<p><strong>Study question: </strong>Is dietary non-enzymatic antioxidant capacity related to semen quality?</p><p><strong>Summary answer: </strong>The only statistically significant association of semen quality parameters with dietary total antioxidant capacity (DTAC) detected was an inverse association between DTAC and ejaculate volume.</p><p><strong>What is known already: </strong>Growing interest exists regarding the role of diet in influencing semen quality. While DTAC is linked to favorable health outcomes, its association with semen quality, especially among men attending infertility clinics, remains understudied.</p><p><strong>Study design size duration: </strong>This cross-sectional study was carried out between June and December of 2020. In total, 1715 participants were included in the final analysis.</p><p><strong>Participants/materials setting methods: </strong>Men who attended an infertility clinic in China were enrolled. Experienced clinical technicians performed the semen analysis. The DTAC indices included the ferric-reducing ability of plasma, oxygen radical absorbance capacity, total reactive antioxidant potential, and Trolox equivalent antioxidant capacity. The quantile regression model was used for multivariate analysis.</p><p><strong>Main results and the role of chance: </strong>After adjustment for a variety of confounding variables, a significant inverse association was identified between DTAC and ejaculate volume (β<sub>continuous FRAP</sub> = -0.015, 95% CI = -0.023, -0.006, β<sub>T3 vs T1</sub> = -0.193, 95% CI = -0.379, -0.006, <i>P</i><sub>trend</sub> = 0.007; β<sub>continuous TRAP</sub> = -0.019, 95% CI = -0.041, 0.002, β<sub>T3 vs T1</sub> = -0.291, 95% CI = -0.469, -0.112, <i>P</i><sub>trend</sub> = 0.002). The majority of DTAC indices have no statistically significant association with semen quality parameters.</p><p><strong>Limitations reasons for caution: </strong>We cannot infer causality because of the nature of the cross-sectional study design. The robustness of the conclusion may be compromised by the exactness of non-enzymatic antioxidant capacity estimation.</p><p><strong>Wider implications of the findings: </strong>Our findings demonstrated no association between DTAC indices and semen quality parameters among men attending an infertility clinic, except for ejaculate volume. Even though our findings are mostly non-significant, they contribute novel knowledge to the field of study while also laying the groundwork for future well-designed studies.</p><p><strong>Study funding/competing interests: </strong>This work was supported by the JieBangGuaShuai Project of Liaoning Province [grant number 2021JH1/10400050], the Clinical Research Cultivation Project of Shengjing Hospital [grant number M1590], and the Outstanding Scientific Fund of Shengjing Hospital [grant number M1150]. The sponsors had no role in study design, or in the collection, analysis, and interpretation of data, or in the writing of the report, or
研究问题:饮食中的非酶抗氧化能力与精液质量有关吗?总结回答:精液质量参数与饲料总抗氧化能力(DTAC)之间唯一有统计学意义的关联是DTAC与射精量之间的负相关。已知情况:人们对饮食在影响精液质量中的作用越来越感兴趣。虽然DTAC与良好的健康结果有关,但它与精液质量的关系,特别是在不育诊所就诊的男性中,仍未得到充分研究。研究设计规模持续时间:本横断面研究于2020年6月至12月进行。总共有1715名参与者被纳入最终分析。参与者/材料设置方法:在中国不孕不育诊所就诊的男性。经验丰富的临床技术人员进行精液分析。DTAC指标包括血浆铁还原能力、氧自由基吸收能力、总活性抗氧化电位和Trolox等效抗氧化能力。多因素分析采用分位数回归模型。主要结果及偶发因素的作用:调整多种混杂变量后,DTAC与射精量呈显著负相关(β连续FRAP = -0.015, 95% CI = -0.023, -0.006, βT3 vs T1 = -0.193, 95% CI = -0.379, -0.006, Ptrend = 0.007;β连续TRAP = -0.019, 95% CI = -0.041, 0.002, βT3 vs T1 = -0.291, 95% CI = -0.469, -0.112, Ptrend = 0.002)。大多数DTAC指标与精液质量参数无显著相关性。谨慎的局限性:由于横断面研究设计的性质,我们不能推断因果关系。结论的稳健性可能会受到非酶抗氧化能力估计的准确性的影响。研究结果的更广泛意义:我们的研究结果表明,除了射精量外,在不育诊所就诊的男性中,DTAC指数和精液质量参数之间没有关联。尽管我们的发现大多不重要,但它们为研究领域贡献了新的知识,同时也为未来精心设计的研究奠定了基础。研究经费/利益竞争:本文由辽宁省节邦瓜槐项目[批准号2021JH1/10400050]、盛京医院临床科研培养项目[批准号M1590]、盛京医院优秀科学基金[批准号M1150]资助。赞助方在研究设计、数据收集、分析和解释、报告撰写或文章发表决定中没有任何作用。没有需要申报的利益冲突。试验注册号:无。
{"title":"Association between dietary total antioxidant capacity and semen quality among men attending an infertility clinic: a cross-sectional study.","authors":"Dong-Hui Huang, Yi-Xiao Zhang, Xiao-Bin Wang, Ming-Hui Sun, Ren-Hao Guo, Xu Leng, Qiang Du, Hong-Yu Chen, Yu-Xin Nan, Qi-Jun Wu, Bo-Chen Pan, Yu-Hong Zhao","doi":"10.1093/hropen/hoad041","DOIUrl":"10.1093/hropen/hoad041","url":null,"abstract":"<p><strong>Study question: </strong>Is dietary non-enzymatic antioxidant capacity related to semen quality?</p><p><strong>Summary answer: </strong>The only statistically significant association of semen quality parameters with dietary total antioxidant capacity (DTAC) detected was an inverse association between DTAC and ejaculate volume.</p><p><strong>What is known already: </strong>Growing interest exists regarding the role of diet in influencing semen quality. While DTAC is linked to favorable health outcomes, its association with semen quality, especially among men attending infertility clinics, remains understudied.</p><p><strong>Study design size duration: </strong>This cross-sectional study was carried out between June and December of 2020. In total, 1715 participants were included in the final analysis.</p><p><strong>Participants/materials setting methods: </strong>Men who attended an infertility clinic in China were enrolled. Experienced clinical technicians performed the semen analysis. The DTAC indices included the ferric-reducing ability of plasma, oxygen radical absorbance capacity, total reactive antioxidant potential, and Trolox equivalent antioxidant capacity. The quantile regression model was used for multivariate analysis.</p><p><strong>Main results and the role of chance: </strong>After adjustment for a variety of confounding variables, a significant inverse association was identified between DTAC and ejaculate volume (β<sub>continuous FRAP</sub> = -0.015, 95% CI = -0.023, -0.006, β<sub>T3 vs T1</sub> = -0.193, 95% CI = -0.379, -0.006, <i>P</i><sub>trend</sub> = 0.007; β<sub>continuous TRAP</sub> = -0.019, 95% CI = -0.041, 0.002, β<sub>T3 vs T1</sub> = -0.291, 95% CI = -0.469, -0.112, <i>P</i><sub>trend</sub> = 0.002). The majority of DTAC indices have no statistically significant association with semen quality parameters.</p><p><strong>Limitations reasons for caution: </strong>We cannot infer causality because of the nature of the cross-sectional study design. The robustness of the conclusion may be compromised by the exactness of non-enzymatic antioxidant capacity estimation.</p><p><strong>Wider implications of the findings: </strong>Our findings demonstrated no association between DTAC indices and semen quality parameters among men attending an infertility clinic, except for ejaculate volume. Even though our findings are mostly non-significant, they contribute novel knowledge to the field of study while also laying the groundwork for future well-designed studies.</p><p><strong>Study funding/competing interests: </strong>This work was supported by the JieBangGuaShuai Project of Liaoning Province [grant number 2021JH1/10400050], the Clinical Research Cultivation Project of Shengjing Hospital [grant number M1590], and the Outstanding Scientific Fund of Shengjing Hospital [grant number M1150]. The sponsors had no role in study design, or in the collection, analysis, and interpretation of data, or in the writing of the report, or ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad041"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10639034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720957","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 : 2023-10-25eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad040
L Cacciottola, F Vitale, J Donnez, M M Dolmans
<p><strong>Study question: </strong>To what extent does regenerative medicine with stem cell therapy help to address infertility issues for future clinical application?</p><p><strong>Summary answer: </strong>Regenerative medicine using different stem cell sources is yielding promising results in terms of protecting the ovarian reserve from damage and senescence, and improving fertility potential in various preclinical settings.</p><p><strong>What is known already: </strong>Regenerative medicine using stem cell therapy is emerging as a potential strategy to address a number of issues in the field of human reproduction. Indeed, different types of adult and fetal mesenchymal stem cells (MSCs) have been tested with promising results, owing to their ability to differentiate into different tissue lineages, move toward specific injured sites (homing), and generate a secretome with wound-healing, proangiogenic, and antioxidant capacities.</p><p><strong>Study design size duration: </strong>Guided by the checklist for preferred reporting items for systematic reviews and meta-analyses, we retrieved relevant studies from PubMed, Medline, and Embase databases until June 2023 using the following keywords: 'mesenchymal stem cells' AND 'ovarian follicles' OR 'ovarian tissue culture' OR 'ovarian follicle culture' OR 'cumulus oocyte complex'. Only peer-reviewed published articles written in English were included.</p><p><strong>Participants/materials setting methods: </strong>The primary outcome for the experimental strategies was evaluation of the ovarian reserve, with a focus on follicle survival, number, and growth. Secondary outcomes involved analyses of other parameters associated with the follicle pool, such as hormones and growth factors, ovarian tissue viability markers including oxidative stress levels, oocyte growth and maturation rates, and of course pregnancy outcomes.</p><p><strong>Main results and the role of chance: </strong>Preclinical studies exploring MSCs from different animal origins and tissue sources in specific conditions were selected (n = 112), including: <i>in vitro</i> culture of granulosa cells, ovarian tissue and isolated ovarian follicles; ovarian tissue transplantation; and systemic or intraovarian injection after gonadotoxic or age-related follicle pool decline. Protecting the ovarian reserve from aging and gonadotoxic damage has been widely tested <i>in vitro</i> and <i>in vivo</i> using murine models and is now yielding initial data in the first ever case series of patients with premature ovarian insufficiency. Use of MSCs as feeder cells in ovarian tissue culture was found to improve follicle outcomes and oocyte competence, bringing us one step closer to future clinical application. MSCs also have proved effective at boosting revascularization in the transplantation site when grafting ovarian tissue in experimental animal models.</p><p><strong>Limitations reasons for caution: </strong>While preclinical results look promising in te
{"title":"Use of mesenchymal stem cells to enhance or restore fertility potential: a systematic review of available experimental strategies.","authors":"L Cacciottola, F Vitale, J Donnez, M M Dolmans","doi":"10.1093/hropen/hoad040","DOIUrl":"10.1093/hropen/hoad040","url":null,"abstract":"<p><strong>Study question: </strong>To what extent does regenerative medicine with stem cell therapy help to address infertility issues for future clinical application?</p><p><strong>Summary answer: </strong>Regenerative medicine using different stem cell sources is yielding promising results in terms of protecting the ovarian reserve from damage and senescence, and improving fertility potential in various preclinical settings.</p><p><strong>What is known already: </strong>Regenerative medicine using stem cell therapy is emerging as a potential strategy to address a number of issues in the field of human reproduction. Indeed, different types of adult and fetal mesenchymal stem cells (MSCs) have been tested with promising results, owing to their ability to differentiate into different tissue lineages, move toward specific injured sites (homing), and generate a secretome with wound-healing, proangiogenic, and antioxidant capacities.</p><p><strong>Study design size duration: </strong>Guided by the checklist for preferred reporting items for systematic reviews and meta-analyses, we retrieved relevant studies from PubMed, Medline, and Embase databases until June 2023 using the following keywords: 'mesenchymal stem cells' AND 'ovarian follicles' OR 'ovarian tissue culture' OR 'ovarian follicle culture' OR 'cumulus oocyte complex'. Only peer-reviewed published articles written in English were included.</p><p><strong>Participants/materials setting methods: </strong>The primary outcome for the experimental strategies was evaluation of the ovarian reserve, with a focus on follicle survival, number, and growth. Secondary outcomes involved analyses of other parameters associated with the follicle pool, such as hormones and growth factors, ovarian tissue viability markers including oxidative stress levels, oocyte growth and maturation rates, and of course pregnancy outcomes.</p><p><strong>Main results and the role of chance: </strong>Preclinical studies exploring MSCs from different animal origins and tissue sources in specific conditions were selected (n = 112), including: <i>in vitro</i> culture of granulosa cells, ovarian tissue and isolated ovarian follicles; ovarian tissue transplantation; and systemic or intraovarian injection after gonadotoxic or age-related follicle pool decline. Protecting the ovarian reserve from aging and gonadotoxic damage has been widely tested <i>in vitro</i> and <i>in vivo</i> using murine models and is now yielding initial data in the first ever case series of patients with premature ovarian insufficiency. Use of MSCs as feeder cells in ovarian tissue culture was found to improve follicle outcomes and oocyte competence, bringing us one step closer to future clinical application. MSCs also have proved effective at boosting revascularization in the transplantation site when grafting ovarian tissue in experimental animal models.</p><p><strong>Limitations reasons for caution: </strong>While preclinical results look promising in te","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad040"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720958","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 : 2023-10-18eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad039
V Vloeberghs, N De Munck, A Racca, I Mateizel, K Wouters, H Tournaye
<p><strong>Study question: </strong>What is the added value of enzymatic processing of testicular biopsies on testicular sperm retrieval (SR) rates for patients with non-obstructive azoospermia (NOA)?</p><p><strong>Summary answer: </strong>In addition to mechanical mincing, enzymatic digestion increased SR rates in testicular biopsies of NOA patients.</p><p><strong>What is known already: </strong>Many studies focus on the surgical approach to optimize recovery of testicular sperm in NOA, and in spite of that, controversy still exists about whether the type of surgery makes any difference as long as multiple biopsies are taken. Few studies, however, focus on the role of the IVF laboratory and the benefit of additional lab procedures, e.g. enzymatic digestion, in order to optimize SR rates.</p><p><strong>Study design size duration: </strong>This retrospective single-center cohort study included all patients who underwent their first testicular sperm extraction (TESE) by open multiple-biopsy method between January 2004 and July 2022. Only patients with a normal karyotype, absence of Y-q deletions and a diagnosis of NOA based on histology were included. The primary outcome was SR rate after mincing and/or enzymes. The secondary outcome was cumulative live birth (CLB) after ICSI with fresh TESE and subsequent ICSI cycles with frozen TESE.</p><p><strong>Participants/materials setting methods: </strong>Multiple biopsies were obtained from the testis, unilaterally or bilaterally, on the day of oocyte retrieval. Upon mechanical mincing, biopsies were investigated for 30 min; when no or insufficient numbers of spermatozoa were observed, enzymatic treatment was performed using Collagenase type IV. Multivariable regression analysis was performed to predict CLB per TESE by adjusting for the following confounding factors: male FSH level, female age, and requirement of enzymatic digestion to find sperm.</p><p><strong>Main results and the role of chance: </strong>We included 118 patients, of whom 72 (61.0%) had successful SR eventually. Spermatozoa were retrieved after mechanical mincing for 28 patients (23.7%; 28/118) or after additional enzymatic digestion for another 44 patients (37.2%; 44/118). Thus, of the 90 patients requiring enzymatic digestion, sperm were retrieved for 44 (48.9%). Male characteristics were not different between patients with SR after mincing or enzymatic digestion, in regard to mean age (34.5 vs 34.5 years), testis volume (10.2 vs 10.6 ml), FSH (17.8 vs 16.9 IU/l), cryptorchidism (21.4 vs 34.1%), varicocele (3.6 vs 4.6%), or histological diagnosis (Sertoli-cell only 53.6 vs 47.7%, maturation arrest 21.4 vs 38.6%, sclerosis/atrophy 25.0 vs 13.6%).Of the 72 patients with sperm available for ICSI, 23/72 (31.9%) achieved a live birth (LB) after the injection with fresh testicular sperm (and fresh or frozen embryo transfers). Of the remaining 49 patients without LB, 34 (69.4%) had supernumerary testicular sperm frozen. Of these 34 patients,
研究问题:对于非梗阻性无精子症(NOA)患者,睾丸活检的酶处理对睾丸精子回收率(SR)的附加值是什么?简要回答:除了机械切碎外,酶消化还增加了NOA患者睾丸活检的SR率。已知情况:许多研究都集中在优化NOA中睾丸精子回收的手术方法上,尽管如此,关于只要进行多次活检,手术类型是否有任何不同,仍然存在争议。然而,很少有研究关注试管婴儿实验室的作用和额外实验室程序的好处,例如酶消化,以优化SR率。研究设计规模持续时间:这项回顾性单中心队列研究包括2004年1月至2022年7月期间通过开放式多次活检方法首次进行睾丸精子提取(TESE)的所有患者。仅包括核型正常、Y-q缺失缺失和根据组织学诊断为NOA的患者。主要结果是切碎和/或酶切后的SR率。次要结果是新鲜TESE ICSI后的累积活产(CLB),以及冷冻TESE的后续ICSI周期。参与者/材料设置方法:在取卵当天,从睾丸单侧或双侧进行多次活检。在机械切碎后,对30例患者进行了活检 min;当没有观察到精子数量或精子数量不足时,使用Ⅳ型胶原酶进行酶处理。通过调整以下混杂因素,进行多变量回归分析,预测每次TESE的CLB:男性FSH水平、女性年龄和酶消化寻找精子的要求。主要结果和机会的作用:我们纳入了118名患者,其中72人(61.0%)最终成功SR。28名患者(23.7%;28/118)在机械切碎后或另外44名患者(37.2%;44/118)在额外的酶消化后回收精子。因此,在90名需要酶消化的患者中,有44名(48.9%)获得了精子。在平均年龄方面,切碎或酶消化后的SR患者的男性特征没有差异(34.5 vs 34.5 年),睾丸体积(10.2 vs 10.6 ml)、FSH(17.8 vs 16.9 IU/l)、隐睾(21.4 vs 34.1%)、精索静脉曲张(3.6 vs 4.6%)或组织学诊断(支持细胞仅53.6 vs 47.7%,成熟停滞21.4 vs 38.6%,硬化/萎缩25.0 vs 13.6%)。在72名可用于ICSI的精子患者中,23/72(31.9%)在注射新鲜睾丸精子(以及新鲜或冷冻胚胎移植)后实现活产(LB)。在剩下的49名没有LB的患者中,34名(69.4%)的睾丸精子冷冻过多。在这34名患者中,19名(55.9%)患者使用冷冻睾丸精子继续进行ICSI,9/19名(47.4%)患者在使用冷冻睾丸精液进行ICSI后获得LB。因此,在回收精子的情况下,每次TESE的总CLB为32/118(27.1%),或每次TESE为32/72(44.4%)。在女性特征(有精子的夫妇)中,只有女性年龄(30.3比32.7 年;P = 0.042)在具有LB的组中显著低于没有LB的组。酶消化后获得的睾丸精子的CLB为31.8%(14/44),而单独切碎后获得的精子CLB为64.3%(18/28)。多变量逻辑回归分析表明,当需要酶消化时,每TESE的CLB显著降低(OR:0.23(0.08-0.7);P = 0.01)。注意的局限性原因:研究的局限性与回顾性设计有关。然而,仅选择具有NOA和特定特征(正常核型和缺失Y-q缺失)的患者,并首次进行TESE,加强了我们的研究结果。研究结果的更广泛含义:与仅机械切碎相比,酶处理提高了NOA患者睾丸活检的SR率,证明了适当的实验室方案的重要性。然而,NOA患者应该被告知,当在酶消化后发现精子时,与那些不需要酶消化的患者相比,他们生下自己基因孩子的机会可能更低。研究资金/竞争利益:无报告。试用注册号:不适用。
{"title":"Enzymatic tissue processing after testicular biopsy in non-obstructive azoospermia enhances sperm retrieval.","authors":"V Vloeberghs, N De Munck, A Racca, I Mateizel, K Wouters, H Tournaye","doi":"10.1093/hropen/hoad039","DOIUrl":"10.1093/hropen/hoad039","url":null,"abstract":"<p><strong>Study question: </strong>What is the added value of enzymatic processing of testicular biopsies on testicular sperm retrieval (SR) rates for patients with non-obstructive azoospermia (NOA)?</p><p><strong>Summary answer: </strong>In addition to mechanical mincing, enzymatic digestion increased SR rates in testicular biopsies of NOA patients.</p><p><strong>What is known already: </strong>Many studies focus on the surgical approach to optimize recovery of testicular sperm in NOA, and in spite of that, controversy still exists about whether the type of surgery makes any difference as long as multiple biopsies are taken. Few studies, however, focus on the role of the IVF laboratory and the benefit of additional lab procedures, e.g. enzymatic digestion, in order to optimize SR rates.</p><p><strong>Study design size duration: </strong>This retrospective single-center cohort study included all patients who underwent their first testicular sperm extraction (TESE) by open multiple-biopsy method between January 2004 and July 2022. Only patients with a normal karyotype, absence of Y-q deletions and a diagnosis of NOA based on histology were included. The primary outcome was SR rate after mincing and/or enzymes. The secondary outcome was cumulative live birth (CLB) after ICSI with fresh TESE and subsequent ICSI cycles with frozen TESE.</p><p><strong>Participants/materials setting methods: </strong>Multiple biopsies were obtained from the testis, unilaterally or bilaterally, on the day of oocyte retrieval. Upon mechanical mincing, biopsies were investigated for 30 min; when no or insufficient numbers of spermatozoa were observed, enzymatic treatment was performed using Collagenase type IV. Multivariable regression analysis was performed to predict CLB per TESE by adjusting for the following confounding factors: male FSH level, female age, and requirement of enzymatic digestion to find sperm.</p><p><strong>Main results and the role of chance: </strong>We included 118 patients, of whom 72 (61.0%) had successful SR eventually. Spermatozoa were retrieved after mechanical mincing for 28 patients (23.7%; 28/118) or after additional enzymatic digestion for another 44 patients (37.2%; 44/118). Thus, of the 90 patients requiring enzymatic digestion, sperm were retrieved for 44 (48.9%). Male characteristics were not different between patients with SR after mincing or enzymatic digestion, in regard to mean age (34.5 vs 34.5 years), testis volume (10.2 vs 10.6 ml), FSH (17.8 vs 16.9 IU/l), cryptorchidism (21.4 vs 34.1%), varicocele (3.6 vs 4.6%), or histological diagnosis (Sertoli-cell only 53.6 vs 47.7%, maturation arrest 21.4 vs 38.6%, sclerosis/atrophy 25.0 vs 13.6%).Of the 72 patients with sperm available for ICSI, 23/72 (31.9%) achieved a live birth (LB) after the injection with fresh testicular sperm (and fresh or frozen embryo transfers). Of the remaining 49 patients without LB, 34 (69.4%) had supernumerary testicular sperm frozen. Of these 34 patients, ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad039"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489649","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 : 2023-10-09eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad038
C De Geyter, L Matt, I De Geyter, R Moffat, C Meier
<p><strong>Study question: </strong>How does subclinical hypothyroidism, defined in infertile women during preconception by thyroid-stimulating hormone (TSH) >2.5 or >4.5 mIU/l, with or without thyroid peroxidase antibodies (anti-TPO) >100 IU/ml, impact thyroid hormone levels during pregnancy and after birth?</p><p><strong>Summary answer: </strong>During pregnancy, TSH levels remain similar to those in preconception, even with supplementary thyroxine, whereas the serum levels of anti-TPO progressively decline.</p><p><strong>What is known already: </strong>Overt hypothyroidism impacts both pregnancy and offspring but randomized clinical trials and cohort studies failed to detect the benefit of treatment with thyroxine in cases with low-threshold TSH or with anti-TPO during pregnancy.</p><p><strong>Study design size duration: </strong>First, the prevalence and reproducibility of two candidate cut-off levels of subclinical hypothyroidism in a cohort of 177 infertile women was compared with 171 women not aiming for pregnancy. Second, the impact of distinct setpoints of TSH in preconception (with or without anti-TPO) was monitored during pregnancy in 87 previously infertile women by high-frequency monitoring of thyroid function. Both studies were carried out from 2007 to 2019.</p><p><strong>Participants/materials setting methods: </strong>Reproducibility and prevalence of subclinical hypothyroidism were examined in infertile women presenting in the fertility care unit of an academic institution. Women not aiming for pregnancy participated as controls. In both groups, TSH and anti-TPO were measured two times on different occasions. In addition, a group of previously infertile women with known preconception setpoints of TSH (with or without anti-TPO) were followed up prospectively throughout pregnancy and after birth. During pregnancy, serum was sampled weekly until Week 12, then monthly until delivery, and once after birth. Only cases with preconception TSH >4.5 mIU/l were supplemented with thyroxine. After collection of all samples, the serum levels of anti-TPO and the major thyroid hormones were measured. Prolactin with known fluctuations during pregnancy was used as reference.</p><p><strong>Main results and the role of chance: </strong>Measures of both TSH and anti-TPO at two different time points were accurate and reproducible. The odds of subclinical hypothyroidism in infertile women and controls were similar. During pregnancy, TSH closely followed preconception TSH levels, whereas serum levels of the thyroid hormones predominantly remained within or above (not below) the reference. Treatment of infertile women with preconception TSH >4.5 mIU/l with thyroxine resulted in higher free thyroxine (fT4) serum levels. The serum levels of anti-TPO declined as pregnancies evolved.</p><p><strong>Limitations reasons for caution: </strong>The numbers of participants both in the prevalence study and in pregnancy did not reach the <i>a priori</i> estimated num
{"title":"In infertile women with subclinical hypothyroidism, with or without thyroid peroxidase antibodies, serum TSH during pregnancy follows preconception values and thyroid hormones remain stable.","authors":"C De Geyter, L Matt, I De Geyter, R Moffat, C Meier","doi":"10.1093/hropen/hoad038","DOIUrl":"10.1093/hropen/hoad038","url":null,"abstract":"<p><strong>Study question: </strong>How does subclinical hypothyroidism, defined in infertile women during preconception by thyroid-stimulating hormone (TSH) >2.5 or >4.5 mIU/l, with or without thyroid peroxidase antibodies (anti-TPO) >100 IU/ml, impact thyroid hormone levels during pregnancy and after birth?</p><p><strong>Summary answer: </strong>During pregnancy, TSH levels remain similar to those in preconception, even with supplementary thyroxine, whereas the serum levels of anti-TPO progressively decline.</p><p><strong>What is known already: </strong>Overt hypothyroidism impacts both pregnancy and offspring but randomized clinical trials and cohort studies failed to detect the benefit of treatment with thyroxine in cases with low-threshold TSH or with anti-TPO during pregnancy.</p><p><strong>Study design size duration: </strong>First, the prevalence and reproducibility of two candidate cut-off levels of subclinical hypothyroidism in a cohort of 177 infertile women was compared with 171 women not aiming for pregnancy. Second, the impact of distinct setpoints of TSH in preconception (with or without anti-TPO) was monitored during pregnancy in 87 previously infertile women by high-frequency monitoring of thyroid function. Both studies were carried out from 2007 to 2019.</p><p><strong>Participants/materials setting methods: </strong>Reproducibility and prevalence of subclinical hypothyroidism were examined in infertile women presenting in the fertility care unit of an academic institution. Women not aiming for pregnancy participated as controls. In both groups, TSH and anti-TPO were measured two times on different occasions. In addition, a group of previously infertile women with known preconception setpoints of TSH (with or without anti-TPO) were followed up prospectively throughout pregnancy and after birth. During pregnancy, serum was sampled weekly until Week 12, then monthly until delivery, and once after birth. Only cases with preconception TSH >4.5 mIU/l were supplemented with thyroxine. After collection of all samples, the serum levels of anti-TPO and the major thyroid hormones were measured. Prolactin with known fluctuations during pregnancy was used as reference.</p><p><strong>Main results and the role of chance: </strong>Measures of both TSH and anti-TPO at two different time points were accurate and reproducible. The odds of subclinical hypothyroidism in infertile women and controls were similar. During pregnancy, TSH closely followed preconception TSH levels, whereas serum levels of the thyroid hormones predominantly remained within or above (not below) the reference. Treatment of infertile women with preconception TSH >4.5 mIU/l with thyroxine resulted in higher free thyroxine (fT4) serum levels. The serum levels of anti-TPO declined as pregnancies evolved.</p><p><strong>Limitations reasons for caution: </strong>The numbers of participants both in the prevalence study and in pregnancy did not reach the <i>a priori</i> estimated num","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad038"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10589916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694837","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 : 2023-09-22eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad037
S Makieva, M K Sachs, M Xie, A Velasco, S El-Hadad, D R Kalaitzopoulos, I Dedes, R Stiller, B Leeners
<p><strong>Study question: </strong>Does double vitrification and thawing of an embryo compromise the chance of live birth after a single blastocyst transfer?</p><p><strong>Summary answer: </strong>The live birth rate (LBR) obtained after double vitrification was comparable to that obtained after single vitrification.</p><p><strong>What is known already: </strong>Double vitrification-warming (DVW) is commonly practiced to accommodate surplus viable embryos suitable for transfer, to allow retesting of inconclusively diagnosed blastocysts in preimplantation genetic testing (PGT), and to circumvent limitations associated with national policies on embryo culture in certain countries. Despite its popularity, the evidence concerning the impact of DVW practice on ART outcomes is limited and lacking credibility. This is the first thorough investigation of clinical pregnancy and LBR following DVW in the case where the first round of vitrification occurred at the zygote stage and the second round occurred at the blastocyst stage in the absence of biopsy.</p><p><strong>Study design size duration: </strong>This is a retrospective observational analysis of n = 407 single blastocyst transfers whereby embryos created by IVF/ICSI were vitrified-warmed once (single vitrification-warming (SVW) n = 310) or twice (DVW, n = 97) between January 2017 and December 2021.</p><p><strong>Participants/materials setting methods: </strong>In the SVW group, blastocysts were vitrified on Day 5/6 and warmed on the day of embryo transfer (ET). In the DVW group, two pronuclear (2PN) zygotes were first vitrified-warmed and then re-vitrified on Day 5/6 and warmed on the day of ET. Exclusion criteria were ETs from PGT and vitrified-warmed oocyte cycles. All of the ETs were single blastocyst transfers performed at the University Hospital Zurich in Switzerland following natural or artificial endometrial preparation.</p><p><strong>Main results and the role of chance: </strong>The biochemical pregnancy rate, clinical pregnancy rate (CPR), and LBR were all comparable between the DVW and SVW groups. The CPR for DVW was 44.3% and for SVW it was 42.3% (<i>P</i> = 0.719). The LBR for DVW was 30.9% and for SVW it was 28.7% (<i>P</i> = 0.675). The miscarriage rate was additionally similar between the groups: 27.9% for DVW and 32.1% for SVW groups (<i>P</i> = 0.765).</p><p><strong>Limitations reasons for caution: </strong>The study is limited by its retrospective nature. Caution should be taken concerning interpretation of these findings in cases where DVW occurs at different stages of embryo development.</p><p><strong>Wider implications of the findings: </strong>The result of the present study on DVW procedure provides a framework for counselling couples on their chance of clinical pregnancy per warming cycle. It additionally provides confidence and reassurance to laboratory professionals in certain countries where national policies limit embryo culture strategies making DVW inevitable.</p><p><s
{"title":"Double vitrification and warming does not compromise the chance of live birth after single unbiopsied blastocyst transfer.","authors":"S Makieva, M K Sachs, M Xie, A Velasco, S El-Hadad, D R Kalaitzopoulos, I Dedes, R Stiller, B Leeners","doi":"10.1093/hropen/hoad037","DOIUrl":"10.1093/hropen/hoad037","url":null,"abstract":"<p><strong>Study question: </strong>Does double vitrification and thawing of an embryo compromise the chance of live birth after a single blastocyst transfer?</p><p><strong>Summary answer: </strong>The live birth rate (LBR) obtained after double vitrification was comparable to that obtained after single vitrification.</p><p><strong>What is known already: </strong>Double vitrification-warming (DVW) is commonly practiced to accommodate surplus viable embryos suitable for transfer, to allow retesting of inconclusively diagnosed blastocysts in preimplantation genetic testing (PGT), and to circumvent limitations associated with national policies on embryo culture in certain countries. Despite its popularity, the evidence concerning the impact of DVW practice on ART outcomes is limited and lacking credibility. This is the first thorough investigation of clinical pregnancy and LBR following DVW in the case where the first round of vitrification occurred at the zygote stage and the second round occurred at the blastocyst stage in the absence of biopsy.</p><p><strong>Study design size duration: </strong>This is a retrospective observational analysis of n = 407 single blastocyst transfers whereby embryos created by IVF/ICSI were vitrified-warmed once (single vitrification-warming (SVW) n = 310) or twice (DVW, n = 97) between January 2017 and December 2021.</p><p><strong>Participants/materials setting methods: </strong>In the SVW group, blastocysts were vitrified on Day 5/6 and warmed on the day of embryo transfer (ET). In the DVW group, two pronuclear (2PN) zygotes were first vitrified-warmed and then re-vitrified on Day 5/6 and warmed on the day of ET. Exclusion criteria were ETs from PGT and vitrified-warmed oocyte cycles. All of the ETs were single blastocyst transfers performed at the University Hospital Zurich in Switzerland following natural or artificial endometrial preparation.</p><p><strong>Main results and the role of chance: </strong>The biochemical pregnancy rate, clinical pregnancy rate (CPR), and LBR were all comparable between the DVW and SVW groups. The CPR for DVW was 44.3% and for SVW it was 42.3% (<i>P</i> = 0.719). The LBR for DVW was 30.9% and for SVW it was 28.7% (<i>P</i> = 0.675). The miscarriage rate was additionally similar between the groups: 27.9% for DVW and 32.1% for SVW groups (<i>P</i> = 0.765).</p><p><strong>Limitations reasons for caution: </strong>The study is limited by its retrospective nature. Caution should be taken concerning interpretation of these findings in cases where DVW occurs at different stages of embryo development.</p><p><strong>Wider implications of the findings: </strong>The result of the present study on DVW procedure provides a framework for counselling couples on their chance of clinical pregnancy per warming cycle. It additionally provides confidence and reassurance to laboratory professionals in certain countries where national policies limit embryo culture strategies making DVW inevitable.</p><p><s","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad037"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241797","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 : 2023-09-14eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad035
Na Chen, Jingyu Li, Yexing Li, Yiyuan Zhang, Jiarong Li, Jie Gao, Jingmei Hu, Linlin Cui, Zi-Jiang Chen
<p><strong>Study question: </strong>What are the factors influencing the occurrence of monozygotic (MZ) twins in offspring conceived by assisted reproductive technology (ART)?</p><p><strong>Summary answer: </strong>Parental ages, the transfer of fresh versus frozen embryos, and the grade of blastocysts are all related to MZ twinning in ART offspring.</p><p><strong>What is known already: </strong>Offspring conceived by ART have significantly increased risk of MZ twins, which may be due to the characteristics of the infertile population. The objective of this study was to explore the incidence of monozygotic (MZ) twins after ART and to clarify the risk factors for MZ twinning.</p><p><strong>Study design size duration: </strong>A total of 255 monozygotic twins were enrolled in this cohort study, and then matched with singletons at a ratio of 1:4 randomly (with 1020 in the control group). All offspring were conceived by single embryo transfer.</p><p><strong>Participants/materials setting methods: </strong>The collected data were divided into the following three aspects for analysis: characteristics of the infertile population, gamete or embryo manipulations, and factors related to embryo development.</p><p><strong>Main results and the role of chance: </strong>The incidence of MZ twins was 1.638% (255 out of 15 567 pregnancies after single embryo transfers). Compared to singleton births, a significantly lower rate of frozen embryo transfers (FET; 78.0% vs 86.1% <i>P</i> = 0.002) was seen amongst the MZ twins. Amongst fresh ETs, the rate of blastocyst transfers in the MZ twins group was higher compared to that in the control group (92.9% vs 75.4%, <i>P</i> = 0.005). We also found that certain grades of blastocysts in terms of trophectoderm (TE) development, inner cell mass + TE development and the classification of 'top-quality' embryos were associated with the incidence of MZ twinning (<i>P</i> = 0.025, <i>P</i> = 0.012, <i>P</i> = 0.020, respectively). Logistic regression analysis revealed that higher paternal age (odds ratio (OR) = 0.94, 95% CI = 0.89-1.00, <i>P</i> = 0.029) and FET (OR = 0.48, 95% CI = 0.33-0.68, <i>P</i> = 0.001) may be protective factors against MZ twinning. However, higher maternal age (OR = 1.07, 95% CI = 1.01-1.13, <i>P</i> = 0.027) and the transfer of blastocysts (OR = 4.31, 95% CI = 1.46-12.73, <i>P</i> = 0.008) appeared to be associated with an increased risk of MZ twinning. Amongst blastocyst transfers, a C grade TE may be protective factor against MZ twinning (B: OR = 1.90, 95% CI = 1.18-3.07, <i>P</i> = 0.009; A: OR = 1.58, 95% CI = 0.93-2.67, <i>P</i> = 0.089).</p><p><strong>Limitations reasons for caution: </strong>First, our definition of MZ twins was based on twins' birth after single embryo transfers (SET), rather than ultrasound examination during early pregnancy. Second, the parental characteristics of the two groups were homogenous, so it was difficult to find any associations between infertility factors and the
{"title":"Risk factors associated with monozygotic twinning in offspring conceived by assisted reproductive technology.","authors":"Na Chen, Jingyu Li, Yexing Li, Yiyuan Zhang, Jiarong Li, Jie Gao, Jingmei Hu, Linlin Cui, Zi-Jiang Chen","doi":"10.1093/hropen/hoad035","DOIUrl":"10.1093/hropen/hoad035","url":null,"abstract":"<p><strong>Study question: </strong>What are the factors influencing the occurrence of monozygotic (MZ) twins in offspring conceived by assisted reproductive technology (ART)?</p><p><strong>Summary answer: </strong>Parental ages, the transfer of fresh versus frozen embryos, and the grade of blastocysts are all related to MZ twinning in ART offspring.</p><p><strong>What is known already: </strong>Offspring conceived by ART have significantly increased risk of MZ twins, which may be due to the characteristics of the infertile population. The objective of this study was to explore the incidence of monozygotic (MZ) twins after ART and to clarify the risk factors for MZ twinning.</p><p><strong>Study design size duration: </strong>A total of 255 monozygotic twins were enrolled in this cohort study, and then matched with singletons at a ratio of 1:4 randomly (with 1020 in the control group). All offspring were conceived by single embryo transfer.</p><p><strong>Participants/materials setting methods: </strong>The collected data were divided into the following three aspects for analysis: characteristics of the infertile population, gamete or embryo manipulations, and factors related to embryo development.</p><p><strong>Main results and the role of chance: </strong>The incidence of MZ twins was 1.638% (255 out of 15 567 pregnancies after single embryo transfers). Compared to singleton births, a significantly lower rate of frozen embryo transfers (FET; 78.0% vs 86.1% <i>P</i> = 0.002) was seen amongst the MZ twins. Amongst fresh ETs, the rate of blastocyst transfers in the MZ twins group was higher compared to that in the control group (92.9% vs 75.4%, <i>P</i> = 0.005). We also found that certain grades of blastocysts in terms of trophectoderm (TE) development, inner cell mass + TE development and the classification of 'top-quality' embryos were associated with the incidence of MZ twinning (<i>P</i> = 0.025, <i>P</i> = 0.012, <i>P</i> = 0.020, respectively). Logistic regression analysis revealed that higher paternal age (odds ratio (OR) = 0.94, 95% CI = 0.89-1.00, <i>P</i> = 0.029) and FET (OR = 0.48, 95% CI = 0.33-0.68, <i>P</i> = 0.001) may be protective factors against MZ twinning. However, higher maternal age (OR = 1.07, 95% CI = 1.01-1.13, <i>P</i> = 0.027) and the transfer of blastocysts (OR = 4.31, 95% CI = 1.46-12.73, <i>P</i> = 0.008) appeared to be associated with an increased risk of MZ twinning. Amongst blastocyst transfers, a C grade TE may be protective factor against MZ twinning (B: OR = 1.90, 95% CI = 1.18-3.07, <i>P</i> = 0.009; A: OR = 1.58, 95% CI = 0.93-2.67, <i>P</i> = 0.089).</p><p><strong>Limitations reasons for caution: </strong>First, our definition of MZ twins was based on twins' birth after single embryo transfers (SET), rather than ultrasound examination during early pregnancy. Second, the parental characteristics of the two groups were homogenous, so it was difficult to find any associations between infertility factors and the ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad035"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241798","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 : 2023-08-15eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad031
M Salih, C Austin, R R Warty, C Tiktin, D L Rolnik, M Momeni, H Rezatofighi, S Reddy, V Smith, B Vollenhoven, F Horta
<p><strong>Study question: </strong>What is the present performance of artificial intelligence (AI) decision support during embryo selection compared to the standard embryo selection by embryologists?</p><p><strong>Summary answer: </strong>AI consistently outperformed the clinical teams in all the studies focused on embryo morphology and clinical outcome prediction during embryo selection assessment.</p><p><strong>What is known already: </strong>The ART success rate is ∼30%, with a worrying trend of increasing female age correlating with considerably worse results. As such, there have been ongoing efforts to address this low success rate through the development of new technologies. With the advent of AI, there is potential for machine learning to be applied in such a manner that areas limited by human subjectivity, such as embryo selection, can be enhanced through increased objectivity. Given the potential of AI to improve IVF success rates, it remains crucial to review the performance between AI and embryologists during embryo selection.</p><p><strong>Study design size duration: </strong>The search was done across PubMed, EMBASE, Ovid Medline, and IEEE Xplore from 1 June 2005 up to and including 7 January 2022. Included articles were also restricted to those written in English. Search terms utilized across all databases for the study were: ('Artificial intelligence' OR 'Machine Learning' OR 'Deep learning' OR 'Neural network') AND ('IVF' OR '<i>in vitro</i> fertili*' OR 'assisted reproductive techn*' OR 'embryo'), where the character '*' refers the search engine to include any auto completion of the search term.</p><p><strong>Participants/materials setting methods: </strong>A literature search was conducted for literature relating to AI applications to IVF. Primary outcomes of interest were accuracy, sensitivity, and specificity of the embryo morphology grade assessments and the likelihood of clinical outcomes, such as clinical pregnancy after IVF treatments. Risk of bias was assessed using the Modified Down and Black Checklist.</p><p><strong>Main results and the role of chance: </strong>Twenty articles were included in this review. There was no specific embryo assessment day across the studies-Day 1 until Day 5/6 of embryo development was investigated. The types of input for training AI algorithms were images and time-lapse (10/20), clinical information (6/20), and both images and clinical information (4/20). Each AI model demonstrated promise when compared to an embryologist's visual assessment. On average, the models predicted the likelihood of successful clinical pregnancy with greater accuracy than clinical embryologists, signifying greater reliability when compared to human prediction. The AI models performed at a median accuracy of 75.5% (range 59-94%) on predicting embryo morphology grade. The correct prediction (Ground Truth) was defined through the use of embryo images according to post embryologists' assessment following local respect
{"title":"Embryo selection through artificial intelligence versus embryologists: a systematic review.","authors":"M Salih, C Austin, R R Warty, C Tiktin, D L Rolnik, M Momeni, H Rezatofighi, S Reddy, V Smith, B Vollenhoven, F Horta","doi":"10.1093/hropen/hoad031","DOIUrl":"10.1093/hropen/hoad031","url":null,"abstract":"<p><strong>Study question: </strong>What is the present performance of artificial intelligence (AI) decision support during embryo selection compared to the standard embryo selection by embryologists?</p><p><strong>Summary answer: </strong>AI consistently outperformed the clinical teams in all the studies focused on embryo morphology and clinical outcome prediction during embryo selection assessment.</p><p><strong>What is known already: </strong>The ART success rate is ∼30%, with a worrying trend of increasing female age correlating with considerably worse results. As such, there have been ongoing efforts to address this low success rate through the development of new technologies. With the advent of AI, there is potential for machine learning to be applied in such a manner that areas limited by human subjectivity, such as embryo selection, can be enhanced through increased objectivity. Given the potential of AI to improve IVF success rates, it remains crucial to review the performance between AI and embryologists during embryo selection.</p><p><strong>Study design size duration: </strong>The search was done across PubMed, EMBASE, Ovid Medline, and IEEE Xplore from 1 June 2005 up to and including 7 January 2022. Included articles were also restricted to those written in English. Search terms utilized across all databases for the study were: ('Artificial intelligence' OR 'Machine Learning' OR 'Deep learning' OR 'Neural network') AND ('IVF' OR '<i>in vitro</i> fertili*' OR 'assisted reproductive techn*' OR 'embryo'), where the character '*' refers the search engine to include any auto completion of the search term.</p><p><strong>Participants/materials setting methods: </strong>A literature search was conducted for literature relating to AI applications to IVF. Primary outcomes of interest were accuracy, sensitivity, and specificity of the embryo morphology grade assessments and the likelihood of clinical outcomes, such as clinical pregnancy after IVF treatments. Risk of bias was assessed using the Modified Down and Black Checklist.</p><p><strong>Main results and the role of chance: </strong>Twenty articles were included in this review. There was no specific embryo assessment day across the studies-Day 1 until Day 5/6 of embryo development was investigated. The types of input for training AI algorithms were images and time-lapse (10/20), clinical information (6/20), and both images and clinical information (4/20). Each AI model demonstrated promise when compared to an embryologist's visual assessment. On average, the models predicted the likelihood of successful clinical pregnancy with greater accuracy than clinical embryologists, signifying greater reliability when compared to human prediction. The AI models performed at a median accuracy of 75.5% (range 59-94%) on predicting embryo morphology grade. The correct prediction (Ground Truth) was defined through the use of embryo images according to post embryologists' assessment following local respect","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad031"},"PeriodicalIF":0.0,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10076934","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 : 2023-06-01eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad027
Mandy Spaan, Martina Pontesilli, Alexandra W van den Belt-Dusebout, Curt W Burger, Marry M van den Heuvel-Eibrink, Anita C J Ravelli, Mariëtte Goddijn, Cornelis B Lambalk, Tessa J Roseboom, Flora E van Leeuwen
<p><strong>Study question: </strong>Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population?</p><p><strong>Summary answer: </strong>After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI.</p><p><strong>What is known already: </strong>There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF.</p><p><strong>Study design size duration: </strong>A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers.</p><p><strong>Participants/materials setting methods: </strong>Children were identified through the mothers' records in the Personal Records Database. Information on the conception method of each child was collected through the mother's medical record. In total, the cohort comprises 89 249 live-born children of subfertile couples, of whom 51 417 were conceived using ART and 37 832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989-2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)).</p><p><strong>Main results and the role of chance: </strong>In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81-1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84-1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08-2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88-1.81) compared to cancer risk in children not conceived by ART.</p><p><strong>Limitations reasons for caution: </strong>The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases.</p><p><strong>Wider implications of the findings: </strong>After a median follow-up of 18 years, children
研究问题与非通过 ART 受孕的亚育夫妇所生子女和普通人群所生子女相比,通过 ART(包括体外受精、卵胞浆内单精子显微注射和冻融胚胎移植)受孕的儿童、青少年和年轻人患癌症的风险是否会增加?在中位随访 18 年后,通过 ART 受孕的儿童患癌症的总体风险没有增加,但在 ICSI 受孕的儿童中观察到风险略有增加:越来越多的证据表明,抗逆转录病毒疗法可能会扰乱胚胎植入前的表观遗传过程,并影响长期健康。最近的研究显示,ICSI 和 FET(非)明显增加了癌症风险,但 IVF(试管婴儿)则没有:进行了一项全国范围的前瞻性追踪历史队列研究,研究对象包括1983年至2011年间在荷兰13家试管婴儿诊所和两家生殖中心之一接受ART治疗的女性和未接受ART治疗的亚健康女性的所有活产后代:通过个人记录数据库(Personal Records Database)中母亲的记录确定子女的身份。每个孩子的受孕方式信息通过母亲的医疗记录收集。队列中共有 89 249 名亚不育夫妇的活产子女,其中 51 417 名是通过抗逆转录病毒疗法受孕的,37 832 名不是(即通过自然受孕、促排卵或人工授精后受孕)。癌症发病率是通过与荷兰癌症登记处(Netherlands Cancer Registry)在 1989-2019 年期间的联系确定的。采用抗逆转录病毒疗法受孕的儿童患癌症的风险与亚健康夫妇所生但未采用抗逆转录病毒疗法受孕的儿童患癌症的风险(危险比(HR))和普通人群儿童患癌症的风险(标准化发病率比(SIR))进行了比较:中位随访 18 年后,共观察到 358 例癌症。与普通人群相比(SIR = 0.96,95% CI = 0.81-1.12),或与非抗逆转录病毒疗法受孕的亚育夫妇的子女相比(HR = 1.06,95% CI = 0.84-1.33),抗逆转录病毒疗法受孕的子女患癌症的总体风险并没有增加。与未通过 ART 受孕的亚育夫妇的子女相比,使用 IVF 或 FET 与癌症风险增加无关,但 ICSI 与风险轻微增加有关(HR = 1.58,95% CI = 1.08-2.31)。与未通过人工授精受孕的儿童相比,年龄较大(≥18 岁,HR = 1.26,95% CI = 0.88-1.81)的儿童在人工授精后患癌症的风险并没有增加:由于病例数量较少,因此必须谨慎解释在采用卵胞浆内单精子显微注射法受孕的儿童中观察到的风险增加:中位随访 18 年后,采用 ART 技术受孕的儿童患癌症的总体风险并没有增加。要调查通过不同类型的抗逆转录病毒疗法受孕的(年轻)成年人患癌症的风险,还需要许多大型研究和长期随访。此外,建议在国际范围内开展联合研究,以提供足够的力量来研究抗逆转录病毒疗法后特定癌症部位的风险:这项工作得到了荷兰癌症协会(NKI 2006-3631)的支持,该协会资助了OMEGA-女性队列,儿童癌症免费协会(KIKA; 147)资助了OMEGA-I-II后代队列。OMEGA-III后代队列得到了阿姆斯特丹生殖与发育研究所博士后奖学金和美国国立卫生研究院尤妮斯-肯尼迪-施莱佛国家儿童健康与人类发展研究所(Eunice Kennedy Shriver National Institute of Child Health & Human Development)的资助,奖金编号为R01HD088393。内容仅代表作者本人,不代表美国国立卫生研究院的官方观点。作者声明不存在利益冲突。试验注册号:N/A:不适用。
{"title":"Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011.","authors":"Mandy Spaan, Martina Pontesilli, Alexandra W van den Belt-Dusebout, Curt W Burger, Marry M van den Heuvel-Eibrink, Anita C J Ravelli, Mariëtte Goddijn, Cornelis B Lambalk, Tessa J Roseboom, Flora E van Leeuwen","doi":"10.1093/hropen/hoad027","DOIUrl":"10.1093/hropen/hoad027","url":null,"abstract":"<p><strong>Study question: </strong>Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population?</p><p><strong>Summary answer: </strong>After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI.</p><p><strong>What is known already: </strong>There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF.</p><p><strong>Study design size duration: </strong>A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers.</p><p><strong>Participants/materials setting methods: </strong>Children were identified through the mothers' records in the Personal Records Database. Information on the conception method of each child was collected through the mother's medical record. In total, the cohort comprises 89 249 live-born children of subfertile couples, of whom 51 417 were conceived using ART and 37 832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989-2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)).</p><p><strong>Main results and the role of chance: </strong>In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81-1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84-1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08-2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88-1.81) compared to cancer risk in children not conceived by ART.</p><p><strong>Limitations reasons for caution: </strong>The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases.</p><p><strong>Wider implications of the findings: </strong>After a median follow-up of 18 years, children","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad027"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/36/hoad027.PMC10279651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710260","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 : 2023-05-22eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad021
K Yin, L Whitaker, E Hojo, S McLenachan, J Walker, G McKillop, C Stubbs, L Priest, M Cruz, N Roberts, H Critchley
<p><strong>Study question: </strong>Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)?</p><p><strong>Summary answer: </strong>Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids.</p><p><strong>What is known already: </strong>SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids.</p><p><strong>Study design size duration: </strong>In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology.</p><p><strong>Participants/materials setting methods: </strong>A cohort of 19 women aged 38-52 years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI).</p><p><strong>Main results and the role of chance: </strong>Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (<i>P</i> = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (<i>P</i> = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (<i>P</i> = 0.17).</p><p><strong>Limitations reasons for caution: </strong>The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected.</p><p><strong>Wider implications of the findings: </strong>The imaging protocol that we have developed represents a
{"title":"Measurement of changes in uterine and fibroid volume during treatment of heavy menstrual bleeding (HMB).","authors":"K Yin, L Whitaker, E Hojo, S McLenachan, J Walker, G McKillop, C Stubbs, L Priest, M Cruz, N Roberts, H Critchley","doi":"10.1093/hropen/hoad021","DOIUrl":"10.1093/hropen/hoad021","url":null,"abstract":"<p><strong>Study question: </strong>Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)?</p><p><strong>Summary answer: </strong>Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids.</p><p><strong>What is known already: </strong>SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids.</p><p><strong>Study design size duration: </strong>In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology.</p><p><strong>Participants/materials setting methods: </strong>A cohort of 19 women aged 38-52 years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI).</p><p><strong>Main results and the role of chance: </strong>Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (<i>P</i> = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (<i>P</i> = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (<i>P</i> = 0.17).</p><p><strong>Limitations reasons for caution: </strong>The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected.</p><p><strong>Wider implications of the findings: </strong>The imaging protocol that we have developed represents a","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad021"},"PeriodicalIF":8.3,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9619544","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 : 2023-05-17eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad020
Wiep R de Ligny, Kathrin Fleischer, Hilde Grens, Didi D M Braat, Jan Peter de Bruin
<p><strong>Study question: </strong>What is the evidence for over-the-counter antioxidant supplements for male infertility?</p><p><strong>Summary answer: </strong>Less than half of over-the-counter antioxidant supplements for male fertility patients have been tested in a clinical trial, and the available clinical trials are generally of poor quality.</p><p><strong>What is known already: </strong>The prevalence of male infertility is rising and, with this, the market for supplements claiming to improve male fertility is expanding. Up to now, there is limited data on the evidence for these over-the-counter supplements.</p><p><strong>Study design size duration: </strong>Amazon, Google Shopping and other relevant shopping websites were searched on 24 June 2022 with the following terms: 'supplements', 'antioxidants', 'vitamins', AND 'male fertility', 'male infertility', 'male subfertility', 'fertility men', 'fertility man'. All supplements with a description of ingredients in English, Dutch, French, Spanish, or German were included. Subsequently, Pubmed and Google Scholar were searched for studies that included the supplements.</p><p><strong>Participants/materials setting methods: </strong>Inclusion criteria were supplements with antioxidant properties, of which the main purpose was to improve male fertility. Included supplements must be available without a doctor's prescription. Supplements containing plant extracts were excluded, as well as supplements of which the content or dosage was not clear. The ingredients, dosage, price and health claims of the supplements were recorded. We assessed whether substances in the supplements exceeded the recommended dietary allowance (RDA) or tolerable upper intake level (UL). All clinical trials and animal studies investigating included supplements were selected for this review. Clinical trials were assessed for risk of bias with a risk of bias tool appropriate for the study design.</p><p><strong>Main results and the role of chance: </strong>There were 34 eligible antioxidant supplements found, containing 48 different active substances. The average price per 30 days was 53.10 US dollars. Most of the supplements (27/34, 79%) contained substances in a dosage exceeding the recommended daily allowance (RDA). All manufacturers of the supplements made health claims related to the improvement of sperm quality or male fertility. For 13 of the 34 supplements (38%), published clinical trials were available, and for one supplement, only an animal study was found. The overall quality of the included studies was poor. Only two supplements were tested in a good quality clinical trial.</p><p><strong>Limitations reasons for caution: </strong>As a consequence of searching shopping websites, a comprehensive search strategy could not be formulated. Most supplements were excluded because they contained plant extracts or because supplement information was not available (in an appropriate language).</p><p><strong>Wider implications o
{"title":"The lack of evidence behind over-the-counter antioxidant supplements for male fertility patients: a scoping review.","authors":"Wiep R de Ligny, Kathrin Fleischer, Hilde Grens, Didi D M Braat, Jan Peter de Bruin","doi":"10.1093/hropen/hoad020","DOIUrl":"10.1093/hropen/hoad020","url":null,"abstract":"<p><strong>Study question: </strong>What is the evidence for over-the-counter antioxidant supplements for male infertility?</p><p><strong>Summary answer: </strong>Less than half of over-the-counter antioxidant supplements for male fertility patients have been tested in a clinical trial, and the available clinical trials are generally of poor quality.</p><p><strong>What is known already: </strong>The prevalence of male infertility is rising and, with this, the market for supplements claiming to improve male fertility is expanding. Up to now, there is limited data on the evidence for these over-the-counter supplements.</p><p><strong>Study design size duration: </strong>Amazon, Google Shopping and other relevant shopping websites were searched on 24 June 2022 with the following terms: 'supplements', 'antioxidants', 'vitamins', AND 'male fertility', 'male infertility', 'male subfertility', 'fertility men', 'fertility man'. All supplements with a description of ingredients in English, Dutch, French, Spanish, or German were included. Subsequently, Pubmed and Google Scholar were searched for studies that included the supplements.</p><p><strong>Participants/materials setting methods: </strong>Inclusion criteria were supplements with antioxidant properties, of which the main purpose was to improve male fertility. Included supplements must be available without a doctor's prescription. Supplements containing plant extracts were excluded, as well as supplements of which the content or dosage was not clear. The ingredients, dosage, price and health claims of the supplements were recorded. We assessed whether substances in the supplements exceeded the recommended dietary allowance (RDA) or tolerable upper intake level (UL). All clinical trials and animal studies investigating included supplements were selected for this review. Clinical trials were assessed for risk of bias with a risk of bias tool appropriate for the study design.</p><p><strong>Main results and the role of chance: </strong>There were 34 eligible antioxidant supplements found, containing 48 different active substances. The average price per 30 days was 53.10 US dollars. Most of the supplements (27/34, 79%) contained substances in a dosage exceeding the recommended daily allowance (RDA). All manufacturers of the supplements made health claims related to the improvement of sperm quality or male fertility. For 13 of the 34 supplements (38%), published clinical trials were available, and for one supplement, only an animal study was found. The overall quality of the included studies was poor. Only two supplements were tested in a good quality clinical trial.</p><p><strong>Limitations reasons for caution: </strong>As a consequence of searching shopping websites, a comprehensive search strategy could not be formulated. Most supplements were excluded because they contained plant extracts or because supplement information was not available (in an appropriate language).</p><p><strong>Wider implications o","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad020"},"PeriodicalIF":8.3,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9601415","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}