Pub Date : 2025-02-15DOI: 10.1016/j.xfnr.2025.100089
Zoé I. Vincent-Mistiaen Ph.D.
Endometriosis, a chronic inflammatory condition, is characterized by the growth of endometrial-like tissue outside the uterus, leading to debilitating pain and infertility. Although retrograde menstruation is widely accepted as a mechanism for the dissemination of endometrial cells to ectopic sites, the processes that enable their survival, invasion, and lesion formation remain incompletely understood. Epithelial-mesenchymal transition (EMT) has emerged as a potential driver, promoting cellular plasticity that supports ectopic implantation and invasion. Epithelial-mesenchymal transition is closely linked to inflammation, with transforming growth factor-β–mediated pathways playing a central role in driving these transitions. Chronic inflammation also induces fibroblast-myofibroblast transition (FMT) and smooth muscle metaplasia, processes that exacerbate fibrosis through excessive extracellular matrix deposition and fibroblast activation. These fibrotic changes worsen symptoms and contribute to disease progression. This review explores EMT and FMT as key mechanistic links between inflammation and fibrosis and discusses how targeting these pathways could offer novel therapeutic strategies to disrupt fibrotic progression, alleviate symptoms, and improve patient outcomes. Additionally, EMT and FMT markers hold promise as diagnostic tools, offering potential for earlier detection and more precise staging of endometriosis.
{"title":"Epithelial-mesenchymal transition links inflammation and fibrosis in the pathogenesis of endometriosis: a narrative review","authors":"Zoé I. Vincent-Mistiaen Ph.D.","doi":"10.1016/j.xfnr.2025.100089","DOIUrl":"10.1016/j.xfnr.2025.100089","url":null,"abstract":"<div><div>Endometriosis, a chronic inflammatory condition, is characterized by the growth of endometrial-like tissue outside the uterus, leading to debilitating pain and infertility. Although retrograde menstruation is widely accepted as a mechanism for the dissemination of endometrial cells to ectopic sites, the processes that enable their survival, invasion, and lesion formation remain incompletely understood. Epithelial-mesenchymal transition (EMT) has emerged as a potential driver, promoting cellular plasticity that supports ectopic implantation and invasion. Epithelial-mesenchymal transition is closely linked to inflammation, with transforming growth factor-β–mediated pathways playing a central role in driving these transitions. Chronic inflammation also induces fibroblast-myofibroblast transition (FMT) and smooth muscle metaplasia, processes that exacerbate fibrosis through excessive extracellular matrix deposition and fibroblast activation. These fibrotic changes worsen symptoms and contribute to disease progression. This review explores EMT and FMT as key mechanistic links between inflammation and fibrosis and discusses how targeting these pathways could offer novel therapeutic strategies to disrupt fibrotic progression, alleviate symptoms, and improve patient outcomes. Additionally, EMT and FMT markers hold promise as diagnostic tools, offering potential for earlier detection and more precise staging of endometriosis.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645032","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 : 2025-01-21DOI: 10.1016/j.xfnr.2025.100088
Yusuf Beebeejaun M.R.C.O.G. , Timothy Copeland Ph.D. , Ippokratis Sarris D.M., F.R.C.O.G. , Marian Showell M.P.H. , Sesh K. Sunkara M.R.C.O.G. , James M.N. Duffy D.Phil.
Objective
With the use of two-dimensional ultrasound (2D US) in embryo transfer (ET) procedures now a widely accepted practice, and preferred over clinical touch (CT), there is growing interest in whether three-dimensional (3D) and four-dimensional (4D) US provide better outcomes for ET compared with traditional 2D methods. We aim to perform a network meta-analysis (NMA) to compare the clinical efficacy and safety of CT, 2D transabdominal (TAUS), 2D transvaginal (TVUS), 3D, and 4D US-guided ET.
Evidence Review
Randomized controlled trials (RCTs) indexed in PubMed, MEDLINE, EMBASE, clinical trial registries, and Cochrane Database of Systematic Reviews were searched from inception to December 2023. Identified RCTs were assessed for trustworthiness using the Trustworthiness in RAndomized Controlled Trials. Statistical analysis for pairwise was performed using Review Manager version 5.3 and NMAs were performed using STATA version 16. Random-effects modeling was used for data-pooling. Key outcomes included clinical pregnancy (CPRs) and live birth rates (LBRs), miscarriage rates, and ectopic pregnancy rates.
Results
Twenty-five RCTs of high integrity assessing 8,884 ET outcomes comparing CT, 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET were included. The NMA identified lower LBR with CT (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.59–1.03) compared with 2D TAUS. There were no significant differences in LBR between other methods, including 2D TVUS vs. 2D TAUS (RR: 1.03, 95% CI: 0.61–1.74), and 3D TAUS vs. 2D TAUS (RR: 1.01, 95% CI: 0.78–1.32). Clinical touch-guided ET was associated with a lower CPR compared with 2D TAUS (RR: 0.83, 95% CI: 0.75–0.91). There was no significant CPR difference comparing 2D TVUS vs. 2D (RR: 0.98, 95% CI: 0.83–1.16), 3D TAUS vs. 2D TAUS (RR 0.98, 95% CI: 0.80–1.20). Four-dimensional TVUS did not show a significant difference in either LBR or CPR compared with 2D TAUS, 3D TAUS, or CT.
Conclusion
For CPR, our study reinforces that ET guided by CT alone is inferior to 2D TAUS-guided transfer. However, when comparing 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET, we found no evidence of significant differences in LBR, CPR, miscarriage rates, or ectopic pregnancy rates. The certainty of evidence for our primary outcome of CPR was rated as moderate, reflecting confidence in the results, but with notable concerns regarding study limitations and paucity of trials assessing the use of 3D and 4D US.
{"title":"Effectiveness of clinical touch, 2D, 3D, and 4D ultrasound guided embryo transfer: a systematic review and network meta-analysis of embryo transfer techniques","authors":"Yusuf Beebeejaun M.R.C.O.G. , Timothy Copeland Ph.D. , Ippokratis Sarris D.M., F.R.C.O.G. , Marian Showell M.P.H. , Sesh K. Sunkara M.R.C.O.G. , James M.N. Duffy D.Phil.","doi":"10.1016/j.xfnr.2025.100088","DOIUrl":"10.1016/j.xfnr.2025.100088","url":null,"abstract":"<div><h3>Objective</h3><div>With the use of two-dimensional ultrasound (2D US) in embryo transfer (ET) procedures now a widely accepted practice, and preferred over clinical touch (CT), there is growing interest in whether three-dimensional (3D) and four-dimensional (4D) US provide better outcomes for ET compared with traditional 2D methods. We aim to perform a network meta-analysis (NMA) to compare the clinical efficacy and safety of CT, 2D transabdominal (TAUS), 2D transvaginal (TVUS), 3D, and 4D US-guided ET.</div></div><div><h3>Evidence Review</h3><div>Randomized controlled trials (RCTs) indexed in PubMed, MEDLINE, EMBASE, clinical trial registries, and Cochrane Database of Systematic Reviews were searched from inception to December 2023. Identified RCTs were assessed for trustworthiness using the Trustworthiness in RAndomized Controlled Trials. Statistical analysis for pairwise was performed using Review Manager version 5.3 and NMAs were performed using STATA version 16. Random-effects modeling was used for data-pooling. Key outcomes included clinical pregnancy (CPRs) and live birth rates (LBRs), miscarriage rates, and ectopic pregnancy rates.</div></div><div><h3>Results</h3><div>Twenty-five RCTs of high integrity assessing 8,884 ET outcomes comparing CT, 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET were included. The NMA identified lower LBR with CT (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.59–1.03) compared with 2D TAUS. There were no significant differences in LBR between other methods, including 2D TVUS vs. 2D TAUS (RR: 1.03, 95% CI: 0.61–1.74), and 3D TAUS vs. 2D TAUS (RR: 1.01, 95% CI: 0.78–1.32). Clinical touch-guided ET was associated with a lower CPR compared with 2D TAUS (RR: 0.83, 95% CI: 0.75–0.91). There was no significant CPR difference comparing 2D TVUS vs. 2D (RR: 0.98, 95% CI: 0.83–1.16), 3D TAUS vs. 2D TAUS (RR 0.98, 95% CI: 0.80–1.20). Four-dimensional TVUS did not show a significant difference in either LBR or CPR compared with 2D TAUS, 3D TAUS, or CT.</div></div><div><h3>Conclusion</h3><div>For CPR, our study reinforces that ET guided by CT alone is inferior to 2D TAUS-guided transfer. However, when comparing 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET, we found no evidence of significant differences in LBR, CPR, miscarriage rates, or ectopic pregnancy rates. The certainty of evidence for our primary outcome of CPR was rated as moderate, reflecting confidence in the results, but with notable concerns regarding study limitations and paucity of trials assessing the use of 3D and 4D US.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644957","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 : 2025-01-21DOI: 10.1016/j.xfnr.2025.100087
Addison W. Alley M.D. , Jonathan E. Constance Ph.D. , Joseph M. Letourneau M.D.
As advances in cancer therapy have significantly improved mortality rates, there is increasing emphasis on improving quality of life for cancer survivors. One such area of focus is in maintaining fertility, as both chemotherapy and radiation therapy carry significant risks of causing infertility through various mechanisms of gonadal injury. Although fertility preservation options exist, such as sperm or egg banking, they are not always available or indicated for all patients. Fertoprotective agents are proposed substances that may serve to protect the gonad from the harmful impacts of cancer therapy to maintain fertility. However, caution must be taken to evaluate whether these agents could act similarly to protect the tumor from anticancer therapies. In this narrative review, we first describe the various mechanisms by which chemotherapy or radiation therapy can cause gonadal harm. We then review the available research on fertoprotective agents and their proposed mechanisms of gonadal protection. Finally, we discuss what evidence exists for interaction with cancer therapy for each agent, with an emphasis on opportunities for future research.
{"title":"Fertoprotective agents and tumor response: a narrative review","authors":"Addison W. Alley M.D. , Jonathan E. Constance Ph.D. , Joseph M. Letourneau M.D.","doi":"10.1016/j.xfnr.2025.100087","DOIUrl":"10.1016/j.xfnr.2025.100087","url":null,"abstract":"<div><div>As advances in cancer therapy have significantly improved mortality rates, there is increasing emphasis on improving quality of life for cancer survivors. One such area of focus is in maintaining fertility, as both chemotherapy and radiation therapy carry significant risks of causing infertility through various mechanisms of gonadal injury. Although fertility preservation options exist, such as sperm or egg banking, they are not always available or indicated for all patients. Fertoprotective agents are proposed substances that may serve to protect the gonad from the harmful impacts of cancer therapy to maintain fertility. However, caution must be taken to evaluate whether these agents could act similarly to protect the tumor from anticancer therapies. In this narrative review, we first describe the various mechanisms by which chemotherapy or radiation therapy can cause gonadal harm. We then review the available research on fertoprotective agents and their proposed mechanisms of gonadal protection. Finally, we discuss what evidence exists for interaction with cancer therapy for each agent, with an emphasis on opportunities for future research.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421240","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}
Pub Date : 2025-01-03DOI: 10.1016/j.xfnr.2024.100086
Krishnika Vetrivel M.B.B.S. , Ayesha Salejee M.B.B.S. , Bheena Kharunyam M.B.B.S. , Hakim-Moulay Dehbi Ph.D. , Spiros Denaxas Ph.D. , Nicholas Freemantle Ph.D. , Bassel H. Al Wattar Ph.D.
Importance
Ovarian hyperstimulation syndrome (OHSS) is a common iatrogenic complication of controlled ovarian stimulation (COS) in assisted conception. OHSS can be life-threatening and associated with significant morbidity. Several measures could help prevent OHSS; however, accurate risk prediction remains a challenge to enable early prevention.
Objective
To review available prediction models for OHSS in women undergoing assisted conception and to identify the best-performing models for their accuracy, generalizability, and applicability.
Evidence review
We searched electronic databases (MEDLINE, EMBASE, and CENTRAL) until October 2023. We included studies reporting on the development or evaluation of models predicting the risk of OHSS outcomes before or during COS among women undergoing assisted conception. We reported on models’ discrimination, calibration, type of validation, and any implementation tools for clinical practice.
Findings
We screened 5,699 citations and included 14 observational cohort studies reporting on 14 prediction models. The median sample size was 782 participants (range 105–256,381), and the majority of models were developed using logistic regression (13/14, 92.9%). The commonest predictor was maternal age (7/14, 50.0%), followed by number of antral and mature follicles (6/14, 42.9%). Six models were internally validated (6/14, 42.9%), and none were externally validated. Only one model had an implementation platform as a smartphone-based application (1/14, 7.1%). Most of the included studies had an unclear risk of bias (7/14, 50.0%), and only three studies were at low risk (3/13, 21.4%).
Conclusion and relevance
There are no clinically appropriate and validated prediction models for OHSS among women undergoing controlled ovarian stimulation. More research is needed to improve their generalizability and applicability into clinical practice.
{"title":"Predicting the risk of ovarian hyperstimulation syndrome in women undergoing assisted reproductive technology treatments: a systematic review and quality assessment of prediction models","authors":"Krishnika Vetrivel M.B.B.S. , Ayesha Salejee M.B.B.S. , Bheena Kharunyam M.B.B.S. , Hakim-Moulay Dehbi Ph.D. , Spiros Denaxas Ph.D. , Nicholas Freemantle Ph.D. , Bassel H. Al Wattar Ph.D.","doi":"10.1016/j.xfnr.2024.100086","DOIUrl":"10.1016/j.xfnr.2024.100086","url":null,"abstract":"<div><h3>Importance</h3><div>Ovarian hyperstimulation syndrome (OHSS) is a common iatrogenic complication of controlled ovarian stimulation (COS) in assisted conception. OHSS can be life-threatening and associated with significant morbidity. Several measures could help prevent OHSS; however, accurate risk prediction remains a challenge to enable early prevention.</div></div><div><h3>Objective</h3><div>To review available prediction models for OHSS in women undergoing assisted conception and to identify the best-performing models for their accuracy, generalizability, and applicability.</div></div><div><h3>Evidence review</h3><div>We searched electronic databases (MEDLINE, EMBASE, and CENTRAL) until October 2023. We included studies reporting on the development or evaluation of models predicting the risk of OHSS outcomes before or during COS among women undergoing assisted conception. We reported on models’ discrimination, calibration, type of validation, and any implementation tools for clinical practice.</div></div><div><h3>Findings</h3><div>We screened 5,699 citations and included 14 observational cohort studies reporting on 14 prediction models. The median sample size was 782 participants (range 105–256,381), and the majority of models were developed using logistic regression (13/14, 92.9%). The commonest predictor was maternal age (7/14, 50.0%), followed by number of antral and mature follicles (6/14, 42.9%). Six models were internally validated (6/14, 42.9%), and none were externally validated. Only one model had an implementation platform as a smartphone-based application (1/14, 7.1%). Most of the included studies had an unclear risk of bias (7/14, 50.0%), and only three studies were at low risk (3/13, 21.4%).</div></div><div><h3>Conclusion and relevance</h3><div>There are no clinically appropriate and validated prediction models for OHSS among women undergoing controlled ovarian stimulation. More research is needed to improve their generalizability and applicability into clinical practice.</div></div><div><h3>PROSPERO</h3><div>CRD42024509423</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428788","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}
Preimplantation genetic testing for polygenic disorders (PGT-P) has been commercially available since 2019. Preimplantation genetic testing for polygenic disorders makes use of polygenic risk scores for conditions that are multifactorial and are significantly influenced by environmental and lifestyle factors. If current predictions are accurate, then absolute risk reductions range from approximately 0.02% to 10.1%, meaning that between 10 and 5,000 in vitro fertilization patients would need to be tested with PGT-P to prevent 1 offspring from becoming affected in the future, depending on the condition and the number of embryos available. Survey and interview data reveal that patients and the public have largely favorable views regarding the use of PGT-P for disease prevention; however, clinicians and professional organizations have many reservations. The use of PGT-P raises multiple social and ethical concerns including the need for adequate counseling, the setting of realistic expectations, the application of distributive justice, the impact of environmental and social determinants of health, and the potential exacerbation of health inequities. Clinicians expressed significant concerns relating to the cost of PGT-P, the potential time-consuming counseling for reproductive endocrinologists and genetic counselors, the intentional creation of supernumerary embryos, and patients’ unrealistic expectations regarding “healthiest disease-free” embryos. Furthermore, current evidence lacks long-term outcome data and generalizability. Before offering PGT-P to patients, additional clinical validation studies are needed. Also, ethical and social considerations raised by PGT-P should be carefully delineated. Systemic practices to increase equitable access to unbiased genetic counseling and reproductive services would be desirable before the ethical implementation of PGT-P.
{"title":"Promises and pitfalls of preimplantation genetic testing for polygenic disorders: a narrative review","authors":"Jaime A. Roura-Monllor M.D., M.S. , Zachary Walker M.D. , Joel M. Reynolds Ph.D. , Greysha Rivera-Cruz M.D. , Avner Hershlag M.D. , Gheona Altarescu M.D. , Sigal Klipstein M.D. , Stacey Pereira Ph.D. , Gabriel Lázaro-Muñoz Ph.D., J.D. , Shai Carmi Ph.D. , Todd Lencz Ph.D. , Ruth Bunker Lathi M.D.","doi":"10.1016/j.xfnr.2024.100085","DOIUrl":"10.1016/j.xfnr.2024.100085","url":null,"abstract":"<div><div>Preimplantation genetic testing for polygenic disorders (PGT-P) has been commercially available since 2019. Preimplantation genetic testing for polygenic disorders makes use of polygenic risk scores for conditions that are multifactorial and are significantly influenced by environmental and lifestyle factors. If current predictions are accurate, then absolute risk reductions range from approximately 0.02% to 10.1%, meaning that between 10 and 5,000 in vitro fertilization patients would need to be tested with PGT-P to prevent 1 offspring from becoming affected in the future, depending on the condition and the number of embryos available. Survey and interview data reveal that patients and the public have largely favorable views regarding the use of PGT-P for disease prevention; however, clinicians and professional organizations have many reservations. The use of PGT-P raises multiple social and ethical concerns including the need for adequate counseling, the setting of realistic expectations, the application of distributive justice, the impact of environmental and social determinants of health, and the potential exacerbation of health inequities. Clinicians expressed significant concerns relating to the cost of PGT-P, the potential time-consuming counseling for reproductive endocrinologists and genetic counselors, the intentional creation of supernumerary embryos, and patients’ unrealistic expectations regarding “healthiest disease-free” embryos. Furthermore, current evidence lacks long-term outcome data and generalizability. Before offering PGT-P to patients, additional clinical validation studies are needed. Also, ethical and social considerations raised by PGT-P should be carefully delineated. Systemic practices to increase equitable access to unbiased genetic counseling and reproductive services would be desirable before the ethical implementation of PGT-P.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134274","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 : 2024-12-04DOI: 10.1016/j.xfnr.2024.100084
Noemie Sachs-Guedj M.D. , Piotr Sokol M.D. , Tania Quesada-López Ph.D. , Thomas Freour Pharm.D., Ph.D. , Nikolaos P. Polyzos Ph.D. , Francisca Martinez Ph.D.
Objective
The aim of this systematic review is to provide the first comprehensive overview of the current knowledge regarding the role of the alpha-Klotho protein in male and female fertility, focusing on the testicle, spermatozoa, ovary, and oocyte.
Evidence Review
A comprehensive literature search was conducted up to March 2024 to determine the role of Klotho (KL, alpha-Klotho) in human reproductive tissues. The search terms included the following: “Klotho” AND “Sperm” OR “Testicle” OR “Oocyte” OR “Ovary” OR “Reproduction” OR “Fertility” OR “Infertility” OR “Gamete” OR “Gonad.” Following Cochrane methodology, the search covered MEDLINE, EMBASE, Cochrane Library, National Center for Biotechnology Information Gene, Tabula Sapiens, GTEx, Trip Database, Google Scholar, medRxiv, Open Grey, Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry, including all relevant studies up to March 2024 without language or publication status restrictions. The focus was on the role of alpha-Klotho in fertility, including studies involving animals and humans and basic experimental or observational designs. After removing duplicates, 2 investigators (N.S-.G., F.M.) independently screened titles and abstracts, with disagreements resolved by a third investigator (P.S.). The search identified a total of 258 articles, of which 18 were selected for the review. Final eligibility was determined by 4 investigators (N.S-.G., P.S., T.Q-.L., F.M.).
Results
The Klotho protein levels decrease with age. This decline influences male fertility by impacting spermatogenesis, sperm maturation, androgen production, and local homeostasis. In women, KL influences ovulatory function by inhibiting hypothalamic gonadotropin-releasing hormone secretion, regulating growth hormone secretion and oocyte quality, and controlling granulosa cells and follicular apoptosis. Overall, animal and human studies indicate that Klotho is an important factor in fertility, contributing to sperm quality and oocyte maturation and development. Additionally, the antioxidant properties of KL may help preserve the integrity of sperm cells and could serve as an effective antioxidant for the cryopreservation of ovarian tissue.
Conclusion
Further research is warranted to fully understand the mechanisms underlying the role of KL protein in human fertility, both as a potential biomarker and as a therapeutic target for infertility treatments and fertility preservation strategies. Advances in functional genetic variations studies will clarify the pathways linking genotype to phenotype in reproductive health.
目的：本系统综述的目的是提供关于α - klotho蛋白在男性和女性生育能力中的作用的最新知识，重点是睾丸、精子、卵巢和卵母细胞。为了确定Klotho （KL, alpha-Klotho）在人类生殖组织中的作用，我们进行了截至2024年3月的全面文献检索。搜索词包括：“克洛索”、“精子”、“睾丸”、“卵母细胞”、“卵巢”、“生殖”、“生育能力”、“不育”、“配子”、“性腺”。按照Cochrane的方法，检索涵盖MEDLINE、EMBASE、Cochrane图书馆、国家生物技术信息基因中心、Tabula Sapiens、GTEx、Trip Database、谷歌Scholar、medRxiv、Open Grey、Central Register of Controlled Trials和World Health Organization International Clinical Trials Registry，包括截至2024年3月的所有相关研究，没有语言或出版状态限制。重点是alpha-Klotho在生育方面的作用，包括涉及动物和人类的研究以及基本的实验或观察设计。在去除重复项后，2名调查人员(n.s. - g.g。， F.M.)独立筛选标题和摘要，分歧由第三方研究者解决（P.S.）。检索共发现258篇文章，其中18篇入选综述。最终入选资格由4名研究者（n.s. - g.g）决定。， p.s., t.q - l。F.M.)。结果Klotho蛋白水平随年龄增长而降低。这种下降通过影响精子发生、精子成熟、雄激素产生和局部稳态来影响男性生育能力。在女性中，KL通过抑制下丘脑促性腺激素释放激素分泌、调节生长激素分泌和卵母细胞质量、控制颗粒细胞和卵泡凋亡来影响排卵功能。总的来说，动物和人体研究表明，Klotho是生育能力的重要因素，有助于精子质量和卵母细胞的成熟和发育。此外，KL的抗氧化特性可能有助于保持精子细胞的完整性，并可作为卵巢组织冷冻保存的有效抗氧化剂。结论KL蛋白在人类生育中的作用机制有待进一步研究，无论是作为潜在的生物标志物，还是作为不孕症治疗和生育保护策略的治疗靶点。功能遗传变异研究的进展将阐明生殖健康中基因型与表型的联系途径。
{"title":"The role of alpha-Klotho protein in male and female reproduction. A systematic review","authors":"Noemie Sachs-Guedj M.D. , Piotr Sokol M.D. , Tania Quesada-López Ph.D. , Thomas Freour Pharm.D., Ph.D. , Nikolaos P. Polyzos Ph.D. , Francisca Martinez Ph.D.","doi":"10.1016/j.xfnr.2024.100084","DOIUrl":"10.1016/j.xfnr.2024.100084","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this systematic review is to provide the first comprehensive overview of the current knowledge regarding the role of the alpha-Klotho protein in male and female fertility, focusing on the testicle, spermatozoa, ovary, and oocyte.</div></div><div><h3>Evidence Review</h3><div>A comprehensive literature search was conducted up to March 2024 to determine the role of Klotho (KL, alpha-Klotho) in human reproductive tissues. The search terms included the following: “Klotho” AND “Sperm” OR “Testicle” OR “Oocyte” OR “Ovary” OR “Reproduction” OR “Fertility” OR “Infertility” OR “Gamete” OR “Gonad.” Following Cochrane methodology, the search covered MEDLINE, EMBASE, Cochrane Library, National Center for Biotechnology Information Gene, Tabula Sapiens, GTEx, Trip Database, Google Scholar, medRxiv, Open Grey, Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry, including all relevant studies up to March 2024 without language or publication status restrictions. The focus was on the role of alpha-Klotho in fertility, including studies involving animals and humans and basic experimental or observational designs. After removing duplicates, 2 investigators (N.S-.G., F.M.) independently screened titles and abstracts, with disagreements resolved by a third investigator (P.S.). The search identified a total of 258 articles, of which 18 were selected for the review. Final eligibility was determined by 4 investigators (N.S-.G., P.S., T.Q-.L., F.M.).</div></div><div><h3>Results</h3><div>The Klotho protein levels decrease with age. This decline influences male fertility by impacting spermatogenesis, sperm maturation, androgen production, and local homeostasis. In women, KL influences ovulatory function by inhibiting hypothalamic gonadotropin-releasing hormone secretion, regulating growth hormone secretion and oocyte quality, and controlling granulosa cells and follicular apoptosis. Overall, animal and human studies indicate that Klotho is an important factor in fertility, contributing to sperm quality and oocyte maturation and development. Additionally, the antioxidant properties of KL may help preserve the integrity of sperm cells and could serve as an effective antioxidant for the cryopreservation of ovarian tissue.</div></div><div><h3>Conclusion</h3><div>Further research is warranted to fully understand the mechanisms underlying the role of KL protein in human fertility, both as a potential biomarker and as a therapeutic target for infertility treatments and fertility preservation strategies. Advances in functional genetic variations studies will clarify the pathways linking genotype to phenotype in reproductive health.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134271","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}
Many adolescents and young women experience dysmenorrhea, a condition that is often trivialized or overlooked but can cause a substantial deterioration in health-related quality of life. Therefore, we conducted a systematic review and meta-analysis to investigate the overall prevalence of symptomatic individuals with ultrasound/magnetic resonance imaging–diagnosed adenomyosis in the 12–25 year-age group. This could inform management and treatment decisions.
Evidence Review
The PubMed/Medline, Embase, and Scopus databases were searched for full-length, English-language reports published between 2015 and 2024. This systematic review with meta-analysis was conducted and reported following the Joanna Briggs Institute methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. We included observational studies that assessed the number of patients with adenomyosis among adolescents and young women, the majority of whom presented with dysmenorrhea. The methodological quality of the included studies and their potential risk of bias were ascertained using the Joanna Briggs Institute Critical Appraisal Tool for Prevalence Studies. The main outcome was the prevalence of adenomyosis among symptomatic adolescents (midpoint of the study age range, <20 years) and young women (midpoint of the study age range, ≥20 years). Three meta-analyses, categorized by age, were performed using Stata to pool adenomyosis prevalence data from selected studies. The risk of endometriosis in women with and without adenomyosis was ultimately assessed as an exploratory and confirmatory investigation by combining the odds ratio estimates from each study using the random-effects model.
Results
Six studies comprising 1,300 individuals met the inclusion criteria. The prevalence of adenomyosis ranged from 5.9% to 46.0%, with an overall weighted mean of 20.7% (95% confidence interval [CI], 11.5–31.6) with high heterogeneity (I2 = 94.8%). The aggregate estimates were as 16.9% (95% CI, 8.8%–27.0%) in the adolescent subgroup and 29.7% (95% CI, 17.5%–43.5%) in the young woman subgroup. The risk of endometriosis in patients with adenomyosis was significantly higher than that in patients without adenomyosis, with a pooled odds ratio of 3.39 (95% CI, 2.11–5.45), without statistically significant heterogeneity across studies.
Conclusion
The findings of the present review should assist clinicians in developing a high index of suspicion for adenomyosis when adolescents and young women present with chronic severe dysmenorrhea and menorrhagia. Limiting the diagnostic delay and considering secondary prevention medical interventions may improve the quality of life and limit the risk of disease progression. Further rigorous prospective analytic studies are required to better defi
{"title":"Prevalence of adenomyosis in symptomatic adolescents and young women: a systematic review and meta-analysis","authors":"Paolo Vercellini M.D. , Camilla Buffo R.M. , Veronica Bandini M.D. , Sonia Cipriani Sc.D. , Francesca Chiaffarino M.Sc. , Paola Viganò Ph.D. , Edgardo Somigliana M.D., Ph.D.","doi":"10.1016/j.xfnr.2024.100083","DOIUrl":"10.1016/j.xfnr.2024.100083","url":null,"abstract":"<div><h3>Objective</h3><div>Many adolescents and young women experience dysmenorrhea, a condition that is often trivialized or overlooked but can cause a substantial deterioration in health-related quality of life. Therefore, we conducted a systematic review and meta-analysis to investigate the overall prevalence of symptomatic individuals with ultrasound/magnetic resonance imaging–diagnosed adenomyosis in the 12–25 year-age group. This could inform management and treatment decisions.</div></div><div><h3>Evidence Review</h3><div>The PubMed/Medline, Embase, and Scopus databases were searched for full-length, English-language reports published between 2015 and 2024. This systematic review with meta-analysis was conducted and reported following the Joanna Briggs Institute methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. We included observational studies that assessed the number of patients with adenomyosis among adolescents and young women, the majority of whom presented with dysmenorrhea. The methodological quality of the included studies and their potential risk of bias were ascertained using the Joanna Briggs Institute Critical Appraisal Tool for Prevalence Studies. The main outcome was the prevalence of adenomyosis among symptomatic adolescents (midpoint of the study age range, <20 years) and young women (midpoint of the study age range, ≥20 years). Three meta-analyses, categorized by age, were performed using Stata to pool adenomyosis prevalence data from selected studies. The risk of endometriosis in women with and without adenomyosis was ultimately assessed as an exploratory and confirmatory investigation by combining the odds ratio estimates from each study using the random-effects model.</div></div><div><h3>Results</h3><div>Six studies comprising 1,300 individuals met the inclusion criteria. The prevalence of adenomyosis ranged from 5.9% to 46.0%, with an overall weighted mean of 20.7% (95% confidence interval [CI], 11.5–31.6) with high heterogeneity (<em>I</em><sup><em>2</em></sup> = 94.8%). The aggregate estimates were as 16.9% (95% CI, 8.8%–27.0%) in the adolescent subgroup and 29.7% (95% CI, 17.5%–43.5%) in the young woman subgroup. The risk of endometriosis in patients with adenomyosis was significantly higher than that in patients without adenomyosis, with a pooled odds ratio of 3.39 (95% CI, 2.11–5.45), without statistically significant heterogeneity across studies.</div></div><div><h3>Conclusion</h3><div>The findings of the present review should assist clinicians in developing a high index of suspicion for adenomyosis when adolescents and young women present with chronic severe dysmenorrhea and menorrhagia. Limiting the diagnostic delay and considering secondary prevention medical interventions may improve the quality of life and limit the risk of disease progression. Further rigorous prospective analytic studies are required to better defi","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134270","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 : 2024-11-16DOI: 10.1016/j.xfnr.2024.100082
Ilya Volodyaev Ph.D. , Anna Ivanova M.Sc. , Elena Korchivaia M.Sc. , Alexey Surnov Ph.D. , Ekaterina Pomerantseva M.D., Ph.D. , Igor N. Lebedev M.D., Ph.D., Dr.Biol.Sc. , Maria L. Semenova Ph.D., Dr.Biol.Sc. , Ilya Mazunin Ph.D.
Chromosomal aberrations, such as whole-chromosome aneuploidies, segmental aneuploidies, whole-chromosome mosaicism, and segmental mosaicism, are key factors influencing embryonic development and the outcomes of fertility programs. This analytic review critically examines the prevalence and origins of these genetic abnormalities, emphasizing the significant maternal contribution to whole-chromosome aneuploidies and the age-related nature of these aberrations. In contrast, segmental aneuploidies, whole-chromosome mosaicism, and segmental mosaicism appear largely age-independent and show considerable variability across studies, mainly due to technical artifacts and methodological differences. By analyzing the accumulated data, scrutinizing methodological discrepancies in preimplantation genetic testing for aneuploidies, and distinguishing between biologic phenomena and artifacts, this review aims to clarify the current understanding of chromosomal aberrations in human embryos and their impact on reproductive health.
{"title":"The chromosomal challenge of human embryos: prevalence of aneuploidy and mosaicism","authors":"Ilya Volodyaev Ph.D. , Anna Ivanova M.Sc. , Elena Korchivaia M.Sc. , Alexey Surnov Ph.D. , Ekaterina Pomerantseva M.D., Ph.D. , Igor N. Lebedev M.D., Ph.D., Dr.Biol.Sc. , Maria L. Semenova Ph.D., Dr.Biol.Sc. , Ilya Mazunin Ph.D.","doi":"10.1016/j.xfnr.2024.100082","DOIUrl":"10.1016/j.xfnr.2024.100082","url":null,"abstract":"<div><div>Chromosomal aberrations, such as whole-chromosome aneuploidies, segmental aneuploidies, whole-chromosome mosaicism, and segmental mosaicism, are key factors influencing embryonic development and the outcomes of fertility programs. This analytic review critically examines the prevalence and origins of these genetic abnormalities, emphasizing the significant maternal contribution to whole-chromosome aneuploidies and the age-related nature of these aberrations. In contrast, segmental aneuploidies, whole-chromosome mosaicism, and segmental mosaicism appear largely age-independent and show considerable variability across studies, mainly due to technical artifacts and methodological differences. By analyzing the accumulated data, scrutinizing methodological discrepancies in preimplantation genetic testing for aneuploidies, and distinguishing between biologic phenomena and artifacts, this review aims to clarify the current understanding of chromosomal aberrations in human embryos and their impact on reproductive health.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134273","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}
Pub Date : 2024-11-06DOI: 10.1016/j.xfnr.2024.100081
Ana K. Rosen Vollmar Ph.D. , Shruthi Mahalingaiah M.D. , Anne Marie Jukic Ph.D.
Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here, we review the scientific evidence showing how the menstrual cycle meets these criteria and should, therefore, be treated as a vital sign. Using key words and controlled vocabulary terms, we performed multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, how it cyclically can impact health conditions, and its associations with long-term postmenopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplemental materials include patient handouts on menstrual cycle tracking and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underused but powerful tool for understanding gynecological and general health.
{"title":"The menstrual cycle as a vital sign: a comprehensive review","authors":"Ana K. Rosen Vollmar Ph.D. , Shruthi Mahalingaiah M.D. , Anne Marie Jukic Ph.D.","doi":"10.1016/j.xfnr.2024.100081","DOIUrl":"10.1016/j.xfnr.2024.100081","url":null,"abstract":"<div><div>Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here, we review the scientific evidence showing how the menstrual cycle meets these criteria and should, therefore, be treated as a vital sign. Using key words and controlled vocabulary terms, we performed multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, how it cyclically can impact health conditions, and its associations with long-term postmenopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplemental materials include patient handouts on menstrual cycle tracking and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underused but powerful tool for understanding gynecological and general health.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134272","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}
Pub Date : 2024-08-30DOI: 10.1016/j.xfnr.2024.100079
Megan R. Sax M.D. , Carolyn Nietupski B.S. , Rachel E. Warwar M.D. , Andreja Moset Zupan B.S. , Emily G. Hurley M.D. , Stacey C. Schutte Ph.D.
Uterine fibroids are exposed to significant mechanical forces due to routine, monthly uterine contractions and have also been found to generate contractions in the junctional zone or inner myometrium. These are not the only mechanical forces that uterine fibroids experience but also compression and strain, or percent change in length, due to the stiff extracellular matrix of the fibroids. The forces may vary by location within the tumor. Strong uterine contractions not only cause pain but may also contribute to uterine fibroid growth, which, in turn, may lead to worsening symptom severity. This review discusses uterine contractions in the nonpregnant uterus and what is known about the impacts of mechanical forces on uterine fibroid cells.
{"title":"Stressed out: how forces from uterine contractions influence fibroid progression, a Narrative Review","authors":"Megan R. Sax M.D. , Carolyn Nietupski B.S. , Rachel E. Warwar M.D. , Andreja Moset Zupan B.S. , Emily G. Hurley M.D. , Stacey C. Schutte Ph.D.","doi":"10.1016/j.xfnr.2024.100079","DOIUrl":"10.1016/j.xfnr.2024.100079","url":null,"abstract":"<div><div>Uterine fibroids are exposed to significant mechanical forces due to routine, monthly uterine contractions and have also been found to generate contractions in the junctional zone or inner myometrium. These are not the only mechanical forces that uterine fibroids experience but also compression and strain, or percent change in length, due to the stiff extracellular matrix of the fibroids. The forces may vary by location within the tumor. Strong uterine contractions not only cause pain but may also contribute to uterine fibroid growth, which, in turn, may lead to worsening symptom severity. This review discusses uterine contractions in the nonpregnant uterus and what is known about the impacts of mechanical forces on uterine fibroid cells.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"5 4","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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