Baris Ata, Barbara Lawrenz, Laura Melado, Raquel Del Gallego, Carol Coughlan, Francisco Ruiz, Laura Marqueta Marques, Ahmed El-Damen, Ibrahim Elkhatib, Human M Fatemi
<p><strong>Study question: </strong>What is the diagnostic performance of the ART-ET screening tool, an easy-to-use non-invasive screening tool for prediction of difficult embryo transfers?</p><p><strong>Summary answer: </strong>A simple scoring of transvaginal ultrasound examination of the cervical canal can predict difficult embryo transfers with high specificity, positive likelihood ratio, and accuracy; the inclusion of cervical position and history of cesarean without a vaginal delivery improved predictive performance.</p><p><strong>What is known already: </strong>Difficult embryo transfer procedures are associated with significantly lower clinical pregnancy and live birth rates, and some interventions may facilitate an anticipated difficult embryo transfer.</p><p><strong>Study design, size, duration: </strong>A diagnostic test study prospectively conducted on 239 single euploid blastocyst transfer procedures between March and December 2023. The sample size was calculated to include about 20 difficult transfer procedures. Physicians conducting the transfers were blinded to screening results.</p><p><strong>Participants/materials, setting, methods: </strong>The study was conducted in two tertiary-level private assisted reproduction centers. The ART-ET Screening tool collected information on patients' body mass index, obstetric history, cervical position, external cervical ostium appearance, and ultrasound examination of the cervical canal. A difficult embryo transfer was defined if one or more of the following occurred during the procedure; use of a malleable obturator to insert the guiding catheter until the internal ostium, use of a forceps to pull the cervix, if there were blood in the transfer catheter following the procedure, if the transfer catheter needed to be reloaded, and if the physician found the procedure difficult.</p><p><strong>Main results and the role of chance: </strong>Ongoing pregnancy rates were 47.6% vs 59.6% after a difficult and easy embryo transfer. With a difficult embryo transfer prevalence of 8.8%, screening score including cervical position, visibility and the length of cervical canal, and obstetric history had the best diagnostic performance with sensitivity of 33.3% (14.59-56.97%), specificity of 99.5% (97.47-99.99%), positive likelihood ratio of 72.67 (9.38-562.73), negative likelihood ratio of 0.67 (0.49-0.91), and an accuracy of 93.7% (89.86-96.45%) for predicting difficult embryo transfers. The simpler cervical ultrasound score also had a good diagnostic performance with a sensitivity of 28.6% (11.28-52.18%), specificity of 98.2% (95.37-99.50%), positive likelihood ratio of 15.57 (4.77-50.84), negative likelihood ratio of 0.73 (0.55-0.95), positive predictive value of 60.0% (31.46-83.03%), negative predictive value of 93.5% (91.59-94.93%), and an accuracy of 93.5% (91.59-94.93%).</p><p><strong>Limitations, reasons for caution: </strong>The diagnostic performance of the proposed ART-ET Screening tool would depe
{"title":"The ART-ET screening tool: an easy-to-use non-invasive screening method to predict difficult embryo transfers in advance.","authors":"Baris Ata, Barbara Lawrenz, Laura Melado, Raquel Del Gallego, Carol Coughlan, Francisco Ruiz, Laura Marqueta Marques, Ahmed El-Damen, Ibrahim Elkhatib, Human M Fatemi","doi":"10.1093/humrep/deaf002","DOIUrl":"https://doi.org/10.1093/humrep/deaf002","url":null,"abstract":"<p><strong>Study question: </strong>What is the diagnostic performance of the ART-ET screening tool, an easy-to-use non-invasive screening tool for prediction of difficult embryo transfers?</p><p><strong>Summary answer: </strong>A simple scoring of transvaginal ultrasound examination of the cervical canal can predict difficult embryo transfers with high specificity, positive likelihood ratio, and accuracy; the inclusion of cervical position and history of cesarean without a vaginal delivery improved predictive performance.</p><p><strong>What is known already: </strong>Difficult embryo transfer procedures are associated with significantly lower clinical pregnancy and live birth rates, and some interventions may facilitate an anticipated difficult embryo transfer.</p><p><strong>Study design, size, duration: </strong>A diagnostic test study prospectively conducted on 239 single euploid blastocyst transfer procedures between March and December 2023. The sample size was calculated to include about 20 difficult transfer procedures. Physicians conducting the transfers were blinded to screening results.</p><p><strong>Participants/materials, setting, methods: </strong>The study was conducted in two tertiary-level private assisted reproduction centers. The ART-ET Screening tool collected information on patients' body mass index, obstetric history, cervical position, external cervical ostium appearance, and ultrasound examination of the cervical canal. A difficult embryo transfer was defined if one or more of the following occurred during the procedure; use of a malleable obturator to insert the guiding catheter until the internal ostium, use of a forceps to pull the cervix, if there were blood in the transfer catheter following the procedure, if the transfer catheter needed to be reloaded, and if the physician found the procedure difficult.</p><p><strong>Main results and the role of chance: </strong>Ongoing pregnancy rates were 47.6% vs 59.6% after a difficult and easy embryo transfer. With a difficult embryo transfer prevalence of 8.8%, screening score including cervical position, visibility and the length of cervical canal, and obstetric history had the best diagnostic performance with sensitivity of 33.3% (14.59-56.97%), specificity of 99.5% (97.47-99.99%), positive likelihood ratio of 72.67 (9.38-562.73), negative likelihood ratio of 0.67 (0.49-0.91), and an accuracy of 93.7% (89.86-96.45%) for predicting difficult embryo transfers. The simpler cervical ultrasound score also had a good diagnostic performance with a sensitivity of 28.6% (11.28-52.18%), specificity of 98.2% (95.37-99.50%), positive likelihood ratio of 15.57 (4.77-50.84), negative likelihood ratio of 0.73 (0.55-0.95), positive predictive value of 60.0% (31.46-83.03%), negative predictive value of 93.5% (91.59-94.93%), and an accuracy of 93.5% (91.59-94.93%).</p><p><strong>Limitations, reasons for caution: </strong>The diagnostic performance of the proposed ART-ET Screening tool would depe","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407208","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}
Daniel R Pfau, Evelyn Cho, Jamison G Clark, Robin E Kruger, Ruth K Chan-Sui, Hadrian Kinnear, Cynthia Dela Cruz, Amanda R Schwartz, Vasantha Padmanabhan, Ariella Shikanov, Molly B Moravek
<p><strong>Study question: </strong>How does testosterone gender-affirming hormone therapy (T-GAHT) impact breeding success in female mice?</p><p><strong>Summary answer: </strong>T-GAHT causes reversible subfertility in female mice and persistent changes to reproductive tract anatomy, gene expression, and hormone receptors.</p><p><strong>What is known already: </strong>Adult female mice implanted with capsules containing 10 mg of testosterone mimic many aspects of reproductive phenotypes of T-GAHT patients, who may desire future gestation while pausing T-GAHT. In mice, oocytes retrieved from T-GAHT mice had decreased IVF rates, and T cessation prior to stimulation improved these outcomes. However, the effects of T-GAHT on breeding have not been examined.</p><p><strong>Study design, size, duration: </strong>Adult female CD1 mice were subcutaneously implanted with capsules containing 10 mg of testosterone or blank controls. In separate studies, capsules were removed after 6 ('short') or 12 weeks ('long' n = 15/group), then mice were paired with proven-breeder CD1 males. Breeding pair success and pup development (15-20/group) were measured for first and second litters, then terminal measurements were taken from dams and their adult offspring (10/group).</p><p><strong>Participants/materials, setting, methods: </strong>The reproductive success of explanted T-GAHT and control mice was investigated by pairing them with proven-breeder CD1 males. Regular observations of dams and litters enabled analysis of fertility and the development of male and female pups for two litters. Terminal measures for dams and/or adult offspring focused on endpoints tied to reproductive tract function and gestation, including reproductive hormones, vaginal cytology, sperm analysis and ovarian and uterine anatomy, histology, and gene expression.</p><p><strong>Main results and the role of chance: </strong>All but one T-GAHT dams gave birth, but the time between pairing and their first birth was longer than controls after long (22.3 ± 1.3 days vs 24.5 ± 3.1) and short (23.2 ± 1.4 days vs 25.5 ± 4) treatments. Dams given long T-GAHT treatment had fewer pups in their first litters (11.9 ± 2.7 pups vs 7.8 ± 3.1) but pup number was unaltered after short treatment (11.5 ± 2.4 pups vs 11.4 ± 3.7). Further, offspring from first litters displayed accelerated puberty. Fertility differences and offspring developmental effects were absent for second gestations and litters. Despite fertility rescue, several anatomical, genetic, and histological changes persisted in T-GAHT dams after two litters. Offspring reproductive system outcomes were not significantly altered once dam fertility was restored. This study powerfully demonstrates a subfertile phenotype in T-GAHT-treated animals that is rescued over time and identifies gonadotropin and steroid hormone signaling as potential mechanisms for further investigation.</p><p><strong>Large scale data: </strong>No large-scale data were generated in t
{"title":"Short and long duration testosterone treatments induce reversable subfertility in female mice using a gestational model of gender-affirming hormone therapy.","authors":"Daniel R Pfau, Evelyn Cho, Jamison G Clark, Robin E Kruger, Ruth K Chan-Sui, Hadrian Kinnear, Cynthia Dela Cruz, Amanda R Schwartz, Vasantha Padmanabhan, Ariella Shikanov, Molly B Moravek","doi":"10.1093/humrep/deaf016","DOIUrl":"https://doi.org/10.1093/humrep/deaf016","url":null,"abstract":"<p><strong>Study question: </strong>How does testosterone gender-affirming hormone therapy (T-GAHT) impact breeding success in female mice?</p><p><strong>Summary answer: </strong>T-GAHT causes reversible subfertility in female mice and persistent changes to reproductive tract anatomy, gene expression, and hormone receptors.</p><p><strong>What is known already: </strong>Adult female mice implanted with capsules containing 10 mg of testosterone mimic many aspects of reproductive phenotypes of T-GAHT patients, who may desire future gestation while pausing T-GAHT. In mice, oocytes retrieved from T-GAHT mice had decreased IVF rates, and T cessation prior to stimulation improved these outcomes. However, the effects of T-GAHT on breeding have not been examined.</p><p><strong>Study design, size, duration: </strong>Adult female CD1 mice were subcutaneously implanted with capsules containing 10 mg of testosterone or blank controls. In separate studies, capsules were removed after 6 ('short') or 12 weeks ('long' n = 15/group), then mice were paired with proven-breeder CD1 males. Breeding pair success and pup development (15-20/group) were measured for first and second litters, then terminal measurements were taken from dams and their adult offspring (10/group).</p><p><strong>Participants/materials, setting, methods: </strong>The reproductive success of explanted T-GAHT and control mice was investigated by pairing them with proven-breeder CD1 males. Regular observations of dams and litters enabled analysis of fertility and the development of male and female pups for two litters. Terminal measures for dams and/or adult offspring focused on endpoints tied to reproductive tract function and gestation, including reproductive hormones, vaginal cytology, sperm analysis and ovarian and uterine anatomy, histology, and gene expression.</p><p><strong>Main results and the role of chance: </strong>All but one T-GAHT dams gave birth, but the time between pairing and their first birth was longer than controls after long (22.3 ± 1.3 days vs 24.5 ± 3.1) and short (23.2 ± 1.4 days vs 25.5 ± 4) treatments. Dams given long T-GAHT treatment had fewer pups in their first litters (11.9 ± 2.7 pups vs 7.8 ± 3.1) but pup number was unaltered after short treatment (11.5 ± 2.4 pups vs 11.4 ± 3.7). Further, offspring from first litters displayed accelerated puberty. Fertility differences and offspring developmental effects were absent for second gestations and litters. Despite fertility rescue, several anatomical, genetic, and histological changes persisted in T-GAHT dams after two litters. Offspring reproductive system outcomes were not significantly altered once dam fertility was restored. This study powerfully demonstrates a subfertile phenotype in T-GAHT-treated animals that is rescued over time and identifies gonadotropin and steroid hormone signaling as potential mechanisms for further investigation.</p><p><strong>Large scale data: </strong>No large-scale data were generated in t","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398878","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}
N Friis Wang, L S Mamsen, J Cadenas, G Saritas, K T Macklon, J Fedder, E Ernst, M L Johannsen, S G Kristensen, T Kelsey, A Kumar, B Kalra, K Løssl, C Yding Andersen
STUDY QUESTION Does maternal age impact hormonal secretions from granulosa cells, theca cells, and the oocyte in human small antral follicles? SUMMARY ANSWER Major hormones secreted by granulosa and theca cells, as well as the oocyte-specific TGF-β members—GDF9, BMP15, and the GDF9/BMP15 heterodimer cumulin—maintain a consistent concentration within the follicular fluid of human small antral follicles, regardless of maternal age. WHAT IS KNOWN ALREADY It is well established that female fertility declines with increasing age. However, it is not known whether this decline is exclusively due to a reduction in oocyte quality and quantity or also involves a decline in the hormone-secreting capabilities of granulosa cells, theca cells, and the oocyte itself. STUDY DESIGN, SIZE, DURATION This is a retrospective study of follicular fluid obtained from human small antral follicles collected in connection with cryopreservation of ovarian tissue at the Laboratory of Reproductive Biology, University Hospital Copenhagen, Rigshospitalet, Denmark, between 2010 and 2020 as part of the hospital’s fertility preservation program. PARTICIPANTS/MATERIALS, SETTING, METHODS Follicular fluid samples from human small antral follicles measuring 3–13 mm in diameter from macroscopically normal ovaries of 381 patients aged 5–43 years were included in the study, provided that at least one of the following parameters was measured: AMH, Inhibin A, Inhibin B, oestradiol (E2), progesterone (P4), androstenedione, testosterone, and/or the oocyte-specific TGF-β members GDF9, BMP15, or cumulin. MAIN RESULTS AND THE ROLE OF CHANCE In a linear regression analysis adjusted for follicular volume, female age did not predict the follicular fluid concentrations of AMH, Inhibin B, Inhibin A, E2, androstenedione, testosterone, GDF9, BMP15, or cumulin. Although a significant association was observed between female age and follicular fluid P4 levels, the predictive value of age was poor, accounting for at most 5% of the variation in P4. LIMITATIONS, REASONS FOR CAUTION Hormonal levels may vary with the degree of atresia in each follicle; however, the health status of the small antral follicles in this study was not characterized. Additionally, we cannot exclude possible age-related differences in human follicles larger than 10 mm, as very few of these were included. Furthermore, we did not include women above the age of 43, despite the potential for more pronounced age-related effects in these patients. WIDER IMPLICATIONS OF THE FINDINGS Our results support the idea that the age-related decline in female fertility is primarily due to a reduction in oocyte quality and quantity, but further research is needed to confirm this. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained, and the authors have no conflicts of interest to declare in relation to this work. TRIAL REGISTRATION NUMBER N/A.
{"title":"Impact of female age on concentrations of reproductive hormones and oocyte-specific growth factors in follicular fluid from human small antral follicles","authors":"N Friis Wang, L S Mamsen, J Cadenas, G Saritas, K T Macklon, J Fedder, E Ernst, M L Johannsen, S G Kristensen, T Kelsey, A Kumar, B Kalra, K Løssl, C Yding Andersen","doi":"10.1093/humrep/deaf017","DOIUrl":"https://doi.org/10.1093/humrep/deaf017","url":null,"abstract":"STUDY QUESTION Does maternal age impact hormonal secretions from granulosa cells, theca cells, and the oocyte in human small antral follicles? SUMMARY ANSWER Major hormones secreted by granulosa and theca cells, as well as the oocyte-specific TGF-β members—GDF9, BMP15, and the GDF9/BMP15 heterodimer cumulin—maintain a consistent concentration within the follicular fluid of human small antral follicles, regardless of maternal age. WHAT IS KNOWN ALREADY It is well established that female fertility declines with increasing age. However, it is not known whether this decline is exclusively due to a reduction in oocyte quality and quantity or also involves a decline in the hormone-secreting capabilities of granulosa cells, theca cells, and the oocyte itself. STUDY DESIGN, SIZE, DURATION This is a retrospective study of follicular fluid obtained from human small antral follicles collected in connection with cryopreservation of ovarian tissue at the Laboratory of Reproductive Biology, University Hospital Copenhagen, Rigshospitalet, Denmark, between 2010 and 2020 as part of the hospital’s fertility preservation program. PARTICIPANTS/MATERIALS, SETTING, METHODS Follicular fluid samples from human small antral follicles measuring 3–13 mm in diameter from macroscopically normal ovaries of 381 patients aged 5–43 years were included in the study, provided that at least one of the following parameters was measured: AMH, Inhibin A, Inhibin B, oestradiol (E2), progesterone (P4), androstenedione, testosterone, and/or the oocyte-specific TGF-β members GDF9, BMP15, or cumulin. MAIN RESULTS AND THE ROLE OF CHANCE In a linear regression analysis adjusted for follicular volume, female age did not predict the follicular fluid concentrations of AMH, Inhibin B, Inhibin A, E2, androstenedione, testosterone, GDF9, BMP15, or cumulin. Although a significant association was observed between female age and follicular fluid P4 levels, the predictive value of age was poor, accounting for at most 5% of the variation in P4. LIMITATIONS, REASONS FOR CAUTION Hormonal levels may vary with the degree of atresia in each follicle; however, the health status of the small antral follicles in this study was not characterized. Additionally, we cannot exclude possible age-related differences in human follicles larger than 10 mm, as very few of these were included. Furthermore, we did not include women above the age of 43, despite the potential for more pronounced age-related effects in these patients. WIDER IMPLICATIONS OF THE FINDINGS Our results support the idea that the age-related decline in female fertility is primarily due to a reduction in oocyte quality and quantity, but further research is needed to confirm this. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained, and the authors have no conflicts of interest to declare in relation to this work. TRIAL REGISTRATION NUMBER N/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"12 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371534","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}
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
<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
{"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}
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
<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
{"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}
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
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.
{"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 (&gt;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 &gt; 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}
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":"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}
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":"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}
A C Kiser, R Hemmert, R Myrer, B T Bucher, K Eilbeck, M Varner, J B Stanford, C M Peterson, A Z Pollack, L V Farland, K C Schliep
<p><strong>Study question: </strong>How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease?</p><p><strong>Summary answer: </strong>For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy.</p><p><strong>What is known already: </strong>Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high inter- and intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.</p><p><strong>Study design, size, duration: </strong>In this validation study, participants (n = 412) of the Utah operative cohort of the ENDO Study (2007-2009) were linked to medical records from the Utah Population Database (UPDB) to compare endometriosis diagnoses from each source. The UPDB is a unique database containing linked data on over 11 million individuals, including statewide ambulatory and inpatient records, state vital records, and University of Utah Health and Intermountain Healthcare electronic healthcare records, capturing most Utah residents.</p><p><strong>Participants/materials, setting, methods: </strong>The ENDO operative cohort consisted of individuals aged 18-44 years with no prior endometriosis diagnosis who underwent gynecologic laparoscopy or laparotomy for a variety of surgical indications. In total, 173 women were diagnosed with endometriosis based on surgical visualization of disease, 35% with superficial endometriosis, 9% with ovarian endometriomas, and 14% with deep infiltrating endometriosis. Contemporary administrative health data from the UPDB included ICD diagnostic codes from Utah Department of Health in-patient and ambulatory surgery records and University of Utah and Intermountain Health electronic health records.</p><p><strong>Main results and the role of chance: </strong>For endometriosis diagnosis, we found relatively high sensitivity (0.88) and specificity (0.87) and substantial agreement (Kappa [Κ] = 0.74). We found similarly high sensitivity, specificity, and agreement for superficial endometriosis (n = 143, 0.86, 0.83, Κ = 0.65) and ovarian endometriomas (n = 38, 0.82, 0.92, Κ = 0.58). However, deep infiltrating endometriosis (n = 58) had lower sensitivity (0.12) and agreement (Κ = 0.17), with high specificity (0.99).</p><p><strong>Limitations, reasons for caution: </strong>Medication prescription data and unstructured data, such as clinical notes, were not included in the UPDB data used for this study. These additional data types could aid in detection of endometriosis. Most participants were white or Asian with Hispanic ethnicity reported 11% of the time,
{"title":"Validation of administrative health data for the identification of endometriosis diagnosis.","authors":"A C Kiser, R Hemmert, R Myrer, B T Bucher, K Eilbeck, M Varner, J B Stanford, C M Peterson, A Z Pollack, L V Farland, K C Schliep","doi":"10.1093/humrep/deae281","DOIUrl":"10.1093/humrep/deae281","url":null,"abstract":"<p><strong>Study question: </strong>How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease?</p><p><strong>Summary answer: </strong>For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy.</p><p><strong>What is known already: </strong>Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high inter- and intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.</p><p><strong>Study design, size, duration: </strong>In this validation study, participants (n = 412) of the Utah operative cohort of the ENDO Study (2007-2009) were linked to medical records from the Utah Population Database (UPDB) to compare endometriosis diagnoses from each source. The UPDB is a unique database containing linked data on over 11 million individuals, including statewide ambulatory and inpatient records, state vital records, and University of Utah Health and Intermountain Healthcare electronic healthcare records, capturing most Utah residents.</p><p><strong>Participants/materials, setting, methods: </strong>The ENDO operative cohort consisted of individuals aged 18-44 years with no prior endometriosis diagnosis who underwent gynecologic laparoscopy or laparotomy for a variety of surgical indications. In total, 173 women were diagnosed with endometriosis based on surgical visualization of disease, 35% with superficial endometriosis, 9% with ovarian endometriomas, and 14% with deep infiltrating endometriosis. Contemporary administrative health data from the UPDB included ICD diagnostic codes from Utah Department of Health in-patient and ambulatory surgery records and University of Utah and Intermountain Health electronic health records.</p><p><strong>Main results and the role of chance: </strong>For endometriosis diagnosis, we found relatively high sensitivity (0.88) and specificity (0.87) and substantial agreement (Kappa [Κ] = 0.74). We found similarly high sensitivity, specificity, and agreement for superficial endometriosis (n = 143, 0.86, 0.83, Κ = 0.65) and ovarian endometriomas (n = 38, 0.82, 0.92, Κ = 0.58). However, deep infiltrating endometriosis (n = 58) had lower sensitivity (0.12) and agreement (Κ = 0.17), with high specificity (0.99).</p><p><strong>Limitations, reasons for caution: </strong>Medication prescription data and unstructured data, such as clinical notes, were not included in the UPDB data used for this study. These additional data types could aid in detection of endometriosis. Most participants were white or Asian with Hispanic ethnicity reported 11% of the time, ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"289-295"},"PeriodicalIF":6.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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