods: </strong>Percoll-selected human spermatozoa were incubated at 37°C for 3.5 h in BWW media with or without foetal cord serum ultrafiltrate (FCSu), sphingosine (Sph), or ceramide (Cer). Spermatozoa were also incubated with or without pharmacological inhibitors of sphingolipid metabolism. Protein tyrosine phosphorylation was determined by immunoblotting. The acrosome reaction was determined by PSA-FTIC labelling of the acrosome and analysed using fluorescence microscopy. Intracellular nitric oxide (NO•) production was determined using a DAF-2DA probe. Immunocytochemistry was performed to localize and assess the functional relationship of key components of lipid signalling in spermatozoa. Sperm viability and motility of the samples were evaluated by the hypo-osmotic swelling (HOS) test and computer-aided sperm analysis (CASA). Statistical differences between groups were determined using ANOVA and Tukey's test. Normal distribution of the data and variance homogeneity were assessed using Shapiro-Wilk and Levene's test, respectively. A difference was considered significant when the P-value was ≤0.05.</p><p><strong>Main results and the role of chance: </strong>S1P mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1. We found that S1PR1 redistributes to the post-acrosomal region upon induction of capacitation. S1P signalling promotes the activation of the PI3K-AKT pathway, leading to NO• production during sperm capacitation. L-NAME, an nitric oxide synthase inhibitor, impaired the Sph- and Cer-dependent capacitation. Additionally, Sph and Cer promote superoxide anion (O2•-) production, and the extracellular addition of superoxide dismutase (SOD) prevented Sph- and Cer-dependent capacitation, suggesting that Sph and Cer stimulate O2•- production during sperm capacitation. Protein kinase type R (PKR), ceramide kinase (CERK), and protein kinase C (PKC) are responsible for translocating and activating sphingosine kinase 1 (SphK1), which is necessary to promo
研究问题：鞘脂在调节人类精子获能中起什么作用？摘要：sphingosin 1-phosphate （S1P）通过与其gi偶联受体S1PR1结合，促进一氧化氮和超氧阴离子等活性氧的产生，从而介导人类精子受精能力的获得。已知情况：生物活性鞘脂，如S1P，是调节许多生理领域和过程的基础，如细胞膜和信号传导、细胞死亡和增殖、细胞迁移和侵袭、炎症和中枢神经系统发育。研究设计、规模、持续时间：从10名健康的非吸烟志愿者（18-30岁）中获得精液样本，以研究S1P在精子中的作用。参与者/材料、环境、方法：percol选择的人精子在BWW培养基中37℃孵育3.5小时，含或不含胎脐带血清超滤液（FCSu）、鞘氨醇（Sph）或神经酰胺（Cer）。精子也在有或没有鞘脂代谢药理学抑制剂的情况下孵育。免疫印迹法测定蛋白酪氨酸磷酸化水平。顶体反应用PSA-FTIC标记法测定，荧光显微镜分析。采用DAF-2DA探针测定细胞内一氧化氮（NO•）的生成。免疫细胞化学用于定位和评估精子中脂质信号关键成分的功能关系。通过低渗透膨胀（HOS）试验和计算机辅助精子分析（CASA）评估精子活力和活力。采用方差分析和Tukey检验确定组间的统计学差异。数据的正态分布和方差齐性分别采用Shapiro-Wilk检验和Levene检验。p值≤0.05时差异被认为是显著的。主要结果和偶然性的作用：S1P通过与其gi偶联受体S1PR1结合介导人类精子受精能力的获得。我们发现S1PR1在诱导获能后重新分布到顶体后区域。S1P信号传导促进PI3K-AKT通路的激活，导致精子获能过程中NO•的产生。L-NAME，一种一氧化氮合酶抑制剂，损害了Sph和cer依赖的能化。此外，Sph和Cer促进了超氧阴离子（O2•-）的产生，细胞外超氧化物歧化酶（SOD）的添加阻止了Sph和Cer依赖的获能，这表明Sph和Cer在精子获能过程中刺激了O2•-的产生。蛋白激酶R （PKR）、神经酰胺激酶（CERK）和蛋白激酶C （PKC）负责鞘氨酸激酶1 （SphK1）的易位和激活，而SphK1是促进精子获能所需的S1P的产生所必需的。大规模数据：无。局限性，谨慎的原因：鞘脂的利用和作用可能在不同种类的精子中有所不同。研究结果的更广泛意义：鞘脂代谢产物如Sph、Cer、S1P和神经酰胺1-磷酸（C1P）在诱导人类精子获能中起着至关重要的作用。我们的研究为人类精子鞘脂的基本过程提供了新的见解，包括C1P在转运和激活SphK1中的重要性，以及S1P信号调节PI3K/AKT/NOS通路以产生NO•以使精子获能。我们是第一个在人类精子中发现PKR的存在及其在SphK1磷酸化活动和随后激活S1P信号中的作用。此外，我们的研究还发现S1PR1和S1PR3分别参与了能化和顶体反应。这些发现揭示了鞘脂驱动人类精子获能的新机制，并为进一步探索生物活性鞘脂代谢物在这一过程中的作用铺平了道路。最后，我们的研究为检查不育男性的脂质谱奠定了基础，因为潜在的差异会影响精子达到受精潜能的功能能力。研究经费/竞争利益：本研究由加拿大卫生研究院（CIHR）资助，资助号PJT-165962 to C.O.F. S.S.获得了muhc Desjardins奖学金。没有相互竞争的利益需要报告。
{"title":"Sphingolipids modulate redox signalling during human sperm capacitation.","authors":"Steven Serafini, Cristian O'Flaherty","doi":"10.1093/humrep/deae268","DOIUrl":"10.1093/humrep/deae268","url":null,"abstract":"<p><strong>Study question: </strong>What role do sphingolipids have in mediating human sperm capacitation?</p><p><strong>Summary answer: </strong>Sphingosine 1-phosphate (S1P) mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1 and promoting production of reactive oxygen species such as nitric oxide and superoxide anion.</p><p><strong>What is known already: </strong>Bioactive sphingolipids, such as S1P, are fundamental for regulating numerous physiological domains and processes, such as cell membranes and signalling, cell death and proliferation, cell migration and invasiveness, inflammation, and central nervous system development.</p><p><strong>Study design, size, duration: </strong>Semen samples were obtained from a cohort of 10 healthy non-smoking volunteers (18-30 years old) to investigate the role of S1P in sperm.</p><p><strong>Participants/materials, setting, methods: </strong>Percoll-selected human spermatozoa were incubated at 37°C for 3.5 h in BWW media with or without foetal cord serum ultrafiltrate (FCSu), sphingosine (Sph), or ceramide (Cer). Spermatozoa were also incubated with or without pharmacological inhibitors of sphingolipid metabolism. Protein tyrosine phosphorylation was determined by immunoblotting. The acrosome reaction was determined by PSA-FTIC labelling of the acrosome and analysed using fluorescence microscopy. Intracellular nitric oxide (NO•) production was determined using a DAF-2DA probe. Immunocytochemistry was performed to localize and assess the functional relationship of key components of lipid signalling in spermatozoa. Sperm viability and motility of the samples were evaluated by the hypo-osmotic swelling (HOS) test and computer-aided sperm analysis (CASA). Statistical differences between groups were determined using ANOVA and Tukey's test. Normal distribution of the data and variance homogeneity were assessed using Shapiro-Wilk and Levene's test, respectively. A difference was considered significant when the P-value was ≤0.05.</p><p><strong>Main results and the role of chance: </strong>S1P mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1. We found that S1PR1 redistributes to the post-acrosomal region upon induction of capacitation. S1P signalling promotes the activation of the PI3K-AKT pathway, leading to NO• production during sperm capacitation. L-NAME, an nitric oxide synthase inhibitor, impaired the Sph- and Cer-dependent capacitation. Additionally, Sph and Cer promote superoxide anion (O2•-) production, and the extracellular addition of superoxide dismutase (SOD) prevented Sph- and Cer-dependent capacitation, suggesting that Sph and Cer stimulate O2•- production during sperm capacitation. Protein kinase type R (PKR), ceramide kinase (CERK), and protein kinase C (PKC) are responsible for translocating and activating sphingosine kinase 1 (SphK1), which is necessary to promo","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"210-225"},"PeriodicalIF":6.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mei-Jou Chen, Nikos Kotsopoulos, Amy Ming-Fang Yen, Kuan-Ting Lin, Mark P Connolly
<p><strong>Study question: </strong>What is the governmental fiscal impact of a new assisted reproduction subsidy scheme based on projected lifetime net taxes attributed to resulting live births in Taiwan?</p><p><strong>Summary answer: </strong>We estimate that the new fertility reimbursement scheme has generated favorable lifetime fiscal gains for the Taiwanese government, resulting in a return on investment (ROI) of NT$5.6 for every NT$1.0 spent based on those families receiving public subsidies for fertility care under the new scheme.</p><p><strong>What is known already: </strong>Globally, there is variation in the amount of public reimbursement for assisted reproduction provided to infertile couples. Cost is an important consideration for many infertile couples that can influence the amount of services provided and the types of services used.</p><p><strong>Study design, size, duration: </strong>The analysis is based on the number of live births resulting from those couples receiving public subsidies for assisted reproduction. The cohort is based on those children born between March 2022 and July 2023.</p><p><strong>Participants/materials, setting, methods: </strong>A lifetime fiscal model was developed to project age-specific lifetime tax revenue and age-dependent benefits likely received from government attributed to the children born. The analysis is based on age-specific projected earnings adjusted for work activity and applied to published income tax burden data, in addition to estimated indirect consumption taxes paid. Furthermore, we estimate the lifetime national insurance contributions per worker, including employer contributions. To account for changes over the modeling period, we increased wages based on historical economic growth, government benefits were increased based on the rate of consumer price inflation rate, and all costs and taxes were discounted at 3.5%.</p><p><strong>Main results and the role of chance: </strong>A child born in Taiwan in 2022 is expected to pay discounted gross tax revenues of NT$7 257 438 and receive NT$5 373 730 in discounted future benefits from the government. Following implementation of the new funding policy, based on the number of resulting births, the cost per live birth is NT$331 918. Applying the cost per live birth, we estimate the discounted net tax revenue to be NT$1 551 789 for each child born from the subsidy. The ROI for the Taiwanese government is estimated at 568% over the lifetime of the IVF-conceived children.</p><p><strong>Limitations, reasons for caution: </strong>Several assumptions are applied in making long-term financial projections. Should economic conditions change dramatically, this could influence the projections described in our work.</p><p><strong>Wider implications of the findings: </strong>The results suggest the government benefits from public subsidy for fertility services when taking into consideration the long-term work activity of these children and future tax reven
{"title":"Estimating the public economic gains in Taiwan from in vitro fertilization (IVF) subsidy changes implemented in 2021.","authors":"Mei-Jou Chen, Nikos Kotsopoulos, Amy Ming-Fang Yen, Kuan-Ting Lin, Mark P Connolly","doi":"10.1093/humrep/deae271","DOIUrl":"10.1093/humrep/deae271","url":null,"abstract":"<p><strong>Study question: </strong>What is the governmental fiscal impact of a new assisted reproduction subsidy scheme based on projected lifetime net taxes attributed to resulting live births in Taiwan?</p><p><strong>Summary answer: </strong>We estimate that the new fertility reimbursement scheme has generated favorable lifetime fiscal gains for the Taiwanese government, resulting in a return on investment (ROI) of NT$5.6 for every NT$1.0 spent based on those families receiving public subsidies for fertility care under the new scheme.</p><p><strong>What is known already: </strong>Globally, there is variation in the amount of public reimbursement for assisted reproduction provided to infertile couples. Cost is an important consideration for many infertile couples that can influence the amount of services provided and the types of services used.</p><p><strong>Study design, size, duration: </strong>The analysis is based on the number of live births resulting from those couples receiving public subsidies for assisted reproduction. The cohort is based on those children born between March 2022 and July 2023.</p><p><strong>Participants/materials, setting, methods: </strong>A lifetime fiscal model was developed to project age-specific lifetime tax revenue and age-dependent benefits likely received from government attributed to the children born. The analysis is based on age-specific projected earnings adjusted for work activity and applied to published income tax burden data, in addition to estimated indirect consumption taxes paid. Furthermore, we estimate the lifetime national insurance contributions per worker, including employer contributions. To account for changes over the modeling period, we increased wages based on historical economic growth, government benefits were increased based on the rate of consumer price inflation rate, and all costs and taxes were discounted at 3.5%.</p><p><strong>Main results and the role of chance: </strong>A child born in Taiwan in 2022 is expected to pay discounted gross tax revenues of NT$7 257 438 and receive NT$5 373 730 in discounted future benefits from the government. Following implementation of the new funding policy, based on the number of resulting births, the cost per live birth is NT$331 918. Applying the cost per live birth, we estimate the discounted net tax revenue to be NT$1 551 789 for each child born from the subsidy. The ROI for the Taiwanese government is estimated at 568% over the lifetime of the IVF-conceived children.</p><p><strong>Limitations, reasons for caution: </strong>Several assumptions are applied in making long-term financial projections. Should economic conditions change dramatically, this could influence the projections described in our work.</p><p><strong>Wider implications of the findings: </strong>The results suggest the government benefits from public subsidy for fertility services when taking into consideration the long-term work activity of these children and future tax reven","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"328-334"},"PeriodicalIF":6.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y Wang, J Park, C Y Zhang, A M Z Jukic, D D Baird, B A Coull, R Hauser, S Mahalingaiah, S Zhang, C L Curry
STUDY QUESTION Can algorithms using wrist temperature, available on compatible models of iPhone and Apple Watch, retrospectively estimate the day of ovulation and predict the next menses start day? SUMMARY ANSWER Algorithms using wrist temperature can provide retrospective ovulation estimates and next menses start day predictions for individuals with typical or atypical cycle lengths. WHAT IS KNOWN ALREADY Wrist skin temperature is affected by hormonal changes associated with the menstrual cycle and can be used to estimate the timing of cycle events. STUDY DESIGN, SIZE, DURATION We conducted a prospective cohort study of 262 menstruating females (899 menstrual cycles) aged 14 and older who logged their menses, performed urine LH testing to define day of ovulation, recorded daily basal body temperature (BBT), and collected overnight wrist temperature. Participants contributed between 2 and 13 menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS Algorithm performance was evaluated for three algorithms: one for retrospective ovulation day estimate in ongoing cycles (Algorithm 1), one for retrospective ovulation day estimate in completed cycles (Algorithm 2), and one for prediction of next menses start day (Algorithm 3). Each algorithm’s performance was evaluated under multiple scenarios, including for participants with all typical cycle lengths (23–35 days) and those with some atypical cycle lengths (<23, >35 days), in cycles with the temperature change of ≥0.2°C typically associated with ovulation, and with any temperature change included. MAIN RESULTS AND ROLE OF CHANCE Two hundred and sixty participants provided 889 cycles. Algorithm 1 provided a retrospective ovulation day estimate in 80.5% of ongoing menstrual cycles of all cycle lengths with ≥0.2°C wrist temperature signal with a mean absolute error (MAE) of 1.59 days (95% CI 1.45, 1.74), with 80.0% of estimates being within ±2 days of ovulation. Retrospective ovulation day in an ongoing cycle (Algorithm 1) was estimated in 81.9% (MAE 1.53 days, 95% CI 1.35, 1.70) of cycles for participants with all typical cycle lengths and 77.7% (MAE 1.71 days, 95% CI 1.42, 2.01) of cycles for participants with atypical cycle lengths. Algorithm 2 provided a retrospective ovulation day estimate in 80.8% of completed menstrual cycles with ≥0.2°C wrist temperature signal with an MAE of 1.22 days (95% CI 1.11, 1.33), with 89.0% of estimates being within ±2 days of ovulation. Wrist temperature provided the next menses start day prediction (Algorithm 3) at the time of ovulation estimate (89.4% within ±3 days of menses start) with an MAE of 1.65 (95% CI 1.52, 1.79) days in cycles with ≥0.2°C wrist temperature signal. LIMITATIONS, REASONS FOR CAUTION There are several limitations, including reliance on LH testing to identify ovulation, which may mislabel some cycles. Additionally, the potential for false retrospective ovulation estimates when no ovulation occurred reinforces the idea that this es
{"title":"Performance of algorithms using wrist temperature for retrospective ovulation day estimate and next menses start day prediction: a prospective cohort study","authors":"Y Wang, J Park, C Y Zhang, A M Z Jukic, D D Baird, B A Coull, R Hauser, S Mahalingaiah, S Zhang, C L Curry","doi":"10.1093/humrep/deaf005","DOIUrl":"https://doi.org/10.1093/humrep/deaf005","url":null,"abstract":"STUDY QUESTION Can algorithms using wrist temperature, available on compatible models of iPhone and Apple Watch, retrospectively estimate the day of ovulation and predict the next menses start day? SUMMARY ANSWER Algorithms using wrist temperature can provide retrospective ovulation estimates and next menses start day predictions for individuals with typical or atypical cycle lengths. WHAT IS KNOWN ALREADY Wrist skin temperature is affected by hormonal changes associated with the menstrual cycle and can be used to estimate the timing of cycle events. STUDY DESIGN, SIZE, DURATION We conducted a prospective cohort study of 262 menstruating females (899 menstrual cycles) aged 14 and older who logged their menses, performed urine LH testing to define day of ovulation, recorded daily basal body temperature (BBT), and collected overnight wrist temperature. Participants contributed between 2 and 13 menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS Algorithm performance was evaluated for three algorithms: one for retrospective ovulation day estimate in ongoing cycles (Algorithm 1), one for retrospective ovulation day estimate in completed cycles (Algorithm 2), and one for prediction of next menses start day (Algorithm 3). Each algorithm’s performance was evaluated under multiple scenarios, including for participants with all typical cycle lengths (23–35 days) and those with some atypical cycle lengths (&lt;23, &gt;35 days), in cycles with the temperature change of ≥0.2°C typically associated with ovulation, and with any temperature change included. MAIN RESULTS AND ROLE OF CHANCE Two hundred and sixty participants provided 889 cycles. Algorithm 1 provided a retrospective ovulation day estimate in 80.5% of ongoing menstrual cycles of all cycle lengths with ≥0.2°C wrist temperature signal with a mean absolute error (MAE) of 1.59 days (95% CI 1.45, 1.74), with 80.0% of estimates being within ±2 days of ovulation. Retrospective ovulation day in an ongoing cycle (Algorithm 1) was estimated in 81.9% (MAE 1.53 days, 95% CI 1.35, 1.70) of cycles for participants with all typical cycle lengths and 77.7% (MAE 1.71 days, 95% CI 1.42, 2.01) of cycles for participants with atypical cycle lengths. Algorithm 2 provided a retrospective ovulation day estimate in 80.8% of completed menstrual cycles with ≥0.2°C wrist temperature signal with an MAE of 1.22 days (95% CI 1.11, 1.33), with 89.0% of estimates being within ±2 days of ovulation. Wrist temperature provided the next menses start day prediction (Algorithm 3) at the time of ovulation estimate (89.4% within ±3 days of menses start) with an MAE of 1.65 (95% CI 1.52, 1.79) days in cycles with ≥0.2°C wrist temperature signal. LIMITATIONS, REASONS FOR CAUTION There are several limitations, including reliance on LH testing to identify ovulation, which may mislabel some cycles. Additionally, the potential for false retrospective ovulation estimates when no ovulation occurred reinforces the idea that this es","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"84 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A M Klimczak, E Osman, M Esbert, R M Yildirim, C Whitehead, N S Herlihy, B M Hanson, L M Roberts, E Seli, R T Scott
STUDY QUESTION Does the use of slush nitrogen (SN) for embryo vitrification improve embryo transfer outcomes compared to liquid nitrogen (LN)? SUMMARY ANSWER SN is a safe method for embryo preservation and significantly improves post-warming survival rates during repeated vitrification–warming cycles; however, after a single freeze–thaw cycle, pregnancy outcomes are not improved when embryos are vitrified with SN compared to LN. WHAT IS KNOWN ALREADY SN is a combination of solid and LN, with a temperature lower than regular LN, and it is an alternative to conventional LN in achieving a faster cooling speed. Studies have shown that SN improves survival in non-human embryos and human oocytes. However, it is unknown whether the use of SN reduces blastocyst damage in humans during vitrification—as indicated by increased survival across multiple vitrification–warming cycles—or whether it enhances pregnancy outcomes in a single vitrification–warming cycle. STUDY DESIGN, SIZE, DURATION Following the pre-clinical trial assessing embryo survival after repeated freeze–thaw cycles using SN and LN on 50 donated embryos per group, a randomized controlled trial was performed, where 253 patients were enrolled between September 2020 and January 2022, and 245 underwent an IVF stimulation, which resulted in at least one blastocyst for cryopreservation. Of those, 121 were allocated to the SN (study), and 124 were allocated to the LN (control) group. Randomization occurred on the day of blastocyst biopsy using a computer-generated block schema. Groups were assigned via opaque envelopes, opened by the embryologist on vitrification day. The patient, physician, and clinical team were blinded to the intervention. PARTICIPANTS/MATERIALS, SETTING, METHODS All couples with female aged between 18 and 42 years old undergoing IVF stimulation at one university-affiliated infertility center, with plan for preimplantation genetic testing for aneuploidy and subsequent single, frozen embryo transfer (FET) were eligible for inclusion in this study. MAIN RESULTS AND THE ROLE OF CHANCE The pre-clinical trial demonstrated significant improvements in blastocyst survival, with the SN group achieving a mean of 7.5 survived vitrification–warming cycles (range: 3–22), significantly surpassing the mean of 3.0 cycles (range: 0–10) in the LN group (P < 0.0001). Following the pre-clinical trial, 223 patients randomized to SN or LN underwent single FET. Baseline characteristics were similar between groups, as were embryology outcomes, including the number of oocytes retrieved, mature oocytes, fertilization rate, and total blastocysts biopsied. No significant differences were observed between the two groups in pregnancy rate, clinical pregnancy rate, sustained implantation rate, or miscarriage rate (P = 0.16, 0.80, 0.49, and 0.74, respectively, using Student’s t-test). A futility analysis indicated no value in continuing recruitment and therefore the study was closed. LIMITATIONS, REASONS
{"title":"A randomized controlled trial comparing embryo vitrification with slush nitrogen to liquid nitrogen in women undergoing frozen embryo transfer: embryology and clinical outcomes","authors":"A M Klimczak, E Osman, M Esbert, R M Yildirim, C Whitehead, N S Herlihy, B M Hanson, L M Roberts, E Seli, R T Scott","doi":"10.1093/humrep/deaf003","DOIUrl":"https://doi.org/10.1093/humrep/deaf003","url":null,"abstract":"STUDY QUESTION Does the use of slush nitrogen (SN) for embryo vitrification improve embryo transfer outcomes compared to liquid nitrogen (LN)? SUMMARY ANSWER SN is a safe method for embryo preservation and significantly improves post-warming survival rates during repeated vitrification–warming cycles; however, after a single freeze–thaw cycle, pregnancy outcomes are not improved when embryos are vitrified with SN compared to LN. WHAT IS KNOWN ALREADY SN is a combination of solid and LN, with a temperature lower than regular LN, and it is an alternative to conventional LN in achieving a faster cooling speed. Studies have shown that SN improves survival in non-human embryos and human oocytes. However, it is unknown whether the use of SN reduces blastocyst damage in humans during vitrification—as indicated by increased survival across multiple vitrification–warming cycles—or whether it enhances pregnancy outcomes in a single vitrification–warming cycle. STUDY DESIGN, SIZE, DURATION Following the pre-clinical trial assessing embryo survival after repeated freeze–thaw cycles using SN and LN on 50 donated embryos per group, a randomized controlled trial was performed, where 253 patients were enrolled between September 2020 and January 2022, and 245 underwent an IVF stimulation, which resulted in at least one blastocyst for cryopreservation. Of those, 121 were allocated to the SN (study), and 124 were allocated to the LN (control) group. Randomization occurred on the day of blastocyst biopsy using a computer-generated block schema. Groups were assigned via opaque envelopes, opened by the embryologist on vitrification day. The patient, physician, and clinical team were blinded to the intervention. PARTICIPANTS/MATERIALS, SETTING, METHODS All couples with female aged between 18 and 42 years old undergoing IVF stimulation at one university-affiliated infertility center, with plan for preimplantation genetic testing for aneuploidy and subsequent single, frozen embryo transfer (FET) were eligible for inclusion in this study. MAIN RESULTS AND THE ROLE OF CHANCE The pre-clinical trial demonstrated significant improvements in blastocyst survival, with the SN group achieving a mean of 7.5 survived vitrification–warming cycles (range: 3–22), significantly surpassing the mean of 3.0 cycles (range: 0–10) in the LN group (P &lt; 0.0001). Following the pre-clinical trial, 223 patients randomized to SN or LN underwent single FET. Baseline characteristics were similar between groups, as were embryology outcomes, including the number of oocytes retrieved, mature oocytes, fertilization rate, and total blastocysts biopsied. No significant differences were observed between the two groups in pregnancy rate, clinical pregnancy rate, sustained implantation rate, or miscarriage rate (P = 0.16, 0.80, 0.49, and 0.74, respectively, using Student’s t-test). A futility analysis indicated no value in continuing recruitment and therefore the study was closed. LIMITATIONS, REASONS","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"32 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Families have been subject to enormous transformations with the emergence of artificial reproductive technology and the appearance of donor-conceived children. These new families are challenged to disclose origins with their children and parents feel concern that conception stories might have an emotional impact on their children. Fertility counsellors still feel ill-equipped on what to recommend to parents because developmental psychology has not designed systematic evidence-based guidelines to address a three-dimensional matter: 'what', 'when', and 'how' to discuss conception stories. The argument developed herein is that professionals working with families in fertility clinics, could benefit from understanding these new family conversational processes of origin storytelling from these three perspectives, not only on 'what' and 'when' but also on the less elaborated 'how' to talk about it. For this purpose, understanding elaborative reminiscing as a specific way of talking about the past that helps children to build autobiographical memories and develop their identity might be key.
{"title":"Beyond the disclosure debate in donor-conception: how do we help families to discuss origin stories with their children?","authors":"Javiera Navarro-Marshall","doi":"10.1093/humrep/deaf004","DOIUrl":"https://doi.org/10.1093/humrep/deaf004","url":null,"abstract":"Families have been subject to enormous transformations with the emergence of artificial reproductive technology and the appearance of donor-conceived children. These new families are challenged to disclose origins with their children and parents feel concern that conception stories might have an emotional impact on their children. Fertility counsellors still feel ill-equipped on what to recommend to parents because developmental psychology has not designed systematic evidence-based guidelines to address a three-dimensional matter: 'what', 'when', and 'how' to discuss conception stories. The argument developed herein is that professionals working with families in fertility clinics, could benefit from understanding these new family conversational processes of origin storytelling from these three perspectives, not only on 'what' and 'when' but also on the less elaborated 'how' to talk about it. For this purpose, understanding elaborative reminiscing as a specific way of talking about the past that helps children to build autobiographical memories and develop their identity might be key.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"6 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P De Corte, I Milhoranca, A S Oberg, T Kurth, S Mechsner, K Heinemann
STUDY QUESTION Does endometriosis affect the mental health of women using oral contraceptives? SUMMARY ANSWER Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small. WHAT IS KNOWN ALREADY Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear. STUDY DESIGN, SIZE, DURATION A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia. The study included 93 541 women newly prescribed oral contraceptives, with or without endometriosis, and without a self-reported history of depression. PARTICIPANTS/MATERIALS, SETTING, METHODS Participant’s mental health was captured using self-administered questionnaires at baseline and every 6–12 months thereafter, asking about any newly occurred episodes of depression. Incidence rates (IRs) of self-reported depression were calculated per 10 000 woman-years. Absolute risk difference (ARD) and number needed to harm (NNH) were calculated with 95% CIs. The association between endometriosis and self-reported depression was estimated through crude and adjusted hazard ratios (HRs) with 95% CI, using stabilized inverse probability of treatment weighting (IPTW). MAIN RESULTS AND THE ROLE OF CHANCE Of the included 93 541 women, 21 090 had endometriosis (49 541 woman-years) and 72 451 had no endometriosis (137 137 woman-years.) Of those with endometriosis, 308 (1.5%) reported an episode of depression (IR: 62.2/10 000, 95% CI: 55.4–69.5) compared to 535 (0.7%) of women without endometriosis (IR 39.0/10 000, 95% CI: 35.8–42.5). The ARD and NNH were 23.2 per 10 000 (95% CI: 15.2–30.9) and 431 (95% CI: 323.7–657.0) respectively. The HR of depression in women with endometriosis was 1.85 (95% CI: 1.60–2.13) using stabilized IPTW to control for age, BMI, smoking, education, and age at menarche. Subgroup and sensitivity analyses showed similar results. LIMITATIONS, REASONS FOR CAUTION While efforts were made to control for confounding factors, residual confounding may still exist. Additionally, the results can only be generalized to users of oral contraceptives. WIDER IMPLICATIONS OF THE FINDINGS These results highlight the importance of considering the mental health implications of endometriosis among women using oral contraceptives. Further research is needed to explore additional contributing factors and potential interventions. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this study. No competing interests apply for this research. TRIAL REGISTRATION NUMBER N/A.
{"title":"Endometriosis and risk of depression among oral contraceptive users: a pooled analysis of cohort studies from 13 countries","authors":"P De Corte, I Milhoranca, A S Oberg, T Kurth, S Mechsner, K Heinemann","doi":"10.1093/humrep/deae299","DOIUrl":"https://doi.org/10.1093/humrep/deae299","url":null,"abstract":"STUDY QUESTION Does endometriosis affect the mental health of women using oral contraceptives? SUMMARY ANSWER Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small. WHAT IS KNOWN ALREADY Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear. STUDY DESIGN, SIZE, DURATION A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia. The study included 93 541 women newly prescribed oral contraceptives, with or without endometriosis, and without a self-reported history of depression. PARTICIPANTS/MATERIALS, SETTING, METHODS Participant’s mental health was captured using self-administered questionnaires at baseline and every 6–12 months thereafter, asking about any newly occurred episodes of depression. Incidence rates (IRs) of self-reported depression were calculated per 10 000 woman-years. Absolute risk difference (ARD) and number needed to harm (NNH) were calculated with 95% CIs. The association between endometriosis and self-reported depression was estimated through crude and adjusted hazard ratios (HRs) with 95% CI, using stabilized inverse probability of treatment weighting (IPTW). MAIN RESULTS AND THE ROLE OF CHANCE Of the included 93 541 women, 21 090 had endometriosis (49 541 woman-years) and 72 451 had no endometriosis (137 137 woman-years.) Of those with endometriosis, 308 (1.5%) reported an episode of depression (IR: 62.2/10 000, 95% CI: 55.4–69.5) compared to 535 (0.7%) of women without endometriosis (IR 39.0/10 000, 95% CI: 35.8–42.5). The ARD and NNH were 23.2 per 10 000 (95% CI: 15.2–30.9) and 431 (95% CI: 323.7–657.0) respectively. The HR of depression in women with endometriosis was 1.85 (95% CI: 1.60–2.13) using stabilized IPTW to control for age, BMI, smoking, education, and age at menarche. Subgroup and sensitivity analyses showed similar results. LIMITATIONS, REASONS FOR CAUTION While efforts were made to control for confounding factors, residual confounding may still exist. Additionally, the results can only be generalized to users of oral contraceptives. WIDER IMPLICATIONS OF THE FINDINGS These results highlight the importance of considering the mental health implications of endometriosis among women using oral contraceptives. Further research is needed to explore additional contributing factors and potential interventions. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this study. No competing interests apply for this research. TRIAL REGISTRATION NUMBER N/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"82 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicolas Gatimel, Guillaume Perez, Eloïse Bruno, David Sagnat, Corinne Rolland, Yan Tanguy-Le-Gac, Emeline Di Donato, Claire Racaud, Roger Léandri, Célia Bettiol, Céline Deraison, Jean-Paul Motta, Eric Huyghe, Nathalie Vergnolle
STUDY QUESTION Does a human fallopian tube (HFT) organoid model offer a favourable apical environment for human sperm survival and motility? SUMMARY ANSWER After differentiation, the apical compartment of a new HFT organoid model provides a favourable environment for sperm motility, which is better than commercial media. WHAT IS KNOWN ALREADY HFTs are the site of major events that are crucial for achieving an ongoing pregnancy, such as gamete survival and competence, fertilization steps, and preimplantation embryo development. In order to better understand the tubal physiology and tubal factors involved in these reproductive functions, and to improve still suboptimal in vitro conditions for gamete preparation and embryo culture during IVF, we sought to develop an HFT organoid model from isolated adult stem cells to allow spermatozoa co-culture in the apical compartment. STUDY DESIGN, SIZE, DURATION Over a 2-year period, fallopian tube tissues were collected for organoid culture purposes from 10 ‘donor’ patients undergoing bilateral salpingectomy by laparoscopy for definitive sterilization. After tissue digestion, isolated cells from the isthmus and ampulla regions were separately seeded in 3D Matrigel and cultured with conventional growth factors for organoid culture and specific factors for differentiation of the female genital tract. PARTICIPANTS/MATERIALS, SETTING, METHODS HFT organoids were characterized by light microscopy, scanning and transmission electron microscopy, immunofluorescence, and transcriptome analysis. Following simultaneous organoid culture on specific inserts, spermatozoa from five donors were placed either in control media or in the apical compartment of colon or HFT organoids (isthmus and ampulla separately) for 96 h. Vitality and motility and kinematic parameters were assessed at 0, 48, and 96 h on 200 spermatozoa in each condition and in duplicate and compared using the Wilcoxon test. MAIN RESULTS AND THE ROLE OF CHANCE Specific fallopian tube differentiation of our model was confirmed by immunofluorescence, transcriptome analysis, and electron microscopy observations that exhibited ciliated and secretory cells. We succeeded in releasing spermatozoa in the apical compartment of HFT organoids and in recovering them for sperm analysis. Sperm vitality values were similar in HFT organoids and in commercial sperm media. We demonstrated a superiority of the HFT organoid apical compartment for sperm motility compared with other controls (colon organoids, organoid culture media, and conventional commercial sperm fertilization media). At 48 h of incubation, progressive sperm motility was higher in the apical compartment of HFT organoids (ampulla 31% ± 17, isthmus 29% ± 15) than in commercial fertilization media (15% ± 15) (P < 0.05) and compared with all other conditions. At 96 h, progressive sperm motility was almost nil (<1%) in all conditions except for spermatozoa in HFT organoids (P < 0.05): 12% ± 15 and
{"title":"Human fallopian tube organoids provide a favourable environment for sperm motility","authors":"Nicolas Gatimel, Guillaume Perez, Eloïse Bruno, David Sagnat, Corinne Rolland, Yan Tanguy-Le-Gac, Emeline Di Donato, Claire Racaud, Roger Léandri, Célia Bettiol, Céline Deraison, Jean-Paul Motta, Eric Huyghe, Nathalie Vergnolle","doi":"10.1093/humrep/deae258","DOIUrl":"https://doi.org/10.1093/humrep/deae258","url":null,"abstract":"STUDY QUESTION Does a human fallopian tube (HFT) organoid model offer a favourable apical environment for human sperm survival and motility? SUMMARY ANSWER After differentiation, the apical compartment of a new HFT organoid model provides a favourable environment for sperm motility, which is better than commercial media. WHAT IS KNOWN ALREADY HFTs are the site of major events that are crucial for achieving an ongoing pregnancy, such as gamete survival and competence, fertilization steps, and preimplantation embryo development. In order to better understand the tubal physiology and tubal factors involved in these reproductive functions, and to improve still suboptimal in vitro conditions for gamete preparation and embryo culture during IVF, we sought to develop an HFT organoid model from isolated adult stem cells to allow spermatozoa co-culture in the apical compartment. STUDY DESIGN, SIZE, DURATION Over a 2-year period, fallopian tube tissues were collected for organoid culture purposes from 10 ‘donor’ patients undergoing bilateral salpingectomy by laparoscopy for definitive sterilization. After tissue digestion, isolated cells from the isthmus and ampulla regions were separately seeded in 3D Matrigel and cultured with conventional growth factors for organoid culture and specific factors for differentiation of the female genital tract. PARTICIPANTS/MATERIALS, SETTING, METHODS HFT organoids were characterized by light microscopy, scanning and transmission electron microscopy, immunofluorescence, and transcriptome analysis. Following simultaneous organoid culture on specific inserts, spermatozoa from five donors were placed either in control media or in the apical compartment of colon or HFT organoids (isthmus and ampulla separately) for 96 h. Vitality and motility and kinematic parameters were assessed at 0, 48, and 96 h on 200 spermatozoa in each condition and in duplicate and compared using the Wilcoxon test. MAIN RESULTS AND THE ROLE OF CHANCE Specific fallopian tube differentiation of our model was confirmed by immunofluorescence, transcriptome analysis, and electron microscopy observations that exhibited ciliated and secretory cells. We succeeded in releasing spermatozoa in the apical compartment of HFT organoids and in recovering them for sperm analysis. Sperm vitality values were similar in HFT organoids and in commercial sperm media. We demonstrated a superiority of the HFT organoid apical compartment for sperm motility compared with other controls (colon organoids, organoid culture media, and conventional commercial sperm fertilization media). At 48 h of incubation, progressive sperm motility was higher in the apical compartment of HFT organoids (ampulla 31% ± 17, isthmus 29% ± 15) than in commercial fertilization media (15% ± 15) (P &lt; 0.05) and compared with all other conditions. At 96 h, progressive sperm motility was almost nil (&lt;1%) in all conditions except for spermatozoa in HFT organoids (P &lt; 0.05): 12% ± 15 and","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"129 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Lee, O Aasmets, R K Arffman, J Laru, H R Rossi, A Salumets, T T Piltonen, E Org
STUDY QUESTION Do polycystic ovary syndrome (PCOS), menstrual cycle phases, and ovulatory status affect reproductive tract (RT) microbiome profiles? SUMMARY ANSWER We identified microbial features associated with menstrual cycle phases in the upper and lower RT microbiome, but only two specific differences in the upper RT according to PCOS status. WHAT IS KNOWN ALREADY The vaginal and uterine microbiome profiles vary throughout the menstrual cycle. Studies have reported alterations in the vaginal microbiome among women diagnosed with PCOS. STUDY DESIGN, SIZE, DURATION This prospective case-control study included a cohort of 37 healthy control women and 52 women diagnosed with PCOS. Microbiome samples were collected from the vagina as vaginal swabs (VS) and from the uterus as endometrial flushing (EF) aspirate samples, and compared according to PCOS diagnosis, the menstrual cycle phases, and ovulatory status, at Oulu University Hospital (Oulu, Finland) from January 2017 to March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 83 VS samples and 80 EF samples were collected. Age and body mass index (BMI) were matched between women with and without PCOS. Clinical characteristics were assessed using blood samples collected between cycle days 2 and 8, and microbial DNA was sequenced on the Ion Torrent platform. Microbial alpha diversity (i.e. the observed number of unique genera and Shannon diversity index) was analysed across sample types, PCOS diagnosis and menstrual cycle phases. Linear mixed-effects models were utilised to identify microbial features in relation to PCOS and the menstrual cycle phases. Associations between the beta diversity of the RT microbiome and PCOS- and cycle-related clinical features were calculated using PERMANOVA. MAIN RESULTS AND THE ROLE OF CHANCE Microbial alpha diversity showed no difference with PCOS (VS: Pobserved feature = 0.836, Pshannon = 0.998; EF: Pobserved feature = 0.366, Pshannon = 0.185), but varied with menstrual cycle phases (VS: Pobserved feature = 0.001, Pshannon = 0.882; EF: Pobserved feature = 0.026, Pshannon = 0.048). No difference was observed in beta diversity based on either PCOS or the menstrual cycle phases (VS: PPCOS = 0.280, Pcycle = 0.115; EF: PPCOS = 0.234, Pcycle = 0.088). In the endometrial flushing samples, we identified two novel microbial features, characterised by the ratio of differential abundance of two genera, associated with PCOS (FDR ≤ 0.1) and 13 novel features associated with the menstrual cycle phases (FDR ≤ 0.1). LIMITATIONS, REASONS FOR CAUTION Although this was the first study to simultaneously analyse, the lower and upper RT microbiome in women with and without PCOS, the limited sample size of anovulatory cases may hinder the detection of differences related to PCOS and ovulatory status. WIDER IMPLICATIONS OF THE FINDINGS The main finding suggests that PCOS and the menstrual cycle phases are associated with specific microbial features in the upper RT, indicating th
{"title":"The reproductive tract microbiome in women with polycystic ovary syndrome and across different menstrual cycle phases","authors":"S Lee, O Aasmets, R K Arffman, J Laru, H R Rossi, A Salumets, T T Piltonen, E Org","doi":"10.1093/humrep/deae270","DOIUrl":"https://doi.org/10.1093/humrep/deae270","url":null,"abstract":"STUDY QUESTION Do polycystic ovary syndrome (PCOS), menstrual cycle phases, and ovulatory status affect reproductive tract (RT) microbiome profiles? SUMMARY ANSWER We identified microbial features associated with menstrual cycle phases in the upper and lower RT microbiome, but only two specific differences in the upper RT according to PCOS status. WHAT IS KNOWN ALREADY The vaginal and uterine microbiome profiles vary throughout the menstrual cycle. Studies have reported alterations in the vaginal microbiome among women diagnosed with PCOS. STUDY DESIGN, SIZE, DURATION This prospective case-control study included a cohort of 37 healthy control women and 52 women diagnosed with PCOS. Microbiome samples were collected from the vagina as vaginal swabs (VS) and from the uterus as endometrial flushing (EF) aspirate samples, and compared according to PCOS diagnosis, the menstrual cycle phases, and ovulatory status, at Oulu University Hospital (Oulu, Finland) from January 2017 to March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 83 VS samples and 80 EF samples were collected. Age and body mass index (BMI) were matched between women with and without PCOS. Clinical characteristics were assessed using blood samples collected between cycle days 2 and 8, and microbial DNA was sequenced on the Ion Torrent platform. Microbial alpha diversity (i.e. the observed number of unique genera and Shannon diversity index) was analysed across sample types, PCOS diagnosis and menstrual cycle phases. Linear mixed-effects models were utilised to identify microbial features in relation to PCOS and the menstrual cycle phases. Associations between the beta diversity of the RT microbiome and PCOS- and cycle-related clinical features were calculated using PERMANOVA. MAIN RESULTS AND THE ROLE OF CHANCE Microbial alpha diversity showed no difference with PCOS (VS: Pobserved feature = 0.836, Pshannon = 0.998; EF: Pobserved feature = 0.366, Pshannon = 0.185), but varied with menstrual cycle phases (VS: Pobserved feature = 0.001, Pshannon = 0.882; EF: Pobserved feature = 0.026, Pshannon = 0.048). No difference was observed in beta diversity based on either PCOS or the menstrual cycle phases (VS: PPCOS = 0.280, Pcycle = 0.115; EF: PPCOS = 0.234, Pcycle = 0.088). In the endometrial flushing samples, we identified two novel microbial features, characterised by the ratio of differential abundance of two genera, associated with PCOS (FDR ≤ 0.1) and 13 novel features associated with the menstrual cycle phases (FDR ≤ 0.1). LIMITATIONS, REASONS FOR CAUTION Although this was the first study to simultaneously analyse, the lower and upper RT microbiome in women with and without PCOS, the limited sample size of anovulatory cases may hinder the detection of differences related to PCOS and ovulatory status. WIDER IMPLICATIONS OF THE FINDINGS The main finding suggests that PCOS and the menstrual cycle phases are associated with specific microbial features in the upper RT, indicating th","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E Gómez, A Brualla, N Almunia, A Zepeda-Hernández, M Valcárcel, I Torres, I Burgos, R Jiménez, A M Villaquirán, L Parmegiani
In recent years, the transfer of more than one embryo has become less frequent to diminish multiple pregnancies. Even so, there is still a risk of one embryo splitting into two or even three. This report presents the case of a triamniotic monochorionic gestation in a 35-year-old woman, obtained after the transfer of a single day 5 embryo that had been previously hatched with a laser and subsequently transferred in a fresh IVF cycle. The morphokinetics of this embryo as well as another eight that produced monozygotic twins were compared with nine embryos that achieved singleton gestations. An artificial intelligence (AI) system was used to perform this analysis objectively. Embryo divisions leading to multiple gestations were slower across all analysed parameters. This was most evident in the time taken to reach the 5-cell stage (t5) (48.74 ± 3.21 versus 44.69 ± 5.61 h) and the morula stage (tM) (85.08 ± 10.00 versus 78.13 ± 5.35 h). Moreover, blastocyst diameter (161.80 ± 26.50 versus 179.10 ± 25.88 μm) and area (21 684 ± 7267.4 versus 26 516 ± 7254.8 μm2) were smaller in these embryos, but the differences did not reach statistical significance. This is the first report, to our knowledge, to use AI to analyse and compare morphokinetic parameters between singleton pregnancies and a group of embryos that produced twin and triplet pregnancies.
{"title":"Artificial intelligence-driven analysis of embryo morphokinetics in singleton, twin, and triplet pregnancies","authors":"E Gómez, A Brualla, N Almunia, A Zepeda-Hernández, M Valcárcel, I Torres, I Burgos, R Jiménez, A M Villaquirán, L Parmegiani","doi":"10.1093/humrep/deae300","DOIUrl":"https://doi.org/10.1093/humrep/deae300","url":null,"abstract":"In recent years, the transfer of more than one embryo has become less frequent to diminish multiple pregnancies. Even so, there is still a risk of one embryo splitting into two or even three. This report presents the case of a triamniotic monochorionic gestation in a 35-year-old woman, obtained after the transfer of a single day 5 embryo that had been previously hatched with a laser and subsequently transferred in a fresh IVF cycle. The morphokinetics of this embryo as well as another eight that produced monozygotic twins were compared with nine embryos that achieved singleton gestations. An artificial intelligence (AI) system was used to perform this analysis objectively. Embryo divisions leading to multiple gestations were slower across all analysed parameters. This was most evident in the time taken to reach the 5-cell stage (t5) (48.74 ± 3.21 versus 44.69 ± 5.61 h) and the morula stage (tM) (85.08 ± 10.00 versus 78.13 ± 5.35 h). Moreover, blastocyst diameter (161.80 ± 26.50 versus 179.10 ± 25.88 μm) and area (21 684 ± 7267.4 versus 26 516 ± 7254.8 μm2) were smaller in these embryos, but the differences did not reach statistical significance. This is the first report, to our knowledge, to use AI to analyse and compare morphokinetic parameters between singleton pregnancies and a group of embryos that produced twin and triplet pregnancies.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"45 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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