Kate Bickendorf, Fang Qi, Kelli Peirce, Rui Wang, Jay Natalwala, Vincent Chapple, Yanhe Liu
STUDY QUESTION Compared to the ‘single biopsy + single vitrification’ approach, do ‘double biopsy + double vitrification’ or ‘single biopsy + double vitrification’ arrangements compromise subsequent clinical outcomes following euploidy blastocyst transfer? SUMMARY ANSWER Both ‘double biopsy + double vitrification’ and ‘single biopsy + double vitrification’ led to reduced live birth/ongoing pregnancy rates and clinical pregnancy rates. WHAT IS KNOWN ALREADY? It is not uncommon to receive inconclusive results following blastocyst biopsy and preimplantation genetic testing for aneuploidy (PGT-A). Often these blastocysts are warmed for re-test after a second biopsy, experiencing ‘double biopsy + double vitrification’. Furthermore, to achieve better workflow, IVF laboratories may choose to routinely vitrify all blastocysts and schedule biopsy at a preferred timing, involving ‘single biopsy + double vitrification’. However, in the current literature, there is a lack of systematic evaluation of both arrangements regarding their potential clinical risks in reference to the most common ‘single biopsy + single vitrification’ approach. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis were performed, with the protocol registered in PROSPERO (CRD42023469143). A search in PUBMED, EMBASE, and the Cochrane Library for relevant studies was carried out on 30 August 2023, using the keywords ‘biopsy’ and ‘vitrification’ and associated variations respectively. Only studies involving frozen transfers of PGT-A tested euploid blastocysts were included, with those involving PGT-M or PGT-SR excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS Study groups included blastocysts having undergone ‘double biopsy + double vitrification’ or ‘single biopsy + double vitrification’, with a ‘single biopsy + single vitrification’ group used as control. The primary outcome was clinical pregnancy, while secondary outcomes included live birth/ongoing pregnancy, miscarriage, and post-warming survival rates. Random effects meta-analysis was performed with risk ratios (RR) and 95% CIs were used to present outcome comparisons. MAIN RESULTS AND THE ROLE OF CHANCE A total of 607 records were identified through the initial search and nine studies (six full articles and three abstracts) were eventually included. Compared to ‘single biopsy + single vitrification’, ‘double biopsy + double vitrification’ was associated with reduced clinical pregnancy rates (six studies, n = 18 754; RR = 0.80, 95% CI = 0.71–0.89; I2 = 0%) and live birth/ongoing pregnancy rates (seven studies, n = 20 964; RR = 0.72, 95% CI = 0.63–0.82; I2 = 0%). However, no significant changes were seen in miscarriage rates (seven studies, n = 22 332; RR = 1.40, 95% CI = 0.92–2.11; I2 = 53%) and post-warming survival rates (three studies, n = 13 562; RR = 1.00, 95% CI = 0.99–1.01; I2 = 0%) following ‘double biopsy + double vitrification’. Furthermore, ‘single biopsy + double vitrification’ was also linked with decrea
{"title":"Impacts of double biopsy and double vitrification on the clinical outcomes following euploid blastocyst transfer: a systematic review and meta-analysis","authors":"Kate Bickendorf, Fang Qi, Kelli Peirce, Rui Wang, Jay Natalwala, Vincent Chapple, Yanhe Liu","doi":"10.1093/humrep/deae235","DOIUrl":"https://doi.org/10.1093/humrep/deae235","url":null,"abstract":"STUDY QUESTION Compared to the ‘single biopsy + single vitrification’ approach, do ‘double biopsy + double vitrification’ or ‘single biopsy + double vitrification’ arrangements compromise subsequent clinical outcomes following euploidy blastocyst transfer? SUMMARY ANSWER Both ‘double biopsy + double vitrification’ and ‘single biopsy + double vitrification’ led to reduced live birth/ongoing pregnancy rates and clinical pregnancy rates. WHAT IS KNOWN ALREADY? It is not uncommon to receive inconclusive results following blastocyst biopsy and preimplantation genetic testing for aneuploidy (PGT-A). Often these blastocysts are warmed for re-test after a second biopsy, experiencing ‘double biopsy + double vitrification’. Furthermore, to achieve better workflow, IVF laboratories may choose to routinely vitrify all blastocysts and schedule biopsy at a preferred timing, involving ‘single biopsy + double vitrification’. However, in the current literature, there is a lack of systematic evaluation of both arrangements regarding their potential clinical risks in reference to the most common ‘single biopsy + single vitrification’ approach. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis were performed, with the protocol registered in PROSPERO (CRD42023469143). A search in PUBMED, EMBASE, and the Cochrane Library for relevant studies was carried out on 30 August 2023, using the keywords ‘biopsy’ and ‘vitrification’ and associated variations respectively. Only studies involving frozen transfers of PGT-A tested euploid blastocysts were included, with those involving PGT-M or PGT-SR excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS Study groups included blastocysts having undergone ‘double biopsy + double vitrification’ or ‘single biopsy + double vitrification’, with a ‘single biopsy + single vitrification’ group used as control. The primary outcome was clinical pregnancy, while secondary outcomes included live birth/ongoing pregnancy, miscarriage, and post-warming survival rates. Random effects meta-analysis was performed with risk ratios (RR) and 95% CIs were used to present outcome comparisons. MAIN RESULTS AND THE ROLE OF CHANCE A total of 607 records were identified through the initial search and nine studies (six full articles and three abstracts) were eventually included. Compared to ‘single biopsy + single vitrification’, ‘double biopsy + double vitrification’ was associated with reduced clinical pregnancy rates (six studies, n = 18 754; RR = 0.80, 95% CI = 0.71–0.89; I2 = 0%) and live birth/ongoing pregnancy rates (seven studies, n = 20 964; RR = 0.72, 95% CI = 0.63–0.82; I2 = 0%). However, no significant changes were seen in miscarriage rates (seven studies, n = 22 332; RR = 1.40, 95% CI = 0.92–2.11; I2 = 53%) and post-warming survival rates (three studies, n = 13 562; RR = 1.00, 95% CI = 0.99–1.01; I2 = 0%) following ‘double biopsy + double vitrification’. Furthermore, ‘single biopsy + double vitrification’ was also linked with decrea","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385650","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}
Simona Bisogno, Joanna Depciuch, Hafsa Gulzar, Maria Florencia Heber, Michał Kobiałka, Łukasz Gąsior, Adrianna Bereta, Anna Pieczara, Kinga Fic, Richard Musson, Gabriel Garcia Gamero, Maria Pardo Martinez, Alba Fornés Pérez, Martina Tatíčková, Zuzana Holubcova, Małgorzata Barańska, Grażyna Ewa Ptak
<p><strong>Study question: </strong>Can oocyte functionality be assessed by observing changes in their intracytoplasmic lipid droplets (LDs) profiles?</p><p><strong>Summary answer: </strong>Lipid profile changes can reliably be detected in human oocytes; lipid changes are linked with maternal age and impaired developmental competence in a mouse model.</p><p><strong>What is known already: </strong>In all cellular components, lipid damage is the earliest manifestation of oxidative stress (OS), which leads to a cascade of negative consequences for organelles and DNA. Lipid damage is marked by the accumulation of LDs. We hypothesized that impaired oocyte functionality resulting from aging and associated OS could be assessed by changes in LDs profile, hereafter called lipid fingerprint (LF).</p><p><strong>Study design, size, duration: </strong>To investigate if it is possible to detect differences in oocyte LF, we subjected human GV-stage oocytes to spectroscopic examinations. For this, a total of 48 oocytes derived from 26 young healthy women (under 33 years of age) with no history of infertility, enrolled in an oocyte donation program, were analyzed. Furthermore, 30 GV human oocytes from 12 women were analyzed by transmission electron microscopy (TEM). To evaluate the effect of oocytes' lipid profile changes on embryo development, a total of 52 C57BL/6 wild-type mice and 125 Gnpat+/- mice were also used.</p><p><strong>Participants/materials, setting, methods: </strong>Human oocytes were assessed by label-free cell imaging via coherent anti-Stokes Raman spectroscopy (CARS). Further confirmation of LF changes was conducted using spontaneous Raman followed by Fourier transform infrared (FTIR) spectroscopies and TEM. Additionally, to evaluate whether LF changes are associated with developmental competence, mouse oocytes and blastocysts were evaluated using TEM and the lipid dyes BODIPY and Nile Red. Mouse embryonic exosomes were evaluated using flow cytometry, FTIR and FT-Raman spectroscopies.</p><p><strong>Main results and the role of chance: </strong>Here we demonstrated progressive changes in the LF of oocytes associated with the woman's age consisting of increased LDs size, area, and number. LF variations in oocytes were detectable also within individual donors. This finding makes LF assessment a promising tool to grade oocytes of the same patient, based on their quality. We next demonstrated age-associated changes in oocytes reflected by lipid peroxidation and composition changes; the accumulation of carotenoids; and alterations of structural properties of lipid bilayers. Finally, using a mouse model, we showed that LF changes in oocytes are negatively associated with the secretion of embryonic exosomes prior to implantation. Deficient exosome secretion disrupts communication between the embryo and the uterus and thus may explain recurrent implantation failures in advanced-age patients.</p><p><strong>Limitations, reasons for caution: </strong>Due t
{"title":"Female-age-dependent changes in the lipid fingerprint of the mammalian oocytes.","authors":"Simona Bisogno, Joanna Depciuch, Hafsa Gulzar, Maria Florencia Heber, Michał Kobiałka, Łukasz Gąsior, Adrianna Bereta, Anna Pieczara, Kinga Fic, Richard Musson, Gabriel Garcia Gamero, Maria Pardo Martinez, Alba Fornés Pérez, Martina Tatíčková, Zuzana Holubcova, Małgorzata Barańska, Grażyna Ewa Ptak","doi":"10.1093/humrep/deae225","DOIUrl":"10.1093/humrep/deae225","url":null,"abstract":"<p><strong>Study question: </strong>Can oocyte functionality be assessed by observing changes in their intracytoplasmic lipid droplets (LDs) profiles?</p><p><strong>Summary answer: </strong>Lipid profile changes can reliably be detected in human oocytes; lipid changes are linked with maternal age and impaired developmental competence in a mouse model.</p><p><strong>What is known already: </strong>In all cellular components, lipid damage is the earliest manifestation of oxidative stress (OS), which leads to a cascade of negative consequences for organelles and DNA. Lipid damage is marked by the accumulation of LDs. We hypothesized that impaired oocyte functionality resulting from aging and associated OS could be assessed by changes in LDs profile, hereafter called lipid fingerprint (LF).</p><p><strong>Study design, size, duration: </strong>To investigate if it is possible to detect differences in oocyte LF, we subjected human GV-stage oocytes to spectroscopic examinations. For this, a total of 48 oocytes derived from 26 young healthy women (under 33 years of age) with no history of infertility, enrolled in an oocyte donation program, were analyzed. Furthermore, 30 GV human oocytes from 12 women were analyzed by transmission electron microscopy (TEM). To evaluate the effect of oocytes' lipid profile changes on embryo development, a total of 52 C57BL/6 wild-type mice and 125 Gnpat+/- mice were also used.</p><p><strong>Participants/materials, setting, methods: </strong>Human oocytes were assessed by label-free cell imaging via coherent anti-Stokes Raman spectroscopy (CARS). Further confirmation of LF changes was conducted using spontaneous Raman followed by Fourier transform infrared (FTIR) spectroscopies and TEM. Additionally, to evaluate whether LF changes are associated with developmental competence, mouse oocytes and blastocysts were evaluated using TEM and the lipid dyes BODIPY and Nile Red. Mouse embryonic exosomes were evaluated using flow cytometry, FTIR and FT-Raman spectroscopies.</p><p><strong>Main results and the role of chance: </strong>Here we demonstrated progressive changes in the LF of oocytes associated with the woman's age consisting of increased LDs size, area, and number. LF variations in oocytes were detectable also within individual donors. This finding makes LF assessment a promising tool to grade oocytes of the same patient, based on their quality. We next demonstrated age-associated changes in oocytes reflected by lipid peroxidation and composition changes; the accumulation of carotenoids; and alterations of structural properties of lipid bilayers. Finally, using a mouse model, we showed that LF changes in oocytes are negatively associated with the secretion of embryonic exosomes prior to implantation. Deficient exosome secretion disrupts communication between the embryo and the uterus and thus may explain recurrent implantation failures in advanced-age patients.</p><p><strong>Limitations, reasons for caution: </strong>Due t","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E Pesonen, V Farrahi, C J Brakenridge, M M Ollila, L C Morin-Papunen, M Nurkkala, T Jämsä, R Korpelainen, L J Moran, T T Piltonen, M Niemelä
<p><strong>Study question: </strong>Are 24-h movement composition and time reallocations between the movement behaviours (moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behaviour (SB), and sleep) differentially associated with cardiometabolic markers in women with polycystic ovary syndrome (PCOS) relative to women without PCOS?</p><p><strong>Summary answer: </strong>There was no difference in 24-h movement composition between the groups, although among women without PCOS, reducing SB time while increasing either MVPA or LPA time was associated with beneficial differences in cardiometabolic markers, whereas in women with PCOS beneficial differences were observed only when SB time was replaced with MVPA.</p><p><strong>What is known already: </strong>Women with PCOS display lower levels of physical activity, higher sedentary time, and less total sleep than women without the syndrome. Exercise interventions among women with PCOS have shown improvements in body composition and insulin sensitivity, while the findings regarding blood pressure, insulin resistance, and lipid profiles are contradictory.</p><p><strong>Study design, size, duration: </strong>This study was part of a prospective, general population-based Northern Finland Birth Cohort 1966 (NFBC1966) (n = 5889 women). At the 31-year and 46-year follow-up, data collection was performed through postal and clinical examinations, including fasting blood samples and anthropometric measurements. Accelerometer data collection of 14 days (n = 2602 women) and a 2-h oral glucose tolerance test (n = 2780 women) were performed at the 46-year follow-up. Participants were identified as women with or without PCOS at age 31 (n = 1883), and the final study population included those who provided valid accelerometer data at age 46 (n = 857).</p><p><strong>Participants/materials, setting, methods: </strong>Women with PCOS (n = 192) were identified based on the 2023 International Evidence-based Guideline, while those who exhibited no PCOS features were considered women without PCOS (controls; n = 665). Accelerometer-measured MVPA, LPA, and SB were combined with self-reported sleep to obtain 24-h compositions. Multivariable regression analysis based on compositional data analysis and isotemporal reallocations were performed to investigate the associations between 24-h movement composition and cardiometabolic markers. Isotemporal reallocations were expressed as differences (%Δ) from the sample's mean.</p><p><strong>Main results and the role of chance: </strong>There was no difference in overall 24-h movement composition between women with PCOS and controls in midlife. The 24-h movement composition was associated with waist circumference, triglycerides, fasting serum insulin, and Homeostatic Model Assessment-insulin resistance (HOMA-IR) in both controls and women with PCOS. Reallocating 15 min from SB to MVPA was associated with favourable differences in cardiometabolic markers
{"title":"24-hour movement behaviours and cardiometabolic markers in women with polycystic ovary syndrome (PCOS): a compositional data analysis.","authors":"E Pesonen, V Farrahi, C J Brakenridge, M M Ollila, L C Morin-Papunen, M Nurkkala, T Jämsä, R Korpelainen, L J Moran, T T Piltonen, M Niemelä","doi":"10.1093/humrep/deae232","DOIUrl":"10.1093/humrep/deae232","url":null,"abstract":"<p><strong>Study question: </strong>Are 24-h movement composition and time reallocations between the movement behaviours (moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behaviour (SB), and sleep) differentially associated with cardiometabolic markers in women with polycystic ovary syndrome (PCOS) relative to women without PCOS?</p><p><strong>Summary answer: </strong>There was no difference in 24-h movement composition between the groups, although among women without PCOS, reducing SB time while increasing either MVPA or LPA time was associated with beneficial differences in cardiometabolic markers, whereas in women with PCOS beneficial differences were observed only when SB time was replaced with MVPA.</p><p><strong>What is known already: </strong>Women with PCOS display lower levels of physical activity, higher sedentary time, and less total sleep than women without the syndrome. Exercise interventions among women with PCOS have shown improvements in body composition and insulin sensitivity, while the findings regarding blood pressure, insulin resistance, and lipid profiles are contradictory.</p><p><strong>Study design, size, duration: </strong>This study was part of a prospective, general population-based Northern Finland Birth Cohort 1966 (NFBC1966) (n = 5889 women). At the 31-year and 46-year follow-up, data collection was performed through postal and clinical examinations, including fasting blood samples and anthropometric measurements. Accelerometer data collection of 14 days (n = 2602 women) and a 2-h oral glucose tolerance test (n = 2780 women) were performed at the 46-year follow-up. Participants were identified as women with or without PCOS at age 31 (n = 1883), and the final study population included those who provided valid accelerometer data at age 46 (n = 857).</p><p><strong>Participants/materials, setting, methods: </strong>Women with PCOS (n = 192) were identified based on the 2023 International Evidence-based Guideline, while those who exhibited no PCOS features were considered women without PCOS (controls; n = 665). Accelerometer-measured MVPA, LPA, and SB were combined with self-reported sleep to obtain 24-h compositions. Multivariable regression analysis based on compositional data analysis and isotemporal reallocations were performed to investigate the associations between 24-h movement composition and cardiometabolic markers. Isotemporal reallocations were expressed as differences (%Δ) from the sample's mean.</p><p><strong>Main results and the role of chance: </strong>There was no difference in overall 24-h movement composition between women with PCOS and controls in midlife. The 24-h movement composition was associated with waist circumference, triglycerides, fasting serum insulin, and Homeostatic Model Assessment-insulin resistance (HOMA-IR) in both controls and women with PCOS. Reallocating 15 min from SB to MVPA was associated with favourable differences in cardiometabolic markers","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375324","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}
René Ecochard, Thomas Bouchard, Rene Leiva, Saman H Abdullah, Hans Boehringer
<p><strong>Study question: </strong>What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window?</p><p><strong>Summary answer: </strong>Both oestrogen and progesterone contribute to a delay in the onset of the fertile window.</p><p><strong>What is known already: </strong>Oestrogen enhances cervical mucus secretion while progesterone inhibits it.</p><p><strong>Study design, size, duration: </strong>Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder.</p><p><strong>Participants/materials, setting, methods: </strong>Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva.</p><p><strong>Main results and the role of chance: </strong>Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4 µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle.</p><p><strong>Limitations, reasons for caution: </strong>This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings.</p><p><strong>Wider implications of the findings: </strong>This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction.</p><p><strong>Study funding/competing interest(s): </strong>The authors declare no conflicts of interest. No funding was provided for this secondary data analysis.<
{"title":"Early menstrual cycle impacts of oestrogen and progesterone on the timing of the fertile window.","authors":"René Ecochard, Thomas Bouchard, Rene Leiva, Saman H Abdullah, Hans Boehringer","doi":"10.1093/humrep/deae236","DOIUrl":"10.1093/humrep/deae236","url":null,"abstract":"<p><strong>Study question: </strong>What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window?</p><p><strong>Summary answer: </strong>Both oestrogen and progesterone contribute to a delay in the onset of the fertile window.</p><p><strong>What is known already: </strong>Oestrogen enhances cervical mucus secretion while progesterone inhibits it.</p><p><strong>Study design, size, duration: </strong>Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder.</p><p><strong>Participants/materials, setting, methods: </strong>Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva.</p><p><strong>Main results and the role of chance: </strong>Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4 µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle.</p><p><strong>Limitations, reasons for caution: </strong>This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings.</p><p><strong>Wider implications of the findings: </strong>This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction.</p><p><strong>Study funding/competing interest(s): </strong>The authors declare no conflicts of interest. No funding was provided for this secondary data analysis.<","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375325","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}
This Directions article examines the mechanisms by which a father's age impacts the health and wellbeing of his children. Such impacts are significant and include adverse birth outcomes, dominant genetic conditions, neuropsychiatric disorders, and a variety of congenital developmental defects. As well as age, a wide variety of environmental and lifestyle factors are also known to impact offspring health via changes mediated by the male germ line. This picture of a dynamic germ line responsive to a wide range of intrinsic and extrinsic factors contrasts with the results of trio studies indicating that the incidence of mutations in the male germ line is low and exhibits a linear, monotonic increase with paternal age (∼two new mutations per year). While the traditional explanation for this pattern of mutation has been the metronomic plod of replication errors, an alternative model pivots around the 'faulty male' hypothesis. According to this concept, the genetic integrity of the male germ line can be dynamically impacted by age and a variety of other factors, and it is the aberrant repair of such damage that drives mutagenesis. Fortunately, DNA proofreading during spermatogenesis is extremely effective and these mutant cells are either repaired or deleted by apoptosis/ferroptosis. There appear to be only two mechanisms by which mutant germ cells can escape this apoptotic fate: (i) if the germ cells acquire a mutation that by enhancing proliferation or suppressing apoptosis, permits their clonal expansion (selfish selection hypothesis) or (ii) if a genetically damaged spermatozoon manages to fertilize an oocyte, which then fixes the damage as a mutation (or epimutation) as a result of defective DNA repair (oocyte collusion hypothesis). Exploration of these proposed mechanisms should not only help us better understand the aetiology of paternal age effects but also inform potential avenues of remediation.
{"title":"Paternal age, de novo mutations, and offspring health? New directions for an ageing problem.","authors":"Robert John Aitken","doi":"10.1093/humrep/deae230","DOIUrl":"https://doi.org/10.1093/humrep/deae230","url":null,"abstract":"<p><p>This Directions article examines the mechanisms by which a father's age impacts the health and wellbeing of his children. Such impacts are significant and include adverse birth outcomes, dominant genetic conditions, neuropsychiatric disorders, and a variety of congenital developmental defects. As well as age, a wide variety of environmental and lifestyle factors are also known to impact offspring health via changes mediated by the male germ line. This picture of a dynamic germ line responsive to a wide range of intrinsic and extrinsic factors contrasts with the results of trio studies indicating that the incidence of mutations in the male germ line is low and exhibits a linear, monotonic increase with paternal age (∼two new mutations per year). While the traditional explanation for this pattern of mutation has been the metronomic plod of replication errors, an alternative model pivots around the 'faulty male' hypothesis. According to this concept, the genetic integrity of the male germ line can be dynamically impacted by age and a variety of other factors, and it is the aberrant repair of such damage that drives mutagenesis. Fortunately, DNA proofreading during spermatogenesis is extremely effective and these mutant cells are either repaired or deleted by apoptosis/ferroptosis. There appear to be only two mechanisms by which mutant germ cells can escape this apoptotic fate: (i) if the germ cells acquire a mutation that by enhancing proliferation or suppressing apoptosis, permits their clonal expansion (selfish selection hypothesis) or (ii) if a genetically damaged spermatozoon manages to fertilize an oocyte, which then fixes the damage as a mutation (or epimutation) as a result of defective DNA repair (oocyte collusion hypothesis). Exploration of these proposed mechanisms should not only help us better understand the aetiology of paternal age effects but also inform potential avenues of remediation.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371735","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}
Zoya Enakshi Ali, Claudia Massarotti, George Liperis, Mina Mincheva, Omar F Ammar, Julia Uraji, Antonio La Marca, Raj Mathur, Helen C O'Neill, Mariana Moura-Ramos, Juan J Fraire-Zamora
{"title":"Role, benefits, and risks of AMH testing for non-ART related indications.","authors":"Zoya Enakshi Ali, Claudia Massarotti, George Liperis, Mina Mincheva, Omar F Ammar, Julia Uraji, Antonio La Marca, Raj Mathur, Helen C O'Neill, Mariana Moura-Ramos, Juan J Fraire-Zamora","doi":"10.1093/humrep/deae234","DOIUrl":"https://doi.org/10.1093/humrep/deae234","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371736","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}
Shuang Liu, Yingnan Zhang, Xin Ma, Chenglin Zhan, Ning Ding, Mai Shi, Wei Zhang, Shubao Yang
<p><strong>Study question: </strong>Does recombinant Lactobacillus expressing granulocyte colony-stimulating factor (G-CSF) have a better protective effect than the current treatment of thin endometrium (TE)?</p><p><strong>Summary answer: </strong>This study suggested that the intrauterine injection of Lactobacillus crispastus (L. crispastus)-pPG612-G-CSF has a positive effect on preventing TE induced by 95% alcohol in mice.</p><p><strong>What is known already: </strong>TE has a negative impact on the success rate of ART in patients, and is usually caused by intrauterine surgery, endometrial infection, or hormone drugs. Exogenous G-CSF can promote endometrial vascular remodelling and increase endometrial receptivity and the embryo implantation rate. Moreover, Lactobacillus plays a crucial role in maintaining and regulating the local microecological balance of the reproductive tract, and it could be a delivery carrier of the endometrial repair drug G-CSF.</p><p><strong>Study design, size, duration: </strong>We constructed engineered L. crispastus strains expressing G-CSF. The mice were divided into five groups: (i) Control group (C, n = 28), uteri were treated with preheated saline solution via intrauterine injection on the third and sixth day of oestrus; (ii) Model group (M, n = 35), where uteri were treated with 95% alcohol on the third day of oestrus and preheated saline solution on the sixth day of oestrus via intrauterine injection; (iii) L. crispatus-pPG612-treatment group (L, n = 45), where uteri were treated with 95% alcohol on the third day of oestrus and 0.1 ml × 108 CFU/ml L. crispatus-pPG612 on the sixth day of oestrus via intrauterine injection; (iv) L. crispatus-pPG612-treatment group (LG, n = 45), where uteri were treated with 95% alcohol on the third day of oestrus and 0.1 ml × 108 CFU/ml L. crispatus-pPG612-G-CSF on the sixth day of oestrus via intrauterine injection; (v) G-CSF-treatment group (G, n = 52), where uteri were treated with 95% alcohol on the third day of oestrus and 30 µg/kg G-CSF on the sixth day of oestrus via intrauterine injection. Then, we compared the effects of L. crispastus, L. crispatus-pPG612-G-CSF and G-CSF on endometrial thickness, angiogenesis, fibrosis, and inflammation in the TE mouse.</p><p><strong>Participants/materials, setting, methods: </strong>We collected uterine tissues for haematoxylin-eosin staining, immunohistochemical staining, Western blot and RT-PCR, as well as serum for ELISA and uterine flushing solution for high-throughput sequencing.</p><p><strong>Main results and the role of chance: </strong>Compared with those in the M group (the mice of the group were intrauterine injected 95% alcohol and treated with saline solution), the L. crispatus-pPG612-G-CSF strain increased the thickness of the endometrium (P < 0.001) and the number of blood vessels and glands (both P < 0.001), enhanced the expression of cytokeratin 19 (CK19) (P < 0.001), vimentin (Vim) (P < 0.001), vascular endothelial grow
研究问题:表达粒细胞集落刺激因子(G-CSF)的重组乳杆菌是否比目前治疗子宫内膜薄(TE)的方法具有更好的保护作用?本研究表明,宫腔内注射脆化乳杆菌(L. crispastus)-pPG612-G-CSF对预防95%酒精诱导的小鼠TE有积极作用:TE对患者抗逆转录病毒疗法的成功率有负面影响,通常由宫腔内手术、子宫内膜感染或激素药物引起。外源性 G-CSF 可促进子宫内膜血管重塑,提高子宫内膜接受性和胚胎着床率。此外,乳酸杆菌在维持和调节生殖道局部微生态平衡方面发挥着重要作用,可作为子宫内膜修复药物 G-CSF 的输送载体:研究设计、规模、持续时间:我们构建了表达G-CSF的L. crispastus工程菌株。小鼠分为五组:(i) 对照组(C,n = 28),在发情第三天和第六天通过宫腔注射预热生理盐水处理子宫;(ii) 模型组(M,n = 35),在发情第三天用 95% 酒精处理子宫,在发情第六天通过宫腔注射预热生理盐水处理子宫;(iii) L. crispatus-pPG612-t 组,在发情第三天用 95% 酒精处理子宫,在发情第六天通过宫腔注射预热生理盐水处理子宫。pPG612处理组(L,n = 45),发情第三天用95%酒精处理子宫,发情第六天宫内注射0.1 ml × 108 CFU/ml L. crispatus-pPG612 通过宫内注射;(iv) L. crispatus-pPG612 处理组(LG,n = 45),发情第三天用 95% 的酒精处理子宫,发情第六天用 0.1 ml × 108 CFU/ml L. crispatus-pPG612-G 处理子宫。(v) G-CSF 处理组(G,n = 52),发情第三天用 95% 酒精处理子宫,发情第六天宫内注射 30 µg/kg G-CSF。然后,我们比较了L. crispastus、L. crispatus-pPG612-G-CSF和G-CSF对TE小鼠子宫内膜厚度、血管生成、纤维化和炎症的影响:我们采集了子宫组织进行血栓素-伊红染色、免疫组化染色、Western blot和RT-PCR,还采集了血清进行ELISA和子宫冲洗液进行高通量测序:与 M 组(该组小鼠宫内注射 95% 酒精并用生理盐水处理)相比,L. crispatus-pPG612-G-CSF 菌株增加了子宫内膜厚度(P 大比例尺数据):不适用:L.crispatus-pPG612-G-CSF菌株疗法在加速TE的修复过程方面具有巨大潜力。然而,我们仅报告了与PI3K/AKT通路相关的基因和蛋白的表达,L. crispatus-pPG612-G-CSF对子宫内膜的修复可能还涉及许多其他机制:该研究结果为 TE 的治疗提供了新思路和新方法:本研究得到了吉林省科技发展计划项目(批准号:20210101232JC)、吉林省教育厅科技计划项目(批准号:JT53101022010)和吉林医科大学博士科研启动基金(批准号:JYBS2021014LK和2022JYBS006KJ)的资助。作者声明,研究过程中不存在任何可能被视为潜在利益冲突的商业或经济关系。
{"title":"Protective effects of engineered Lactobacillus crispatus strains expressing G-CSF on thin endometrium of mice.","authors":"Shuang Liu, Yingnan Zhang, Xin Ma, Chenglin Zhan, Ning Ding, Mai Shi, Wei Zhang, Shubao Yang","doi":"10.1093/humrep/deae190","DOIUrl":"10.1093/humrep/deae190","url":null,"abstract":"<p><strong>Study question: </strong>Does recombinant Lactobacillus expressing granulocyte colony-stimulating factor (G-CSF) have a better protective effect than the current treatment of thin endometrium (TE)?</p><p><strong>Summary answer: </strong>This study suggested that the intrauterine injection of Lactobacillus crispastus (L. crispastus)-pPG612-G-CSF has a positive effect on preventing TE induced by 95% alcohol in mice.</p><p><strong>What is known already: </strong>TE has a negative impact on the success rate of ART in patients, and is usually caused by intrauterine surgery, endometrial infection, or hormone drugs. Exogenous G-CSF can promote endometrial vascular remodelling and increase endometrial receptivity and the embryo implantation rate. Moreover, Lactobacillus plays a crucial role in maintaining and regulating the local microecological balance of the reproductive tract, and it could be a delivery carrier of the endometrial repair drug G-CSF.</p><p><strong>Study design, size, duration: </strong>We constructed engineered L. crispastus strains expressing G-CSF. The mice were divided into five groups: (i) Control group (C, n = 28), uteri were treated with preheated saline solution via intrauterine injection on the third and sixth day of oestrus; (ii) Model group (M, n = 35), where uteri were treated with 95% alcohol on the third day of oestrus and preheated saline solution on the sixth day of oestrus via intrauterine injection; (iii) L. crispatus-pPG612-treatment group (L, n = 45), where uteri were treated with 95% alcohol on the third day of oestrus and 0.1 ml × 108 CFU/ml L. crispatus-pPG612 on the sixth day of oestrus via intrauterine injection; (iv) L. crispatus-pPG612-treatment group (LG, n = 45), where uteri were treated with 95% alcohol on the third day of oestrus and 0.1 ml × 108 CFU/ml L. crispatus-pPG612-G-CSF on the sixth day of oestrus via intrauterine injection; (v) G-CSF-treatment group (G, n = 52), where uteri were treated with 95% alcohol on the third day of oestrus and 30 µg/kg G-CSF on the sixth day of oestrus via intrauterine injection. Then, we compared the effects of L. crispastus, L. crispatus-pPG612-G-CSF and G-CSF on endometrial thickness, angiogenesis, fibrosis, and inflammation in the TE mouse.</p><p><strong>Participants/materials, setting, methods: </strong>We collected uterine tissues for haematoxylin-eosin staining, immunohistochemical staining, Western blot and RT-PCR, as well as serum for ELISA and uterine flushing solution for high-throughput sequencing.</p><p><strong>Main results and the role of chance: </strong>Compared with those in the M group (the mice of the group were intrauterine injected 95% alcohol and treated with saline solution), the L. crispatus-pPG612-G-CSF strain increased the thickness of the endometrium (P < 0.001) and the number of blood vessels and glands (both P < 0.001), enhanced the expression of cytokeratin 19 (CK19) (P < 0.001), vimentin (Vim) (P < 0.001), vascular endothelial grow","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043926","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}
Anar Murphy, Mark S Lapczynski, Glenn Proctor, Timothy R Glynn, Alice D Domar, Sofia Gameiro, Giles A Palmer, Michael G Collins
<p><strong>Study question: </strong>What is the prevalence of occupational stress, somatization, and burnout reported by UK and US, embryologists and the impact of work conditions on these well-being outcomes?</p><p><strong>Summary answer: </strong>Surveyed UK and US embryologists reported moderate perceived stress, low somatic symptom severity, high levels of burnout, and overall stressful work conditions, but with differences that could be due to country-specific occupational and employment characteristics.</p><p><strong>What is known already?: </strong>Spanish, UK, US, and international surveys have identified high levels of occupational stress, somatization, burnout, and occupational health issues among embryologists. These issues have been attributed to embryologists' occupational challenges and work conditions.</p><p><strong>Study design, size, duration: </strong>A cross-sectional web-based survey was sent to 253 embryologists working in UK ART/IVF clinics and 487 embryologists working in US ART/IVF clinics.</p><p><strong>Participants/materials, setting, methods: </strong>Participants self-reported their stress levels, somatization, burnout, and work conditions. Proportions across the Perceived Stress Scale (PSS), Patient Health Questionnaire (PHQ-15), Maslach Burnout Inventory-General Survey (MBI-GS), a single-item work unit grade (A-F), and customized occupational and sociodemographic questionnaires were calculated using descriptive statistics. Welch's t-test was utilized to compare PSS and PHQ-15 scores between groups. Risk ratios were calculated using log-binomial regression for all models except for levels of anxiety related to performing cryostorage tasks, for which Poisson models were used.</p><p><strong>Main results and the role of chance: </strong>In total, 50.6% (128) of the embryologists in the UK and 50.1% (244) in the US completed the survey. Both groups self-reported moderate PSS and low PHQ-15 scores, although fewer UK embryologists scored high on the MBI cynicism dimension than their US colleagues (43% UK vs 60% US embryologists, P < 0.05). The UK and US embryologists did not differ on the MBI exhaustion dimension with both scoring high for exhaustion (59% UK vs 62% US). Although 81% and 80% of UK and US embryologists, respectively, reported working overtime, more embryologists in the UK reported being adequately compensated. Increasing levels of anxiety-related to cryostorage showed a dose-dependent increased risk of burnout on at least two MBI-GS dimensions only in the UK group, and, a dose-dependent likelihood of higher PSS and PHQ-15 scores in both groups.</p><p><strong>Limitations, reasons for caution: </strong>Since the two groups were surveyed 9 months apart and were self-reporting, the study is limited by the differences in responsibilities, scheduling, and workload specific to the time of year.</p><p><strong>Wider implications of the findings: </strong>Work-related health issues and occupational challenges shared by
{"title":"Comparison of embryologist stress, somatization, and burnout reported by embryologists working in UK HFEA-licensed ART/IVF clinics and USA ART/IVF clinics.","authors":"Anar Murphy, Mark S Lapczynski, Glenn Proctor, Timothy R Glynn, Alice D Domar, Sofia Gameiro, Giles A Palmer, Michael G Collins","doi":"10.1093/humrep/deae191","DOIUrl":"10.1093/humrep/deae191","url":null,"abstract":"<p><strong>Study question: </strong>What is the prevalence of occupational stress, somatization, and burnout reported by UK and US, embryologists and the impact of work conditions on these well-being outcomes?</p><p><strong>Summary answer: </strong>Surveyed UK and US embryologists reported moderate perceived stress, low somatic symptom severity, high levels of burnout, and overall stressful work conditions, but with differences that could be due to country-specific occupational and employment characteristics.</p><p><strong>What is known already?: </strong>Spanish, UK, US, and international surveys have identified high levels of occupational stress, somatization, burnout, and occupational health issues among embryologists. These issues have been attributed to embryologists' occupational challenges and work conditions.</p><p><strong>Study design, size, duration: </strong>A cross-sectional web-based survey was sent to 253 embryologists working in UK ART/IVF clinics and 487 embryologists working in US ART/IVF clinics.</p><p><strong>Participants/materials, setting, methods: </strong>Participants self-reported their stress levels, somatization, burnout, and work conditions. Proportions across the Perceived Stress Scale (PSS), Patient Health Questionnaire (PHQ-15), Maslach Burnout Inventory-General Survey (MBI-GS), a single-item work unit grade (A-F), and customized occupational and sociodemographic questionnaires were calculated using descriptive statistics. Welch's t-test was utilized to compare PSS and PHQ-15 scores between groups. Risk ratios were calculated using log-binomial regression for all models except for levels of anxiety related to performing cryostorage tasks, for which Poisson models were used.</p><p><strong>Main results and the role of chance: </strong>In total, 50.6% (128) of the embryologists in the UK and 50.1% (244) in the US completed the survey. Both groups self-reported moderate PSS and low PHQ-15 scores, although fewer UK embryologists scored high on the MBI cynicism dimension than their US colleagues (43% UK vs 60% US embryologists, P < 0.05). The UK and US embryologists did not differ on the MBI exhaustion dimension with both scoring high for exhaustion (59% UK vs 62% US). Although 81% and 80% of UK and US embryologists, respectively, reported working overtime, more embryologists in the UK reported being adequately compensated. Increasing levels of anxiety-related to cryostorage showed a dose-dependent increased risk of burnout on at least two MBI-GS dimensions only in the UK group, and, a dose-dependent likelihood of higher PSS and PHQ-15 scores in both groups.</p><p><strong>Limitations, reasons for caution: </strong>Since the two groups were surveyed 9 months apart and were self-reporting, the study is limited by the differences in responsibilities, scheduling, and workload specific to the time of year.</p><p><strong>Wider implications of the findings: </strong>Work-related health issues and occupational challenges shared by","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092811","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}
E S de Vos, A G M G J Mulders, A H J Koning, S P Willemsen, M Rousian, B B van Rijn, E A P Steegers, R P M Steegers-Theunissen
{"title":"Reply: Doppler ultrasound and first trimester pregnancy: not always a happy marriage.","authors":"E S de Vos, A G M G J Mulders, A H J Koning, S P Willemsen, M Rousian, B B van Rijn, E A P Steegers, R P M Steegers-Theunissen","doi":"10.1093/humrep/deae177","DOIUrl":"10.1093/humrep/deae177","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046617","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}
Mingzhu Cao, Qiwang Lin, Zhi Liu, Yanshan Lin, Qing Huang, Yang Fu, Yang Zhang, Hang Shi, Chongyang Duan, Haiying Liu, Jianqiao Liu
<p><strong>Study question: </strong>Can a simplified ovarian hyperstimulation syndrome (OHSS) risk assessment index be developed and validated with sufficient discrimination of moderate/severe OHSS from those without OHSS?</p><p><strong>Summary answer: </strong>This easy-to-use OHSS risk assessment index shows good discriminative power and high calibration accuracy in internal and external validation cohorts.</p><p><strong>What is known already: </strong>An early alert and risk stratification is critical to prevent the occurrence of OHSS. We have previously developed a multi-stage smartphone app-based prediction model to evaluate the risk of OHSS, but app use might not be so convenient in many primary institutions. A simplified OHSS risk assessment index has been required.</p><p><strong>Study design, size, duration: </strong>This training and internal validation of an OHSS risk assessment index used retrospective cohort data from January 2016 to December 2020. External validation was performed with a prospective cohort database from January 2021 to May 2022. There were 15 066 cycles in the training cohort, 6502 cycles in the internal validation cohort, and 8097 cycles in the external validation cohort.</p><p><strong>Participants/materials, setting, methods: </strong>This study was performed in the reproductive medicine center of a tertiary hospital. Infertile women who underwent ovarian stimulation were included. Data were extracted from the local database with detailed medical records. A multi-stage risk assessment index was constructed at multiple stages. The first stage was before the initiation of ovarian stimulation, the second was before the ovulation trigger, the third was after oocyte retrieval, and the last stage was on the embryo transfer day if fresh embryo transfer was scheduled.</p><p><strong>Main results and the role of chance: </strong>We established a simplified multi-stage risk assessment index for moderate/severe OHSS, the performance of which was further evaluated with discrimination and calibration abilities in training and internal and external validation cohorts. The discrimination abilities of the OHSS risk assessment index were determined with C-statistics. C-statistics in training (Stages 1-4: 0.631, 0.692, 0.751, 0.788, respectively) and internal (Stages 1-4: 0.626, 0.642, 0.755, 0.771, respectively) and external validation (Stages 1-4: 0.668, 0.670, 0.754, 0.773, respectively) cohorts were all increased from Stage 1 to 3 with similar trends, and were comparable between Stages 3 and 4. Calibration plots showed high agreement between observed and predicted cases in all three cohorts. Incidences of OHSS based on diverse risk stratification (negligible risk, low risk, medium risk, and high risk) were 0%, 0.6%, 2.7%, and 8.3% in the training cohort, 0%, 0.6%, 3.3%, and 8.5% in the internal validation cohort, and 0.1%, 1.1%, 4.1%, and 7.2% in the external validation cohort.</p><p><strong>Limitations, reasons for caution: </st
{"title":"Optimized personalized management approach for moderate/severe OHSS: development and prospective validation of an OHSS risk assessment index.","authors":"Mingzhu Cao, Qiwang Lin, Zhi Liu, Yanshan Lin, Qing Huang, Yang Fu, Yang Zhang, Hang Shi, Chongyang Duan, Haiying Liu, Jianqiao Liu","doi":"10.1093/humrep/deae197","DOIUrl":"10.1093/humrep/deae197","url":null,"abstract":"<p><strong>Study question: </strong>Can a simplified ovarian hyperstimulation syndrome (OHSS) risk assessment index be developed and validated with sufficient discrimination of moderate/severe OHSS from those without OHSS?</p><p><strong>Summary answer: </strong>This easy-to-use OHSS risk assessment index shows good discriminative power and high calibration accuracy in internal and external validation cohorts.</p><p><strong>What is known already: </strong>An early alert and risk stratification is critical to prevent the occurrence of OHSS. We have previously developed a multi-stage smartphone app-based prediction model to evaluate the risk of OHSS, but app use might not be so convenient in many primary institutions. A simplified OHSS risk assessment index has been required.</p><p><strong>Study design, size, duration: </strong>This training and internal validation of an OHSS risk assessment index used retrospective cohort data from January 2016 to December 2020. External validation was performed with a prospective cohort database from January 2021 to May 2022. There were 15 066 cycles in the training cohort, 6502 cycles in the internal validation cohort, and 8097 cycles in the external validation cohort.</p><p><strong>Participants/materials, setting, methods: </strong>This study was performed in the reproductive medicine center of a tertiary hospital. Infertile women who underwent ovarian stimulation were included. Data were extracted from the local database with detailed medical records. A multi-stage risk assessment index was constructed at multiple stages. The first stage was before the initiation of ovarian stimulation, the second was before the ovulation trigger, the third was after oocyte retrieval, and the last stage was on the embryo transfer day if fresh embryo transfer was scheduled.</p><p><strong>Main results and the role of chance: </strong>We established a simplified multi-stage risk assessment index for moderate/severe OHSS, the performance of which was further evaluated with discrimination and calibration abilities in training and internal and external validation cohorts. The discrimination abilities of the OHSS risk assessment index were determined with C-statistics. C-statistics in training (Stages 1-4: 0.631, 0.692, 0.751, 0.788, respectively) and internal (Stages 1-4: 0.626, 0.642, 0.755, 0.771, respectively) and external validation (Stages 1-4: 0.668, 0.670, 0.754, 0.773, respectively) cohorts were all increased from Stage 1 to 3 with similar trends, and were comparable between Stages 3 and 4. Calibration plots showed high agreement between observed and predicted cases in all three cohorts. Incidences of OHSS based on diverse risk stratification (negligible risk, low risk, medium risk, and high risk) were 0%, 0.6%, 2.7%, and 8.3% in the training cohort, 0%, 0.6%, 3.3%, and 8.5% in the internal validation cohort, and 0.1%, 1.1%, 4.1%, and 7.2% in the external validation cohort.</p><p><strong>Limitations, reasons for caution: </st","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139891","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}