Pub Date : 2022-10-01DOI: 10.1016/j.xfnr.2022.06.003
Judy E. Stern Ph.D , Leslie V. Farland Sc.D. , Sunah S. Hwang M.D., M.P.H., Ph.D. , Dmitry Dukhovny M.D., M.P.H. , Charles C. Coddington M.D. , Howard J. Cabral Ph.D. , Stacey A. Missmer Sc.D. , Eugene Declercq Ph.D. , Hafsatou Diop M.D., M.P.H.
Assisted reproductive technology (ART, defined here as including only in vitro fertilization and related technologies) is associated with increased adverse pregnancy, neonatal, and childhood developmental outcomes, even in singletons. The comparison group for many of these studies has often been a fertile population that conceived without assistance. The Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART) was initiated to define a subfertile population with which to compare ART outcomes. Over >10 years, we have used the MOSART database to not only study pregnancy abnormalities and delivery complications but also evaluate ongoing health of women, infants, and children. This article will review studies from the MOSART in the context of how they compare with those of other investigations. We will present MOSART studies that identified the influence of ART and subfertility/infertility on adverse pregnancy (pregnancy hypertensive disorder, gestational diabetes, and placental abnormality) and delivery (preterm birth and low birth weight) outcomes as well as on maternal and child hospitalizations. We will provide evidence that although subfertility/infertility increases the risk of adverse outcomes, there is additional risk associated with the use of ART. Studies exploring the contribution of placental abnormalities as a factor adding to this increased ART-associated risk will be described.
{"title":"Assisted reproductive technology or infertility: What underlies adverse outcomes? Lessons from the Massachusetts Outcome Study of Assisted Reproductive Technology","authors":"Judy E. Stern Ph.D , Leslie V. Farland Sc.D. , Sunah S. Hwang M.D., M.P.H., Ph.D. , Dmitry Dukhovny M.D., M.P.H. , Charles C. Coddington M.D. , Howard J. Cabral Ph.D. , Stacey A. Missmer Sc.D. , Eugene Declercq Ph.D. , Hafsatou Diop M.D., M.P.H.","doi":"10.1016/j.xfnr.2022.06.003","DOIUrl":"10.1016/j.xfnr.2022.06.003","url":null,"abstract":"<div><p>Assisted reproductive technology (ART, defined here as including only in vitro fertilization and related technologies) is associated with increased adverse pregnancy, neonatal, and childhood developmental outcomes, even in singletons. The comparison group for many of these studies has often been a fertile population that conceived without assistance. The Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART) was initiated to define a subfertile population with which to compare ART outcomes. Over >10 years, we have used the MOSART database to not only study pregnancy abnormalities and delivery complications but also evaluate ongoing health of women, infants, and children. This article will review studies from the MOSART in the context of how they compare with those of other investigations. We will present MOSART studies that identified the influence of ART and subfertility/infertility on adverse pregnancy (pregnancy hypertensive disorder, gestational diabetes, and placental abnormality) and delivery (preterm birth and low birth weight) outcomes as well as on maternal and child hospitalizations. We will provide evidence that although subfertility/infertility increases the risk of adverse outcomes, there is additional risk associated with the use of ART. Studies exploring the contribution of placental abnormalities as a factor adding to this increased ART-associated risk will be described.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9733832/pdf/nihms-1834461.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10361445","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 : 2022-10-01DOI: 10.1016/j.xfnr.2022.07.004
Mia A. Charifson M.A. , Dorice Vieira M.A., M.P.H. , Jacquelyn Shaw M.D. , Siobhan Kehoe M.D. , Gwendolyn P. Quinn Ph.D.
Objective
To systematically review and summarize the literaure on nongenetic risk factors that may contribute to the racial disparity in uterine fibroids (UF) that disproportionality impacts Black individuals at 2-3 times the rate of White individuals and how the racial disparity has been studied to date.
Evidence Review
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol checklist guided the systematic review process. From January 1 to June 1, 2021, relevant articles were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library. Multiple investigators screened, assessed, extracted, and critically appraised the data.
Results
A total of 44 articles examined the relationship among UFs, race/ethnicity, and nongenetic risk factors, including cardiometabolic features, comorbidities, diet, chemical exposures, vitamin D levels, reproductive characteristics and socioeconomic factors, and life experiences. Most studies reported on the same 3 cohort study populations, and there was inconsistent statistical reporting of the race/ethnicity, risk factors, and UF relationship.
Conclusion
Many potential risk factors related to the racial disparity in UF have been studied thus far. There is still little conclusive evidence regarding which risk factors are the greatest contributors to racial disparities in UF. Promising areas of research deserve greater attention and a greater diversity of study populations and analytical methods.
目的系统回顾和总结有关非遗传危险因素可能导致黑人比例失调率为白人2-3倍的子宫肌瘤(UF)种族差异的文献,以及迄今为止有关种族差异的研究情况。证据评价系统评价和荟萃分析方案的首选报告项目清单指导了系统评价过程。从2021年1月1日至6月1日,检索PubMed、EMBASE、Web of Science和Cochrane Library的相关文章。多位研究者对数据进行筛选、评估、提取和批判性评估。结果共有44篇文章研究了UFs、种族/民族和非遗传风险因素之间的关系,包括心脏代谢特征、合并症、饮食、化学物质暴露、维生素D水平、生殖特征和社会经济因素以及生活经历。大多数研究报告了相同的3个队列研究人群,关于种族/民族、危险因素和UF关系的统计报告不一致。结论目前已经研究了许多与UF种族差异相关的潜在危险因素。关于哪些风险因素是佛罗里达大学种族差异的最大贡献者,仍然没有确凿的证据。有前途的研究领域应该得到更多的关注,研究人群和分析方法应该更加多样化。
{"title":"Why are Black individuals disproportionately burdened with uterine fibroids and how are we examining this disparity? A systematic review","authors":"Mia A. Charifson M.A. , Dorice Vieira M.A., M.P.H. , Jacquelyn Shaw M.D. , Siobhan Kehoe M.D. , Gwendolyn P. Quinn Ph.D.","doi":"10.1016/j.xfnr.2022.07.004","DOIUrl":"10.1016/j.xfnr.2022.07.004","url":null,"abstract":"<div><h3>Objective</h3><p><span>To systematically review and summarize the literaure on nongenetic risk factors that may contribute to the racial disparity in </span>uterine fibroids (UF) that disproportionality impacts Black individuals at 2-3 times the rate of White individuals and how the racial disparity has been studied to date.</p></div><div><h3>Evidence Review</h3><p>The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol checklist guided the systematic review process. From January 1 to June 1, 2021, relevant articles were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library. Multiple investigators screened, assessed, extracted, and critically appraised the data.</p></div><div><h3>Results</h3><p><span>A total of 44 articles examined the relationship among UFs, race/ethnicity, and nongenetic risk factors, including cardiometabolic features, comorbidities, diet, chemical exposures, vitamin D levels, reproductive characteristics and socioeconomic factors, and life experiences. Most studies reported on the same 3 </span>cohort study populations, and there was inconsistent statistical reporting of the race/ethnicity, risk factors, and UF relationship.</p></div><div><h3>Conclusion</h3><p>Many potential risk factors related to the racial disparity in UF have been studied thus far. There is still little conclusive evidence regarding which risk factors are the greatest contributors to racial disparities in UF. Promising areas of research deserve greater attention and a greater diversity of study populations and analytical methods.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126655210","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 : 2022-10-01DOI: 10.1016/j.xfnr.2022.07.001
Jawaria Amir M.D. , Sonali Gupta M.D. , Maria Amir B.B.A. , Roohi Jeelani M.D.
The transgender and nonbinary (TGNB) communities face unique challenges when deciding to forego or pursue fertility because of gender-affirming medical or surgical interventions. Options for these patients have historically been limited because of overt discrimination within the healthcare system. The purpose of this comprehensive review is to discuss trends in TGNB reproductive access and healthcare over the past 2 decades and survey past and current legislation regarding TGNB reproductive rights. To better identify barriers for TGNB population and trends regarding fertility preservation, our review examines the attitudes, knowledge, and beliefs of both TGNB persons and healthcare providers. Second, we conduct a review of past and present legislation regarding reproductive rights and access related to TGNB care. The findings of our review demonstrate a failure to meet the standard of care for TGNB individuals in regard to fertility care, which likely contributes to the low uptake of fertility preservation services among this population. Furthermore, we find that healthcare providers must play a crucial role in advocating for systemic changes that can help alleviate barriers and provide equitable, gender-affirming care for TGNB individuals across the reproductive health spectrum.
{"title":"Trends in fertility preservation and barriers encountered by transgender individuals: where we started and have we progressed? A comprehensive review","authors":"Jawaria Amir M.D. , Sonali Gupta M.D. , Maria Amir B.B.A. , Roohi Jeelani M.D.","doi":"10.1016/j.xfnr.2022.07.001","DOIUrl":"10.1016/j.xfnr.2022.07.001","url":null,"abstract":"<div><p><span><span>The transgender and nonbinary (TGNB) communities face unique challenges when deciding to forego or pursue fertility because of gender-affirming medical or surgical interventions. Options for these patients have historically been limited because of overt discrimination within the healthcare system. The purpose of this comprehensive review is to discuss trends in TGNB reproductive access and healthcare over the past 2 decades and survey past and current legislation regarding TGNB reproductive rights. To better identify barriers for TGNB population and trends regarding </span>fertility preservation, our review examines the attitudes, knowledge, and beliefs of both TGNB persons and healthcare providers. Second, we conduct a review of past and present legislation regarding reproductive rights and access related to TGNB care. The findings of our review demonstrate a failure to meet the standard of care for TGNB individuals in regard to fertility care, which likely contributes to the low uptake of fertility preservation services among this population. Furthermore, we find that healthcare providers must play a crucial role in advocating for systemic changes that can help alleviate barriers and provide equitable, gender-affirming care for TGNB individuals across the </span>reproductive health spectrum.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131515714","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}
Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases that play a critical role in morphogenesis, wound healing, and tissue repair. Uterine fibroids (UFs) are benign, fibrous smooth muscle tumors with excessive deposition of the extracellular matrix rich in interstitial collagen. This systematic review aims to rigorously assess current literature evaluating the role of MMPs in the pathoetiology of UFs.
Evidence Review
A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was conducted within PubMed, Embase, and Scopus databases. A data informationist was engaged to develop a comprehensive search strategy. Studies examining the MMP levels in leiomyoma and myometrium were searched. Two investigators independently screened and identified articles. Observational and interventional studies involving human subject research published in English up to January 2022 were included. Animal subject research, non-English articles, and reviews were excluded. The articles were assessed for risk of bias using the Newcastle-Ottawa scale. One investigator extracted the data, and a second investigator checked the accuracy. The extracted data were synthesized descriptively.
Results
The initial search yielded 235 articles. After reviewing titles, abstracts, and full texts, 30 observational studies were judged to meet the inclusion criteria. The expression levels of MMPs in leiomyomas and myometrium varied among subtypes of MMPs. Nine studies reported elevated levels of MMP-2 expression and activity in leiomyoma cells compared with those in myometrium cells, whereas 1 study found a decreased level of MMP-2 expression. Two studies reported higher mRNA levels of MMPs in the secretory phase than in the proliferative phase. Two studies examined the relationship between MMP-1, -3, -9 genotypes and leiomyoma, and no association was found. One study examined the difference in MMP expression levels among leiomyoma, uterine smooth muscle tumor of uncertain malignant potential, and leiomyosarcoma and found higher MMP-2 expression in leiomyosarcoma than in leiomyoma. The effects of estradiol on MMP expression and activity levels were examined in 2 studies. One study reported an upregulation of MMP-2 expression in leiomyomas by the administration of estradiol. Another study found that estradiol decreased MMP-2 activity in leiomyoma. We also identified studies that examined the effects of selective estrogen receptor modulators, gonadotropin-releasing hormone agonists, and selective progesterone receptor modulators on MMPs expression and activity in patients with UFs.
Conclusion
Data were mostly consistent regarding the expression and activity levels of MMPs in uterine leiomyomas. All
{"title":"A systematic review of matrix metalloproteinases as potential biomarkers for uterine fibroids","authors":"Kazuma Onishi M.D., M.P.H. , Jiahui Zhang M.D. , Jaime F. Blanck M.L.I.S., M.P.A. , Bhuchitra Singh M.D., M.P.H., M.S., M.B.A.","doi":"10.1016/j.xfnr.2022.07.003","DOIUrl":"10.1016/j.xfnr.2022.07.003","url":null,"abstract":"<div><h3>Objective</h3><p><span><span>Matrix metalloproteinases<span> (MMPs) are zinc-containing endopeptidases that play a critical role in </span></span>morphogenesis<span>, wound healing, and tissue repair<span>. Uterine fibroids<span><span> (UFs) are benign, fibrous smooth muscle tumors with excessive deposition of the </span>extracellular matrix rich in interstitial collagen. This </span></span></span></span>systematic review aims to rigorously assess current literature evaluating the role of MMPs in the pathoetiology of UFs.</p></div><div><h3>Evidence Review</h3><p>A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was conducted within PubMed, Embase, and Scopus databases. A data informationist was engaged to develop a comprehensive search strategy. Studies examining the MMP levels in leiomyoma and myometrium were searched. Two investigators independently screened and identified articles. Observational and interventional studies involving human subject research published in English up to January 2022 were included. Animal subject research, non-English articles, and reviews were excluded. The articles were assessed for risk of bias using the Newcastle-Ottawa scale. One investigator extracted the data, and a second investigator checked the accuracy. The extracted data were synthesized descriptively.</p></div><div><h3>Results</h3><p>The initial search yielded 235 articles. After reviewing titles, abstracts, and full texts, 30 observational studies were judged to meet the inclusion criteria. The expression levels of MMPs in leiomyomas and myometrium varied among subtypes of MMPs. Nine studies reported elevated levels of MMP-2 expression and activity in leiomyoma cells compared with those in myometrium cells, whereas 1 study found a decreased level of MMP-2 expression. Two studies reported higher mRNA levels of MMPs in the secretory phase than in the proliferative phase. Two studies examined the relationship between MMP-1, -3, -9 genotypes and leiomyoma, and no association was found. One study examined the difference in MMP expression levels among leiomyoma, uterine smooth muscle tumor of uncertain malignant potential, and leiomyosarcoma<span><span><span> and found higher MMP-2 expression in leiomyosarcoma than in leiomyoma. The effects of estradiol on MMP expression and activity levels were examined in 2 studies. One study reported an upregulation of MMP-2 expression in leiomyomas by the administration of estradiol. Another study found that estradiol decreased MMP-2 activity in leiomyoma. We also identified studies that examined the effects of selective estrogen receptor modulators, gonadotropin-releasing hormone agonists, and </span>selective progesterone receptor modulators on MMPs expression and activity </span>in patients with UFs.</span></p></div><div><h3>Conclusion</h3><p>Data were mostly consistent regarding the expression and activity levels of MMPs in uterine leiomyomas. All ","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124364706","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 : 2022-07-01DOI: 10.1016/j.xfnr.2022.05.003
Carry Verberkt M.D. , Saskia J.M. Klein Meuleman M.D. , Johannes C.F. Ket , Madelon van Wely M.D., Ph.D. , Eva Bouwsma M.D., Ph.D. , Judith A.F. Huirne M.D., Ph.D.
Objective
To assess the effect of a uterine niche resection on fertility and pregnancy outcomes. We compared these outcomes in women with and without infertility, as we hypothesized that in the group with infertility, the presence of the niche may contribute to the failure to conceive. The focus on reproductive and pregnancy outcomes as well as the differentiation in study populations is novel and has not been a topic of research up until now.
Evidence Review
The databases PubMed, Embase, and Web of Science were systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines from inception until July 19, 2021. Randomized controlled trials (RCTs), cohort studies, case-control studies, and case series with at least 10 women were included if they reported fertility and/or pregnancy outcomes after any type of niche surgery among women with infertility or without the diagnosis of infertility. The risk of bias and quality of the included studies were assessed using the Cochrane risk-of-bias tool, the Newcastle-Ottawa Scale, and a set of niche-specific criteria. The primary outcome was live birth rate. The secondary outcomes included pregnancy and miscarriage rates, occurrence of an ectopic pregnancy, uterine dehiscence, and other obstetric complications. A meta-analysis was performed for the outcomes live birth, pregnancy, and miscarriage rates. The proportion with corresponding 95% confidence interval (CI) was calculated for each individual study, stratified for type of surgery and fertility status.
Results
A total of 3,825 records were identified, of which 21 articles were included (1 RCT, 1 case series, and 5 prospective and 14 retrospective cohort studies). The RCT compared a surgical intervention with expectant management, whereas the other studies had an observational design. Sixteen studies reported on fertility outcomes in women with infertility (n = 648), and 5 studies reported on fertility outcomes in women without a diagnosis of infertility (n = 237). The reported surgical procedures were hysteroscopic niche resection (HNR) (n = 14), vaginal niche resection (n = 7), laparoscopic niche resection (n = 7), and laparotomic niche resection (n = 2). The overall methodological quality of included studies was moderate to poor with a high risk of bias. The statistical heterogeneity among the included studies ranged between 0 and 88%. Overall, the effect of a niche resection on the live birth rate was lower in women without infertility than in women with infertility: 36% (95% CI, 26 %–46%) vs. 54% (95% CI, 44%–64%).The live birth rates per different operative technique showed similar trends: HNR, 52% (95% CI, 40%–64%) vs. 55% (95% CI, 38%–71%); laparoscopic niche resection, 36% (95% CI, 25%–48%) vs. 42% (95% CI, 30%–55%); and vaginal niche resection, 25% (95% CI, 9%–46%) vs. 60% (95% CI, 52%–67%). The only RCT performed showed
{"title":"Fertility and pregnancy outcomes after a uterine niche resection in women with and without infertility: a systematic review and meta-analysis","authors":"Carry Verberkt M.D. , Saskia J.M. Klein Meuleman M.D. , Johannes C.F. Ket , Madelon van Wely M.D., Ph.D. , Eva Bouwsma M.D., Ph.D. , Judith A.F. Huirne M.D., Ph.D.","doi":"10.1016/j.xfnr.2022.05.003","DOIUrl":"https://doi.org/10.1016/j.xfnr.2022.05.003","url":null,"abstract":"<div><h3>Objective</h3><p>To assess the effect of a uterine niche resection on fertility and pregnancy outcomes. We compared these outcomes in women with and without infertility, as we hypothesized that in the group with infertility, the presence of the niche may contribute to the failure to conceive. The focus on reproductive and pregnancy outcomes as well as the differentiation in study populations is novel and has not been a topic of research up until now.</p></div><div><h3>Evidence Review</h3><p>The databases PubMed, Embase, and Web of Science were systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines from inception until July 19, 2021. Randomized controlled trials (RCTs), cohort studies, case-control studies, and case series with at least 10 women were included if they reported fertility and/or pregnancy outcomes after any type of niche surgery among women with infertility or without the diagnosis of infertility. The risk of bias and quality of the included studies were assessed using the Cochrane risk-of-bias tool, the Newcastle-Ottawa Scale, and a set of niche-specific criteria. The primary outcome was live birth rate. The secondary outcomes included pregnancy and miscarriage rates, occurrence of an ectopic pregnancy, uterine dehiscence, and other obstetric complications. A meta-analysis was performed for the outcomes live birth, pregnancy, and miscarriage rates. The proportion with corresponding 95% confidence interval (CI) was calculated for each individual study, stratified for type of surgery and fertility status.</p></div><div><h3>Results</h3><p>A total of 3,825 records were identified, of which 21 articles were included (1 RCT, 1 case series, and 5 prospective and 14 retrospective cohort studies). The RCT compared a surgical intervention with expectant management, whereas the other studies had an observational design. Sixteen studies reported on fertility outcomes in women with infertility (n = 648), and 5 studies reported on fertility outcomes in women without a diagnosis of infertility (n = 237). The reported surgical procedures were hysteroscopic niche resection (HNR) (n = 14), vaginal niche resection (n = 7), laparoscopic niche resection (n = 7), and laparotomic niche resection (n = 2). The overall methodological quality of included studies was moderate to poor with a high risk of bias. The statistical heterogeneity among the included studies ranged between 0 and 88%. Overall, the effect of a niche resection on the live birth rate was lower in women without infertility than in women with infertility: 36% (95% CI, 26 %–46%) vs. 54% (95% CI, 44%–64%).The live birth rates per different operative technique showed similar trends: HNR, 52% (95% CI, 40%–64%) vs. 55% (95% CI, 38%–71%); laparoscopic niche resection, 36% (95% CI, 25%–48%) vs. 42% (95% CI, 30%–55%); and vaginal niche resection, 25% (95% CI, 9%–46%) vs. 60% (95% CI, 52%–67%). The only RCT performed showed","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666571922000068/pdfft?md5=45b3b2be112c9a70b7a01eff9c5657a5&pid=1-s2.0-S2666571922000068-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91634640","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 : 2022-07-01DOI: 10.1016/j.xfnr.2022.06.001
Michelle Volovsky M.D. , Hadi Ramadan M.D. , Seifeldin Sadek M.D. , Elena M. Golub B.A. , Esther M. Sarino M.L.I.S. , Jaime Blanck M.L.I.S., M.P.I. , David F. Archer M.D. , James H. Segars M.D.
Objective
To evaluate the role of the plasminogen activator (PA) system throughout the endometrial cycle, including the effects of intrauterine contraception, and assess the contribution of genetic mutations in the PA system to the clinical problem of heavy menstrual bleeding (HMB).
Evidence Review
This was a systematic review of the PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases from 1966 until the search date in October 2021. The publications included were cohort studies, observational studies, case reports, case studies, and case-control studies. Literature reviews were excluded. Abstracts were screened by 3 investigators independently, with subsequent review by the senior investigator to assess study quality. The Risk of Bias In Non-Randomized Studies of Interventions assessment tool was used to evaluate potential sources of bias in the included studies.
Results
A total of 2,021 unique articles were identified, 38 of which qualified for full review, with 17 excluded during that process, leaving 21 articles that met all criteria. Studies reported that the activity of the PA system in the endometrium changed throughout the menstrual cycle, with increases in tissue PA and PA inhibitor 1 (PAI-1) activity surrounding the menstrual phase. Greater fibrinolytic activity was also observed in the endometrial samples of women with HMB as well as those with copper intrauterine devices. Conversely, levonorgestrel intrauterine devices were associated with a decrease in the tissue PA–to–PAI-1 ratio, hence reduced fibrinolysis. Mutations of the PAI-1 and α2-antiplasmin genes were found to affect the PA system and are associated with HMB.
Conclusion
Genetic mutations that affect the PA system and are linked to alterations in menstrual bleeding, such as PAI-1 and α2-antiplasmin, have been identified. Further research is needed to ascertain whether additional mutations, and genetic polymorphisms, not only affect the PA system but may also explain some cases of HMB that are yet to be classified.
{"title":"A systematic review of the plasminogen activator system in the endometrium and its role in menstruation and abnormal uterine bleeding","authors":"Michelle Volovsky M.D. , Hadi Ramadan M.D. , Seifeldin Sadek M.D. , Elena M. Golub B.A. , Esther M. Sarino M.L.I.S. , Jaime Blanck M.L.I.S., M.P.I. , David F. Archer M.D. , James H. Segars M.D.","doi":"10.1016/j.xfnr.2022.06.001","DOIUrl":"https://doi.org/10.1016/j.xfnr.2022.06.001","url":null,"abstract":"<div><h3>Objective</h3><p>To evaluate the role of the plasminogen activator<span> (PA) system throughout the endometrial cycle<span>, including the effects of intrauterine contraception, and assess the contribution of genetic mutations in the PA system to the clinical problem of heavy menstrual bleeding (HMB).</span></span></p></div><div><h3>Evidence Review</h3><p><span>This was a systematic review of the PubMed, Embase, </span><span>ClinicalTrials.gov</span><svg><path></path></svg><span>, and Cochrane Library databases from 1966 until the search date in October 2021. The publications included were cohort studies, observational studies, case reports, case studies, and case-control studies. Literature reviews were excluded. Abstracts were screened by 3 investigators independently, with subsequent review by the senior investigator to assess study quality. The Risk of Bias In Non-Randomized Studies of Interventions assessment tool was used to evaluate potential sources of bias in the included studies.</span></p></div><div><h3>Results</h3><p><span><span>A total of 2,021 unique articles were identified, 38 of which qualified for full review, with 17 excluded during that process, leaving 21 articles that met all criteria. Studies reported that the activity of the PA system in the endometrium<span> changed throughout the menstrual cycle, with increases in tissue PA and </span></span>PA inhibitor 1<span><span> (PAI-1) activity surrounding the menstrual phase. Greater fibrinolytic activity was also observed in the endometrial samples of women with HMB as well as those with copper </span>intrauterine devices<span>. Conversely, levonorgestrel intrauterine devices were associated with a decrease in the tissue PA–to–PAI-1 ratio, hence reduced fibrinolysis. Mutations of the PAI-1 and α</span></span></span><sub>2</sub>-antiplasmin genes were found to affect the PA system and are associated with HMB.</p></div><div><h3>Conclusion</h3><p>Genetic mutations that affect the PA system and are linked to alterations in menstrual bleeding, such as PAI-1 and α<sub>2</sub><span>-antiplasmin, have been identified. Further research is needed to ascertain whether additional mutations, and genetic polymorphisms, not only affect the PA system but may also explain some cases of HMB that are yet to be classified.</span></p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91634641","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 : 2022-07-01DOI: 10.1016/j.xfnr.2022.05.002
Jasmine Aly M.D. , Lindsey Choi D.O. , Alicia Y. Christy M.D., M.H.S.C.R.
It is important to closely examine trends in reproduction during a pandemic because it provides not only the foundation for an improved future response but also crucial insights regarding the disparate impact across different races and socioeconomic classes. The coronavirus disease 2019 pandemic is a prime example of the impact a pandemic can have on a nation’s reproductive health. Contraception and abortion access became more difficult with more barriers to access, likely contributing to increasing unintended pregnancy rates. Underrepresented minorities and vulnerable populations were disproportionately affected by the virus on their reproductive health as well as by the virus itself. As the first ever messenger ribonucleic acid vaccine in conjunction with the lack of inclusion of pregnant and peripartum women in initial studies and conflicting and misinformation on social media, the initial role of the coronavirus disease 2019 vaccine in women of reproductive age was unclear. Further research inclusive of this group of women has led to the consensus by major medical societies to recommend vaccination of women regardless of pregnancy or lactating status.
Examining these topics in depth will lead to the development of strategies that can be employed to mitigate the negative effects on reproductive health during the current pandemic and can also be applied to future strategic plans to prevent similar negative outcomes.
{"title":"The impact of coronavirus on reproduction: contraceptive access, pregnancy rates, pregnancy delay, and the role of vaccination","authors":"Jasmine Aly M.D. , Lindsey Choi D.O. , Alicia Y. Christy M.D., M.H.S.C.R.","doi":"10.1016/j.xfnr.2022.05.002","DOIUrl":"https://doi.org/10.1016/j.xfnr.2022.05.002","url":null,"abstract":"<div><p>It is important to closely examine trends in reproduction during a pandemic because it provides not only the foundation for an improved future response but also crucial insights regarding the disparate impact across different races and socioeconomic classes. The coronavirus disease 2019 pandemic is a prime example of the impact a pandemic can have on a nation’s reproductive health. Contraception and abortion access became more difficult with more barriers to access, likely contributing to increasing unintended pregnancy rates. Underrepresented minorities and vulnerable populations were disproportionately affected by the virus on their reproductive health as well as by the virus itself. As the first ever messenger ribonucleic acid vaccine in conjunction with the lack of inclusion of pregnant and peripartum women in initial studies and conflicting and misinformation on social media, the initial role of the coronavirus disease 2019 vaccine in women of reproductive age was unclear. Further research inclusive of this group of women has led to the consensus by major medical societies to recommend vaccination of women regardless of pregnancy or lactating status.</p><p>Examining these topics in depth will lead to the development of strategies that can be employed to mitigate the negative effects on reproductive health during the current pandemic and can also be applied to future strategic plans to prevent similar negative outcomes.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666571922000056/pdfft?md5=61cfbe546256242e42d5aaef330e1939&pid=1-s2.0-S2666571922000056-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91634639","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 : 2022-07-01DOI: 10.1016/j.xfnr.2022.06.002
Huy Phuong Tran M.Sc. , Thuy Thi-Thanh Tran M.D. , Ly Thi Le Ph.D. , Bao The Pham Ph.D. , Sang Ngoc-Thanh Vu Ph.D. , Loc Thai Ly M.D. , Tuyet Thi-Diem Hoang M.D.
Objective
To investigate the effectiveness of the endometrial receptivity array (ERA) test on in vitro fertilization (IVF) outcomes.
Evidence Review
The PubMed/MEDLINE, ScienceDirect, and Scopus databases were searched. We included studies investigating IVF outcomes between patients who underwent standard embryo transfer and personalized embryo transfer (PET) guided by the ERA results. The main outcome measures were the implantation rate, clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, and live birth rate (LBR). The random-effects model was applied to pool data. We evaluated cohort and randomized controlled trial studies using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and the Cochrane Collaboration tool.
Results
Seventeen studies (7,052 patients, 4 randomized controlled trials, and 13 cohort studies) were included in this meta-analysis. Personalized embryo transfer on the basis of ERA was not found to optimize the gestational outcomes, including the implantation rate (risk ratio [RR], 1; 95% confidence interval [CI], 0.83–1.2), clinical pregnancy rate (RR, 0.99; 95% CI, 0.85–1.15), ongoing pregnancy rate (RR, 0.99; 95% CI, 0.89–1.11), and miscarriage rate (RR, 1.12; 95% CI, 0.81–1.54). Further subgroup analysis indicated that patients undergoing PET in the first IVF cycle had a markedly increased LBR (RR, 1.24; 95% CI, 1.03–1.49). Conversely, PET among patients with a history of recurrent implantation failure did not enhance the LBR (RR, 0.86; 95% CI, 0.64–1.36).
Conclusion
Endometrial receptivity array shows no significant improvement in IVF outcomes except in the LBR for patients undergoing the first IVF cycle. Additional research is required to ascertain the efficacy of ERA before achieving wider usage.
{"title":"The impact of an endometrial receptivity array on personalizing embryo transfer for patients with infertility: a meta-analysis","authors":"Huy Phuong Tran M.Sc. , Thuy Thi-Thanh Tran M.D. , Ly Thi Le Ph.D. , Bao The Pham Ph.D. , Sang Ngoc-Thanh Vu Ph.D. , Loc Thai Ly M.D. , Tuyet Thi-Diem Hoang M.D.","doi":"10.1016/j.xfnr.2022.06.002","DOIUrl":"https://doi.org/10.1016/j.xfnr.2022.06.002","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the effectiveness of the endometrial receptivity array (ERA) test on in vitro fertilization (IVF) outcomes.</p></div><div><h3>Evidence Review</h3><p>The PubMed/MEDLINE, ScienceDirect, and Scopus databases were searched. We included studies investigating IVF outcomes between patients who underwent standard embryo transfer and personalized embryo transfer (PET) guided by the ERA results. The main outcome measures were the implantation rate, clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, and live birth rate (LBR). The random-effects model was applied to pool data. We evaluated cohort and randomized controlled trial studies using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and the Cochrane Collaboration tool.</p></div><div><h3>Results</h3><p>Seventeen studies (7,052 patients, 4 randomized controlled trials, and 13 cohort studies) were included in this meta-analysis. Personalized embryo transfer on the basis of ERA was not found to optimize the gestational outcomes, including the implantation rate (risk ratio [RR], 1; 95% confidence interval [CI], 0.83–1.2), clinical pregnancy rate (RR, 0.99; 95% CI, 0.85–1.15), ongoing pregnancy rate (RR, 0.99; 95% CI, 0.89–1.11), and miscarriage rate (RR, 1.12; 95% CI, 0.81–1.54). Further subgroup analysis indicated that patients undergoing PET in the first IVF cycle had a markedly increased LBR (RR, 1.24; 95% CI, 1.03–1.49). Conversely, PET among patients with a history of recurrent implantation failure did not enhance the LBR (RR, 0.86; 95% CI, 0.64–1.36).</p></div><div><h3>Conclusion</h3><p>Endometrial receptivity array shows no significant improvement in IVF outcomes except in the LBR for patients undergoing the first IVF cycle. Additional research is required to ascertain the efficacy of ERA before achieving wider usage.</p></div><div><h3>PROSPERO Number</h3><p>CRD42021255124.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666571922000081/pdfft?md5=3e0c4e8ba38486f01c72b7acf6bdab25&pid=1-s2.0-S2666571922000081-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91679618","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 : 2022-05-01DOI: 10.1016/j.xfnr.2022.05.001
Cristian D. Piccini , Julia A. Tessari , Candice C. Moro , Bruna M. Rocha , Lucas A. Hauschild , Marcelle J. Anzolch MD. , Edison Capp M.D., Ph.D. , Helena von Eye Corleta M.D., Ph.D.
Uterine leiomyomas are the most common pelvic tumor affecting women. Seventy percent of women will present with them at some point in their lives. Despite this, there is a lack of appropriate pharmacotherapeutic agents and preventive measures, and its etiology and pathophysiology are not properly understood, mainly because of the lack of reliable in vivo models. A systematized review was performed to analyze all reported vivo models of uterine fibroids, consolidate current understanding, and guide further research on the topic. We aim to contribute to those who wish to develop novel models and those who want to reproduce current ones to study the effects of new drugs on the disease or its pathogenic mechanisms. Literature searches with the key words “leiomyoma,” “myoma,” “fibroid,” “uterine fibroid,” “xenografting,” and “experimental animal model” were conducted in PubMed, Embase, and LILACS. Several novel models of leiomyomas have been proposed lately for a variety of animal species. We have discussed the findings, advantages, and limitations of the existing animal models of uterine fibroids, besides explaining the rationale behind their use. Researchers must be aware of limitations of the existing models and choose the model that best fits their needs. To facilitate reproducibility and translation of findings, methods must be described in detail. Given the context, special attention should be paid when providing conclusions. Besides equivalent histology and immunomarkers, a trustworthy model should also display all of the genetic expressions of human myomas.
{"title":"Animal models of uterine leiomyomas: a review","authors":"Cristian D. Piccini , Julia A. Tessari , Candice C. Moro , Bruna M. Rocha , Lucas A. Hauschild , Marcelle J. Anzolch MD. , Edison Capp M.D., Ph.D. , Helena von Eye Corleta M.D., Ph.D.","doi":"10.1016/j.xfnr.2022.05.001","DOIUrl":"10.1016/j.xfnr.2022.05.001","url":null,"abstract":"<div><p><span>Uterine leiomyomas<span> are the most common pelvic tumor<span> affecting women. Seventy percent of women will present with them at some point in their lives. Despite this, there is a lack of appropriate pharmacotherapeutic agents and preventive measures, and its etiology and pathophysiology are not properly understood, mainly because of the lack of reliable in vivo models. A systematized review was performed to analyze all reported vivo models of uterine fibroids, consolidate current understanding, and guide further research on the topic. We aim to contribute to those who wish to develop novel models and those who want to reproduce current ones to study the effects of new </span></span></span>drugs on the disease or its pathogenic mechanisms. Literature searches with the key words “leiomyoma,” “myoma,” “fibroid,” “uterine fibroid,” “xenografting,” and “experimental animal model” were conducted in PubMed, Embase, and LILACS. Several novel models of leiomyomas have been proposed lately for a variety of animal species. We have discussed the findings, advantages, and limitations of the existing animal models of uterine fibroids, besides explaining the rationale behind their use. Researchers must be aware of limitations of the existing models and choose the model that best fits their needs. To facilitate reproducibility and translation of findings, methods must be described in detail. Given the context, special attention should be paid when providing conclusions. Besides equivalent histology and immunomarkers, a trustworthy model should also display all of the genetic expressions of human myomas.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133185002","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 : 2022-05-01DOI: 10.1016/j.xfnr.2022.02.002
Angelos Youssef M.D. , Marie-Louise P. van der Hoorn M.D., Ph.D. , Johannes M.M. van Lith M.D., Ph.D. , Rik van Eekelen Ph.D. , Nadia A. du Fossé M.D. , Lisa E.E. L.O. Lashley M.D., Ph.D.
Objective
To identify models predicting live birth or ongoing pregnancy in couples with unexplained recurrent pregnancy loss (RPL) and evaluate the risk of bias, performance, generalizability, and applicability of these models.
Evidence Review
A systematic literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library until December 2020. Studies were eligible for inclusion if they were original studies predicting pregnancy outcome in patients with unexplained RPL and presented a tool that allowed for individual predictions. The risk of bias and applicability of the studies were assessed using the Prediction model Risk of Bias Assessment Tool. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement was used to assess reporting quality.
Results
The search yielded 1,170 unique articles that were screened on the basis of the title and abstract. Seven studies were included: 1 prospective cohort study and 6 retrospective cohort studies. The recommended steps for the development of a prediction model were not followed by any of the studies, although 6 were published before the Prediction model Risk of Bias Assessment Tool and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines. The included studies had a high risk of bias and were not externally validated.
Conclusion
International guidelines recommend supportive care programs with prognostic counseling for couples with unexplained RPL. This information manages the expectations of couples and improves their ability to make an informed decision regarding further pregnancy attempts. On the basis of the results of this study, we cannot recommend the use of any of the studied prediction models in clinical practice to prevent overestimation of chances and false belief.
目的确定预测不明原因复发性妊娠丢失(RPL)夫妇活产或持续妊娠的模型,并评估这些模型的偏倚风险、性能、通用性和适用性。在PubMed, Embase, Web of Science和Cochrane Library中进行了系统的文献检索,直到2020年12月。如果研究是预测不明原因RPL患者妊娠结局的原始研究,并且提供了允许个体预测的工具,则该研究有资格纳入。使用预测模型偏倚风险评估工具评估研究的偏倚风险和适用性。个体预后或诊断陈述的透明报告多变量预测模型用于评估报告质量。结果根据标题和摘要筛选出1170篇独特的文章。纳入7项研究:1项前瞻性队列研究和6项回顾性队列研究。尽管有6项研究在《预测模型偏倚风险评估工具》和《个体预后或诊断多变量预测模型透明报告》指南发布之前发表,但没有任何研究遵循建立预测模型的建议步骤。纳入的研究存在高偏倚风险,且未经过外部验证。结论:国际指南推荐对不明原因RPL夫妇的支持性护理方案和预后咨询。这些信息管理夫妇的期望,并提高他们在进一步怀孕尝试方面做出明智决定的能力。根据本研究的结果,我们不建议在临床实践中使用任何研究的预测模型,以防止对机会的高估和错误的信念。
{"title":"Prognosis in unexplained recurrent pregnancy loss: a systematic review and quality assessment of current clinical prediction models","authors":"Angelos Youssef M.D. , Marie-Louise P. van der Hoorn M.D., Ph.D. , Johannes M.M. van Lith M.D., Ph.D. , Rik van Eekelen Ph.D. , Nadia A. du Fossé M.D. , Lisa E.E. L.O. Lashley M.D., Ph.D.","doi":"10.1016/j.xfnr.2022.02.002","DOIUrl":"10.1016/j.xfnr.2022.02.002","url":null,"abstract":"<div><h3>Objective</h3><p>To identify models predicting live birth or ongoing pregnancy in couples with unexplained recurrent pregnancy loss (RPL) and evaluate the risk of bias, performance, generalizability, and applicability of these models.</p></div><div><h3>Evidence Review</h3><p>A systematic literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library until December 2020. Studies were eligible for inclusion if they were original studies predicting pregnancy outcome in patients with unexplained RPL and presented a tool that allowed for individual predictions. The risk of bias and applicability of the studies were assessed using the Prediction model Risk of Bias Assessment Tool. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement was used to assess reporting quality.</p></div><div><h3>Results</h3><p>The search yielded 1,170 unique articles that were screened on the basis of the title and abstract. Seven studies were included: 1 prospective cohort study and 6 retrospective cohort studies. The recommended steps for the development of a prediction model were not followed by any of the studies, although 6 were published before the Prediction model Risk of Bias Assessment Tool and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines. The included studies had a high risk of bias and were not externally validated.</p></div><div><h3>Conclusion</h3><p>International guidelines recommend supportive care programs with prognostic counseling for couples with unexplained RPL. This information manages the expectations of couples and improves their ability to make an informed decision regarding further pregnancy attempts. On the basis of the results of this study, we cannot recommend the use of any of the studied prediction models in clinical practice to prevent overestimation of chances and false belief.</p></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666571922000020/pdfft?md5=3f2924c1cab7476e5130c0ffbd091b7b&pid=1-s2.0-S2666571922000020-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44951172","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}