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Association between dietary total antioxidant capacity and semen quality among men attending an infertility clinic: a cross-sectional study. 膳食总抗氧化能力与不育诊所男性精液质量之间的关系:一项横断面研究。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-10-31 eCollection Date: 2023-01-01 DOI: 10.1093/hropen/hoad041
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
<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。
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引用次数: 0
Use of mesenchymal stem cells to enhance or restore fertility potential: a systematic review of available experimental strategies. 利用间充质干细胞增强或恢复生育潜能:对现有实验策略的系统回顾。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-10-25 eCollection Date: 2023-01-01 DOI: 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
研究问题:在未来的临床应用中,再生医学与干细胞治疗在多大程度上有助于解决不孕症问题?摘要回答:使用不同干细胞来源的再生医学在保护卵巢储备免受损伤和衰老,以及在各种临床前环境中提高生育潜力方面取得了有希望的结果。已知情况:使用干细胞疗法的再生医学正在成为解决人类生殖领域许多问题的潜在策略。事实上,由于不同类型的成体和胎儿间充质干细胞(MSCs)能够分化成不同的组织谱系,向特定的损伤部位移动(归巢),并产生具有伤口愈合、促血管生成和抗氧化能力的分泌组,因此已经得到了有希望的结果。研究设计规模持续时间:在系统评价和荟萃分析首选报告项目清单的指导下,我们从PubMed, Medline和Embase数据库检索了相关研究,直到2023年6月,使用以下关键词:“间充质干细胞”和“卵巢卵泡”或“卵巢组织培养”或“卵巢卵泡培养”或“卵丘卵母细胞复合体”。只收录了同行评议的已发表的英文文章。参与者/材料设置方法:实验策略的主要结果是评估卵巢储备,重点是卵泡存活、数量和生长。次要结果包括分析与卵泡池相关的其他参数,如激素和生长因子、卵巢组织活力标记(包括氧化应激水平)、卵母细胞生长和成熟率,当然还有妊娠结局。主要结果及机会的作用:选择在特定条件下探索不同动物来源和组织来源的MSCs的临床前研究(n = 112),包括:颗粒细胞、卵巢组织和离体卵巢卵泡的体外培养;卵巢组织移植;在促性腺毒性或年龄相关性卵泡池下降后进行全身或卵巢内注射。保护卵巢储备免受衰老和促性腺毒素损伤已经在体外和体内使用小鼠模型进行了广泛的测试,现在在首次卵巢功能不全患者的病例系列中获得了初步数据。在卵巢组织培养中使用MSCs作为饲养细胞可以改善卵泡结果和卵母细胞的能力,使我们向未来的临床应用又迈进了一步。在实验动物模型中移植卵巢组织时,MSCs也被证明能有效促进移植部位的血运重建。局限性:尽管在不同的实验模型(特别是在体外使用各种哺乳动物实验模型和在体内使用小鼠模型)中,临床前结果在保护卵巢储备方面看起来很有希望,但在这种方法被认为是安全的并在临床环境中成功实施之前,还有很多工作要做。研究结果的更广泛含义:一方面,所有收集到的数据表明,再生医学技术在生殖医学领域未来临床应用的创新技术中正在迅速取得进展。在证明了MSC在临床前环境中的有效性之后,在MSC能够安全有效地用于不同的临床应用之前,还有很多工作要做。研究经费/竞争利益:本研究得到了比利时国家科学研究基金会(FNRS-PDR T.0077.14, FNRS-CDR J.0063.20,以及授予Marie-Madeleine Dolmans的5/4/150/5赠款)、spciaux de Recherche基金会和St Luc基金会的资助。这些作者都没有任何竞争利益需要披露。注册号:无。
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引用次数: 0
Enzymatic tissue processing after testicular biopsy in non-obstructive azoospermia enhances sperm retrieval. 非梗阻性无精子症睾丸活检后的酶组织处理增强了精子回收。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-10-18 eCollection Date: 2023-01-01 DOI: 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":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the added value of enzymatic processing of testicular biopsies on testicular sperm retrieval (SR) rates for patients with non-obstructive azoospermia (NOA)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In addition to mechanical mincing, enzymatic digestion increased SR rates in testicular biopsies of NOA patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;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}
引用次数: 0
In infertile women with subclinical hypothyroidism, with or without thyroid peroxidase antibodies, serum TSH during pregnancy follows preconception values and thyroid hormones remain stable. 在患有亚临床甲状腺功能减退症的不孕妇女中,无论是否有甲状腺过氧化物酶抗体,妊娠期血清TSH都遵循先入为主的值,甲状腺激素保持稳定。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-10-09 eCollection Date: 2023-01-01 DOI: 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
研究问题:亚临床甲状腺功能减退症是如何在不孕妇女怀孕前通过促甲状腺激素(TSH)>2.5或>4.5 mIU/l定义的,有或没有甲状腺过氧化物酶抗体(抗TPO)>100 IU/ml,影响妊娠期和产后甲状腺激素水平?简要回答:在妊娠期间,即使补充了甲状腺素,TSH水平仍与妊娠前相似,而血清抗TPO水平逐渐下降。已知情况:显性甲状腺功能减退对妊娠和后代都有影响,但随机临床试验和队列研究未能发现在妊娠期低阈值TSH或抗TPO患者中使用甲状腺素治疗的益处。研究设计规模持续时间:首先,在177名不孕妇女和171名不打算怀孕的妇女的队列中,比较了亚临床甲状腺功能减退症两个候选临界水平的患病率和可重复性。其次,通过对甲状腺功能的高频监测,在87名既往不孕妇女的妊娠期间监测了孕前TSH的不同设定点(有或没有抗TPO)的影响。这两项研究都是在2007年至2019年进行的。参与者/材料设置方法:在一家学术机构的生育护理室检查不孕妇女的亚临床甲状腺功能减退症的再现性和患病率。不打算怀孕的妇女作为对照参加。在两组中,在不同的场合测量TSH和抗TPO两次。此外,对一组具有已知TSH预设值(含或不含抗TPO)的既往不孕妇女在整个妊娠期和出生后进行前瞻性随访。在怀孕期间,每周对血清进行采样,直到第12周,然后每月进行一次,直到分娩,并在出生后进行一次。只有在孕前TSH>4.5mIU/l的病例中才补充甲状腺素。采集所有样本后,测量血清抗TPO和主要甲状腺激素水平。妊娠期间已知波动的催乳素被用作参考。主要结果和偶然性的作用:TSH和抗TPO在两个不同时间点的测量是准确和可重复的。不孕妇女和对照组患亚临床甲状腺功能减退症的几率相似。在妊娠期间,TSH与孕前TSH水平密切相关,而血清甲状腺激素水平主要保持在参考值之内或之上(而不是低于参考值)。用甲状腺素治疗孕前TSH>4.5 mIU/l的不孕妇女可提高血清游离甲状腺素(fT4)水平。血清抗TPO水平随着妊娠的发展而下降。谨慎的局限性原因:患病率研究和妊娠期的参与者人数都没有达到先验估计的数字。出于伦理原因,先入为主TSH>4.5mIU/l的患者接受甲状腺素治疗。这一发现仅适用于不孕妇女。研究结果的更广泛含义:我们建议使用>4.5 mIU/l作为妊娠前补充甲状腺素的血清TSH阈值。在妊娠期间,fT4可能是监测甲状腺功能的更好标志物。持续妊娠期间抗TPO抗体水平的持续下降必须被视为一种保护因素。研究资金/竞争利益:本研究的流行率部分得到了Merck Serono,Geneva(TH006/ERM200007-603)的支持。在罗氏诊断公司的财政支持下(2017年11月1721日,瑞士Rotkreuz),对后续妊娠期间收集的血清样本进行了激素测量。I.D.G.得到了瑞士巴塞尔再生基金会的资助。所有作者均声明不存在利益冲突。试验注册号:巴塞尔大学研究数据库,项目编号576691(2007)。
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引用次数: 0
Double vitrification and warming does not compromise the chance of live birth after single unbiopsied blastocyst transfer. 单次未经调理的胚泡移植后,双重玻璃化和加温不会影响活产的机会。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-09-22 eCollection Date: 2023-01-01 DOI: 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
研究问题:胚胎的双重玻璃化和解冻是否会影响单次胚泡移植后活产的机会?简要回答:双重玻璃化后获得的活产率(LBR)与单次玻璃化后的活产率相当。已知情况:双玻璃化加温(DVW)通常用于容纳适合移植的剩余活胚胎,允许在植入前基因测试(PGT)中对未确诊的胚泡进行重新测试,并规避某些国家胚胎培养国家政策的限制。尽管DVW实践很受欢迎,但有关DVW实践对ART结果影响的证据有限,缺乏可信度。这是首次对DVW后的临床妊娠和LBR进行彻底调查,其中第一轮玻璃化发生在受精卵阶段,第二轮发生在没有活检的胚泡阶段。研究设计规模持续时间:这是对n = 407单次胚泡移植,其中IVF/ICSI产生的胚胎被玻璃化加温一次(单次玻璃化加温(SVW)n = 310)或两次(DVW = 97)。参与者/材料设置方法:在SVW组中,胚泡在第5/6天玻璃化,并在胚胎移植(ET)当天加温。在DVW组中,两个原核(2PN)受精卵首先玻璃化加温,然后在第5/6天再次玻璃化,并在ET当天加温。排除标准为PGT和玻璃化加温卵母细胞周期中的ET。所有的ET都是在瑞士苏黎世大学医院进行的天然或人工子宫内膜制备后的单胚泡移植。主要结果和机会的作用:DVW组和SVW组的生化妊娠率、临床妊娠率(CPR)和LBR均具有可比性。DVW的心肺复苏率为44.3%,SVW为42.3%(P = DVW和SVW的LBR分别为30.9%和28.7%(P = 两组流产率相似:DVW组为27.9%,SVW组为32.1%(P = 0.765)。谨慎的局限性原因:该研究受到其回顾性的限制。在胚胎发育的不同阶段发生DVW的情况下,应注意对这些发现的解释。研究结果的更广泛含义:目前对DVW程序的研究结果为咨询夫妇在每个升温周期的临床妊娠机会提供了一个框架。它还为某些国家的实验室专业人员提供了信心和保证,这些国家的国家政策限制了胚胎培养策略,使DVW不可避免。研究资金/竞争利益:这项工作得到了苏黎世大学“重新加载人类生殖”大学研究优先项目的支持。作者无需声明与本研究相关的利益冲突。试用注册号:不适用。
{"title":"Double vitrification and warming does not compromise the chance of live birth after single unbiopsied blastocyst transfer.","authors":"S Makieva,&nbsp;M K Sachs,&nbsp;M Xie,&nbsp;A Velasco,&nbsp;S El-Hadad,&nbsp;D R Kalaitzopoulos,&nbsp;I Dedes,&nbsp;R Stiller,&nbsp;B Leeners","doi":"10.1093/hropen/hoad037","DOIUrl":"10.1093/hropen/hoad037","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does double vitrification and thawing of an embryo compromise the chance of live birth after a single blastocyst transfer?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The live birth rate (LBR) obtained after double vitrification was comparable to that obtained after single vitrification.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;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% (&lt;i&gt;P&lt;/i&gt; = 0.719). The LBR for DVW was 30.9% and for SVW it was 28.7% (&lt;i&gt;P&lt;/i&gt; = 0.675). The miscarriage rate was additionally similar between the groups: 27.9% for DVW and 32.1% for SVW groups (&lt;i&gt;P&lt;/i&gt; = 0.765).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;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}
引用次数: 0
Risk factors associated with monozygotic twinning in offspring conceived by assisted reproductive technology. 与辅助生殖技术孕育的后代单卵双胞胎相关的风险因素。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-09-14 eCollection Date: 2023-01-01 DOI: 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
研究问题:通过辅助生殖技术(ART)受孕的后代中,影响单卵(MZ)双胞胎发生的因素是什么?简要回答:父母年龄、新鲜胚胎与冷冻胚胎的移植以及胚泡的等级都与ART后代的MZ配对有关。已知情况:通过ART受孕的后代患MZ双胞胎的风险显著增加,这可能是由于不孕人群的特点。本研究的目的是探讨ART后单卵(MZ)双胞胎的发生率,并阐明MZ双胞胎的危险因素。研究设计规模持续时间:共有255对单卵双胞胎参与了这项队列研究,然后以1:4的比例随机与单卵双胞胎配对(对照组为1020对)。所有的后代都是通过单胚胎移植受孕的。参与者/材料设置方法:收集的数据分为以下三个方面进行分析:不育群体的特征、配子或胚胎操作以及与胚胎发育相关的因素。主要结果和偶然性的作用:MZ双胞胎的发生率为1.638%(15例中有255例) 567例单胚胎移植后妊娠)。与单胎分娩相比,冷冻胚胎移植率显著降低(FET;78.0%vs 86.1%P = 0.002)。在新鲜ET中,MZ双胞胎组的胚泡转移率高于对照组(92.9%vs 75.4%,P = 0.005)。我们还发现,在滋养外胚层(TE)发育、内细胞质量+TE发育和“优质”胚胎分类方面,某些级别的胚泡与MZ孪晶的发生率有关(P = 0.025,P = 0.012,P = 0.020)。Logistic回归分析显示,较高的父亲年龄(优势比(OR)) = 0.94,95%CI = 0.89-1.00,P = 0.029)和FET(OR = 0.48,95%CI = 0.33-0.68,P = 0.001)可能是防止MZ孪晶的保护因素。然而,较高的产妇年龄(OR = 1.07,95%CI = 1.01-1.13,P = 0.027)和胚泡转移(OR = 4.31195%CI = 1.46-12.73,P = 0.008)似乎与MZ孪晶的风险增加有关。在胚泡转移中,C级TE可能是防止MZ孪晶的保护因子(B:OR = 1.90,95%CI = 1.18-3.07,P = 0.009;A: 或 = 1.58,95%CI = 0.93-2.67,P = 0.089)。注意的局限性原因:首先,我们对MZ双胞胎的定义是基于单胚胎移植(SET)后双胞胎的出生,而不是妊娠早期的超声检查。其次,两组的父母特征是同质的,因此很难发现不育因素与MZ双胞胎的发病率之间的任何关联。研究结果的更广泛含义:对MZ结对风险因素的多方面分析为高危人群的临床干预提供了一些信息。研究资助/利益竞争:本研究得到了国家重点技术研究与发展计划(2022YFC2704404)、中国医学科学院医学科学创新基金(2021-I2M-5-001)、山东省泰山学者青年专家计划(tsqn201909195)、基础科学中心计划(31988101)、,山东省重点研发计划项目(2020ZLYS02)。所有作者都没有利益冲突需要声明。试用注册号:不适用。
{"title":"Risk factors associated with monozygotic twinning in offspring conceived by assisted reproductive technology.","authors":"Na Chen,&nbsp;Jingyu Li,&nbsp;Yexing Li,&nbsp;Yiyuan Zhang,&nbsp;Jiarong Li,&nbsp;Jie Gao,&nbsp;Jingmei Hu,&nbsp;Linlin Cui,&nbsp;Zi-Jiang Chen","doi":"10.1093/hropen/hoad035","DOIUrl":"10.1093/hropen/hoad035","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What are the factors influencing the occurrence of monozygotic (MZ) twins in offspring conceived by assisted reproductive technology (ART)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Parental ages, the transfer of fresh versus frozen embryos, and the grade of blastocysts are all related to MZ twinning in ART offspring.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;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% &lt;i&gt;P&lt;/i&gt; = 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%, &lt;i&gt;P&lt;/i&gt; = 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 (&lt;i&gt;P&lt;/i&gt; = 0.025, &lt;i&gt;P&lt;/i&gt; = 0.012, &lt;i&gt;P&lt;/i&gt; = 0.020, respectively). Logistic regression analysis revealed that higher paternal age (odds ratio (OR) = 0.94, 95% CI = 0.89-1.00, &lt;i&gt;P&lt;/i&gt; = 0.029) and FET (OR = 0.48, 95% CI = 0.33-0.68, &lt;i&gt;P&lt;/i&gt; = 0.001) may be protective factors against MZ twinning. However, higher maternal age (OR = 1.07, 95% CI = 1.01-1.13, &lt;i&gt;P&lt;/i&gt; = 0.027) and the transfer of blastocysts (OR = 4.31, 95% CI = 1.46-12.73, &lt;i&gt;P&lt;/i&gt; = 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, &lt;i&gt;P&lt;/i&gt; = 0.009; A: OR = 1.58, 95% CI = 0.93-2.67, &lt;i&gt;P&lt;/i&gt; = 0.089).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;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}
引用次数: 0
Embryo selection through artificial intelligence versus embryologists: a systematic review. 通过人工智能与胚胎学家进行胚胎选择:系统回顾。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-08-15 eCollection Date: 2023-01-01 DOI: 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
研究问题:在胚胎选择过程中,与胚胎学家的标准胚胎选择相比,人工智能(AI)决策支持目前的表现如何?总结回答:在胚胎选择评估中,AI在所有以胚胎形态和临床结果预测为重点的研究中始终优于临床团队。已知情况:抗逆转录病毒治疗的成功率约为30%,令人担忧的趋势是,女性年龄的增长与相当糟糕的结果相关。因此,一直在努力通过开发新技术来解决这一低成功率问题。随着人工智能的出现,机器学习有可能以这样一种方式应用,即受人类主观性限制的领域,如胚胎选择,可以通过增加客观性来增强。鉴于人工智能在提高试管婴儿成功率方面的潜力,在胚胎选择过程中回顾人工智能和胚胎学家之间的表现仍然至关重要。研究设计规模持续时间:检索于2005年6月1日至2022年1月7日期间在PubMed、EMBASE、Ovid Medline和IEEE explore中完成。纳入的文章也仅限于用英文撰写的文章。该研究在所有数据库中使用的搜索词是:(“人工智能”或“机器学习”或“深度学习”或“神经网络”)和(“试管婴儿”或“体外受精*”或“辅助生殖技术*”或“胚胎”),其中字符“*”指的是搜索引擎,包括任何自动完成的搜索词。参与者/材料设置方法:检索人工智能在试管婴儿中的应用相关文献。主要研究结果是胚胎形态分级评估的准确性、敏感性和特异性,以及临床结果的可能性,如体外受精治疗后的临床妊娠。使用修改的Down和Black检查表评估偏倚风险。主要结果和偶然性的作用:本综述纳入了20篇文章。研究期间没有确定胚胎发育的具体评估日期,从胚胎发育第1天到第5/6天进行研究。训练AI算法的输入类型为图像加延时(10/20)、临床信息(6/20)、图像加临床信息(4/20)。与胚胎学家的视觉评估相比,每个人工智能模型都显示出了希望。平均而言,这些模型预测临床成功怀孕的可能性比临床胚胎学家更准确,与人类预测相比,这意味着更高的可靠性。人工智能模型在预测胚胎形态等级方面的中位准确率为75.5%(范围为59-94%)。正确的预测(Ground Truth)是根据后胚胎学家的评估,根据当地各自的指导方针,通过使用胚胎图像来定义的。使用盲测数据集,胚胎学家的预测准确率为65.4%(范围47-75%),与原始的当地各自评估提供的基础真理相同。同样,人工智能模型通过使用患者临床治疗信息预测临床妊娠的中位准确率为77.8%(范围68-90%),而由胚胎学家进行预测的中位准确率为64%(范围58-76%)。当图像/延时和临床信息输入相结合时,人工智能模型的中位数准确率为81.5%(范围为67-98%),而临床胚胎学家的中位数准确率为51%(范围为43-59%)。局限性:谨慎的原因:本综述的结果是基于尚未在临床环境中进行前瞻性评价的研究。此外,由于研究的异质性、人工智能模型的开发、使用的数据库以及研究的设计和质量,对所有研究进行公平比较被认为是不可行的。研究结果的更广泛含义:人工智能为体外受精领域和胚胎选择提供了相当大的希望。然而,开发人员对临床结果的看法需要转变,从成功植入到持续妊娠或活产。此外,现有模型主要关注本地生成的数据库,许多模型缺乏外部验证。研究经费/竞争利益:本研究由莫纳什数据未来研究所资助。所有作者无利益冲突需要声明。注册号:CRD42021256333。
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引用次数: 2
Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011. 1983-2011年通过抗逆转录病毒疗法受孕的儿童、青少年和年轻成人的癌症风险。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-06-01 eCollection Date: 2023-01-01 DOI: 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。
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引用次数: 0
Measurement of changes in uterine and fibroid volume during treatment of heavy menstrual bleeding (HMB). 测量大量月经出血(HMB)治疗期间子宫和肌瘤体积的变化。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-05-22 eCollection Date: 2023-01-01 DOI: 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
研究问题:应用一种无偏见的方法分析磁共振(MR)图像,是否可以发现使用选择性孕酮受体调节剂醋酸乌利司他(SPRM-UPA)治疗月经过多(HMB)三个12周疗程对子宫或子宫肌瘤体积有任何影响?应用无偏见的方法分析核磁共振图像显示,用SPRM-UPA治疗HMB与子宫体积或子宫肌瘤体积的显著缩小无关:SPRM-UPA对治疗HMB具有疗效。然而,关于 SPRM-UPA 是否对子宫体积和子宫肌瘤有影响,其作用机制(MoA)尚不十分明确,而且关于 SPRM-UPA 是否对子宫体积和子宫肌瘤有影响的报道不一,使用的方法也可能存在偏差:在一项前瞻性临床研究(无对比研究)中,19 名患有 HMB 的妇女接受了为期 12 个月的 SPRM-UPA 治疗,并通过高分辨率结构性 MRI 和立体学评估了子宫和肌瘤的大小:19名年龄在38-52岁之间的妇女(8名患有子宫肌瘤,11名没有子宫肌瘤)接受了三个为期12周、每天服用5毫克SPRM-UPA的疗程,在两个疗程之间停药四周。在基线以及治疗 6 个月和 12 个月后,采用现代设计立体学的 Cavalieri 方法并结合磁共振成像(MRI),对子宫体积和肌瘤总体积进行了无偏估计:Bland-Altman图显示,子宫肌瘤和子宫体积的测量具有良好的评分者内重复性和评分者间重复性。就所有患者而言,双向方差分析结果显示,在使用 SPRM-UPA 两或三个疗程后,子宫体积并未显著缩小(P = 0.51),如果将有肌瘤和无肌瘤的妇女组分开考虑,情况也是如此(P = 0.63)。单因素方差分析结果显示,8 名子宫肌瘤患者的肌瘤总体积并没有显著减少(P = 0.17):这项研究是在一个相对较小的妇女群体中进行的,随后利用所获得的数据进行的模拟显示,在三个时间点和最多 50 人的群体中,α(I 类误差)和 beta(II 类误差)分别设定为 95% 的显著性和 80% 的功率,至少需要招募 35 名患者,才有可能拒绝零假设(子宫肌瘤总体积没有显著减少):我们开发的成像方案代表了一种测量子宫和子宫肌瘤体积的通用范例,可随时纳入未来的 HMB 医学治疗研究中。在本研究中,SPRM-UPA 在经过两个或三个为期 12 周的疗程后,子宫体积或子宫肌瘤的总体积(约半数患者存在子宫肌瘤)均未能显著缩小。这一发现为利用针对激素依赖性的治疗策略管理 HMB 提供了新的视角:UPA与HMB常规治疗(UCON)试验由EME计划(医学研究理事会(MRC)和美国国立卫生研究院(NIHR))(12/206/52)资助。医学研究理事会(MRC)中心对生殖健康中心(CRH)的资助(G1002033和MR/N022556/1)也在此表示感谢。H.C. 从拜耳股份公司(Bayer AG)获得实验室耗材和工作人员的临床研究支持,并为拜耳股份公司、PregLem SA、Gedeon Richter、Vifor Pharma UK Ltd、艾伯维公司(AbbVie Inc.H.C. 因一篇关于异常子宫出血的文章从 UpToDate 获得版税。L.W. 获得了罗氏诊断公司的资助(付给机构)。所有其他作者均无冲突声明:此处报告的研究是 UCON 临床试验(注册号 ISRCTN:20426843)中的一项嵌入式作用机制研究(无对比研究)。
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引用次数: 0
The lack of evidence behind over-the-counter antioxidant supplements for male fertility patients: a scoping review. 男性不育患者服用非处方抗氧化剂补充剂缺乏证据:一项范围审查。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-05-17 eCollection Date: 2023-01-01 DOI: 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
研究问题:非处方抗氧化补充剂治疗男性不育症的证据是什么?概要回答:用于男性不育患者的非处方抗氧化剂补充剂中,只有不到一半经过了临床试验,而且现有的临床试验通常质量较差。已知情况:男性不育症的患病率正在上升,与此同时,声称能提高男性生育能力的补品市场也在扩大。到目前为止,关于这些非处方补充剂的证据数据有限。研究设计规模持续时间:于2022年6月24日在亚马逊、谷歌购物和其他相关购物网站上搜索以下术语:“补品”、“抗氧化剂”、“维生素”和“男性生育能力”、“男性不育”、“男性低生育能力”、“生育能力男性”、“生育能力男性”。所有用英语、荷兰语、法语、西班牙语或德语描述成分的补充剂都被包括在内。随后,Pubmed和Google Scholar搜索了包含这些补充剂的研究。受试者/材料设置方法:纳入标准为抗氧化补充剂,其主要目的是提高男性生育能力。包括补充剂必须在没有医生处方的情况下获得。排除了含有植物提取物的补充剂,以及含量或剂量不明确的补充剂。记录了补充剂的成分、剂量、价格和健康声明。我们评估了补充剂中的物质是否超过了推荐膳食允许量(RDA)或可容忍的最高摄入量(UL)。所有临床试验和动物研究都被选为本综述的研究对象。使用适合研究设计的偏倚风险评估工具评估临床试验的偏倚风险。主要结果和偶然性的作用:共发现34种符合条件的抗氧化剂补充剂,含有48种不同的活性物质。每30天的平均价格为53.10美元。大多数补充剂(27/ 34,79%)所含物质的剂量超过了建议的每日允许量(RDA)。所有补品制造商都声称能提高精子质量或男性生育能力。对于34种补充剂中的13种(38%),已发表的临床试验是可用的,而对于一种补充剂,只发现了动物研究。纳入研究的总体质量较差。只有两种补品在高质量的临床试验中进行了测试。限制:谨慎的原因:搜索购物网站的结果,一个全面的搜索策略无法制定。大多数补充剂被排除在外,因为它们含有植物提取物,或者因为补充剂信息不可用(以适当的语言)。研究结果的更广泛意义:这是首次对男性生育补品市场进行深入研究的综述,该市场面向不育患者和其他寻求提高生育能力的男性。早期的评论只关注已发表临床试验的补充剂。然而,我们发现超过一半的补充剂没有经过临床试验。据我们所知,这篇综述是第一次评估补充剂的剂量与RDA的关系。与文献一致,我们发现关于男性生育补充剂的证据通常质量较差。这篇综述应该敦促制药公司在随机对照试验中评估他们的产品,以便为人们提供确凿的信息。研究经费/竞争利益:W.R.d.L.的研究职位由Goodlife Pharma提供无限制的资助。w.r.d.l., k.f.和J.P.d.B.是Impryl®临床试验的研究小组成员,Impryl®是本综述中包括的补充剂之一。注册号:无。
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引用次数: 0
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