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}
Pub Date : 2024-01-17eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae001
Cristina Valle-Hita, Albert Salas-Huetos, María Fernández de la Puente, María Ángeles Martínez, Silvia Canudas, Antoni Palau-Galindo, Cristina Mestres, José María Manzanares, Michelle M Murphy, Montse Marquès, Jordi Salas-Salvadó, Nancy Babio
<p><strong>Study question: </strong>Is ultra-processed food (UPF) consumption associated with semen quality parameters?</p><p><strong>Summary answer: </strong>Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age.</p><p><strong>What is known already: </strong>The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited.</p><p><strong>Study design size duration: </strong>A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023.</p><p><strong>Participants/materials setting methods: </strong>UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters.</p><p><strong>Main results and the role of chance: </strong>Sperm concentration (<i>β</i>: -1.42 × 10<sup>6</sup> spz./ml; 95% CI: -2.72 to -0.12) and motility (<i>β</i>: -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption (<i>β</i>: -1.50 × 10<sup>6</sup> spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms.</p><p><strong>Limitations reasons for caution: </strong>Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out.</p><p><strong>Wider implications of the findings: </strong>This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-ter
研究问题：超加工食品（UPF）消费量与精液质量参数是否相关？在育龄男性中，较高的 UPF 消费量与精子总数、精子浓度和总活力成反比：过去几十年来，UPF 的摄入量一直在上升，这已被证明与多种慢性疾病（如糖尿病或心血管疾病）呈正相关。然而，有关其对精液质量潜在影响的科学证据仍然非常有限：利用 2021 年 2 月至 2023 年 4 月期间参加 Led-Fertyl（精液图和其他男性生育能力相关参数的生活方式和环境决定因素）研究的 200 名健康男性（平均年龄为 28.4 ± 5.5 岁）的数据进行了横断面分析：使用经过验证的 143 项半定量食物频率问卷，根据 NOVA 分类系统估算 UPF 消耗量（UPF 能量百分比）。主要结果包括精子总数、精子浓度、精子活力、总活力、渐进活力和正常精子形态。显微参数使用相差显微镜和计算机辅助精子分析系统（CASA）进行分析。精液样本按照世界卫生组织 2010 年标准进行采集和检测。多变量线性回归模型用于估算UPF三分位数与精液质量参数之间的关系：主要结果和偶然性的作用：与最低的参与者相比，UPF值最高的参与者的精子浓度（β：-1.42 × 106 spz./ml；95% CI：-2.72 至 -0.12）和活力（β：-7.83%；95% CI：-15.16 至 -0.51）较低。当分析 UPF 消费每增加 10%的能量时，精子数量也出现了类似的关联（β：-1.50 × 106 spz.；95% CI：-2.83 至 -0.17）。从理论上讲，用未加工或微量加工食品消费的 10%能量替代 UPF 消费的 10%能量，与较高的精子总数、精子浓度、总活力、渐进活力和正常精子形态有关：横断面研究无法得出因果推论。研究结果的广泛影响：这项研究表明，食用 UPF 可能会对某些精液质量参数产生影响。此外，选择食用未经加工或加工程度较低的食品而不食用UPF可能对精液质量有益。如果这些结果能在未来采用不同长期设计的流行病学研究中得到重复，那么这些新发现将为更新甚至设计预防和干预计划以解决育龄男性不育问题提供有价值的见解：本研究得到了西班牙政府生物医学研究官方资助机构ISCIII（通过Fondo de Investigación para la Salud (FIS)）、欧盟ERDF/ESF（"A way to make Europe"/"Investing in your future"[PI21/01447]）和塔拉戈纳省议会（2021/11-No.Exp. 8004330008-2021-0022642）的支持。J.S.-S.衷心感谢 ICREA 在 ICREA Academia 计划下提供的资助。C.V.-H. 获得了加泰罗尼亚自治区政府（2022 FI_B100108）的博士前期资助。M.Á.M. 获得了 Sara Borrell 博士后奖学金（CD21/00045-Instituto de Salud Carlos III (ISCIII)）。M.F.d.l.P.获得了罗维拉-伊-维尔吉利大学（Rovira i Virgili University）和塔拉戈纳省议会（Diputació de Tarragona）的博士前期资助（2020-PMF-PIPF-8）。所有作者均无利益冲突：不适用。
{"title":"Ultra-processed food consumption and semen quality parameters in the Led-Fertyl study.","authors":"Cristina Valle-Hita, Albert Salas-Huetos, María Fernández de la Puente, María Ángeles Martínez, Silvia Canudas, Antoni Palau-Galindo, Cristina Mestres, José María Manzanares, Michelle M Murphy, Montse Marquès, Jordi Salas-Salvadó, Nancy Babio","doi":"10.1093/hropen/hoae001","DOIUrl":"10.1093/hropen/hoae001","url":null,"abstract":"<p><strong>Study question: </strong>Is ultra-processed food (UPF) consumption associated with semen quality parameters?</p><p><strong>Summary answer: </strong>Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age.</p><p><strong>What is known already: </strong>The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited.</p><p><strong>Study design size duration: </strong>A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023.</p><p><strong>Participants/materials setting methods: </strong>UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters.</p><p><strong>Main results and the role of chance: </strong>Sperm concentration (<i>β</i>: -1.42 × 10<sup>6</sup> spz./ml; 95% CI: -2.72 to -0.12) and motility (<i>β</i>: -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption (<i>β</i>: -1.50 × 10<sup>6</sup> spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms.</p><p><strong>Limitations reasons for caution: </strong>Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out.</p><p><strong>Wider implications of the findings: </strong>This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-ter","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 1","pages":"hoae001"},"PeriodicalIF":8.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10813743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571676","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 : 2024-01-11eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae003
Gui-Quan Meng, Yaling Wang, Chen Luo, Yu-Mei Tan, Yong Li, Chen Tan, Chaofeng Tu, Qian-Jun Zhang, Liang Hu, Huan Zhang, Lan-Lan Meng, Chun-Yu Liu, Leiyu Deng, Guang-Xiu Lu, Ge Lin, Juan Du, Yue-Qiu Tan, Yanwei Sha, Lingbo Wang, Wen-Bin He
<p><strong>Study question: </strong>Are there other pathogenic genes for asthenoteratozoospermia (AT)?</p><p><strong>Summary answer: </strong><i>DNAH3</i> is a novel candidate gene for AT in humans and mice.</p><p><strong>What is known already: </strong>AT is a major cause of male infertility. Several genes underlying AT have been reported; however, the genetic aetiology remains unknown in a majority of affected men.</p><p><strong>Study design size duration: </strong>A total of 432 patients with AT were recruited in this study. <i>DNAH3</i> mutations were identified by whole-exome sequencing (WES). <i>Dnah3</i> knockout mice were generated using the genome editing tool. The morphology and motility of sperm from <i>Dnah3</i> knockout mice were investigated. The entire study was conducted over 3 years.</p><p><strong>Participants/materials setting methods: </strong>WES was performed on 432 infertile patients with AT. In addition, two lines of <i>Dnah3</i> knockout mice were generated. Haematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunostaining, and computer-aided sperm analysis (CASA) were performed to investigate the morphology and motility of the spermatozoa. ICSI was used to overcome the infertility of one patient and of the <i>Dnah3</i> knockout mice.</p><p><strong>Main results and the role of chance: </strong><i>DNAH3</i> biallelic variants were identified in three patients from three unrelated families. H&E staining revealed various morphological abnormalities in the flagella of sperm from the patients, and TEM and immunostaining further showed the loss of the central pair of microtubules, a dislocated mitochondrial sheath and fibrous sheath, as well as a partial absence of the inner dynein arms. In addition, the two <i>Dnah3</i> knockout mouse lines demonstrated AT. One patient and the <i>Dnah3</i> knockout mice showed good treatment outcomes after ICSI.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>This is a preliminary report suggesting that defects in <i>DNAH3</i> can lead to asthenoteratozoospermia in humans and mice. The pathogenic mechanism needs to be further examined in a future study.</p><p><strong>Wider implications of the findings: </strong>Our findings show that <i>DNAH3</i> is a novel candidate gene for AT in humans and mice and provide crucial insights into the biological underpinnings of this disorder. The findings may also be beneficial for counselling affected individuals.</p><p><strong>Study funding/competing interests: </strong>This work was supported by grants from National Natural Science Foundation of China (82201773, 82101961, 82171608, 32322017, 82071697, and 81971447), National Key Research and Development Program of China (2022YFC2702604), Scientific Research Foundation of the Health Committee of Hunan Province (B202301039323, B202301039518), Hunan Provincial Natural Science Foundation (2023JJ30716), the Medical Innovation Proje
{"title":"Bi-allelic variants in <i>DNAH3</i> cause male infertility with asthenoteratozoospermia in humans and mice.","authors":"Gui-Quan Meng, Yaling Wang, Chen Luo, Yu-Mei Tan, Yong Li, Chen Tan, Chaofeng Tu, Qian-Jun Zhang, Liang Hu, Huan Zhang, Lan-Lan Meng, Chun-Yu Liu, Leiyu Deng, Guang-Xiu Lu, Ge Lin, Juan Du, Yue-Qiu Tan, Yanwei Sha, Lingbo Wang, Wen-Bin He","doi":"10.1093/hropen/hoae003","DOIUrl":"10.1093/hropen/hoae003","url":null,"abstract":"<p><strong>Study question: </strong>Are there other pathogenic genes for asthenoteratozoospermia (AT)?</p><p><strong>Summary answer: </strong><i>DNAH3</i> is a novel candidate gene for AT in humans and mice.</p><p><strong>What is known already: </strong>AT is a major cause of male infertility. Several genes underlying AT have been reported; however, the genetic aetiology remains unknown in a majority of affected men.</p><p><strong>Study design size duration: </strong>A total of 432 patients with AT were recruited in this study. <i>DNAH3</i> mutations were identified by whole-exome sequencing (WES). <i>Dnah3</i> knockout mice were generated using the genome editing tool. The morphology and motility of sperm from <i>Dnah3</i> knockout mice were investigated. The entire study was conducted over 3 years.</p><p><strong>Participants/materials setting methods: </strong>WES was performed on 432 infertile patients with AT. In addition, two lines of <i>Dnah3</i> knockout mice were generated. Haematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunostaining, and computer-aided sperm analysis (CASA) were performed to investigate the morphology and motility of the spermatozoa. ICSI was used to overcome the infertility of one patient and of the <i>Dnah3</i> knockout mice.</p><p><strong>Main results and the role of chance: </strong><i>DNAH3</i> biallelic variants were identified in three patients from three unrelated families. H&E staining revealed various morphological abnormalities in the flagella of sperm from the patients, and TEM and immunostaining further showed the loss of the central pair of microtubules, a dislocated mitochondrial sheath and fibrous sheath, as well as a partial absence of the inner dynein arms. In addition, the two <i>Dnah3</i> knockout mouse lines demonstrated AT. One patient and the <i>Dnah3</i> knockout mice showed good treatment outcomes after ICSI.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>This is a preliminary report suggesting that defects in <i>DNAH3</i> can lead to asthenoteratozoospermia in humans and mice. The pathogenic mechanism needs to be further examined in a future study.</p><p><strong>Wider implications of the findings: </strong>Our findings show that <i>DNAH3</i> is a novel candidate gene for AT in humans and mice and provide crucial insights into the biological underpinnings of this disorder. The findings may also be beneficial for counselling affected individuals.</p><p><strong>Study funding/competing interests: </strong>This work was supported by grants from National Natural Science Foundation of China (82201773, 82101961, 82171608, 32322017, 82071697, and 81971447), National Key Research and Development Program of China (2022YFC2702604), Scientific Research Foundation of the Health Committee of Hunan Province (B202301039323, B202301039518), Hunan Provincial Natural Science Foundation (2023JJ30716), the Medical Innovation Proje","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 1","pages":"hoae003"},"PeriodicalIF":8.3,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10834362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682038","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}
Laszlo Nanassy, B. Schoepper, A. Schultze-Mosgau, M. Depenbusch, Tanja K Eggersmann, R. Hiller, G. Griesinger
{"title":"Double vitrification and warming does not compromise the chance of live birth—a potential invalid conclusion","authors":"Laszlo Nanassy, B. Schoepper, A. Schultze-Mosgau, M. Depenbusch, Tanja K Eggersmann, R. Hiller, G. Griesinger","doi":"10.1093/hropen/hoad049","DOIUrl":"https://doi.org/10.1093/hropen/hoad049","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139386155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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