Anna Melgaard, Claus Høstrup Vestergaard, Ulrik Schiøler Kesmodel, Bettina Wulff Risør, Axel Forman, Krina T Zondervan, Mintu Nath, Dolapo Ayansina, Philippa T K Saunders, Andrew W Horne, Lucky Saraswat, Dorte Rytter
<p><strong>Study question: </strong>How does pre-diagnosis use of hospital care differentiate between women later diagnosed with endometriosis and age-matched controls without a diagnosis?</p><p><strong>Summary answer: </strong>Women with hospital-diagnosed endometriosis had more frequent hospital contacts in the 10 years leading up to the diagnosis compared to women without a diagnosis of endometriosis, and the contacts were related to registered diagnoses in nearly all of the included ICD-10 chapters for the entire period.</p><p><strong>What is known already: </strong>Only a few studies have investigated the utilization of health care among women with endometriosis in the time before diagnosis, but current research shows that women with endometriosis have a higher utilization compared to women without diagnosed endometriosis. To our knowledge, no study has investigated the type of contact related to the higher utilization by using the ICD-10 diagnoses registered to the hospital contact.</p><p><strong>Study design, size, duration: </strong>This study was conducted as a national Danish registry-based case-control study of 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017.</p><p><strong>Participants/materials, setting, methods: </strong>Using density sampling, we identified 21 616 cases. Each case was matched on age at the date of diagnosis (index date) to five women without hospital-diagnosed endometriosis (n = 108 080) at the time of matching. The utilization and registered ICD-10 diagnoses related to the hospital contact were included for the 10 years before the index date.</p><p><strong>Main results and the role of chance: </strong>The probability of having a high number of hospital contacts (six or more) was more common among women with endometriosis (68.6%) compared to women without endometriosis (55.7%) In general, women without endometriosis were more likely to have fewer than six contacts. The diagnoses registered to the contact among cases were related to a greater variety of ICD-10 chapters when compared to controls with the same number of contacts. For nearly all of the included ICD-10 chapters, women with endometriosis were more likely to have a diagnosis over the entire period compared to controls, with the only exception being in the chapter related to pregnancy.</p><p><strong>Limitations, reasons for caution: </strong>Our results are only applicable for women with hospital-based diagnosed endometriosis since we were not able to include women diagnosed at the general practitioner or private gynecologists. We were not able to make a causal interpretation, as we do not have information on the onset of symptoms of the included diseases. The association may be overestimated due to detection bias. However, a sensitivity analysis only changed the results slightly, indicating a low risk of this bias.</p><p><strong>Wider implications of the findings: </str
研究问题：诊断前使用医院护理如何区分后来诊断为子宫内膜异位症的妇女和未诊断的年龄匹配的对照组？概要回答：在诊断出子宫内膜异位症之前的10年里，与没有诊断出子宫内膜异位症的女性相比，患有子宫内膜异位症的女性与医院的接触更频繁，而且在整个期间，这些接触与ICD-10中几乎所有章节的登记诊断有关。已知情况：只有少数研究调查了诊断前子宫内膜异位症妇女对医疗保健的利用情况，但目前的研究表明，与未诊断为子宫内膜异位症的妇女相比，患有子宫内膜异位症的妇女对医疗保健的利用更高。据我们所知，没有研究调查过使用医院联系人登记的ICD-10诊断与较高利用率相关的接触类型。研究设计、规模、持续时间：本研究是丹麦一项以登记为基础的病例对照研究，纳入1229696名女性。病例为2000年1月1日至2017年12月31日期间首次在医院诊断为子宫内膜异位症的妇女。参与者/材料、环境、方法：采用密度抽样法，共发现21 616例病例。每个病例在诊断日期（索引日期）的年龄与5名在匹配时没有医院诊断的子宫内膜异位症的妇女（n = 108080）相匹配。纳入索引日期前10年与医院接触相关的ICD-10使用情况和登记诊断。主要结果和偶然性的作用：子宫内膜异位症患者（68.6%）与非子宫内膜异位症患者（55.7%）相比，与医院接触次数较多（6次或更多）的可能性更大。总的来说，没有子宫内膜异位症的女性更有可能少于6次接触。与接触人数相同的对照组相比，病例中接触者的诊断与ICD-10章节的多样性更大。在ICD-10的几乎所有章节中，与对照组相比，患有子宫内膜异位症的女性在整个期间更有可能被诊断出来，唯一的例外是与怀孕有关的章节。局限性和谨慎的原因：我们的结果只适用于在医院诊断为子宫内膜异位症的妇女，因为我们不能包括在全科医生或私人妇科医生诊断的妇女。我们无法作出因果解释，因为我们没有关于所包括疾病症状发作的信息。由于检测偏差，这种关联可能被高估。然而，敏感性分析只略微改变了结果，表明这种偏倚的风险很低。研究结果的更广泛意义：这项研究与之前的研究一致，表明子宫内膜异位症前的医疗保健利用并不一定局限于子宫内膜异位症相关症状，子宫内膜异位症可能与许多其他疾病有关。未来的研究可能会探索子宫内膜异位症诊断后的医院联系和原因/诊断，以进一步阐明我们的结果是由于多种病理模式还是更确切地说是子宫内膜异位症女性在诊断前的误诊表达。研究资金/竞争利益：本研究由使用机器学习发现子宫内膜异位症项目（FEMaLe/101017562）资助，该项目已获得欧盟地平线2020研究与创新计划和Helsefonden （21-B-0141）的资助。A.W.H.获得了NIHR、CSO、罗氏诊断和妇女福利组织的资助。A.W.H.该机构从Theramex、Joii、Gesynta和Gedeon Richter那里获得了咨询费。A.W.H.该机构获得了Theramex和Gedeon Richter的讲座酬金。A.W.H.在一项专利申请中被列为共同发明人（英国专利申请号2217921.2，国际专利申请号2217921.2）。PCT / GB2023/053076)。P.T.K.S.英国爱丁堡大学（University of Edinburgh）获得了Gesynta Pharma AB和BenevolentAI Bio Ltd.的咨询费。P.T.K.S的机构（爱丁堡大学）宣布一项专利申请（英国专利申请号2310300.5）。雄激素在子宫内膜异位症诊断策略中的应用。P.T.K.S.是世界子宫内膜异位症协会的财务主管，爱丁堡皇家学会的奖学金，皇家妇产科学院的科学顾问。试验注册号：无。
{"title":"Exploring pre-diagnosis hospital contacts in women with endometriosis using ICD-10: a Danish case-control study.","authors":"Anna Melgaard, Claus Høstrup Vestergaard, Ulrik Schiøler Kesmodel, Bettina Wulff Risør, Axel Forman, Krina T Zondervan, Mintu Nath, Dolapo Ayansina, Philippa T K Saunders, Andrew W Horne, Lucky Saraswat, Dorte Rytter","doi":"10.1093/humrep/deae273","DOIUrl":"https://doi.org/10.1093/humrep/deae273","url":null,"abstract":"<p><strong>Study question: </strong>How does pre-diagnosis use of hospital care differentiate between women later diagnosed with endometriosis and age-matched controls without a diagnosis?</p><p><strong>Summary answer: </strong>Women with hospital-diagnosed endometriosis had more frequent hospital contacts in the 10 years leading up to the diagnosis compared to women without a diagnosis of endometriosis, and the contacts were related to registered diagnoses in nearly all of the included ICD-10 chapters for the entire period.</p><p><strong>What is known already: </strong>Only a few studies have investigated the utilization of health care among women with endometriosis in the time before diagnosis, but current research shows that women with endometriosis have a higher utilization compared to women without diagnosed endometriosis. To our knowledge, no study has investigated the type of contact related to the higher utilization by using the ICD-10 diagnoses registered to the hospital contact.</p><p><strong>Study design, size, duration: </strong>This study was conducted as a national Danish registry-based case-control study of 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017.</p><p><strong>Participants/materials, setting, methods: </strong>Using density sampling, we identified 21 616 cases. Each case was matched on age at the date of diagnosis (index date) to five women without hospital-diagnosed endometriosis (n = 108 080) at the time of matching. The utilization and registered ICD-10 diagnoses related to the hospital contact were included for the 10 years before the index date.</p><p><strong>Main results and the role of chance: </strong>The probability of having a high number of hospital contacts (six or more) was more common among women with endometriosis (68.6%) compared to women without endometriosis (55.7%) In general, women without endometriosis were more likely to have fewer than six contacts. The diagnoses registered to the contact among cases were related to a greater variety of ICD-10 chapters when compared to controls with the same number of contacts. For nearly all of the included ICD-10 chapters, women with endometriosis were more likely to have a diagnosis over the entire period compared to controls, with the only exception being in the chapter related to pregnancy.</p><p><strong>Limitations, reasons for caution: </strong>Our results are only applicable for women with hospital-based diagnosed endometriosis since we were not able to include women diagnosed at the general practitioner or private gynecologists. We were not able to make a causal interpretation, as we do not have information on the onset of symptoms of the included diseases. The association may be overestimated due to detection bias. However, a sensitivity analysis only changed the results slightly, indicating a low risk of this bias.</p><p><strong>Wider implications of the findings: </str","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863321","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 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":""},"PeriodicalIF":6.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dwayne R Tucker, Anna F Lee, Natasha L Orr, Fahad T Alotaibi, Heather L Noga, Christina Williams, Catherine Allaire, Mohamed A Bedaiwy, David G Huntsman, Martin Köbel, Michael S Anglesio, Paul J Yong
STUDY QUESTION Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes? SUMMARY ANSWER Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity. WHAT IS KNOWN ALREADY Somatic cancer-driver mutations including those involving the PTEN and ARID1A genes exist in endometriosis without cancer; however, their clinical impact remains unclear. STUDY DESIGN, SIZE, DURATION This prospective longitudinal study involved endometriosis tissue and clinical data from 126 participants who underwent surgery at a tertiary center for endometriosis (2013–2017), with a follow-up period of 5–9 years. PARTICIPANTS/MATERIALS, SETTING, METHODS PTEN and ARID1A loss was assessed using established immunohistochemistry (IHC) methods as proxies for somatic loss by two independent raters. PTEN and ARID1A status for each participant was defined as loss (loss in at least one sample for a participant) or retained (no loss in all samples for a participant). Primary analyses examined associations between PTEN and ARID1A loss and disease burden based on anatomic subtype (superficial peritoneal endometriosis (SUP), deep endometriosis (DE), ovarian endometrioma (OMA)) and rASRM stage (I–IV). Secondary analyses explored associations of PTEN and ARID1A loss with demographics, surgical difficulty, and pain scores (baseline and follow-up). Additionally, using previously published data on KRAS codon 12 mutations for this cohort, we investigated associations between variables in the primary and secondary analyses and acquiring two or more somatic events (PTEN loss, ARID1A loss, or KRAS mutation) in this cohort. The risk of reoperation over the 5–9 years was also examined. MAIN RESULTS AND THE ROLE OF CHANCE PTEN loss (68.3%; 86 participants) exceeded ARID1A loss (24.6%; 31 participants). Inter-rater reliability was substantial for PTEN (k = 0.69; 95% CI: 0.62–0.77) and ARID1A (k = 0.64; 95% CI: 0.51–0.77). PTEN loss was significantly associated with more severe anatomic subtypes (P < 0.001; participants with SUP only = 46.4%; participants with DE only or OMA only = 72.7%; participants with mixed subtypes = 85.1%), and higher stages (P = 0.024; Stage I = 47.8%; Stage II = 73.7%; Stage III = 80.8%; Stage IV = 81.0%). Results were similar for ARID1A loss, albeit with smaller sample size limiting power. PTEN loss was further associated with non-White ethnicities (P = 0.017) and greater surgical difficulty (more frequent need for ureterolysis) (P = 0.02). There were no differences in pain scores (baseline or follow-up) based on PTEN or ARID1A status. Reoperation was uncommon (13.5% of the cohort), and patterns in reoperation rates based on the presence of somatic alterations did not reach statistical significance. LIMITATIONS, REASONS FOR CAUTION Sequencing was not performed to determin
{"title":"Somatic PTEN and ARID1A loss and endometriosis disease burden: a longitudinal study","authors":"Dwayne R Tucker, Anna F Lee, Natasha L Orr, Fahad T Alotaibi, Heather L Noga, Christina Williams, Catherine Allaire, Mohamed A Bedaiwy, David G Huntsman, Martin Köbel, Michael S Anglesio, Paul J Yong","doi":"10.1093/humrep/deae269","DOIUrl":"https://doi.org/10.1093/humrep/deae269","url":null,"abstract":"STUDY QUESTION Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes? SUMMARY ANSWER Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity. WHAT IS KNOWN ALREADY Somatic cancer-driver mutations including those involving the PTEN and ARID1A genes exist in endometriosis without cancer; however, their clinical impact remains unclear. STUDY DESIGN, SIZE, DURATION This prospective longitudinal study involved endometriosis tissue and clinical data from 126 participants who underwent surgery at a tertiary center for endometriosis (2013–2017), with a follow-up period of 5–9 years. PARTICIPANTS/MATERIALS, SETTING, METHODS PTEN and ARID1A loss was assessed using established immunohistochemistry (IHC) methods as proxies for somatic loss by two independent raters. PTEN and ARID1A status for each participant was defined as loss (loss in at least one sample for a participant) or retained (no loss in all samples for a participant). Primary analyses examined associations between PTEN and ARID1A loss and disease burden based on anatomic subtype (superficial peritoneal endometriosis (SUP), deep endometriosis (DE), ovarian endometrioma (OMA)) and rASRM stage (I–IV). Secondary analyses explored associations of PTEN and ARID1A loss with demographics, surgical difficulty, and pain scores (baseline and follow-up). Additionally, using previously published data on KRAS codon 12 mutations for this cohort, we investigated associations between variables in the primary and secondary analyses and acquiring two or more somatic events (PTEN loss, ARID1A loss, or KRAS mutation) in this cohort. The risk of reoperation over the 5–9 years was also examined. MAIN RESULTS AND THE ROLE OF CHANCE PTEN loss (68.3%; 86 participants) exceeded ARID1A loss (24.6%; 31 participants). Inter-rater reliability was substantial for PTEN (k = 0.69; 95% CI: 0.62–0.77) and ARID1A (k = 0.64; 95% CI: 0.51–0.77). PTEN loss was significantly associated with more severe anatomic subtypes (P &lt; 0.001; participants with SUP only = 46.4%; participants with DE only or OMA only = 72.7%; participants with mixed subtypes = 85.1%), and higher stages (P = 0.024; Stage I = 47.8%; Stage II = 73.7%; Stage III = 80.8%; Stage IV = 81.0%). Results were similar for ARID1A loss, albeit with smaller sample size limiting power. PTEN loss was further associated with non-White ethnicities (P = 0.017) and greater surgical difficulty (more frequent need for ureterolysis) (P = 0.02). There were no differences in pain scores (baseline or follow-up) based on PTEN or ARID1A status. Reoperation was uncommon (13.5% of the cohort), and patterns in reoperation rates based on the presence of somatic alterations did not reach statistical significance. LIMITATIONS, REASONS FOR CAUTION Sequencing was not performed to determin","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"13 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858420","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}
Lauren A Wise, Tanran R Wang, Sinna Pilgaard Ulrichsen, Dmitrii Krivorotko, Ellen M Mikkelsen, Andrea S Kuriyama, Anne Sofie Dam Laursen, Marie Dahl Jørgensen, Michael L Eisenberg, Kenneth J Rothman, Henrik Toft Sorensen, Elizabeth E Hatch
STUDY QUESTION To what extent is male physical activity (PA) associated with fecundability (per-cycle probability of conception)? SUMMARY ANSWER Preconception levels of vigorous, moderate, or total PA were not consistently associated with fecundability across Danish and North American cohorts, but there was suggestive evidence that bicycling with a ‘soft, comfort seat’ was associated with reduced fecundability in both cohorts, especially among males with greater BMI. WHAT IS KNOWN ALREADY Among males, some studies indicate that moderate PA might improve fertility, whereas vigorous PA, especially bicycling, might be detrimental. STUDY DESIGN, SIZE, DURATION We assessed the association between male PA and fecundability among couples participating in two preconception cohort studies: SnartForaeldre.dk (SF) in Denmark (2011–2023) and Pregnancy Study Online (PRESTO) in North America (2013–2024). We restricted analyses to 4921 males (1088 in SF and 3833 in PRESTO) who had been trying to conceive with their partners for ≤6 cycles at enrollment. PARTICIPANTS/MATERIALS, SETTING, METHODS At baseline, male partners reported data on medical history, lifestyle, behavioral, anthropometric factors, and their PA levels using different instruments [SF: International Physical Activity Questionnaire (IPAQ); PRESTO: average annual hours/week and type]. Both cohorts included additional questions on bicycling (frequency, bike seat type). After linking couple data at baseline, the female partner completed follow-up questionnaires to update their pregnancy status every 8 weeks for 12 months or until conception, whichever occurred first. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, controlling for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE Average hours/week of vigorous PA, moderate PA, and total metabolic equivalents of task were generally inversely associated with fecundability in SF, but not PRESTO. While there was little association with bicycling overall in either cohort, we observed an inverse association for bicycling using a ‘soft, comfort seat’ (≥3 vs 0 h/week: SF: FR = 0.75, 95% CI: 0.53–1.05; PRESTO: FR = 0.81, 95% CI: 0.62–1.07) but not a ‘hard, racing-style seat’ (≥3 vs 0 h/week: SF: FR = 1.16, 95% CI: 0.95–1.41; PRESTO: FR = 1.06, 95% CI: 0.89–1.28). Among males with BMI ≥25 kg/m2, associations with bicycling using a ‘soft, comfort seat’ were similar or stronger (≥3 vs 0 h/week: SF: FR = 0.75, 95% CI: 0.45–1.24; PRESTO: FR = 0.73, 95% CI: 0.52–1.03). LIMITATIONS, REASONS FOR CAUTION Misclassification of PA was likely the most important study limitation because we ascertained PA only once at enrollment using different instruments in each cohort. We would expect misclassification of PA to be non-differential given the prospective study design. Additional weaknesses include the narrow range of PA levels evaluated, reduced precision when stratifying the data by selected covariates, and
研究问题 男性体力活动（PA）在多大程度上与受孕率（每周期受孕概率）有关？在丹麦和北美的队列中，受孕前的剧烈、适度或总体体力活动水平与受孕率的关系并不一致，但有提示性证据表明，在这两个队列中，骑 "柔软舒适座椅 "的自行车与受孕率降低有关，尤其是在体重指数（BMI）较大的男性中。在男性中，一些研究表明，适度的体育锻炼可能会提高生育能力，而剧烈的体育锻炼，尤其是骑自行车，可能会对生育能力不利。研究设计、规模、持续时间 我们评估了参与两项孕前队列研究的夫妇中男性运动量与受孕率之间的关系：这两项研究分别是丹麦的 SnartForaeldre.dk（SF）（2011-2023 年）和北美的在线妊娠研究（PRESTO）（2013-2024 年）。我们将分析对象限定为 4921 名男性（SF 为 1088 名，PRESTO 为 3833 名），这些男性在注册时已与伴侣尝试受孕≤6 个周期。参与者/材料、地点、方法 在基线时，男性伴侣使用不同的工具报告有关病史、生活方式、行为、人体测量因素及其 PA 水平的数据[SF：国际体力活动问卷 (IPAQ)；PRESTO：年平均小时/周和类型]。两个队列都包括有关骑自行车（频率、自行车座椅类型）的附加问题。在连接基线时的夫妻数据后，女性伴侣每 8 周填写一次随访问卷，以更新其怀孕状况，持续 12 个月或直到受孕，以先发生者为准。在控制潜在混杂因素的情况下，我们使用比例概率回归模型来估算受孕率（FRs）和 95% CIs。主要结果和偶然性的作用 在 SF 中，每周平均剧烈运动时间、中等运动时间和任务总代谢当量一般与受孕率成反比，但在 PRESTO 中并非如此。虽然在这两个队列中，骑自行车与受孕率的总体关系不大，但我们观察到，使用 "柔软舒适的座椅 "骑自行车与受孕率呈反比关系（≥3 小时/周 vs 0 小时/周）：SF：FR = 0.75，95% CI：0.53-1.05；PRESTO：FR = 0.81，95% CI：0.62-1.07），但与 "硬质赛车式座椅 "无关（≥3 vs 0 小时/周：SF：FR = 1.16，95% CI：0.62-1.07）：SF：FR = 1.16，95% CI：0.95-1.41；Presto：FR = 1.06，95% CI：0.89-1.28）。在体重指数（BMI）≥25 kg/m2 的男性中，使用 "柔软舒适的座椅 "与骑自行车的相关性相似或更强（≥3 小时 vs 0 小时/周：SF：FR = 0.75，95% CI：0.45-1.24；Presto：FR = 0.73，95% CI：0.52-1.03）。局限性、注意事项 PA 的误分类可能是最重要的研究局限性，因为我们只在每个队列中使用不同的工具在注册时确定 PA 一次。鉴于前瞻性研究的设计，我们预计 PA 的误分类是无差别的。其他不足之处还包括：所评估的 PA 水平范围较窄；根据选定的协变量对数据进行分层时，精度有所降低；由于非西班牙裔白人参与者所占比例较大，且队列仅限于怀孕计划者，因此可推广性有限。研究结果的广泛意义 可能有必要进一步评估骑自行车对男性生育能力的潜在有害影响，并进一步考虑自行车座椅类型和体重指数的影响。研究经费/合作利益 本研究得到了美国国家卫生与健康研究所（NICHD）R21-HD072326、R01-HD086742、R01 HD105863 和 R03-HD094117 号基金的资助。这些资助机构没有参与研究设计、数据收集、分析和解释、报告撰写或文章发表的决定。L.A.W. 是艾伯维公司（AbbVie, Inc.她还接受了瑞士精密诊断公司（家用妊娠测试）和 Kindara.com（生育应用程序）的实物捐赠，用于在线妊娠研究（PRESTO）的原始数据收集。所有这些关系均用于与本手稿无关的工作。M.L.E.是Legacy、Doveras、VSeat、Hannah、Illumicell、HisTurn和Next的顾问，并持有这些公司的股票。其他作者无利益冲突需要声明。试验注册号为 n/a。
{"title":"A prospective study of male physical activity and fecundability","authors":"Lauren A Wise, Tanran R Wang, Sinna Pilgaard Ulrichsen, Dmitrii Krivorotko, Ellen M Mikkelsen, Andrea S Kuriyama, Anne Sofie Dam Laursen, Marie Dahl Jørgensen, Michael L Eisenberg, Kenneth J Rothman, Henrik Toft Sorensen, Elizabeth E Hatch","doi":"10.1093/humrep/deae275","DOIUrl":"https://doi.org/10.1093/humrep/deae275","url":null,"abstract":"STUDY QUESTION To what extent is male physical activity (PA) associated with fecundability (per-cycle probability of conception)? SUMMARY ANSWER Preconception levels of vigorous, moderate, or total PA were not consistently associated with fecundability across Danish and North American cohorts, but there was suggestive evidence that bicycling with a ‘soft, comfort seat’ was associated with reduced fecundability in both cohorts, especially among males with greater BMI. WHAT IS KNOWN ALREADY Among males, some studies indicate that moderate PA might improve fertility, whereas vigorous PA, especially bicycling, might be detrimental. STUDY DESIGN, SIZE, DURATION We assessed the association between male PA and fecundability among couples participating in two preconception cohort studies: SnartForaeldre.dk (SF) in Denmark (2011–2023) and Pregnancy Study Online (PRESTO) in North America (2013–2024). We restricted analyses to 4921 males (1088 in SF and 3833 in PRESTO) who had been trying to conceive with their partners for ≤6 cycles at enrollment. PARTICIPANTS/MATERIALS, SETTING, METHODS At baseline, male partners reported data on medical history, lifestyle, behavioral, anthropometric factors, and their PA levels using different instruments [SF: International Physical Activity Questionnaire (IPAQ); PRESTO: average annual hours/week and type]. Both cohorts included additional questions on bicycling (frequency, bike seat type). After linking couple data at baseline, the female partner completed follow-up questionnaires to update their pregnancy status every 8 weeks for 12 months or until conception, whichever occurred first. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, controlling for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE Average hours/week of vigorous PA, moderate PA, and total metabolic equivalents of task were generally inversely associated with fecundability in SF, but not PRESTO. While there was little association with bicycling overall in either cohort, we observed an inverse association for bicycling using a ‘soft, comfort seat’ (≥3 vs 0 h/week: SF: FR = 0.75, 95% CI: 0.53–1.05; PRESTO: FR = 0.81, 95% CI: 0.62–1.07) but not a ‘hard, racing-style seat’ (≥3 vs 0 h/week: SF: FR = 1.16, 95% CI: 0.95–1.41; PRESTO: FR = 1.06, 95% CI: 0.89–1.28). Among males with BMI ≥25 kg/m2, associations with bicycling using a ‘soft, comfort seat’ were similar or stronger (≥3 vs 0 h/week: SF: FR = 0.75, 95% CI: 0.45–1.24; PRESTO: FR = 0.73, 95% CI: 0.52–1.03). LIMITATIONS, REASONS FOR CAUTION Misclassification of PA was likely the most important study limitation because we ascertained PA only once at enrollment using different instruments in each cohort. We would expect misclassification of PA to be non-differential given the prospective study design. Additional weaknesses include the narrow range of PA levels evaluated, reduced precision when stratifying the data by selected covariates, and ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"58 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832138","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}
Mats Brännström, Jana Ekberg, Lars Sandman, Thomas Davidson
STUDY QUESTION What is the cost per live birth after live donor uterus transplantation in a Swedish clinical trial setting? SUMMARY ANSWER The total cost per child, from a health care perspective, was calculated to be €124 894 and if only surgically successful transplants are considered, the total cost per live birth was €107 120. WHAT IS KNOWN ALREADY Uterus transplantation has proved to be a feasible treatment for uterine factor infertility by accomplished live births, both after live donor and deceased donor transplantation procedures. Our previous study, the only existing cost analysis of uterus transplantation, found that the initial (up to 2 months after surgeries) societal costs of preoperative interventions, live donor uterus transplantation surgeries, and postoperative care were between €50 000 and €100 000 (mean €74 000) in Year 2020 values per uterus transplantation. That study also included costs of sick leave for both donors and recipients. STUDY DESIGN, SIZE, DURATION This real-data health economic cost study is based on a prospective cohort study, which included nine live donor uterus transplantation procedures. Study duration included the time from the first pre-transplantation investigation until postoperative controls after graft removal. PARTICIPANTS/MATERIALS, SETTING, METHODS Recipients, live donors, and neonates of nine uterus transplantation procedures participated. The recipients and donors underwent pre-transplantation investigations with imaging, laboratory tests, and psychological/medical screening. In vitro fertilization with embryo cryopreservation was performed in advance of transplantation. Donor hysterectomy and transplantation were by laparotomy and the recipient received immunosuppression. Pregnancy attempts by ET started 1 year after transplantation and delivery was by caesarean section. Hysterectomy was performed either after birth of one or two children, after graft failure, or after multiple pregnancy failures. Nine transplantation procedures resulted in seven surgically successful (adequate blood flow and regular menstruations) grafts and six women delivered a total of nine children. MAIN RESULTS AND THE ROLE OF CHANCE The total cost of preoperative investigations, live donor uterus transplantation, postoperative care, immunosuppression, IVF, follow-up, pregnancy care, delivery, and graft removal after completed childbirth(s) or failure to achieve live birth was calculated, based on inclusion of cost for six women, giving birth to a total of nine children, and three women, with no childbirth. Cost for live donors was also included in the analysis. The total cost per child was calculated to be €124 894. However, if only surgical successful transplants (seven out of nine transplants) are considered, the cost per live birth was €107 120. The cost for preoperative preparations with IVF, surgeries, and postoperative follow-up during the initial 2 months was around 53% of total costs. Smaller sub-costs were those
{"title":"The costs per live birth after uterus transplantation: results of the Swedish live donor trial","authors":"Mats Brännström, Jana Ekberg, Lars Sandman, Thomas Davidson","doi":"10.1093/humrep/deae272","DOIUrl":"https://doi.org/10.1093/humrep/deae272","url":null,"abstract":"STUDY QUESTION What is the cost per live birth after live donor uterus transplantation in a Swedish clinical trial setting? SUMMARY ANSWER The total cost per child, from a health care perspective, was calculated to be €124 894 and if only surgically successful transplants are considered, the total cost per live birth was €107 120. WHAT IS KNOWN ALREADY Uterus transplantation has proved to be a feasible treatment for uterine factor infertility by accomplished live births, both after live donor and deceased donor transplantation procedures. Our previous study, the only existing cost analysis of uterus transplantation, found that the initial (up to 2 months after surgeries) societal costs of preoperative interventions, live donor uterus transplantation surgeries, and postoperative care were between €50 000 and €100 000 (mean €74 000) in Year 2020 values per uterus transplantation. That study also included costs of sick leave for both donors and recipients. STUDY DESIGN, SIZE, DURATION This real-data health economic cost study is based on a prospective cohort study, which included nine live donor uterus transplantation procedures. Study duration included the time from the first pre-transplantation investigation until postoperative controls after graft removal. PARTICIPANTS/MATERIALS, SETTING, METHODS Recipients, live donors, and neonates of nine uterus transplantation procedures participated. The recipients and donors underwent pre-transplantation investigations with imaging, laboratory tests, and psychological/medical screening. In vitro fertilization with embryo cryopreservation was performed in advance of transplantation. Donor hysterectomy and transplantation were by laparotomy and the recipient received immunosuppression. Pregnancy attempts by ET started 1 year after transplantation and delivery was by caesarean section. Hysterectomy was performed either after birth of one or two children, after graft failure, or after multiple pregnancy failures. Nine transplantation procedures resulted in seven surgically successful (adequate blood flow and regular menstruations) grafts and six women delivered a total of nine children. MAIN RESULTS AND THE ROLE OF CHANCE The total cost of preoperative investigations, live donor uterus transplantation, postoperative care, immunosuppression, IVF, follow-up, pregnancy care, delivery, and graft removal after completed childbirth(s) or failure to achieve live birth was calculated, based on inclusion of cost for six women, giving birth to a total of nine children, and three women, with no childbirth. Cost for live donors was also included in the analysis. The total cost per child was calculated to be €124 894. However, if only surgical successful transplants (seven out of nine transplants) are considered, the cost per live birth was €107 120. The cost for preoperative preparations with IVF, surgeries, and postoperative follow-up during the initial 2 months was around 53% of total costs. Smaller sub-costs were those ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"18 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825579","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}
Wenqiang Li, Nanxi Jia, Hongbin Chi, Siyan Zhan, Lin Zeng
STUDY QUESTION Do the infertility core outcome set and standardized definitions affect the outcome selection for randomized controlled trials, and what aspects should be further improved in the future? SUMMARY ANSWER Intrauterine pregnancy demonstrated the highest uptake level, whereas others were low, especially in neonatal outcomes; as time progresses, the target sample size increases, and with prospective registration, the consistency between outcomes reported in registrations and infertility core outcome set improves significantly. WHAT IS KNOWN ALREADY The infertility core outcome set, published on 30 November 2020, aims to standardize outcome reporting and prevent selective reporting bias; however, there is a paucity of research evaluating its actual adoption, which is crucial for the timely promotion of transparency, standardization, adjustment of development strategies, and efficient resource utilization. STUDY DESIGN, SIZE, DURATION This cross-sectional study included 1673 eligible randomized controlled trial registrations for infertility in 18 registries from March 2004 to July 2024 based on registry entries. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 4625 infertility-related studies from 1 November 1999 to 26 July 2024 were retrieved in the World Health Organization International Clinical Trials Registry Platform. Finally, 1673 randomized controlled trial registrations were selected and divided into four period groups. Period, target sample size, prospective registration, blinding, support, and countries/regions were potential influencing factors. The consistency of outcomes, definitions, and standardized denominators of randomized controlled trial registry entries with the recommendations of the infertility core outcome set were the main outcomes. Independent retrieval, screening, data extraction, and consistency evaluations by two assessors and expert consultations were conducted to assess the uptake and potential influencing factors of the infertility core outcome set in randomized controlled trials involving infertile patients undergoing in vitro fertilization. MAIN RESULTS AND THE ROLE OF CHANCE Results reveal that the reporting level in the pregnancy domain was significantly higher than that in the neonatal domain (13.6% vs 5.7%). Intrauterine pregnancy (66.9%), live birth (27.6%), and miscarriage (26.5%) had relatively high uptake levels. The uptake of most core outcomes and domains, as well as the total number of reported core outcomes, showed statistically significant differences based on period, target sample size, and prospective registration. Multivariable analyses supported the above finding. Reasons responsible for the results may be attributed to the lack of effective promotional measures, as well as the limited researcher awareness regarding this core outcome set. LIMITATIONS, REASONS FOR CAUTION Some results in this study may have been influenced by the subjective judgment of the evaluators due to the complexi
不孕不育的核心结局集和标准化定义是否会影响随机对照试验的结局选择？未来哪些方面需要进一步改进？宫内妊娠表现出最高的摄取水平，而其他情况则较低，特别是在新生儿结局中；随着时间的推移，目标样本量增加，并且在前瞻性登记中，登记中报告的结果与不孕症核心结果集之间的一致性显著提高。2020年11月30日发布的不孕症核心结局集旨在规范结果报告并防止选择性报告偏差；然而，缺乏评估其实际采用情况的研究，这对于及时促进透明度、标准化、调整发展战略和有效利用资源至关重要。研究设计、规模、持续时间本横断面研究纳入了2004年3月至2024年7月18个登记中心的1673例符合条件的不孕症随机对照试验登记。参与者/材料、环境、方法从世界卫生组织国际临床试验注册平台检索1999年11月1日至2024年7月26日期间共4625项与不孕症相关的研究。最后，选取1673例随机对照试验注册患者，将其分为4个时期组。时间、目标样本量、前瞻性登记、盲法、支持和国家/地区是潜在的影响因素。结果、定义和随机对照试验注册条目与不孕症核心结局集推荐的标准化分母的一致性是主要结局。通过独立检索、筛选、数据提取和一致性评估，通过两位评估员和专家咨询来评估在涉及接受体外受精的不孕症患者的随机对照试验中不孕症核心结局集的吸收和潜在影响因素。结果显示妊娠期的报告率明显高于新生儿期（13.6% vs 5.7%）。宫内妊娠（66.9%）、活产（27.6%）和流产（26.5%）的摄取水平相对较高。大多数核心结局和领域的吸收，以及报告的核心结局的总数，显示出基于时间、目标样本量和前瞻性登记的统计学显著差异。多变量分析支持上述发现。造成这一结果的原因可能是由于缺乏有效的推广措施，以及研究人员对这一核心结果集的认识有限。由于注册信息的复杂性，本研究的一些结果可能会受到评价者主观判断的影响。研究结果的更广泛意义大多数核心结果或领域的吸收正在增加，但尚不理想。此外，上升趋势不能仅仅归因于不孕症核心结局集的发表。促进吸收的关键是深入探索和认识促进和阻碍不孕症核心结局集吸收的因素，进一步扩大和宣传核心结局集，促进多学科或多利益相关者合作。研究经费/竞争利益(S)本研究由首都卫生促进与研究基金（CFH 2024-2G-4097）和北京市临床重点专科建设项目专项基金资助。作者无利益冲突需要申报。试验注册号http://www.comet-initiative.org/Studies/Details/3184
{"title":"Assessing the uptake of infertility core outcome set in IVF randomized controlled trials","authors":"Wenqiang Li, Nanxi Jia, Hongbin Chi, Siyan Zhan, Lin Zeng","doi":"10.1093/humrep/deae255","DOIUrl":"https://doi.org/10.1093/humrep/deae255","url":null,"abstract":"STUDY QUESTION Do the infertility core outcome set and standardized definitions affect the outcome selection for randomized controlled trials, and what aspects should be further improved in the future? SUMMARY ANSWER Intrauterine pregnancy demonstrated the highest uptake level, whereas others were low, especially in neonatal outcomes; as time progresses, the target sample size increases, and with prospective registration, the consistency between outcomes reported in registrations and infertility core outcome set improves significantly. WHAT IS KNOWN ALREADY The infertility core outcome set, published on 30 November 2020, aims to standardize outcome reporting and prevent selective reporting bias; however, there is a paucity of research evaluating its actual adoption, which is crucial for the timely promotion of transparency, standardization, adjustment of development strategies, and efficient resource utilization. STUDY DESIGN, SIZE, DURATION This cross-sectional study included 1673 eligible randomized controlled trial registrations for infertility in 18 registries from March 2004 to July 2024 based on registry entries. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 4625 infertility-related studies from 1 November 1999 to 26 July 2024 were retrieved in the World Health Organization International Clinical Trials Registry Platform. Finally, 1673 randomized controlled trial registrations were selected and divided into four period groups. Period, target sample size, prospective registration, blinding, support, and countries/regions were potential influencing factors. The consistency of outcomes, definitions, and standardized denominators of randomized controlled trial registry entries with the recommendations of the infertility core outcome set were the main outcomes. Independent retrieval, screening, data extraction, and consistency evaluations by two assessors and expert consultations were conducted to assess the uptake and potential influencing factors of the infertility core outcome set in randomized controlled trials involving infertile patients undergoing in vitro fertilization. MAIN RESULTS AND THE ROLE OF CHANCE Results reveal that the reporting level in the pregnancy domain was significantly higher than that in the neonatal domain (13.6% vs 5.7%). Intrauterine pregnancy (66.9%), live birth (27.6%), and miscarriage (26.5%) had relatively high uptake levels. The uptake of most core outcomes and domains, as well as the total number of reported core outcomes, showed statistically significant differences based on period, target sample size, and prospective registration. Multivariable analyses supported the above finding. Reasons responsible for the results may be attributed to the lack of effective promotional measures, as well as the limited researcher awareness regarding this core outcome set. LIMITATIONS, REASONS FOR CAUTION Some results in this study may have been influenced by the subjective judgment of the evaluators due to the complexi","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"45 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820782","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}
Ali Mourad, Wael Jamal, Robert Hemmings, Artak Tadevosyan, Simon Phillips, Isaac-Jacques Kadoch
STUDY QUESTION Does adjuvant growth hormone (GH) therapy in GnRH antagonist cycles improve reproductive outcomes in the general IVF population? SUMMARY ANSWER Empiric adjuvant GH therapy in GnRH antagonist cycles does not improve IVF stimulation results or reproductive outcomes, including implantation, miscarriage, and clinical pregnancy rates. WHAT IS KNOWN ALREADY Previous evidence regarding the benefits of GH therapy in IVF cycles has been inconclusive due to the lack of well-designed, large-scale randomized controlled trials (RCTs) in the general IVF population. STUDY DESIGN, SIZE, DURATION This is a phase III open-label RCT involving 288 patients undergoing antagonist IVF cycles at the Ovo clinic in Montreal, Canada, between June 2014 and January 2020. Patients were randomly assigned at a 1:1 ratio to either the GH or control group. The intervention group received daily 2.5 mg subcutaneous injections of GH from Day 1 of ovarian stimulation until the day of oocyte retrieval, while the control group received standard ovarian stimulation without any adjuvant therapy. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were expected normal responders. All embryo transfers, both fresh and frozen, resulting from the studied IVF cycle were included in an intention-to-treat and per-protocol analyses. The primary outcome was the clinical pregnancy rate, while secondary outcomes included the number of retrieved oocytes, good-quality embryos, maturation, fertilization, implantation, and miscarriage rates. MAIN RESULTS AND THE ROLE OF CHANCE A total of 288 patients were recruited and randomly assigned at a 1:1 ratio to either the GH or the control group. After excluding cycle cancellations and patients who did not undergo transfer, 105 patients remained in each group. The overall mean age was 38.0 years, the mean BMI was 25.11 kg/m2 and the mean anti-Müllerian hormone was 2.51 ng/ml. The cycle characteristics were similar between both groups. No differences were observed regarding the total dose of gonadotropins (4600 versus 4660 IU for the GH and control groups, respectively, P = 0.752), days of stimulation (11.4 versus 11.7 days, P = 0.118), and endometrial thickness (10.63 versus 10.94 mm, P = 0.372). Both the intention to treat (ITT) and per protocol analyses yielded similar results for stimulation outcomes. In the ITT analysis, no differences were found in the number of follicles ≥15 mm (7.8 versus 7.1, P = 0.212), retrieved oocytes (11.7 versus 11.2, P = 0.613), mature oocytes (8.5 versus 8.6, P = 0.851), maturation rate (73.8 versus 78.4%, P = 0.060), fertilization rate (64.3 versus 67.2%, P = 0.388), and good quality embryos (2.5 versus 2.6, P = 0.767). Reproductive outcomes in fresh embryo transfer showed no difference for implantation rate (38.2 versus 39.5%, P = 0.829), miscarriage rate (26.5 versus 31.1%, P = 0.653), clinical pregnancy rate (43.6 versus 50.0%, P = 0.406, rate difference, 95% CI: −0.06 [−0.22, 0.09]), and live birth rate (32.1
{"title":"Empirical use of growth hormone in IVF is useless: the largest randomized controlled trial","authors":"Ali Mourad, Wael Jamal, Robert Hemmings, Artak Tadevosyan, Simon Phillips, Isaac-Jacques Kadoch","doi":"10.1093/humrep/deae251","DOIUrl":"https://doi.org/10.1093/humrep/deae251","url":null,"abstract":"STUDY QUESTION Does adjuvant growth hormone (GH) therapy in GnRH antagonist cycles improve reproductive outcomes in the general IVF population? SUMMARY ANSWER Empiric adjuvant GH therapy in GnRH antagonist cycles does not improve IVF stimulation results or reproductive outcomes, including implantation, miscarriage, and clinical pregnancy rates. WHAT IS KNOWN ALREADY Previous evidence regarding the benefits of GH therapy in IVF cycles has been inconclusive due to the lack of well-designed, large-scale randomized controlled trials (RCTs) in the general IVF population. STUDY DESIGN, SIZE, DURATION This is a phase III open-label RCT involving 288 patients undergoing antagonist IVF cycles at the Ovo clinic in Montreal, Canada, between June 2014 and January 2020. Patients were randomly assigned at a 1:1 ratio to either the GH or control group. The intervention group received daily 2.5 mg subcutaneous injections of GH from Day 1 of ovarian stimulation until the day of oocyte retrieval, while the control group received standard ovarian stimulation without any adjuvant therapy. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were expected normal responders. All embryo transfers, both fresh and frozen, resulting from the studied IVF cycle were included in an intention-to-treat and per-protocol analyses. The primary outcome was the clinical pregnancy rate, while secondary outcomes included the number of retrieved oocytes, good-quality embryos, maturation, fertilization, implantation, and miscarriage rates. MAIN RESULTS AND THE ROLE OF CHANCE A total of 288 patients were recruited and randomly assigned at a 1:1 ratio to either the GH or the control group. After excluding cycle cancellations and patients who did not undergo transfer, 105 patients remained in each group. The overall mean age was 38.0 years, the mean BMI was 25.11 kg/m2 and the mean anti-Müllerian hormone was 2.51 ng/ml. The cycle characteristics were similar between both groups. No differences were observed regarding the total dose of gonadotropins (4600 versus 4660 IU for the GH and control groups, respectively, P = 0.752), days of stimulation (11.4 versus 11.7 days, P = 0.118), and endometrial thickness (10.63 versus 10.94 mm, P = 0.372). Both the intention to treat (ITT) and per protocol analyses yielded similar results for stimulation outcomes. In the ITT analysis, no differences were found in the number of follicles ≥15 mm (7.8 versus 7.1, P = 0.212), retrieved oocytes (11.7 versus 11.2, P = 0.613), mature oocytes (8.5 versus 8.6, P = 0.851), maturation rate (73.8 versus 78.4%, P = 0.060), fertilization rate (64.3 versus 67.2%, P = 0.388), and good quality embryos (2.5 versus 2.6, P = 0.767). Reproductive outcomes in fresh embryo transfer showed no difference for implantation rate (38.2 versus 39.5%, P = 0.829), miscarriage rate (26.5 versus 31.1%, P = 0.653), clinical pregnancy rate (43.6 versus 50.0%, P = 0.406, rate difference, 95% CI: −0.06 [−0.22, 0.09]), and live birth rate (32.1 ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"41 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823192","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}
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":"https://doi.org/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":""},"PeriodicalIF":6.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julian J Koplin, Molly Johnston, Amy N S Webb, Andrea Whittaker, Catherine Mills
Artificial intelligence (AI) has the potential to standardize and automate important aspects of fertility treatment, improving clinical outcomes. One promising application of AI in the fertility clinic is the use of machine learning (ML) tools to assess embryos for transfer. The successful clinical implementation of these tools in ways that do not erode consumer trust requires an awareness of the ethical issues that these technologies raise, and the development of strategies to manage any ethical concerns. However, to date, there has been little published literature on the ethics of using ML in embryo assessment. This mini-review contributes to this nascent area of discussion by surveying the key ethical concerns raised by ML technologies in healthcare and medicine more generally, and identifying which are germane to the use of ML in the assessment of embryos. We report concerns about the ‘dehumanization’ of human reproduction, algorithmic bias, responsibility, transparency and explainability, deskilling, and justice.
{"title":"Ethics of artificial intelligence in embryo assessment: mapping the terrain","authors":"Julian J Koplin, Molly Johnston, Amy N S Webb, Andrea Whittaker, Catherine Mills","doi":"10.1093/humrep/deae264","DOIUrl":"https://doi.org/10.1093/humrep/deae264","url":null,"abstract":"Artificial intelligence (AI) has the potential to standardize and automate important aspects of fertility treatment, improving clinical outcomes. One promising application of AI in the fertility clinic is the use of machine learning (ML) tools to assess embryos for transfer. The successful clinical implementation of these tools in ways that do not erode consumer trust requires an awareness of the ethical issues that these technologies raise, and the development of strategies to manage any ethical concerns. However, to date, there has been little published literature on the ethics of using ML in embryo assessment. This mini-review contributes to this nascent area of discussion by surveying the key ethical concerns raised by ML technologies in healthcare and medicine more generally, and identifying which are germane to the use of ML in the assessment of embryos. We report concerns about the ‘dehumanization’ of human reproduction, algorithmic bias, responsibility, transparency and explainability, deskilling, and justice.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"3 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805481","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}
K Allen-Brady, L E Verrilli, B A Austin, J M Letourneau, E B Johnstone, C K Welt
<p><strong>Study question: </strong>Is there an increased risk of reproductive or colon cancer in women with Turner syndrome and their family members?</p><p><strong>Summary answer: </strong>Our data suggest that there is an increased risk for sigmoid colon cancer in women with Turner syndrome and an increased prostate cancer risk in second- and third-degree male relatives.</p><p><strong>What is known already: </strong>Turner syndrome has been associated with lower risk of breast cancer, but increased risk of gonadoblastoma and colon cancer in some, but not all studies. There is also evidence for a genetic predisposition to sex chromosome aneuploidy, which may indicate a predisposition to Turner syndrome and the associated cancer risk in family members.</p><p><strong>Study design, size, duration: </strong>The study was a retrospective case-control study of women with Turner syndrome diagnosed from 1995 to 2021, their relatives, and population subjects from Utah.</p><p><strong>Participants/materials, setting, methods: </strong>Women with Turner syndrome were identified using International Classification of Disease (ICD) codes in electronic medical records from two major Utah healthcare systems and reviewed for accuracy. Women with Turner syndrome were linked to genealogy in the Utah Population Database. Cancer diagnoses (breast, ovarian, endometrial, colon, testicular, and prostate) were determined for women with Turner syndrome and their relatives using the Utah Cancer Registry. Live births to women with Turner syndrome were identified by linked birth certificates. The relative risk of cancer in women with Turner syndrome and in relatives was estimated by comparison to population rates matched by age, sex, and birthplace.</p><p><strong>Main results and the role of chance: </strong>We identified 289 women with Turner syndrome. Sigmoid colon cancer was increased in women with Turner syndrome (OR [95% CI] 24.2 [2.9, 87.4]; P = 0.0032). There were 233 women with Turner syndrome who had at least three generations of genealogical data. There was an increased risk of Turner syndrome in first- (OR [95% CI] 18.08 [2.19, 65.32]; P = 0.0057) and second-degree relatives (9.62 [1.17, 34.74]; P = 0.019), although numbers were very small. There was an increased risk of prostate cancer in second- (1.8 [1.4, 2.2]; P < 0.001) and third-degree relatives (1.3 [1.1, 1.5]; P < 0.001). There was no increased risk of colon cancer in relatives.</p><p><strong>Limitations, reasons for caution: </strong>Based on the small number of sigmoid colon cancer cases, it is possible that our data have overestimated the colon cancer risk. Limitations include the identification of Turner syndrome by a diagnosis code in one of the two major health systems in Utah. The population is largely northern European with 9.3% of the women self-identified as Hispanic and 2.4% as Native American or multiple races. The results may not be generalizable to other populations.</p><p><strong>Wider impli
{"title":"Turner syndrome: fertility, familial clustering, and cancer risk.","authors":"K Allen-Brady, L E Verrilli, B A Austin, J M Letourneau, E B Johnstone, C K Welt","doi":"10.1093/humrep/deae266","DOIUrl":"https://doi.org/10.1093/humrep/deae266","url":null,"abstract":"<p><strong>Study question: </strong>Is there an increased risk of reproductive or colon cancer in women with Turner syndrome and their family members?</p><p><strong>Summary answer: </strong>Our data suggest that there is an increased risk for sigmoid colon cancer in women with Turner syndrome and an increased prostate cancer risk in second- and third-degree male relatives.</p><p><strong>What is known already: </strong>Turner syndrome has been associated with lower risk of breast cancer, but increased risk of gonadoblastoma and colon cancer in some, but not all studies. There is also evidence for a genetic predisposition to sex chromosome aneuploidy, which may indicate a predisposition to Turner syndrome and the associated cancer risk in family members.</p><p><strong>Study design, size, duration: </strong>The study was a retrospective case-control study of women with Turner syndrome diagnosed from 1995 to 2021, their relatives, and population subjects from Utah.</p><p><strong>Participants/materials, setting, methods: </strong>Women with Turner syndrome were identified using International Classification of Disease (ICD) codes in electronic medical records from two major Utah healthcare systems and reviewed for accuracy. Women with Turner syndrome were linked to genealogy in the Utah Population Database. Cancer diagnoses (breast, ovarian, endometrial, colon, testicular, and prostate) were determined for women with Turner syndrome and their relatives using the Utah Cancer Registry. Live births to women with Turner syndrome were identified by linked birth certificates. The relative risk of cancer in women with Turner syndrome and in relatives was estimated by comparison to population rates matched by age, sex, and birthplace.</p><p><strong>Main results and the role of chance: </strong>We identified 289 women with Turner syndrome. Sigmoid colon cancer was increased in women with Turner syndrome (OR [95% CI] 24.2 [2.9, 87.4]; P = 0.0032). There were 233 women with Turner syndrome who had at least three generations of genealogical data. There was an increased risk of Turner syndrome in first- (OR [95% CI] 18.08 [2.19, 65.32]; P = 0.0057) and second-degree relatives (9.62 [1.17, 34.74]; P = 0.019), although numbers were very small. There was an increased risk of prostate cancer in second- (1.8 [1.4, 2.2]; P < 0.001) and third-degree relatives (1.3 [1.1, 1.5]; P < 0.001). There was no increased risk of colon cancer in relatives.</p><p><strong>Limitations, reasons for caution: </strong>Based on the small number of sigmoid colon cancer cases, it is possible that our data have overestimated the colon cancer risk. Limitations include the identification of Turner syndrome by a diagnosis code in one of the two major health systems in Utah. The population is largely northern European with 9.3% of the women self-identified as Hispanic and 2.4% as Native American or multiple races. The results may not be generalizable to other populations.</p><p><strong>Wider impli","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806890","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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