Background: Spermatogenesis is a temperature-sensitive process, and elevation in temperature hampers this process quickly and significantly. We studied the molecular effects of testicular heating on piRNAs and gene expression in rat testicular germ cells.
Methods: We generated a cryptorchid rat model by displacing the testis from the scrotal sac (34 °C) to the abdominal area (37 °C) and sacrificed animals after 1 day, 3 days, and 5 days. Pachytene spermatocytes and round spermatids were purified using elutriation centrifugation and percoll gradient methods. We performed transcriptome sequencing in pachytene spermatocytes and round spermatids to identify differentially expressed piRNAs and their probable targets, i.e., TE transcripts and mRNAs.
Results: As a result of heat stress, we observed significant upregulation of piRNAs and TE transcripts in testicular germ cells. In addition to this, piRNA biogenesis machinery and heat shock proteins (Hsp70 and Hsp90 family members) were upregulated. mRNAs have also been proposed as targets for piRNAs; therefore, we shortlisted certain piRNA-mRNA pairs with an inverse relationship of expression. We observed that in testicular heat stress, the heat shock proteins go hand-in-hand with the upregulation of piRNA biogenesis machinery. The dysregulation of piRNAs in heat-stressed germ cells, increased ping-pong activity, and disturbed expression of piRNA target transcripts suggest a connection between piRNAs, mRNAs, and TE transcripts.
Conclusions: In heat stress, piRNAs, piRNA machinery, and heat shock proteins are activated to deal with low levels of stress, which is followed by a rescue approach in prolonged stressaccompained by high TE activity to allow genetic mutations, perhaps for survival and adaptability.
{"title":"Heat stress induced piRNA alterations in pachytene spermatocytes and round spermatids.","authors":"Poonam Mehta, Shruti Sethi, Santosh Kumar Yadav, Gopal Gupta, Rajender Singh","doi":"10.1186/s12958-024-01249-z","DOIUrl":"10.1186/s12958-024-01249-z","url":null,"abstract":"<p><strong>Background: </strong>Spermatogenesis is a temperature-sensitive process, and elevation in temperature hampers this process quickly and significantly. We studied the molecular effects of testicular heating on piRNAs and gene expression in rat testicular germ cells.</p><p><strong>Methods: </strong>We generated a cryptorchid rat model by displacing the testis from the scrotal sac (34 °C) to the abdominal area (37 °C) and sacrificed animals after 1 day, 3 days, and 5 days. Pachytene spermatocytes and round spermatids were purified using elutriation centrifugation and percoll gradient methods. We performed transcriptome sequencing in pachytene spermatocytes and round spermatids to identify differentially expressed piRNAs and their probable targets, i.e., TE transcripts and mRNAs.</p><p><strong>Results: </strong>As a result of heat stress, we observed significant upregulation of piRNAs and TE transcripts in testicular germ cells. In addition to this, piRNA biogenesis machinery and heat shock proteins (Hsp70 and Hsp90 family members) were upregulated. mRNAs have also been proposed as targets for piRNAs; therefore, we shortlisted certain piRNA-mRNA pairs with an inverse relationship of expression. We observed that in testicular heat stress, the heat shock proteins go hand-in-hand with the upregulation of piRNA biogenesis machinery. The dysregulation of piRNAs in heat-stressed germ cells, increased ping-pong activity, and disturbed expression of piRNA target transcripts suggest a connection between piRNAs, mRNAs, and TE transcripts.</p><p><strong>Conclusions: </strong>In heat stress, piRNAs, piRNA machinery, and heat shock proteins are activated to deal with low levels of stress, which is followed by a rescue approach in prolonged stressaccompained by high TE activity to allow genetic mutations, perhaps for survival and adaptability.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"87"},"PeriodicalIF":4.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-23DOI: 10.1186/s12958-024-01258-y
Linying Jiang, Yuhan Qiu, Lijuan Xu, Ruiqi Chang, Fan He
Purpose: To summarize the findings of relevant randomized controlled trials (RCTs) and conduct a meta-analysis to investigate the potential effect of aromatase inhibitors on preventing moderate to severe ovarian hyperstimulation syndrome (OHSS) in infertile women undergoing in vitro fertilization (IVF).
Methods: We searched for relevant RCTs in electronic databases, including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (from inception to August 2023). In addition, we manually searched the related reviews and reference lists of included studies for further relevant studies. We included RCTs where aromatase inhibitors prescribed either during controlled ovarian stimulation (COS) or in early luteal phase. The meta-analysis was performed using RevMan 5.4.1 software. The primary outcome was the incidence of moderate to severe OHSS. A descriptive analysis was conducted in cases where a meta-analysis was not feasible due to heterogeneity or lack of comparable data.
Results: 2858 records were retrieved and 12 RCTs were finally included. Letrozole was administered in the treatment group during COS in seven RCTs, whereas in the early luteal phase in five RCTs. Compared with the control group, the risk of moderate to severe OHSS significantly reduced by 55% in the letrozole group (RR 0.45, 95% CI 0.32 to 0.64, I2 = 0%, 5 RCTs, 494 patients). Moreover, serum estradiol (E2) levels on hCG trigger day significantly decreased with the administration of letrozole during COS (MD -847.23, 95% CI -1398.00 to -296.47, I2 = 93%, 5 RCTs, 374 patients). And serum E2 levels on the 4th, 5th and 7th to 10th day after hCG trigger were also significantly lower than those in the control group when letrozole was administered in the early luteal phase.
Conclusions: Patients with high risk of OHSS probably benefit from letrozole, which has been revealed to reduce the incidence of moderate to severe OHSS by this systematic review. However, the very limited number of participants and the quality of the included studies does not allow to recommend letrozole for the prevention of severe OHSS.
目的:总结相关随机对照试验(RCTs)的结果并进行荟萃分析,研究芳香化酶抑制剂对预防体外受精(IVF)不孕妇女中度至重度卵巢过度刺激综合征(OHSS)的潜在影响:我们在MEDLINE、Embase、Cochrane对照试验中央注册中心(CENTRAL)和ClinicalTrials.gov等电子数据库中检索了相关的RCT(从开始到2023年8月)。此外,我们还人工检索了相关综述和纳入研究的参考文献列表,以进一步了解相关研究。我们纳入了在控制性卵巢刺激(COS)期间或黄体早期使用芳香化酶抑制剂的 RCT 研究。荟萃分析使用 RevMan 5.4.1 软件进行。主要结果是中度至重度OHSS的发生率。在因异质性或缺乏可比数据而无法进行荟萃分析的情况下,进行了描述性分析。结果:共检索到2858条记录,最终纳入了12项研究。在 7 项研究中,治疗组在 COS 期间使用来曲唑,而在 5 项研究中,治疗组在黄体早期使用来曲唑。与对照组相比,来曲唑组发生中度至重度OHSS的风险显著降低了55%(RR 0.45,95% CI 0.32至0.64,I2 = 0%,5项研究,494名患者)。此外,在 COS 期间服用来曲唑后,hCG 触发日的血清雌二醇(E2)水平显著下降(MD -847.23,95% CI -1398.00 至 -296.47,I2 = 93%,5 项 RCT,374 名患者)。在黄体早期使用来曲唑时,hCG触发后第4天、第5天、第7天至第10天的血清E2水平也明显低于对照组:结论:来曲唑能降低中度至重度OHSS的发生率,因此高风险OHSS患者可能会从来曲唑中获益。然而,来曲唑的参与人数和纳入研究的质量都非常有限,因此不能推荐来曲唑用于预防重度OHSS。
{"title":"Effect of aromatase inhibitors for preventing ovarian hyperstimulation syndrome in infertile patients undergoing in vitro fertilization: a systematic review and meta-analysis.","authors":"Linying Jiang, Yuhan Qiu, Lijuan Xu, Ruiqi Chang, Fan He","doi":"10.1186/s12958-024-01258-y","DOIUrl":"10.1186/s12958-024-01258-y","url":null,"abstract":"<p><strong>Purpose: </strong>To summarize the findings of relevant randomized controlled trials (RCTs) and conduct a meta-analysis to investigate the potential effect of aromatase inhibitors on preventing moderate to severe ovarian hyperstimulation syndrome (OHSS) in infertile women undergoing in vitro fertilization (IVF).</p><p><strong>Methods: </strong>We searched for relevant RCTs in electronic databases, including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (from inception to August 2023). In addition, we manually searched the related reviews and reference lists of included studies for further relevant studies. We included RCTs where aromatase inhibitors prescribed either during controlled ovarian stimulation (COS) or in early luteal phase. The meta-analysis was performed using RevMan 5.4.1 software. The primary outcome was the incidence of moderate to severe OHSS. A descriptive analysis was conducted in cases where a meta-analysis was not feasible due to heterogeneity or lack of comparable data.</p><p><strong>Results: </strong>2858 records were retrieved and 12 RCTs were finally included. Letrozole was administered in the treatment group during COS in seven RCTs, whereas in the early luteal phase in five RCTs. Compared with the control group, the risk of moderate to severe OHSS significantly reduced by 55% in the letrozole group (RR 0.45, 95% CI 0.32 to 0.64, I<sup>2</sup> = 0%, 5 RCTs, 494 patients). Moreover, serum estradiol (E2) levels on hCG trigger day significantly decreased with the administration of letrozole during COS (MD -847.23, 95% CI -1398.00 to -296.47, I<sup>2</sup> = 93%, 5 RCTs, 374 patients). And serum E2 levels on the 4th, 5th and 7th to 10th day after hCG trigger were also significantly lower than those in the control group when letrozole was administered in the early luteal phase.</p><p><strong>Conclusions: </strong>Patients with high risk of OHSS probably benefit from letrozole, which has been revealed to reduce the incidence of moderate to severe OHSS by this systematic review. However, the very limited number of participants and the quality of the included studies does not allow to recommend letrozole for the prevention of severe OHSS.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"85"},"PeriodicalIF":4.2,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-23DOI: 10.1186/s12958-024-01250-6
Ying Yao, Bin Wang, Kaihua Yu, Ji Song, Liyan Wang, Xuehong Zhang, Yulan Li
Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.
{"title":"Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis.","authors":"Ying Yao, Bin Wang, Kaihua Yu, Ji Song, Liyan Wang, Xuehong Zhang, Yulan Li","doi":"10.1186/s12958-024-01250-6","DOIUrl":"10.1186/s12958-024-01250-6","url":null,"abstract":"<p><p>Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"86"},"PeriodicalIF":4.2,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.1186/s12958-024-01256-0
Haiying Sun, Juan Wang, Peiying Fu, Ting Zhou, Ronghua Liu
Study objective: Cesarean scar pregnancy (CSP) is a type of ectopic pregnancy associated with severe complications, including significant hemorrhage, the potential need for hysterectomy, and life-threatening risks. Currently, two classification methods exist for CSP: Vial (type Ia and IIa) and Chinese Expert's Consensus (type Ib, type IIb, and type IIIb). However, these methods have limitations in guiding the selection of appropriate treatment plans for CSP. The purpose of this study was to systematically evaluate the effectiveness of various treatments for CSP within our clinic.
Method: Our study included 906 patients with CSP from January 2013 to December 2018. The chi-squared test and logistic analysis were used to compare the clinical characteristics. The median and interquartile range (IQR) was calculated. We also analyzed whether preoperative application of methotrexate (MTX) could improve surgical outcomes and the relevant characteristics of misdiagnosed CSP patients.
Results: There was a significant difference in gestational age, gestational sac diameter, gestational sac width, gestational sac area, remnant myometrial thickness, vaginal bleeding and preoperative hemoglobin levels (p < 0.001) but not in the incidence of residual tissue (p = 0.053). The other factors (intraoperative blood loss, hemoglobin decline, first hemoglobin after operation, total hospital stay, hospital stay after operation, transfusion and duration of catheter drain) were significantly different (p < 0.001). For type Ia and type Ib CSP, 39.3% and 40.2% of patients were treated with dilatation and curettage (D&E) under ultrasound, respectively. For type IIa and type IIIb CSP, 29.9% and 62.7% of patients were treated with laparotomy, respectively. There were no differences in surgical methods, residual tissue and reoperation between the MTX and non-MTX groups (p = 0.20), but liver damage, hospital stay and pain perception were more remarkable in the MTX group. It is noteworthy that 14% of the patients were misdiagnosed with an intrauterine pregnancy. The incidence of misdiagnosis in type IIa CSP patients was higher than that in type Ia CSP patients (p < 0.001).
Conclusion: For type I CSP patients, D&E under ultrasound or D&E under hysteroscopy should be recommended. For type IIIb CSP patients, operative resection should be used. It is currently difficult to choose the appropriate treatment methods for type IIa or type IIb CSP patients.
{"title":"Systematic evaluation of the efficacy of treatments for cesarean scar pregnancy.","authors":"Haiying Sun, Juan Wang, Peiying Fu, Ting Zhou, Ronghua Liu","doi":"10.1186/s12958-024-01256-0","DOIUrl":"10.1186/s12958-024-01256-0","url":null,"abstract":"<p><strong>Study objective: </strong>Cesarean scar pregnancy (CSP) is a type of ectopic pregnancy associated with severe complications, including significant hemorrhage, the potential need for hysterectomy, and life-threatening risks. Currently, two classification methods exist for CSP: Vial (type I<sup>a</sup> and II<sup>a</sup>) and Chinese Expert's Consensus (type I<sup>b</sup>, type II<sup>b</sup>, and type III<sup>b</sup>). However, these methods have limitations in guiding the selection of appropriate treatment plans for CSP. The purpose of this study was to systematically evaluate the effectiveness of various treatments for CSP within our clinic.</p><p><strong>Method: </strong>Our study included 906 patients with CSP from January 2013 to December 2018. The chi-squared test and logistic analysis were used to compare the clinical characteristics. The median and interquartile range (IQR) was calculated. We also analyzed whether preoperative application of methotrexate (MTX) could improve surgical outcomes and the relevant characteristics of misdiagnosed CSP patients.</p><p><strong>Results: </strong>There was a significant difference in gestational age, gestational sac diameter, gestational sac width, gestational sac area, remnant myometrial thickness, vaginal bleeding and preoperative hemoglobin levels (p < 0.001) but not in the incidence of residual tissue (p = 0.053). The other factors (intraoperative blood loss, hemoglobin decline, first hemoglobin after operation, total hospital stay, hospital stay after operation, transfusion and duration of catheter drain) were significantly different (p < 0.001). For type I<sup>a</sup> and type I<sup>b</sup> CSP, 39.3% and 40.2% of patients were treated with dilatation and curettage (D&E) under ultrasound, respectively. For type II<sup>a</sup> and type III<sup>b</sup> CSP, 29.9% and 62.7% of patients were treated with laparotomy, respectively. There were no differences in surgical methods, residual tissue and reoperation between the MTX and non-MTX groups (p = 0.20), but liver damage, hospital stay and pain perception were more remarkable in the MTX group. It is noteworthy that 14% of the patients were misdiagnosed with an intrauterine pregnancy. The incidence of misdiagnosis in type II<sup>a</sup> CSP patients was higher than that in type I<sup>a</sup> CSP patients (p < 0.001).</p><p><strong>Conclusion: </strong>For type I CSP patients, D&E under ultrasound or D&E under hysteroscopy should be recommended. For type III<sup>b</sup> CSP patients, operative resection should be used. It is currently difficult to choose the appropriate treatment methods for type II<sup>a</sup> or type II<sup>b</sup> CSP patients.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"84"},"PeriodicalIF":4.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Besides adenine triphosphate (ATP) production for sustaining motility, the mitochondria of sperm also host other critical cellular functions during germ cell development and fertilization including calcium homeostasis, generation of reactive oxygen species (ROS), apoptosis, and in some cases steroid hormone biosynthesis. Normal mitochondrial membrane potential with optimal mitochondrial performance is essential for sperm motility, capacitation, acrosome reaction, and DNA integrity.
Results: Defects in the sperm mitochondrial function can severely harm the fertility potential of males. The role of sperm mitochondria in fertilization and its final fate after fertilization is still controversial. Here, we review the current knowledge on human sperm mitochondria characteristics and their physiological and pathological conditions, paying special attention to improvements in assistant reproductive technology and available treatments to ameliorate male infertility.
Conclusion: Although mitochondrial variants associated with male infertility have potential clinical use, research is limited. Further understanding is needed to determine how these characteristics lead to adverse pregnancy outcomes and affect male fertility potential.
背景:精子线粒体除了产生维持精子运动的三磷酸腺嘌呤(ATP)外,在生殖细胞发育和受精过程中还承担着其他重要的细胞功能,包括钙平衡、活性氧(ROS)生成、细胞凋亡以及某些情况下的类固醇激素生物合成。正常的线粒体膜电位和最佳的线粒体性能对精子的运动、获能、顶体反应和 DNA 完整性至关重要:结果:精子线粒体功能缺陷会严重损害男性的生育能力。精子线粒体在受精过程中的作用以及受精后的最终归宿仍存在争议。在此,我们回顾了目前有关人类精子线粒体特征及其生理和病理状况的知识,并特别关注了辅助生殖技术的改进和改善男性不育症的现有治疗方法:结论:尽管与男性不育有关的线粒体变异具有潜在的临床应用价值,但相关研究还很有限。结论:虽然与男性不育有关的线粒体变异具有潜在的临床应用价值,但研究还很有限,需要进一步了解这些特征是如何导致不良妊娠结局和影响男性生育潜力的。
{"title":"The impact of mitochondrial impairments on sperm function and male fertility: a systematic review.","authors":"Minoo Vahedi Raad, Amir Masoud Firouzabadi, Maryam Tofighi Niaki, Ralf Henkel, Farzaneh Fesahat","doi":"10.1186/s12958-024-01252-4","DOIUrl":"10.1186/s12958-024-01252-4","url":null,"abstract":"<p><strong>Background: </strong>Besides adenine triphosphate (ATP) production for sustaining motility, the mitochondria of sperm also host other critical cellular functions during germ cell development and fertilization including calcium homeostasis, generation of reactive oxygen species (ROS), apoptosis, and in some cases steroid hormone biosynthesis. Normal mitochondrial membrane potential with optimal mitochondrial performance is essential for sperm motility, capacitation, acrosome reaction, and DNA integrity.</p><p><strong>Results: </strong>Defects in the sperm mitochondrial function can severely harm the fertility potential of males. The role of sperm mitochondria in fertilization and its final fate after fertilization is still controversial. Here, we review the current knowledge on human sperm mitochondria characteristics and their physiological and pathological conditions, paying special attention to improvements in assistant reproductive technology and available treatments to ameliorate male infertility.</p><p><strong>Conclusion: </strong>Although mitochondrial variants associated with male infertility have potential clinical use, research is limited. Further understanding is needed to determine how these characteristics lead to adverse pregnancy outcomes and affect male fertility potential.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"83"},"PeriodicalIF":4.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Exploring the molecular mechanisms of primordial germ cell (PGC) migration and the involvement of gonadal somatic cells in gonad development is valuable for comprehending the origins and potential treatments of reproductive-related diseases.
Methods: Diaphanous related formin 1 (Diaph1, also known as mDia1) was screened by analyzing publicly available datasets (ATAC-seq, DNase-seq, and RNA-seq). Subsequently, the CRISPR-Cas9 technology was used to construct Diaph1 knockout mice to investigate the role of Diaph1 in gonad development.
Results: Based on data from public databases, a differentially expressed gene Diaph1, was identified in the migration of mouse PGC. Additionally, the number of PGCs was significantly reduced in Diaph1 knockout mice compared to wild type mice, and the expression levels of genes related to proliferation (Dicer1, Mcm9), adhesion (E-cadherin, Cdh1), and migration (Cxcr4, Hmgcr, Dazl) were significantly decreased. Diaph1 knockout also inhibited Leydig cell proliferation and induced apoptosis in the testis, as well as granulosa cell apoptosis in the ovary. Moreover, the sperm count in the epididymal region and the count of ovarian follicles were significantly reduced in Diaph1 knockout mice, resulting in decreased fertility, concomitant with lowered levels of serum testosterone and estradiol. Further research found that in Diaph1 knockout mice, the key enzymes involved in testosterone synthesis (CYP11A1, 3β-HSD) were decreased in Leydig cells, and the estradiol-associated factor (FSH receptor, AMH) in granulosa cells were also downregulated.
Conclusions: Overall, our findings indicate that the knockout of Diaph1 can disrupt the expression of factors that regulate sex hormone production, leading to impaired secretion of sex hormones, ultimately resulting in damage to reproductive function. These results provide a new perspective on the molecular mechanisms underlying PGC migration and gonadal development, and offer valuable insights for further research on the causes, diagnosis, and treatment of related diseases.
{"title":"Diaph1 knockout inhibits mouse primordial germ cell proliferation and affects gonadal development.","authors":"Xin Zhao, Chunbiao Fan, Tongtong Qie, Xinrui Fu, Xiaoshuang Chen, Yujia Wang, Yuan Wu, Xinyao Fu, Kesong Shi, Wenlong Yan, Haiquan Yu","doi":"10.1186/s12958-024-01257-z","DOIUrl":"10.1186/s12958-024-01257-z","url":null,"abstract":"<p><strong>Background: </strong>Exploring the molecular mechanisms of primordial germ cell (PGC) migration and the involvement of gonadal somatic cells in gonad development is valuable for comprehending the origins and potential treatments of reproductive-related diseases.</p><p><strong>Methods: </strong>Diaphanous related formin 1 (Diaph1, also known as mDia1) was screened by analyzing publicly available datasets (ATAC-seq, DNase-seq, and RNA-seq). Subsequently, the CRISPR-Cas9 technology was used to construct Diaph1 knockout mice to investigate the role of Diaph1 in gonad development.</p><p><strong>Results: </strong>Based on data from public databases, a differentially expressed gene Diaph1, was identified in the migration of mouse PGC. Additionally, the number of PGCs was significantly reduced in Diaph1 knockout mice compared to wild type mice, and the expression levels of genes related to proliferation (Dicer1, Mcm9), adhesion (E-cadherin, Cdh1), and migration (Cxcr4, Hmgcr, Dazl) were significantly decreased. Diaph1 knockout also inhibited Leydig cell proliferation and induced apoptosis in the testis, as well as granulosa cell apoptosis in the ovary. Moreover, the sperm count in the epididymal region and the count of ovarian follicles were significantly reduced in Diaph1 knockout mice, resulting in decreased fertility, concomitant with lowered levels of serum testosterone and estradiol. Further research found that in Diaph1 knockout mice, the key enzymes involved in testosterone synthesis (CYP11A1, 3β-HSD) were decreased in Leydig cells, and the estradiol-associated factor (FSH receptor, AMH) in granulosa cells were also downregulated.</p><p><strong>Conclusions: </strong>Overall, our findings indicate that the knockout of Diaph1 can disrupt the expression of factors that regulate sex hormone production, leading to impaired secretion of sex hormones, ultimately resulting in damage to reproductive function. These results provide a new perspective on the molecular mechanisms underlying PGC migration and gonadal development, and offer valuable insights for further research on the causes, diagnosis, and treatment of related diseases.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"82"},"PeriodicalIF":4.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1186/s12958-024-01242-6
Lei Jin, Keyi Si, Zhou Li, Hui He, Li Wu, Bingxin Ma, Xinling Ren, Bo Huang
Background: The occurrence of blastocyst collapse may become an indicator of preimplantation embryo quality assessment. It has been reported that collapsing blastocysts can lead to higher rates of aneuploidy and poorer clinical outcomes, but more large-scale studies are needed to explore this relationship. This study explored the characteristics of blastocyst collapse identified and quantified by artificial intelligence and explored the associations between blastocyst collapse and embryo ploidy, morphological quality, and clinical outcomes.
Methods: This observational study included data from 3288 biopsied blastocysts in 1071 time-lapse preimplantation genetic testing cycles performed between January 2019 and February 2023 at a single academic fertility center. All transferred blastocysts are euploid blastocysts. The artificial intelligence recognized blastocyst collapse in time-lapse microscopy videos and then registered the collapsing times, and the start time, the recovery duration, the shrinkage percentage of each collapse. The effects of blastocyst collapse and embryo ploidy, pregnancy, live birth, miscarriage, and embryo quality were studied using available data from 1196 euploid embryos and 1300 aneuploid embryos.
Results: 5.6% of blastocysts collapsed at least once only before the full blastocyst formation (tB), 19.4% collapsed at least once only after tB, and 3.1% collapsed both before and after tB. Multiple collapses of blastocysts after tB (times ≥ 2) are associated with higher aneuploid rates (54.6%, P > 0.05; 70.5%, P < 0.001; 72.5%, P = 0.004; and 71.4%, P = 0.049 in blastocysts collapsed 1, 2, 3 or ≥ 4 times), which remained significant after adjustment for confounders (OR = 2.597, 95% CI 1.464-4.607, P = 0.001). Analysis of the aneuploid embryos showed a higher ratio of collapses and multiple collapses after tB in monosomies and embryos with subchromosomal deletion of segmental nature (P < 0.001). Blastocyst collapse was associated with delayed embryonic development and declined blastocyst quality. There is no significant difference in pregnancy and live birth rates between collapsing and non-collapsing blastocysts.
Conclusions: Blastocyst collapse is common during blastocyst development. This study underlined that multiple blastocyst collapses after tB may be an independent risk factor for aneuploidy which should be taken into account by clinicians and embryologists when selecting blastocysts for transfer.
{"title":"Multiple collapses of blastocysts after full blastocyst formation is an independent risk factor for aneuploidy - a study based on AI and manual validation.","authors":"Lei Jin, Keyi Si, Zhou Li, Hui He, Li Wu, Bingxin Ma, Xinling Ren, Bo Huang","doi":"10.1186/s12958-024-01242-6","DOIUrl":"10.1186/s12958-024-01242-6","url":null,"abstract":"<p><strong>Background: </strong>The occurrence of blastocyst collapse may become an indicator of preimplantation embryo quality assessment. It has been reported that collapsing blastocysts can lead to higher rates of aneuploidy and poorer clinical outcomes, but more large-scale studies are needed to explore this relationship. This study explored the characteristics of blastocyst collapse identified and quantified by artificial intelligence and explored the associations between blastocyst collapse and embryo ploidy, morphological quality, and clinical outcomes.</p><p><strong>Methods: </strong>This observational study included data from 3288 biopsied blastocysts in 1071 time-lapse preimplantation genetic testing cycles performed between January 2019 and February 2023 at a single academic fertility center. All transferred blastocysts are euploid blastocysts. The artificial intelligence recognized blastocyst collapse in time-lapse microscopy videos and then registered the collapsing times, and the start time, the recovery duration, the shrinkage percentage of each collapse. The effects of blastocyst collapse and embryo ploidy, pregnancy, live birth, miscarriage, and embryo quality were studied using available data from 1196 euploid embryos and 1300 aneuploid embryos.</p><p><strong>Results: </strong>5.6% of blastocysts collapsed at least once only before the full blastocyst formation (tB), 19.4% collapsed at least once only after tB, and 3.1% collapsed both before and after tB. Multiple collapses of blastocysts after tB (times ≥ 2) are associated with higher aneuploid rates (54.6%, P > 0.05; 70.5%, P < 0.001; 72.5%, P = 0.004; and 71.4%, P = 0.049 in blastocysts collapsed 1, 2, 3 or ≥ 4 times), which remained significant after adjustment for confounders (OR = 2.597, 95% CI 1.464-4.607, P = 0.001). Analysis of the aneuploid embryos showed a higher ratio of collapses and multiple collapses after tB in monosomies and embryos with subchromosomal deletion of segmental nature (P < 0.001). Blastocyst collapse was associated with delayed embryonic development and declined blastocyst quality. There is no significant difference in pregnancy and live birth rates between collapsing and non-collapsing blastocysts.</p><p><strong>Conclusions: </strong>Blastocyst collapse is common during blastocyst development. This study underlined that multiple blastocyst collapses after tB may be an independent risk factor for aneuploidy which should be taken into account by clinicians and embryologists when selecting blastocysts for transfer.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"81"},"PeriodicalIF":4.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis.
Methods: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses.
Results: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis.
Conclusions: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.
背景:功能失调的子宫蠕动似乎在阻碍被诊断患有子宫腺肌症的妇女的胚胎着床方面起着关键作用。本研究旨在探讨在使用激素替代疗法(HRT)方案的冷冻胚胎移植(FET)周期中使用催产素受体拮抗剂是否能提高受腺肌症影响的不孕妇女的体外受精(IVF)结果:2018年1月至2022年6月期间,我们的生殖中心为确诊患有子宫腺肌症的不孕妇女实施了IVF-FET HRT周期。采用倾向得分匹配法,以 1:1 的比例在两组之间选择匹配的受试者。随后,168 名妇女在 FET 期间接受了催产素受体拮抗剂治疗,组成研究组,而匹配的 168 名妇女在未接受该拮抗剂治疗的情况下接受了 FET,组成对照组。我们对两组的基线和周期特征进行了比较分析,并进行了其他亚组分析:研究组的早期流产率明显低于对照组,但两组在临床妊娠率、持续妊娠率和活产率方面没有显著差异。多变量分析显示,使用催产素受体拮抗剂与子宫腺肌症妇女的早期流产率呈负相关。按年龄、不孕类型和胚胎移植日进行的亚组分析表明,与对照组相比,特定亚组的早期流产率大幅下降:研究组中年龄≥ 37 岁的女性、继发性不孕患者和接受第 3 天胚胎移植的患者。此外,根据子宫腺肌症类型进行的亚组分析表明,在弥漫性子宫腺肌症妇女中,研究组的临床妊娠率、持续妊娠率和活产率均显著高于对照组:结论:在 FET 期间使用催产素受体拮抗剂可降低子宫腺肌症妇女的早期流产率。
{"title":"Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study.","authors":"Po-Wen Lin, Chyi-Uei Chern, Chia-Jung Li, Pei-Hsuan Lin, Kuan-Hao Tsui, Li-Te Lin","doi":"10.1186/s12958-024-01255-1","DOIUrl":"10.1186/s12958-024-01255-1","url":null,"abstract":"<p><strong>Background: </strong>Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis.</p><p><strong>Methods: </strong>Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses.</p><p><strong>Results: </strong>The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis.</p><p><strong>Conclusions: </strong>Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"79"},"PeriodicalIF":4.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms.
Methods: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET).
Results: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups.
Conclusion: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.
背景:近年来,得益于临床技术的不断进步和保留生育能力的优势,胚胎冷冻保存的应用在全球范围内迅速增长。然而,在发展的同时,人们对其安全性的担忧也一直存在。大量研究强调,冷冻胚胎移植(FET)导致围产期并发症的风险升高,如胎龄过大(LGA)和妊娠期高血压疾病。因此,探讨胚胎冷冻保存的潜在风险及其相关机制势在必行:鉴于对临床样本的严格伦理限制,我们在本研究中采用了小鼠模型。我们设立了三个实验组:自然受孕(NC)组、新鲜胚胎移植(Fresh-ET)组和 FET 组。计算胚胎冷冻后的囊胚形成率和植入率。根据胎儿和胎盘重量评估 FET 对胎儿生长的影响。进行了胎盘 RNA-seq,包括各种比较的综合分析(Fresh-ET vs. NC、FET vs. NC 和 FET vs. Fresh-ET):结果:观察到胚胎冷冻后囊胚形成率和植入率降低。与NC组相比,新鲜-ET导致胎儿体重显著下降,而FET则逆转了这种下降趋势。RNA-seq分析表明,FET中的大部分表达变化都是从Fresh-ET中继承下来的,而仅由胚胎冷冻引起的变化是温和的。意想不到的是,某些在 Fresh-ET 中发生变化的基因在 FET 中趋于恢复。进一步分析表明,这种回归可能是 FET 改善胎儿生长受限的原因。在 FET 和 Fresh-ET 组中,印记基因的表达均受到破坏:结论:根据我们在小鼠模型上的实验数据,与其他体外操作相比,胚胎冷冻对 Fresh-ET 的影响较小。然而,胚胎发育潜能的损害和胎盘中基因的改变仍表明这是一项有风险的操作。
{"title":"Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.","authors":"Qin-Yu Luo, Si-Wei Zhang, Hai-Yan Wu, Jia-Ying Mo, Jia-En Yu, Ren-Ke He, Zhao-Ying Jiang, Ke-Jing Zhu, Xue-Ying Liu, Zhong-Liang Lin, Jian-Zhong Sheng, Yu Zhang, Yan-Ting Wu, He-Feng Huang","doi":"10.1186/s12958-024-01241-7","DOIUrl":"10.1186/s12958-024-01241-7","url":null,"abstract":"<p><strong>Background: </strong>In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms.</p><p><strong>Methods: </strong>Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET).</p><p><strong>Results: </strong>Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups.</p><p><strong>Conclusion: </strong>Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"22 1","pages":"80"},"PeriodicalIF":4.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children’s Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636–0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759–0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741–0.884). We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.
{"title":"The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation","authors":"Yu-Heng Xiao, Yu-Lin Hu, Xing-Yu Lv, Li-Juan Huang, Li-Hong Geng, Pu Liao, Yu-Bin Ding, Chang-Chun Niu","doi":"10.1186/s12958-024-01251-5","DOIUrl":"https://doi.org/10.1186/s12958-024-01251-5","url":null,"abstract":"To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children’s Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636–0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759–0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741–0.884). We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"51 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141572586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}