{"title":"Reply: Inaccurate measures of outcomes in the two-sample Mendelian randomization of vitamin D with miscarriage.","authors":"Feng Zhang, Jingtao Huang, Gangting Zhang, Mengyang Dai, Tailang Yin, Chunyu Huang, Jue Liu, Yan Zhang","doi":"10.1093/hropen/hoae026","DOIUrl":"10.1093/hropen/hoae026","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae026"},"PeriodicalIF":8.3,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-27eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae025
Qian Yang, Yangbo Sun, Deborah A Lawlor
{"title":"Inaccurate measures of outcomes in the two-sample Mendelian randomization of vitamin D with miscarriage.","authors":"Qian Yang, Yangbo Sun, Deborah A Lawlor","doi":"10.1093/hropen/hoae025","DOIUrl":"10.1093/hropen/hoae025","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae025"},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae024
Jian Xu, Di Mao, Chunlin Liu, Ling Sun
<p><strong>Study question: </strong>Is SARS-CoV-2 infection in IVF-conceived early pregnancy associated with a higher risk of miscarriage?</p><p><strong>Summary answer: </strong>Infection with SARS-CoV-2 during early pregnancy in women conceiving by IVF may not be associated with an increased rate of miscarriage.</p><p><strong>What is known already: </strong>In naturally conceived pregnancies, most findings have shown that SARS-CoV-2 infection does not increase the risk of miscarriage, while some studies have shown that SARS-CoV-2 infection is associated with a higher risk of miscarriage.</p><p><strong>Study design size duration: </strong>A matched retrospective cohort study was conducted in a tertiary hospital-based reproductive medicine center. The infection group included women who contracted coronavirus disease 2019 (COVID-19) before 20 weeks gestation from 6 December 2022 to 10 January 2023. Each infected woman was matched with three historical control subjects from 1 January 2018 to 31 May 2022.</p><p><strong>Participants/materials setting methods: </strong>The infection group was matched with historical control subjects based on female age (±1 year), number of gestational sacs, number of previous miscarriages, BMI (±2 kg/cm<sup>2</sup>), main causes of infertility, gestational week, and fresh versus frozen embryo transfer.</p><p><strong>Main results and the role of chance: </strong>A total of 150 pregnant women infected with COVID-19 before 20 weeks of gestation were included in the infection group, which was matched at a 3:1 ratio with 450 historically pregnant controls. There were no significant differences in age, BMI, and endometrial thickness between the two groups. The overall incidence of miscarriage was not significantly different between the infection group and the control group (4.7% versus 5.8%, <i>P</i> = 0.68). When the infection group was stratified into three subgroups based on the gestational age at the onset of infection (0-7 + 6, 8-11 + 6, and 12-19 + 6 weeks), no significant differences were observed in the incidence of miscarriage between the infection group and the matched control group in any of the subgroups (9.8% versus 13.8%, <i>P</i> = 0.60; 5.4% versus 4.5%, <i>P</i> = 1.00; and 1.4% versus 1.9%, <i>P</i> = 1.00, respectively).</p><p><strong>Limitations reasons for caution: </strong>The major limitation of this study is the relatively small sample size; therefore, caution is suggested when drawing any definitive conclusions. Nonetheless, our study is the largest sample study of the influence of COVID-19 infection on the miscarriage rate in early pregnancy after IVF.</p><p><strong>Wider implications of the findings: </strong>Our findings may provide important insights for reproductive physicians and obstetricians during preconception and early pregnancy counseling.</p><p><strong>Study funding/competing interests: </strong>This study was supported by the Natural Science Foundation of Guangdong Province (No. 2023A15
{"title":"SARS-CoV-2 infection in IVF-conceived early pregnancy and the risk of miscarriage: a matched retrospective cohort study.","authors":"Jian Xu, Di Mao, Chunlin Liu, Ling Sun","doi":"10.1093/hropen/hoae024","DOIUrl":"10.1093/hropen/hoae024","url":null,"abstract":"<p><strong>Study question: </strong>Is SARS-CoV-2 infection in IVF-conceived early pregnancy associated with a higher risk of miscarriage?</p><p><strong>Summary answer: </strong>Infection with SARS-CoV-2 during early pregnancy in women conceiving by IVF may not be associated with an increased rate of miscarriage.</p><p><strong>What is known already: </strong>In naturally conceived pregnancies, most findings have shown that SARS-CoV-2 infection does not increase the risk of miscarriage, while some studies have shown that SARS-CoV-2 infection is associated with a higher risk of miscarriage.</p><p><strong>Study design size duration: </strong>A matched retrospective cohort study was conducted in a tertiary hospital-based reproductive medicine center. The infection group included women who contracted coronavirus disease 2019 (COVID-19) before 20 weeks gestation from 6 December 2022 to 10 January 2023. Each infected woman was matched with three historical control subjects from 1 January 2018 to 31 May 2022.</p><p><strong>Participants/materials setting methods: </strong>The infection group was matched with historical control subjects based on female age (±1 year), number of gestational sacs, number of previous miscarriages, BMI (±2 kg/cm<sup>2</sup>), main causes of infertility, gestational week, and fresh versus frozen embryo transfer.</p><p><strong>Main results and the role of chance: </strong>A total of 150 pregnant women infected with COVID-19 before 20 weeks of gestation were included in the infection group, which was matched at a 3:1 ratio with 450 historically pregnant controls. There were no significant differences in age, BMI, and endometrial thickness between the two groups. The overall incidence of miscarriage was not significantly different between the infection group and the control group (4.7% versus 5.8%, <i>P</i> = 0.68). When the infection group was stratified into three subgroups based on the gestational age at the onset of infection (0-7 + 6, 8-11 + 6, and 12-19 + 6 weeks), no significant differences were observed in the incidence of miscarriage between the infection group and the matched control group in any of the subgroups (9.8% versus 13.8%, <i>P</i> = 0.60; 5.4% versus 4.5%, <i>P</i> = 1.00; and 1.4% versus 1.9%, <i>P</i> = 1.00, respectively).</p><p><strong>Limitations reasons for caution: </strong>The major limitation of this study is the relatively small sample size; therefore, caution is suggested when drawing any definitive conclusions. Nonetheless, our study is the largest sample study of the influence of COVID-19 infection on the miscarriage rate in early pregnancy after IVF.</p><p><strong>Wider implications of the findings: </strong>Our findings may provide important insights for reproductive physicians and obstetricians during preconception and early pregnancy counseling.</p><p><strong>Study funding/competing interests: </strong>This study was supported by the Natural Science Foundation of Guangdong Province (No. 2023A15","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae024"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-12eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae014
Sofia Makieva, Elisa Giacomini, Giulia Maria Scotti, Dejan Lazarevic, Valentina Pavone, Jessica Ottolina, Ludovica Bartiromo, Matteo Schimberni, Marco Morelli, Alessandra Alteri, Sabrina Minetto, Giovanni Tonon, Massimo Candiani, Enrico Papaleo, Paola Viganò
<p><strong>Study question: </strong>Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)?</p><p><strong>Summary answer: </strong>Aneuploid embryo-derived EVs contain transcripts of <i>PPM1J</i>, <i>LINC00561</i>, <i>ANKRD34C</i>, and <i>TMED10</i> with differential abundance from euploid embryo-derived EVs and induce upregulation of <i>MUC1</i> transcript in dESCs.</p><p><strong>What is known already: </strong>We have previously reported that IVF embryos secrete EVs that can be internalized by ESCs, conceptualizing that successful implantation to the endometrium is facilitated by EVs. Whether these EVs may additionally serve as biomarkers of ploidy status is unknown.</p><p><strong>Study design size duration: </strong>Embryos destined for biopsy for preimplantation genetic testing for aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 μl) were collected from euploid (n = 175) and aneuploid (n = 140) embryos at cleavage (Days 1-3) stage and from euploid (n = 187) and aneuploid (n = 142) embryos at blastocyst (Days 3-5) stage. Media samples from n = 35 cleavage-stage embryos were pooled in order to obtain five euploid and four aneuploid pools. Similarly, media samples from blastocysts were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy.</p><p><strong>Participants/materials setting methods: </strong>EVs were isolated from pools of media by differential centrifugation and EV-RNA sequencing was performed following a single-cell approach that circumvents RNA extraction. ESCs were decidualized (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) and incubated for 24 h with EVs (50 ng/ml). RNA sequencing was performed on ESCs.</p><p><strong>Main results and the role of chance: </strong>Aneuploid cleavage stage embryos secreted EVs that were less abundant in RNA fragments originating from the genes <i>PPM1J</i> (log2fc = -5.13, <i>P</i> = 0.011), <i>LINC00561</i> (log2fc = -7.87, <i>P</i> = 0.010), and <i>ANKRD34C</i> (log2fc = -7.30, <i>P</i> = 0.017) and more abundant in <i>TMED10</i> (log2fc = 1.63, <i>P</i> = 0.025) compared to EVs of euploid embryos. Decidualization <i>per se</i> induced downregulation of <i>MUC1</i> (log2fc = -0.54, <i>P</i> = 0.0028) in ESCs as a prerequisite for the establishment of receptive endometrium. The expression of <i>MUC1</i> transcript in decidualized ESCs was significantly increased following treatment with aneuploid compared to euploid embryo-secreted EVs (log2fc = 0.85, <i>P</i> = 0.0201).</p><p><strong>Large scale data: </strong>Raw data have been uploaded to GEO (accession number GSE234338).</p><p><strong>Limitations reasons for caution: </strong>The findings of the study will require validation utilizing a second cohort of EV samples.</p><p><stro
{"title":"Extracellular vesicles secreted by human aneuploid embryos present a distinct transcriptomic profile and upregulate MUC1 transcription in decidualised endometrial stromal cells.","authors":"Sofia Makieva, Elisa Giacomini, Giulia Maria Scotti, Dejan Lazarevic, Valentina Pavone, Jessica Ottolina, Ludovica Bartiromo, Matteo Schimberni, Marco Morelli, Alessandra Alteri, Sabrina Minetto, Giovanni Tonon, Massimo Candiani, Enrico Papaleo, Paola Viganò","doi":"10.1093/hropen/hoae014","DOIUrl":"10.1093/hropen/hoae014","url":null,"abstract":"<p><strong>Study question: </strong>Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)?</p><p><strong>Summary answer: </strong>Aneuploid embryo-derived EVs contain transcripts of <i>PPM1J</i>, <i>LINC00561</i>, <i>ANKRD34C</i>, and <i>TMED10</i> with differential abundance from euploid embryo-derived EVs and induce upregulation of <i>MUC1</i> transcript in dESCs.</p><p><strong>What is known already: </strong>We have previously reported that IVF embryos secrete EVs that can be internalized by ESCs, conceptualizing that successful implantation to the endometrium is facilitated by EVs. Whether these EVs may additionally serve as biomarkers of ploidy status is unknown.</p><p><strong>Study design size duration: </strong>Embryos destined for biopsy for preimplantation genetic testing for aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 μl) were collected from euploid (n = 175) and aneuploid (n = 140) embryos at cleavage (Days 1-3) stage and from euploid (n = 187) and aneuploid (n = 142) embryos at blastocyst (Days 3-5) stage. Media samples from n = 35 cleavage-stage embryos were pooled in order to obtain five euploid and four aneuploid pools. Similarly, media samples from blastocysts were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy.</p><p><strong>Participants/materials setting methods: </strong>EVs were isolated from pools of media by differential centrifugation and EV-RNA sequencing was performed following a single-cell approach that circumvents RNA extraction. ESCs were decidualized (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) and incubated for 24 h with EVs (50 ng/ml). RNA sequencing was performed on ESCs.</p><p><strong>Main results and the role of chance: </strong>Aneuploid cleavage stage embryos secreted EVs that were less abundant in RNA fragments originating from the genes <i>PPM1J</i> (log2fc = -5.13, <i>P</i> = 0.011), <i>LINC00561</i> (log2fc = -7.87, <i>P</i> = 0.010), and <i>ANKRD34C</i> (log2fc = -7.30, <i>P</i> = 0.017) and more abundant in <i>TMED10</i> (log2fc = 1.63, <i>P</i> = 0.025) compared to EVs of euploid embryos. Decidualization <i>per se</i> induced downregulation of <i>MUC1</i> (log2fc = -0.54, <i>P</i> = 0.0028) in ESCs as a prerequisite for the establishment of receptive endometrium. The expression of <i>MUC1</i> transcript in decidualized ESCs was significantly increased following treatment with aneuploid compared to euploid embryo-secreted EVs (log2fc = 0.85, <i>P</i> = 0.0201).</p><p><strong>Large scale data: </strong>Raw data have been uploaded to GEO (accession number GSE234338).</p><p><strong>Limitations reasons for caution: </strong>The findings of the study will require validation utilizing a second cohort of EV samples.</p><p><stro","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae014"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-28eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae013
Xinyu Li, Yunying Lin, Xiaoyue Cheng, Guangxin Yao, Jufang Yao, Shuanggang Hu, Qinling Zhu, Yuan Wang, Ying Ding, Yao Lu, Jia Qi, Hanting Zhao, Xuejiao Bian, Yanzhi Du, Kang Sun, Hugo Vankelecom, Yun Sun
<p><strong>Study question: </strong>Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)?</p><p><strong>Summary answer: </strong>Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation.</p><p><strong>What is known already: </strong>Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear.</p><p><strong>Study design size duration: </strong>Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed <i>in vitro</i> using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group).</p><p><strong>Participants/materials setting methods: </strong>Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored <i>in vivo</i> in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed.</p><p><strong>Main results and the role of chance: </strong>Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe<sup>2+</sup> (<i>P
作者未报告任何利益冲突。
{"title":"Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.","authors":"Xinyu Li, Yunying Lin, Xiaoyue Cheng, Guangxin Yao, Jufang Yao, Shuanggang Hu, Qinling Zhu, Yuan Wang, Ying Ding, Yao Lu, Jia Qi, Hanting Zhao, Xuejiao Bian, Yanzhi Du, Kang Sun, Hugo Vankelecom, Yun Sun","doi":"10.1093/hropen/hoae013","DOIUrl":"10.1093/hropen/hoae013","url":null,"abstract":"<p><strong>Study question: </strong>Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)?</p><p><strong>Summary answer: </strong>Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation.</p><p><strong>What is known already: </strong>Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear.</p><p><strong>Study design size duration: </strong>Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed <i>in vitro</i> using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group).</p><p><strong>Participants/materials setting methods: </strong>Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored <i>in vivo</i> in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed.</p><p><strong>Main results and the role of chance: </strong>Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe<sup>2+</sup> (<i>P","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae013"},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-24eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae012
Chun-Wei Chien, Yen-An Tang, Shuen-Lin Jeng, Hsien-An Pan, H Sunny Sun
<p><strong>Study question: </strong>Do embryos with longer telomere length (TL) at the blastocyst stage have a higher capacity to survive after frozen-thawed embryo transfer (FET)?</p><p><strong>Summary answer: </strong>Digitally estimated TL using low-pass whole genome sequencing (WGS) data from the preimplantation genetic testing for aneuploidy (PGT-A) process demonstrates that blastocyst TL is the most essential factor associated with likelihood of implantation.</p><p><strong>What is known already: </strong>The lifetime TL is established in the early cleavage cycles following fertilization through a recombination-based lengthening mechanism and starts erosion beyond the blastocyst stage. In addition, a telomerase-mediated slow erosion of TL in human fetuses has been observed from a gestational age of 6-11 weeks. Finally, an abnormal shortening of telomeres is likely involved in embryo loss during early development.</p><p><strong>Study design size duration: </strong>Blastocyst samples were obtained from patients who underwent PGT-A and FET in an IVF center from March 2015 to May 2018. Digitally estimated mitochondrial copy number (mtCN) and TL were used to study associations with the implantation potential of each embryo.</p><p><strong>Participants/materials setting and methods: </strong>In total, 965 blastocysts from 232 cycles (164 patients) were available to investigate the biological and clinical relevance of TL. A WGS-based workflow was applied to determine the ploidy of each embryo. Data from low-pass WGS-PGT-A were used to estimate the mtCN and TL for each embryo. Single-variant and multi-variant logistic regression, decision tree, and random forest models were applied to study various factors in association with the implantation potential of each embryo.</p><p><strong>Main results and the role of chance: </strong>Of the 965 blastocysts originally available, only 216 underwent FET. While mtCN from the transferred embryos is significantly associated with the ploidy call of each embryo, mtCN has no role in impacting IVF outcomes after an embryo transfer in these women. The results indicate that mtCN is a marker of embryo aneuploidy. On the other hand, digitally estimated TL is the most prominent univariant factor and showed a significant positive association with pregnancy outcomes (<i>P</i> < 0.01, odds ratio 79.1). We combined several maternal and embryo parameters to study the joint effects on successful implantation. The machine learning models, namely decision tree and random forest, were trained and yielded classification accuracy of 0.82 and 0.91, respectively. Taken together, these results support the vital role of TL in governing implantation potential, perhaps through the ability to control embryo survival after transfer.</p><p><strong>Limitations reasons for caution: </strong>The small sample size limits our study as only 216 blastocysts were transferred. The number was further reduced to 153 blastocysts, where pregnancy outcome
{"title":"Blastocyst telomere length predicts successful implantation after frozen-thawed embryo transfer.","authors":"Chun-Wei Chien, Yen-An Tang, Shuen-Lin Jeng, Hsien-An Pan, H Sunny Sun","doi":"10.1093/hropen/hoae012","DOIUrl":"10.1093/hropen/hoae012","url":null,"abstract":"<p><strong>Study question: </strong>Do embryos with longer telomere length (TL) at the blastocyst stage have a higher capacity to survive after frozen-thawed embryo transfer (FET)?</p><p><strong>Summary answer: </strong>Digitally estimated TL using low-pass whole genome sequencing (WGS) data from the preimplantation genetic testing for aneuploidy (PGT-A) process demonstrates that blastocyst TL is the most essential factor associated with likelihood of implantation.</p><p><strong>What is known already: </strong>The lifetime TL is established in the early cleavage cycles following fertilization through a recombination-based lengthening mechanism and starts erosion beyond the blastocyst stage. In addition, a telomerase-mediated slow erosion of TL in human fetuses has been observed from a gestational age of 6-11 weeks. Finally, an abnormal shortening of telomeres is likely involved in embryo loss during early development.</p><p><strong>Study design size duration: </strong>Blastocyst samples were obtained from patients who underwent PGT-A and FET in an IVF center from March 2015 to May 2018. Digitally estimated mitochondrial copy number (mtCN) and TL were used to study associations with the implantation potential of each embryo.</p><p><strong>Participants/materials setting and methods: </strong>In total, 965 blastocysts from 232 cycles (164 patients) were available to investigate the biological and clinical relevance of TL. A WGS-based workflow was applied to determine the ploidy of each embryo. Data from low-pass WGS-PGT-A were used to estimate the mtCN and TL for each embryo. Single-variant and multi-variant logistic regression, decision tree, and random forest models were applied to study various factors in association with the implantation potential of each embryo.</p><p><strong>Main results and the role of chance: </strong>Of the 965 blastocysts originally available, only 216 underwent FET. While mtCN from the transferred embryos is significantly associated with the ploidy call of each embryo, mtCN has no role in impacting IVF outcomes after an embryo transfer in these women. The results indicate that mtCN is a marker of embryo aneuploidy. On the other hand, digitally estimated TL is the most prominent univariant factor and showed a significant positive association with pregnancy outcomes (<i>P</i> < 0.01, odds ratio 79.1). We combined several maternal and embryo parameters to study the joint effects on successful implantation. The machine learning models, namely decision tree and random forest, were trained and yielded classification accuracy of 0.82 and 0.91, respectively. Taken together, these results support the vital role of TL in governing implantation potential, perhaps through the ability to control embryo survival after transfer.</p><p><strong>Limitations reasons for caution: </strong>The small sample size limits our study as only 216 blastocysts were transferred. The number was further reduced to 153 blastocysts, where pregnancy outcome","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae012"},"PeriodicalIF":0.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Study question: </strong>Is there a causal relationship between 25-hydroxyvitamin D (25OHD) and miscarriage?</p><p><strong>Summary answer: </strong>In this study, little evidence of a causal relationship was found between low serum 25OHD concentration or vitamin D deficiency and the risk of miscarriages.</p><p><strong>What is known already: </strong>Associations between low vitamin D levels and increased risk of miscarriage have been reported, but causality is unclear.</p><p><strong>Study design size duration: </strong>The latest and largest genome-wide association studies (GWAS) for serum 25OHD concentration (n = 417 580), vitamin D deficiency (426 cases and 354 812 controls), miscarriage (16 906 cases and 149 622 controls), and the number of miscarriages (n = 78 700) were used to explore the causal association between serum vitamin D levels and miscarriage by two-sample Mendelian randomization analysis.</p><p><strong>Participants/materials setting methods: </strong>This study was based on summary GWAS results from the FinnGen database and the UK Biobank. The random-effect inverse-variance weighted method was regarded as the primary analysis; MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods. MR-Egger intercept analysis and MR-PRESSO were employed to test pleiotropy, and Cochran's Q statistic and leave-one-out sensitivity analysis were used to determine the heterogeneity and robustness of the overall estimates, respectively.</p><p><strong>Main results and the role of chance: </strong>There was insufficient evidence of causal associations between serum 25OHD concentration and miscarriage (odds ratio (OR) = 0.995, 95% CI: 0.888 to 1.114, <i>P</i> = 0.927), or the number of miscarriages (β = -0.004, 95% CI: -0.040 to 0.032, <i>P</i> = 0.829). Furthermore, little evidence of causality between genetically determined vitamin D deficiency to miscarriage (OR = 0.993, 95% CI: 0.966 to 1.021, <i>P</i> = 0.624), or the number of miscarriages (β = 0.001, 95% CI: -0.009 to 0.011, <i>P</i> = 0.828), was observed. The results of the sensitivity analysis were robust, and no significant heterogeneity or horizontal pleiotropy was found.</p><p><strong>Limitations reasons for caution: </strong>This study is limited by the absence of female-specific GWAS data and the limited amount of GWAS data available for this study, as well as the need for caution in generalizing the findings to non-European ethnic groups.</p><p><strong>Wider implications of the findings: </strong>These findings enhance the current understanding of the intricate association between vitamin D and pregnancy outcomes, challenging prevailing beliefs regarding the strong association with miscarriage. The results provide a special perspective that may prompt further exploration and potentially offer insights for guiding future research and informing clinical guidelines pertaining to th
{"title":"No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study.","authors":"Feng Zhang, Jingtao Huang, Gangting Zhang, Mengyang Dai, Tailang Yin, Chunyu Huang, Jue Liu, Yan Zhang","doi":"10.1093/hropen/hoae011","DOIUrl":"10.1093/hropen/hoae011","url":null,"abstract":"<p><strong>Study question: </strong>Is there a causal relationship between 25-hydroxyvitamin D (25OHD) and miscarriage?</p><p><strong>Summary answer: </strong>In this study, little evidence of a causal relationship was found between low serum 25OHD concentration or vitamin D deficiency and the risk of miscarriages.</p><p><strong>What is known already: </strong>Associations between low vitamin D levels and increased risk of miscarriage have been reported, but causality is unclear.</p><p><strong>Study design size duration: </strong>The latest and largest genome-wide association studies (GWAS) for serum 25OHD concentration (n = 417 580), vitamin D deficiency (426 cases and 354 812 controls), miscarriage (16 906 cases and 149 622 controls), and the number of miscarriages (n = 78 700) were used to explore the causal association between serum vitamin D levels and miscarriage by two-sample Mendelian randomization analysis.</p><p><strong>Participants/materials setting methods: </strong>This study was based on summary GWAS results from the FinnGen database and the UK Biobank. The random-effect inverse-variance weighted method was regarded as the primary analysis; MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods. MR-Egger intercept analysis and MR-PRESSO were employed to test pleiotropy, and Cochran's Q statistic and leave-one-out sensitivity analysis were used to determine the heterogeneity and robustness of the overall estimates, respectively.</p><p><strong>Main results and the role of chance: </strong>There was insufficient evidence of causal associations between serum 25OHD concentration and miscarriage (odds ratio (OR) = 0.995, 95% CI: 0.888 to 1.114, <i>P</i> = 0.927), or the number of miscarriages (β = -0.004, 95% CI: -0.040 to 0.032, <i>P</i> = 0.829). Furthermore, little evidence of causality between genetically determined vitamin D deficiency to miscarriage (OR = 0.993, 95% CI: 0.966 to 1.021, <i>P</i> = 0.624), or the number of miscarriages (β = 0.001, 95% CI: -0.009 to 0.011, <i>P</i> = 0.828), was observed. The results of the sensitivity analysis were robust, and no significant heterogeneity or horizontal pleiotropy was found.</p><p><strong>Limitations reasons for caution: </strong>This study is limited by the absence of female-specific GWAS data and the limited amount of GWAS data available for this study, as well as the need for caution in generalizing the findings to non-European ethnic groups.</p><p><strong>Wider implications of the findings: </strong>These findings enhance the current understanding of the intricate association between vitamin D and pregnancy outcomes, challenging prevailing beliefs regarding the strong association with miscarriage. The results provide a special perspective that may prompt further exploration and potentially offer insights for guiding future research and informing clinical guidelines pertaining to th","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae011"},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-15eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae007
Edgardo Somigliana, Alessandra Chinè, Marco Reschini, Gianfranco Fornelli, Ludovica Basili, Andrea Busnelli, Paola Viganò, Ludovico Muzii
{"title":"Reply: A paradox? Which paradox?","authors":"Edgardo Somigliana, Alessandra Chinè, Marco Reschini, Gianfranco Fornelli, Ludovica Basili, Andrea Busnelli, Paola Viganò, Ludovico Muzii","doi":"10.1093/hropen/hoae007","DOIUrl":"10.1093/hropen/hoae007","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 1","pages":"hoae007"},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-30eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae005
Yingchun Guo, Lei Jia, Haitao Zeng, Peng Sun, Wenlong Su, Tingting Li, Xiaoyan Liang, Cong Fang
<p><strong>Study question: </strong>Does a matrix-free culture system supplemented with neurotrophic factor 4 (NT4) improve human <i>in vitro</i> follicular development and meiotic maturation, ultimately resulting in fertilizable oocytes?</p><p><strong>Summary answer: </strong>NT4 supplementation of <i>in vitro</i> culture significantly enhances the growth, steroid hormone production, and maturity potential of human secondary follicles derived from fresh ovarian medulla (from post- and pre-pubertal patients), thereby yielding fertilizable oocytes.</p><p><strong>What is known already: </strong>Reconstituting folliculogenesis <i>in vitro</i> is of paramount importance in the realms of fertility preservation, reproductive biology research, and reproductive toxicity assessments. However, the efficiency of <i>in vitro</i> culture systems remains suboptimal, as the attainment of fertilizable oocytes from <i>in vitro</i> growth (IVG) of human follicles remains unachieved, with the data being particularly scant regarding follicles from prepubertal girls. We have previously found that mouse oocytes from secondary follicles derived from IVG are deficient in neuroendocrine regulation. NT4 and its corresponding receptor have been identified in human follicles. Significantly, the addition of NT4 during the IVG process markedly enhances both follicle growth and oocyte maturation rates in mice.</p><p><strong>Study design size duration: </strong>Fresh medulla tissue obtained during tissue preparation for ovarian tissue cryopreservation (OTC) were collected from 10 patients aged from 6 to 21 years old, all of whom had undergone unilateral oophorectomy as a means of fertility preservation. Isolated secondary follicles were individually cultured <i>in vitro</i> with or without NT4 in a matrix-free system.</p><p><strong>Participants/materials setting methods: </strong>Secondary follicles, extracted via enzymatic digestion and mechanical disruption from each patient, were randomly allocated to either a control group or an NT4-supplemented group (100 ng/ml), followed by individual culture on an ultra-low attachment plate. Follicle growth and viability were assessed by microscopy. Levels of anti-Müllerian hormone (AMH), estradiol, and progesterone in the medium were quantified. An oocyte-specific marker was identified using confocal fluorescence microscopy following DEAD box polypeptide 4 (DDX4) staining. The competence of individual oocytes for maturation and fertilization were assessed after IVM and ICSI with donated sperm samples.</p><p><strong>Main results and the role of chance: </strong>Overall, isolated follicles from both groups survived up to 6 weeks with increasing diameters over the duration (<i>P</i> < 0.05), reaching terminal diameters of almost 1 mm with confirmed steroidogenesis and expression of oocyte marker (DDX4), and producing morphologically normal MII oocytes. When compared with the control group, the NT4 group had a similar initial follicular dia
研究问题补充神经营养因子 4（NT4）的无基质培养系统是否能改善人类体外卵泡的发育和减数分裂成熟，并最终产生可受精的卵母细胞？在体外培养中补充 NT4 能显著提高来自新鲜卵巢髓质（来自青春期后和青春期前患者）的人类次级卵泡的生长、类固醇激素分泌和成熟潜能，从而产生可受精的卵母细胞：在体外重建卵泡生成对于生育力保存、生殖生物学研究和生殖毒性评估至关重要。然而，体外培养系统的效率仍未达到最佳水平，因为人类卵泡体外生长（IVG）获得可受精卵细胞的目标仍未实现，尤其是青春期前少女卵泡的相关数据更是少之又少。我们以前曾发现，从 IVG 衍生的次级卵泡中获得的小鼠卵母细胞缺乏神经内分泌调节。在人类卵泡中发现了 NT4 及其相应的受体。值得注意的是，在IVG过程中添加NT4能显著提高小鼠卵泡的生长率和卵母细胞的成熟率：在卵巢组织冷冻保存（OTC）的组织制备过程中获得的新鲜髓质组织取自 10 名年龄在 6 至 21 岁之间的患者，他们都接受了单侧输卵管切除术，以此作为保留生育能力的一种手段。分离的次级卵泡在无基质系统中与或不与NT4单独进行体外培养：通过酶解和机械破坏从每位患者身上提取的次级卵泡被随机分配到对照组或NT4添加组（100 ng/ml），然后在超低附着力平板上进行单独培养。卵泡的生长和活力由显微镜进行评估。对培养基中抗苗勒氏管激素（AMH）、雌二醇和孕酮的水平进行量化。使用共聚焦荧光显微镜对 DEAD box 多肽 4（DDX4）染色后，确定了一种卵母细胞特异性标记物。用捐赠的精子样本进行体外受精和卵胞浆内单精子显微注射后，对单个卵母细胞的成熟和受精能力进行了评估：总体而言，两组分离卵泡的存活期均长达 6 周，且在存活期内直径不断增大（P P P P P 大规模数据）：不适用：本研究的研究对象是所有确诊为重型地中海贫血的患者。该培养系统对其他疾病患者是否有效仍是未知数。由于所选的 NT4 剂量是根据小鼠的剂量发现确定的，因此在人类 IVG 系统中使用的最佳剂量需要进一步确认。本研究获得的卵母细胞和胚胎尚未进行倍性状态或表观遗传学特征的量化：研究结果的更广泛意义：在组织制备过程中获得的新鲜髓质组织可作为保存女性生育能力的珍贵可受精卵细胞来源，即使是青春期前的少女也不例外，而且不会造成肿瘤再次传入的威胁。在对该系统进行进一步表征和优化后，该培养系统有望成为未来研究的有力工具，用于全面探索人类卵泡发育机制和进行生殖毒性评估：本研究得到了国家重点研发计划（批准号：2022YFC2703000）和国家自然科学基金（批准号：82271651和81871214）的资助。本研究中用于人卵泡体外培养的培养基已申请中国国家发明专利（专利号：202211330660.7）。该专利的发明人依次为Y.G.、C.F.和 X.L.。
{"title":"Neurotrophin-4 promotes <i>in vitro</i> development and maturation of human secondary follicles yielding metaphase II oocytes and successful blastocyst formation.","authors":"Yingchun Guo, Lei Jia, Haitao Zeng, Peng Sun, Wenlong Su, Tingting Li, Xiaoyan Liang, Cong Fang","doi":"10.1093/hropen/hoae005","DOIUrl":"10.1093/hropen/hoae005","url":null,"abstract":"<p><strong>Study question: </strong>Does a matrix-free culture system supplemented with neurotrophic factor 4 (NT4) improve human <i>in vitro</i> follicular development and meiotic maturation, ultimately resulting in fertilizable oocytes?</p><p><strong>Summary answer: </strong>NT4 supplementation of <i>in vitro</i> culture significantly enhances the growth, steroid hormone production, and maturity potential of human secondary follicles derived from fresh ovarian medulla (from post- and pre-pubertal patients), thereby yielding fertilizable oocytes.</p><p><strong>What is known already: </strong>Reconstituting folliculogenesis <i>in vitro</i> is of paramount importance in the realms of fertility preservation, reproductive biology research, and reproductive toxicity assessments. However, the efficiency of <i>in vitro</i> culture systems remains suboptimal, as the attainment of fertilizable oocytes from <i>in vitro</i> growth (IVG) of human follicles remains unachieved, with the data being particularly scant regarding follicles from prepubertal girls. We have previously found that mouse oocytes from secondary follicles derived from IVG are deficient in neuroendocrine regulation. NT4 and its corresponding receptor have been identified in human follicles. Significantly, the addition of NT4 during the IVG process markedly enhances both follicle growth and oocyte maturation rates in mice.</p><p><strong>Study design size duration: </strong>Fresh medulla tissue obtained during tissue preparation for ovarian tissue cryopreservation (OTC) were collected from 10 patients aged from 6 to 21 years old, all of whom had undergone unilateral oophorectomy as a means of fertility preservation. Isolated secondary follicles were individually cultured <i>in vitro</i> with or without NT4 in a matrix-free system.</p><p><strong>Participants/materials setting methods: </strong>Secondary follicles, extracted via enzymatic digestion and mechanical disruption from each patient, were randomly allocated to either a control group or an NT4-supplemented group (100 ng/ml), followed by individual culture on an ultra-low attachment plate. Follicle growth and viability were assessed by microscopy. Levels of anti-Müllerian hormone (AMH), estradiol, and progesterone in the medium were quantified. An oocyte-specific marker was identified using confocal fluorescence microscopy following DEAD box polypeptide 4 (DDX4) staining. The competence of individual oocytes for maturation and fertilization were assessed after IVM and ICSI with donated sperm samples.</p><p><strong>Main results and the role of chance: </strong>Overall, isolated follicles from both groups survived up to 6 weeks with increasing diameters over the duration (<i>P</i> < 0.05), reaching terminal diameters of almost 1 mm with confirmed steroidogenesis and expression of oocyte marker (DDX4), and producing morphologically normal MII oocytes. When compared with the control group, the NT4 group had a similar initial follicular dia","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 1","pages":"hoae005"},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139901139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Study question: </strong>Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer?</p><p><strong>Summary answer: </strong>Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer.</p><p><strong>What is known already: </strong>Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer.</p><p><strong>Study design size duration: </strong>We conducted an extensive literature search for relevant studies published through to 31 December 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were '(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm)'.</p><p><strong>Participants/materials setting methods: </strong>We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle-Ottawa scale and the Methodological Index for Non-Randomized Studies.</p><p><strong>Main results and the role of chance: </strong>This meta-analysis included 69 non-randomized studies, with 32 234 patients referred for sperm analysis and 23 178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8-12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16-30%) and 9% (95% CI, 8-10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22-33%), 13% (95% CI, 10-17%), and 20% (95% CI, 15-25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27-41%), 24% (14-35%), and 9% (5
{"title":"Fertility preservation in adult male patients with cancer: a systematic review and meta-analysis.","authors":"Qing Li, Qiong-Yu Lan, Wen-Bing Zhu, Li-Qing Fan, Chuan Huang","doi":"10.1093/hropen/hoae006","DOIUrl":"10.1093/hropen/hoae006","url":null,"abstract":"<p><strong>Study question: </strong>Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer?</p><p><strong>Summary answer: </strong>Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer.</p><p><strong>What is known already: </strong>Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer.</p><p><strong>Study design size duration: </strong>We conducted an extensive literature search for relevant studies published through to 31 December 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were '(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm)'.</p><p><strong>Participants/materials setting methods: </strong>We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle-Ottawa scale and the Methodological Index for Non-Randomized Studies.</p><p><strong>Main results and the role of chance: </strong>This meta-analysis included 69 non-randomized studies, with 32 234 patients referred for sperm analysis and 23 178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8-12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16-30%) and 9% (95% CI, 8-10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22-33%), 13% (95% CI, 10-17%), and 20% (95% CI, 15-25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27-41%), 24% (14-35%), and 9% (5","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 1","pages":"hoae006"},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10882264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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