Human reproduction最新文献

{"title":"Single-cell analysis comparing early-stage oocytes from fresh and slow-frozen/thawed human ovarian cortex reveals minimal impact of cryopreservation on the oocyte transcriptome.","authors":"J H Machlin, D F Hannum, A S K Jones, T Schissel, K Potocsky, E E Marsh, S Hammoud, V Padmanabhan, J Z Li, A Shikanov","doi":"10.1093/humrep/deaf009","DOIUrl":"https://doi.org/10.1093/humrep/deaf009","url":null,"abstract":"<p><strong>Study question: </strong>Does the slow-freezing and thawing process have a negative impact on the transcriptome of oocytes isolated from early-stage human follicles compared to fresh controls?</p><p><strong>Summary answer: </strong>The transcriptional profiles of fresh and frozen/thawed oocytes did not cluster separately, indicating undetectable differences between the two groups when compared to within-donor heterogeneity.</p><p><strong>What is known already: </strong>Previous studies using histological analysis of follicle morphology, density, and stage distribution in slow-frozen/thawed human ovarian cortex compared to fresh controls showed no differences between the two groups. Clinical cases reported in the past 10 years have demonstrated that transplanted slow-frozen/thawed and fresh ovarian cortex restored normal serum FSH levels and regular menstrual cycles by 5 months. However, the slow-frozen and thawed tissue resulted in lower rates of pregnancies and live births, albeit not statistically significant.</p><p><strong>Study design, size, duration: </strong>We utilized single-cell RNA-sequencing (scRNAseq) of 144 human oocytes isolated from cadaver ovaries obtained from three donors.</p><p><strong>Participants/materials, setting, methods: </strong>Human ovarian cortex from three healthy premenopausal donors 16, 18, and 27 years old was cut into squares measuring 10 × 10 × 1 mm3 and either slow-frozen and thawed or processed fresh. First, using a novel method for isolating live oocytes from primordial and primary follicles, the ovarian cortex squares were fragmented with a McIlwain tissue chopper and enzymatically digested. Next, oocytes were mechanically denuded under a dissection microscope and placed individually into wells containing lysis buffer for scRNAseq. Lysed single oocytes were subjected to library prep using the seqWell PlexWell rapid single-cell RNA protocol. Pooled libraries were subjected to 150-bp paired-end sequencing on the NovaSeq6000 Illumina platform. In total, we sequenced 144 oocytes-24 oocytes isolated fresh and 24 oocytes isolated after slow-freezing and thawing from each of the three donors. Additionally, we performed histological analysis of fresh and frozen/thawed ovarian cortex tissue from all three donors using hematoxylin and eosin staining and analyzed morphology, follicle density, and follicle stage distribution differences between fresh and cryopreserved ovarian cortex.</p><p><strong>Main results and the role of chance: </strong>The histological analysis revealed no differences in follicle stage distribution or follicle morphology between conditions, with the percentage of normal follicles in fresh and frozen/thawed tissue, respectively, as 86.7% and 91.0% for Donor 1, 91.7% and 92.5% for Donor 2, and 96.1% and 91.1% for Donor 3. The follicle density per mm3 in fresh and frozen/thawed tissue, respectively, was 279.4 and 235.8 for Donor 1, 662.2 and 553.5 for Donor 2, and 55.8 and 71.4 for Donor ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370746","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}

{"title":"Long-term risk of endometrial cancer after assisted reproductive technology.","authors":"Mandy Spaan, Alexandra W van den Belt-Dusebout, Cornelis B Lambalk, Hester van Boven, Laura L van Loendersloot, Frank J M Broekmans, Joop S E Laven, Evert J P van Santbrink, Annemiek W Nap, Lucette A J van der Westerlaken, Ben J Cohlen, Astrid E P Cantineau, Jesper M J Smeenk, Minouche M van Rumste, Mariëtte Goddijn, Ron J T van Golde, Paul A M Meeuwissen, Jan P de Bruin, Gabriële M Ouwens, Miranda A Gerritsma, Michael Schaapveld, Curt W Burger, Flora E van Leeuwen","doi":"10.1093/humrep/deaf018","DOIUrl":"https://doi.org/10.1093/humrep/deaf018","url":null,"abstract":"<p><strong>Study question: </strong>What is the risk of endometrial cancer after long-term follow-up in women treated with ART between 1983 and 2001 compared with women in the general population and subfertile women who did not undergo ART?</p><p><strong>Summary answer: </strong>The risk of endometrial cancer is not increased in women who underwent ART in the Netherlands between 1983 and 2001, neither compared with women from the general population nor compared with subfertile women not treated with ART.</p><p><strong>What is known already: </strong>Concerns have been raised that subfertility treatment may be associated with increased risk of endometrial cancer. However, published studies show inconsistent results regarding the effects of ovarian stimulation and specific subfertility diagnoses on endometrial cancer risk.</p><p><strong>Study design, size, duration: </strong>A nationwide historic cohort study (the OMEGA-cohort) was conducted to examine the risk of cancer in women after ovarian stimulation for ART. The OMEGA-cohort comprises 30 625 women who received ovarian stimulation for ART (ART group) in 1983-2000 and 9988 subfertile women not treated with ART (non-ART group). After a median follow-up of 24 years, endometrial cancer incidence was ascertained through linkage with the Netherlands Cancer Registry. Endometrial cancer risk in the cohort was compared with that in the general population using person-years analyses, and between the ART group and non-ART group using multivariable Cox regression analyses.</p><p><strong>Participants/materials, setting, methods: </strong>Detailed ART-treatment data were obtained from the medical records and complete information on parity and age at first birth was obtained through linkage with the Personal Records Database. Information on hysterectomy and endometriosis was collected through linkage with the Dutch Nationwide Pathology Databank (Palga). Data about lifestyle factors, including BMI, were obtained through a self-administered questionnaire.</p><p><strong>Main results and the role of chance: </strong>After a median follow-up duration of 24 years, 137 endometrial cancers were diagnosed. Endometrial cancer risk after ART was not significantly increased compared with that in the general population (standardized incidence ratio = 1.19; 95% CI = 0.97-1.44) nor compared with that in the non-ART group (multivariably adjusted hazard ratio = 1.11; 95% CI = 0.74-1.67). Risk of endometrial cancer did not increase with longer follow-up or with more ART cycles, and the risk within the cohort, did not vary by cause of subfertility (male, tubal, unexplained, and other). Irrespective of ART treatment, endometrial cancer risk was increased in obese women and women with endometriosis, but decreased among parous women and women who used oral contraceptives.</p><p><strong>Limitations, reasons for caution: </strong>Although the findings of the study are reassuring, the median age of the women at the end of follow-up ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370796","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}

{"title":"The numbers of biopsied cells in routine clinical process of preimplantation genetic testing (PGT) do not affect the pregnancy outcomes of embryos","authors":"Ling Ding, Nan Wang, Jialin Jia, Chuan Long, Ying Kuo, Xiaomeng Wang, Fanqing Xu, Yixin Ren, Mochen Ma, Zhongwei Wang, Xiaodan Shi, Jin Huang, Xiaohui Zhu, Lixue Chen, Yanbo Ji, Ping Liu, Rong Li, Ying Lian, Jie Qiao, Liying Yan","doi":"10.1093/humrep/deaf001","DOIUrl":"https://doi.org/10.1093/humrep/deaf001","url":null,"abstract":"STUDY QUESTION Does the number of biopsied trophectoderm cells sampled for preimplantation genetic testing for monogenic disease (PGT-M) affect subsequent clinical outcomes for those selected embryos? SUMMARY ANSWER The number of biopsied cells does not affect the pregnancy outcome of preimplantation genetically tested embryos. WHAT IS KNOWN ALREADY The successful execution of PGT relies on the availability of a certain number of high-quality biopsied cells. Evidence in the literature has reported that blastocyst biopsies may have a negative impact on clinical outcomes. STUDY DESIGN, SIZE, DURATION A retrospective cohort study including 850 single-blastocyst transfer cycles from 605 couples between May 2014 and August 2024 was conducted at Peking University Third Hospital. The primary clinical outcome measure was the biochemical pregnancy rate, while other indicators such as the live birth rate, the clinical pregnancy rate, and the miscarriage rate were also recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 850 blastocysts obtained from routine PGT-M cycles. Based on biopsied cell numbers, data were categorized into four groups: Group 1 (1–5 cells) (n = 234), Group 2 (6–10 cells) (n = 328), Group 3 (11–15 cells) (n = 192), and Group 4 (>15 cells) (n = 96). MAIN RESULTS AND THE ROLE OF CHANCE The number of cells biopsied from the embryo did not significantly affect either the biochemical pregnancy rate or the live birth rate in the routine PGT process (P > 0.05). There were 129 of 234 embryos (55.1%) in the 1–5 biopsied cell group, 183 of the 328 embryos (55.8%) with 6–10 biopsied cells, 92 of 192 embryos (47.9%) with 11–15 biopsied cells, and 48 of 96 (50.0%) embryos with more than 15 biopsied cells which achieved successful pregnancies. The live birth rates were 42.7%, 49.7%, 43.2%, and 43.8% for each of the biopsy groups, respectively. LIMITATIONS, REASONS FOR CAUTION Data for this study were collected from one center only, therefore multicenter, large-scale cohort studies are essential to confirm the accuracy and the reliability of this study. WIDER IMPLICATIONS OF THE FINDINGS The number of biopsied cells in a blastocyst is associated with the embryo quality and hatching status. The conclusion of this study emphasizes that routine procedures during the biopsy process do not affect pregnancy outcomes. It is crucial to strike a balance between minimizing damage to the blastocyst’s developmental potential and achieving the highest possible detection efficiency for PGT-M. STUDY FUNDING/COMPETING INTEREST(S) This project is funded by the National Key Research and Development Program of China (2019YFA0801401, 2019YFA0110001) and the National Natural Science Foundation of China (82125013). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER N/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"40 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083827","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}

{"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":"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":"391-396"},"PeriodicalIF":6.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788202/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"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":"280-288"},"PeriodicalIF":6.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788223/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Double versus single stimulation in young low prognosis patients followed by a fresh embryo transfer: a randomized controlled trial (DUOSTIM-fresh).","authors":"","doi":"10.1093/humrep/deae289","DOIUrl":"10.1093/humrep/deae289","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"397"},"PeriodicalIF":6.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947971","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}

{"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}

{"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}

{"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}

{"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 (<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","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}