Thomas Bamford, Amy Barrie, Sue Montgomery, Rima Dhillon-Smith, Alison Campbell, Christina Easter, Arri Coomarasamy
<p><strong>Background: </strong>A time lapse system (TLS) is utilized in some fertility clinics with the aim of predicting embryo viability and chance of live birth during IVF. It has been hypothesized that aneuploid embryos display altered morphokinetics as a consequence of their abnormal chromosome complement. Since aneuploidy is one of the fundamental reasons for IVF failure and miscarriage, attention has focused on utilizing morphokinetics to develop models to non-invasively risk stratify embryos for ploidy status. This could avoid or reduce the costs associated with pre-implantation genetic testing for aneuploidy (PGT-A). Furthermore, TLS have provided an understanding of the true prevalence of other dysmorphisms. Hypothetically, the incorporation of morphological features into a model could act synergistically, improving a model's discriminative ability to predict ploidy status.</p><p><strong>Objective and rationale: </strong>The aim of this systematic review and meta-analysis was to investigate associations between ploidy status and morphokinetic or morphological features commonly denoted on a TLS. This will determine the feasibility of a prediction model for euploidy and summarize the most useful prognostic markers to be included in model development.</p><p><strong>Search methods: </strong>Five separate searches were conducted in Medline, Embase, PubMed and Cinahl from inception to 1 July 2021. Search terms and word variants included, among others, PGT-A, ploidy, morphokinetics and time lapse, and the latter were successively substituted for the following morphological parameters: fragmentation, multinucleation, abnormal cleavage and contraction. Studies were limited to human studies.</p><p><strong>Outcomes: </strong>Overall, 58 studies were included incorporating over 40 000 embryos. All except one study had a moderate risk of bias in at least one domain when assessed by the quality in prognostic studies tool. Ten morphokinetic variables were significantly delayed in aneuploid embryos. When excluding studies using less reliable genetic technologies, the most notable variables were: time to eight cells (t8, 1.13 h, 95% CI: 0.21-2.05; three studies; n = 742; I2 = 0%), t9 (2.27 h, 95% CI: 0.5-4.03; two studies; n = 671; I2 = 33%), time to formation of a full blastocyst (tB, 1.99 h, 95% CI 0.15-3.81; four studies; n = 1640; I2 = 76%) and time to expanded blastocyst (tEB, 2.35 h, 95% CI: 0.06-4.63; four studies; n = 1640; I2 = 83%). There is potentially some prognostic potential in the degree of fragmentation, multinucleation persisting to the four-cell stage and frequency of embryo contractions. Reverse cleavage was associated with euploidy in this meta-analysis; however, this article argues that these are likely spurious results requiring further investigation. There was no association with direct unequal cleavage in an embryo that progressed to a blastocyst, or with multinucleation assessed on Day 2 or at the two-cell stage. However, owing
{"title":"Morphological and morphokinetic associations with aneuploidy: a systematic review and meta-analysis.","authors":"Thomas Bamford, Amy Barrie, Sue Montgomery, Rima Dhillon-Smith, Alison Campbell, Christina Easter, Arri Coomarasamy","doi":"10.1093/humupd/dmac022","DOIUrl":"https://doi.org/10.1093/humupd/dmac022","url":null,"abstract":"<p><strong>Background: </strong>A time lapse system (TLS) is utilized in some fertility clinics with the aim of predicting embryo viability and chance of live birth during IVF. It has been hypothesized that aneuploid embryos display altered morphokinetics as a consequence of their abnormal chromosome complement. Since aneuploidy is one of the fundamental reasons for IVF failure and miscarriage, attention has focused on utilizing morphokinetics to develop models to non-invasively risk stratify embryos for ploidy status. This could avoid or reduce the costs associated with pre-implantation genetic testing for aneuploidy (PGT-A). Furthermore, TLS have provided an understanding of the true prevalence of other dysmorphisms. Hypothetically, the incorporation of morphological features into a model could act synergistically, improving a model's discriminative ability to predict ploidy status.</p><p><strong>Objective and rationale: </strong>The aim of this systematic review and meta-analysis was to investigate associations between ploidy status and morphokinetic or morphological features commonly denoted on a TLS. This will determine the feasibility of a prediction model for euploidy and summarize the most useful prognostic markers to be included in model development.</p><p><strong>Search methods: </strong>Five separate searches were conducted in Medline, Embase, PubMed and Cinahl from inception to 1 July 2021. Search terms and word variants included, among others, PGT-A, ploidy, morphokinetics and time lapse, and the latter were successively substituted for the following morphological parameters: fragmentation, multinucleation, abnormal cleavage and contraction. Studies were limited to human studies.</p><p><strong>Outcomes: </strong>Overall, 58 studies were included incorporating over 40 000 embryos. All except one study had a moderate risk of bias in at least one domain when assessed by the quality in prognostic studies tool. Ten morphokinetic variables were significantly delayed in aneuploid embryos. When excluding studies using less reliable genetic technologies, the most notable variables were: time to eight cells (t8, 1.13 h, 95% CI: 0.21-2.05; three studies; n = 742; I2 = 0%), t9 (2.27 h, 95% CI: 0.5-4.03; two studies; n = 671; I2 = 33%), time to formation of a full blastocyst (tB, 1.99 h, 95% CI 0.15-3.81; four studies; n = 1640; I2 = 76%) and time to expanded blastocyst (tEB, 2.35 h, 95% CI: 0.06-4.63; four studies; n = 1640; I2 = 83%). There is potentially some prognostic potential in the degree of fragmentation, multinucleation persisting to the four-cell stage and frequency of embryo contractions. Reverse cleavage was associated with euploidy in this meta-analysis; however, this article argues that these are likely spurious results requiring further investigation. There was no association with direct unequal cleavage in an embryo that progressed to a blastocyst, or with multinucleation assessed on Day 2 or at the two-cell stage. However, owing","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 5","pages":"656-686"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9991529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J A Wessel,N A Danhof,R van Eekelen,M P Diamond,R S Legro,K Peeraer,T M D'Hooghe,M Erdem,T Dankert,B J Cohlen,C Thyagaraju,B W J Mol,M Showell,M van Wely,M H Mochtar,R Wang
BACKGROUNDIntrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. Individual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of individual studies by obtaining the IPD, and allows analyses on treatment-covariate interactions to identify couples who benefit most from a particular treatment.OBJECTIVE AND RATIONALEWe performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment-covariate interactions for important baseline characteristics in couples undergoing IUI.SEARCH METHODSWe searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA.OUTCOMESSeven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n = 1511) compared gonadotrophins with CC, and one (n = 900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12-1.51, I2 = 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33-3.54, I2 = 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (≤75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05-1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94-1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45-1.96; RR 0.81, 95% CI 0.32-2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when c
背景:宫内人工授精结合卵巢刺激(IUI-OS)是治疗不明原因不孕症的一线治疗方法。促性腺激素、来曲唑和枸橼酸克罗米芬(CC)是IUI-OS中常用的药物，在多个汇总数据荟萃分析中进行了比较，存在很大的异质性，没有对事件发生时间结局进行分析。个体参与者数据荟萃分析(IPD- ma)被认为是证据合成的黄金标准，因为它可以通过获得IPD来抵消个体研究报告的不足，并允许对治疗-协变量相互作用进行分析，以确定从特定治疗中获益最多的夫妇。目的和理由:我们进行了IPD-MA，以比较促性腺激素、来曲唑和CC对卵巢刺激的有效性和安全性，并探讨治疗-协变量相互作用对进行IUI的夫妇重要基线特征的影响。检索方法我们检索了MEDLINE、EMBASE、CENTRAL、CINAHL和PsycINFO等电子数据库，检索时间从其成立到2021年6月28日。我们纳入了比较IUI-OS与促性腺激素、来曲唑和CC在不明原因不孕夫妇中的作用的随机对照试验(rct)。我们联系了符合条件的随机对照试验的作者分享IPD，并建立了IUI IPD- ma协作。主要有效性结局是活产，主要安全性结局是多胎妊娠。次要结果是其他生殖结果，包括导致活产的受孕时间。我们进行了一期随机效应IPD-MA。结果:22项符合条件的随机对照试验中有7项(31.8%)提供了2495对夫妇的IPD(参与22项随机对照试验的3997对夫妇中有62.4%)，其中2411对患有不明原因不孕症，并纳入了IPD- ma。6项随机对照试验(n = 1511)比较了促性腺激素与CC, 1项随机对照试验(n = 900)比较了促性腺激素、来曲唑和CC。中等确定性证据显示，与CC相比，促性腺激素增加了活产率(6项随机对照试验，2058名妇女，RR 1.30, 95% CI 1.12-1.51, I2 = 26%)。低确定性证据显示，与CC相比，促性腺激素也可能增加多胎妊娠率(6项rct, 2058名妇女，RR 2.17, 95% CI 1.33-3.54, I2 = 69%)。多胎妊娠的异质性可以用促性腺激素起始剂量和取消标准选择的差异来解释。低起始剂量促性腺激素(≤75 IU)的随机对照试验的事后敏感性分析证实，与CC相比，活产率增加(5项随机对照试验，1457名女性，RR 1.26, 95% CI 1.05-1.51)，但仅对取消标准更严格的随机对照试验进行分析，显示活产率的证据不确凿(4项随机对照试验，1238名女性，RR 1.15, 95% CI 0.94-1.41)。对于多胎妊娠，两项敏感性分析均显示促性腺激素与CC之间没有结论性发现(RR 0.94, 95% CI 0.45-1.96;RR 0.81, 95% CI 0.32-2.03)。中等确定性证据显示，与CC相比，促性腺激素减少了受孕至活产的时间(6项随机对照试验，2058名妇女，HR 1.37, 95% CI 1.15-1.63, I2 = 22%)。没有发现治疗-协变量(女性年龄、BMI或原发性与继发性不孕症)相互作用的有力证据。在不明原因不孕的夫妇接受IUI-OS时，与CC相比，促性腺激素增加了活产的机会，缩短了受孕时间，以更高的多胎妊娠率为代价，如果不区分取消标准或起始剂量的策略。治疗效果在不同年龄、BMI或原发性与继发性不孕的女性中似乎没有差异。在较低的起始剂量和更严格的取消标准的现代实践中，不同药物的有效性和安全性似乎都是可以接受的，因此干预措施的可获得性、成本和患者的偏好应该是临床决策的因素。由于与来曲唑比较的证据是基于一项提供IPD的随机对照试验，因此需要进一步的随机对照试验来曲唑与其他治疗不明原因不孕症的干预措施进行比较。
{"title":"Ovarian stimulation strategies for intrauterine insemination in couples with unexplained infertility: a systematic review and individual participant data meta-analysis.","authors":"J A Wessel,N A Danhof,R van Eekelen,M P Diamond,R S Legro,K Peeraer,T M D'Hooghe,M Erdem,T Dankert,B J Cohlen,C Thyagaraju,B W J Mol,M Showell,M van Wely,M H Mochtar,R Wang","doi":"10.1093/humupd/dmac021","DOIUrl":"https://doi.org/10.1093/humupd/dmac021","url":null,"abstract":"BACKGROUNDIntrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. Individual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of individual studies by obtaining the IPD, and allows analyses on treatment-covariate interactions to identify couples who benefit most from a particular treatment.OBJECTIVE AND RATIONALEWe performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment-covariate interactions for important baseline characteristics in couples undergoing IUI.SEARCH METHODSWe searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA.OUTCOMESSeven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n = 1511) compared gonadotrophins with CC, and one (n = 900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12-1.51, I2 = 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33-3.54, I2 = 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (≤75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05-1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94-1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45-1.96; RR 0.81, 95% CI 0.32-2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when c","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"1136 ","pages":"733-746"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138506283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C S Uldbjerg, T Koch, Y-H Lim, L S Gregersen, C S Olesen, A-M Andersson, H Frederiksen, B A Coull, R Hauser, A Juul, E V Bräuner
<p><strong>Background: </strong>Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing body of literature has recognized that endocrine disrupting chemicals (EDCs) may play an important role in this global trend, but the association has not yet been fully established.</p><p><strong>Objective and rationale: </strong>EDCs can interfere with normal hormone function and metabolism and play a role in pubertal onset. We aimed to systematically identify and evaluate the current evidence on the timing of pubertal onset in girls and boys following prenatal or postnatal exposures to xenobiotic EDCs.</p><p><strong>Search methods: </strong>Following PRISMA guidelines, we performed a systematic literature search of original peer-reviewed publications in the PubMed database through a block search approach using a combination of index MeSH and free text search terms. Publications were considered if they covered biomarkers of prenatal or postnatal exposures to xenobiotic EDCs (European Commission's list of category 1 EDCs) measured in maternal or child biospecimen and pubertal onset defined by the progression of the following milestones (and assessed in terms of the following measures): menarche (age), thelarche (Tanner staging) and pubarche (Tanner staging), in girls, and genital stage (Tanner staging), testicular volume (ml) and pubarche (Tanner staging), in boys.</p><p><strong>Outcomes: </strong>The literature search resulted in 703 references, of which we identified 52 publications fulfilling the eligibility criteria for the qualitative trend synthesis and 23 publications for the meta-analysis. The qualitative trend synthesis provided data on 103 combinations of associations between prenatal or postnatal exposure to EDC compounds groups and puberty outcomes and the meta-analysis enabled 18 summary risk estimates of meta-associations.</p><p><strong>Wider implications: </strong>Statistically significant associations in the qualitative trend synthesis suggested that postnatal exposure to phthalates may be associated with earlier thelarche and later pubarche. However, we did not find consistent evidence in the meta-analysis for associations between timing of pubertal onset in girls and boys and exposures to any of the studied xenobiotic EDCs. We were not able to identify specific pre- or postnatal windows of exposure as particularly critical and susceptible for effects of EDCs. Current evidence is subject to several methodological challenges and inconsistencies and evidence on specific exposure-outcome associations remains too scarce to firmly confirm EDC exposure as a risk factor for changes in age of pubertal onset in the general child population. To create a more uniform foundation for future comparison of evidence and to strengthen pooled studies, we recommend the use of more standardized approaches in the choice of statistical analyses, with ex
{"title":"Prenatal and postnatal exposures to endocrine disrupting chemicals and timing of pubertal onset in girls and boys: a systematic review and meta-analysis.","authors":"C S Uldbjerg, T Koch, Y-H Lim, L S Gregersen, C S Olesen, A-M Andersson, H Frederiksen, B A Coull, R Hauser, A Juul, E V Bräuner","doi":"10.1093/humupd/dmac013","DOIUrl":"https://doi.org/10.1093/humupd/dmac013","url":null,"abstract":"<p><strong>Background: </strong>Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing body of literature has recognized that endocrine disrupting chemicals (EDCs) may play an important role in this global trend, but the association has not yet been fully established.</p><p><strong>Objective and rationale: </strong>EDCs can interfere with normal hormone function and metabolism and play a role in pubertal onset. We aimed to systematically identify and evaluate the current evidence on the timing of pubertal onset in girls and boys following prenatal or postnatal exposures to xenobiotic EDCs.</p><p><strong>Search methods: </strong>Following PRISMA guidelines, we performed a systematic literature search of original peer-reviewed publications in the PubMed database through a block search approach using a combination of index MeSH and free text search terms. Publications were considered if they covered biomarkers of prenatal or postnatal exposures to xenobiotic EDCs (European Commission's list of category 1 EDCs) measured in maternal or child biospecimen and pubertal onset defined by the progression of the following milestones (and assessed in terms of the following measures): menarche (age), thelarche (Tanner staging) and pubarche (Tanner staging), in girls, and genital stage (Tanner staging), testicular volume (ml) and pubarche (Tanner staging), in boys.</p><p><strong>Outcomes: </strong>The literature search resulted in 703 references, of which we identified 52 publications fulfilling the eligibility criteria for the qualitative trend synthesis and 23 publications for the meta-analysis. The qualitative trend synthesis provided data on 103 combinations of associations between prenatal or postnatal exposure to EDC compounds groups and puberty outcomes and the meta-analysis enabled 18 summary risk estimates of meta-associations.</p><p><strong>Wider implications: </strong>Statistically significant associations in the qualitative trend synthesis suggested that postnatal exposure to phthalates may be associated with earlier thelarche and later pubarche. However, we did not find consistent evidence in the meta-analysis for associations between timing of pubertal onset in girls and boys and exposures to any of the studied xenobiotic EDCs. We were not able to identify specific pre- or postnatal windows of exposure as particularly critical and susceptible for effects of EDCs. Current evidence is subject to several methodological challenges and inconsistencies and evidence on specific exposure-outcome associations remains too scarce to firmly confirm EDC exposure as a risk factor for changes in age of pubertal onset in the general child population. To create a more uniform foundation for future comparison of evidence and to strengthen pooled studies, we recommend the use of more standardized approaches in the choice of statistical analyses, with ex","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 5","pages":"687-716"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434240/pdf/dmac013.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDOffering fertility preservation (FP) prior to gonadotoxic therapy, including cancer care and gender-affirming treatment, is now considered standard of care. Periodically, parents and children disagree about whether to pursue FP. However, it is unknown how often this occurs and how disagreement is handled when it arises. Moreover, there is no clear guidance on how to resolve these difficult situations.OBJECTIVE AND RATIONALEThe purpose of this scoping review is to provide an overview of available research evidence about parent-child disagreement regarding FP in order to establish that disagreement occurs in practice, understand the basis for disagreement and explore suggestions for how such disputes could be resolved. Based on our findings, we offer a discussion of the ethical principles at stake when disagreement occurs, which can be used to guide clinicians' approaches when these challenging scenarios present.SEARCH METHODSA comprehensive literature search was run in several databases, including PubMed/Medline, Embase and the Cochrane Library. The search was performed in February 2021 and updated in August 2021. Articles were included in the final review if they discussed how parents or children wanted their views on FP taken into account, presented evidence that parent-child discordance regarding FP exists, discussed how to handle disagreement in a particular case or offered general suggestions for how to approach parent-child discordance about FP. Studies were excluded if the patients were adult only (age 18 years and older), pertained to fertility-sparing treatments (e.g. gonad shielding, gonadopexy) rather than fertility-preserving treatments (e.g. testicular tissue cryopreservation, ovarian tissue cryopreservation, oocyte cryopreservation or sperm cryopreservation) or explored the views of clinicians but not patients or parents. Meta-synthesis was used to synthesize and interpret data across included studies and thematic analysis was used to identify common patterns and themes.OUTCOMESIn total, 755 publications were screened, 118 studies underwent full-text review and 35 studies were included in the final review. Of these studies, 7 discussed how parents or children wanted their opinions to be incorporated, 11 presented evidence that discordance exists between parents and children regarding FP, 4 discussed how disagreement was handled in a particular case and 21 offered general suggestions for how to approach parent-child disagreement. There was a range of study designs, including quantitative and qualitative studies, case studies, ethical analyses and commentaries. From the thematic analysis, four general themes regarding FP disagreement emerged, and four themes relating to the ethical principles at stake in parent-child disagreement were identified. The general themes were: adolescents typically desire to participate in FP decision-making; some parents prefer not to involve their children; minors may feel more favorably about FP
{"title":"Navigating parent-child disagreement about fertility preservation in minors: scoping review and ethical considerations.","authors":"Michelle Bayefsky,Dorice Vieira,Arthur Caplan,Gwendolyn Quinn","doi":"10.1093/humupd/dmac019","DOIUrl":"https://doi.org/10.1093/humupd/dmac019","url":null,"abstract":"BACKGROUNDOffering fertility preservation (FP) prior to gonadotoxic therapy, including cancer care and gender-affirming treatment, is now considered standard of care. Periodically, parents and children disagree about whether to pursue FP. However, it is unknown how often this occurs and how disagreement is handled when it arises. Moreover, there is no clear guidance on how to resolve these difficult situations.OBJECTIVE AND RATIONALEThe purpose of this scoping review is to provide an overview of available research evidence about parent-child disagreement regarding FP in order to establish that disagreement occurs in practice, understand the basis for disagreement and explore suggestions for how such disputes could be resolved. Based on our findings, we offer a discussion of the ethical principles at stake when disagreement occurs, which can be used to guide clinicians' approaches when these challenging scenarios present.SEARCH METHODSA comprehensive literature search was run in several databases, including PubMed/Medline, Embase and the Cochrane Library. The search was performed in February 2021 and updated in August 2021. Articles were included in the final review if they discussed how parents or children wanted their views on FP taken into account, presented evidence that parent-child discordance regarding FP exists, discussed how to handle disagreement in a particular case or offered general suggestions for how to approach parent-child discordance about FP. Studies were excluded if the patients were adult only (age 18 years and older), pertained to fertility-sparing treatments (e.g. gonad shielding, gonadopexy) rather than fertility-preserving treatments (e.g. testicular tissue cryopreservation, ovarian tissue cryopreservation, oocyte cryopreservation or sperm cryopreservation) or explored the views of clinicians but not patients or parents. Meta-synthesis was used to synthesize and interpret data across included studies and thematic analysis was used to identify common patterns and themes.OUTCOMESIn total, 755 publications were screened, 118 studies underwent full-text review and 35 studies were included in the final review. Of these studies, 7 discussed how parents or children wanted their opinions to be incorporated, 11 presented evidence that discordance exists between parents and children regarding FP, 4 discussed how disagreement was handled in a particular case and 21 offered general suggestions for how to approach parent-child disagreement. There was a range of study designs, including quantitative and qualitative studies, case studies, ethical analyses and commentaries. From the thematic analysis, four general themes regarding FP disagreement emerged, and four themes relating to the ethical principles at stake in parent-child disagreement were identified. The general themes were: adolescents typically desire to participate in FP decision-making; some parents prefer not to involve their children; minors may feel more favorably about FP","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"962 1","pages":"747-762"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138506291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oliwia W Mlodawska, Priyanka Saini, J Brandon Parker, Jian-Jun Wei, Serdar E Bulun, Melissa A Simon, Debabrata Chakravarti
<p><strong>Background: </strong>Uterine leiomyomas, also known as uterine fibroids or myomas, are the most common benign gynecological tumors and are found in women of reproductive and postmenopausal age. There is an exceptionally high prevalence of this tumor in women by the age of 50 years. Black women are particularly affected, with an increased incidence, earlier age of onset, larger and faster growing fibroids and greater severity of symptoms as compared to White women. Although advances in identifying genetic and environmental factors to delineate these fibroids have already been made, only recently has the role of epigenomics in the pathogenesis of this disease been considered.</p><p><strong>Objective and rationale: </strong>Over recent years, studies have identified multiple epigenomic aberrations that may contribute to leiomyoma development and growth. This review will focus on the most recent discoveries in three categories of epigenomic changes found in uterine fibroids, namely aberrant DNA methylation, histone tail modifications and histone variant exchange, and their translation into altered target gene architecture and transcriptional outcome. The findings demonstrating how the altered 3D shape of the enhancer can regulate gene expression from millions of base pairs away will be discussed. Additionally, translational implications of these discoveries and potential roadblocks in leiomyoma treatment will be addressed.</p><p><strong>Search methods: </strong>A comprehensive PubMed search was performed to identify published articles containing keywords relevant to the focus of the review, such as: uterine leiomyoma, uterine fibroids, epigenetic alterations, epigenomics, stem cells, chromatin modifications, extracellular matrix [ECM] organization, DNA methylation, enhancer, histone post-translational modifications and dysregulated gene expression. Articles until September 2021 were explored and evaluated to identify relevant updates in the field. Most of the articles focused on in the discussion were published between 2015 and 2021, although some key discoveries made before 2015 were included for background information and foundational purposes. We apologize to the authors whose work was not included because of space restrictions or inadvertent omission.</p><p><strong>Outcomes: </strong>Chemical alterations to the DNA structure and of nucleosomal histones, without changing the underlying DNA sequence, have now been implicated in the phenotypic manifestation of uterine leiomyomas. Genome-wide DNA methylation analysis has revealed subsets of either suppressed or overexpressed genes accompanied by aberrant promoter methylation. Furthermore, differential promoter access resulting from altered 3D chromatin structure and histone modifications plays a role in regulating transcription of key genes thought to be involved in leiomyoma etiology. The dysregulated genes function in tumor suppression, apoptosis, angiogenesis, ECM formation, a variety o
{"title":"Epigenomic and enhancer dysregulation in uterine leiomyomas.","authors":"Oliwia W Mlodawska, Priyanka Saini, J Brandon Parker, Jian-Jun Wei, Serdar E Bulun, Melissa A Simon, Debabrata Chakravarti","doi":"10.1093/humupd/dmac008","DOIUrl":"https://doi.org/10.1093/humupd/dmac008","url":null,"abstract":"<p><strong>Background: </strong>Uterine leiomyomas, also known as uterine fibroids or myomas, are the most common benign gynecological tumors and are found in women of reproductive and postmenopausal age. There is an exceptionally high prevalence of this tumor in women by the age of 50 years. Black women are particularly affected, with an increased incidence, earlier age of onset, larger and faster growing fibroids and greater severity of symptoms as compared to White women. Although advances in identifying genetic and environmental factors to delineate these fibroids have already been made, only recently has the role of epigenomics in the pathogenesis of this disease been considered.</p><p><strong>Objective and rationale: </strong>Over recent years, studies have identified multiple epigenomic aberrations that may contribute to leiomyoma development and growth. This review will focus on the most recent discoveries in three categories of epigenomic changes found in uterine fibroids, namely aberrant DNA methylation, histone tail modifications and histone variant exchange, and their translation into altered target gene architecture and transcriptional outcome. The findings demonstrating how the altered 3D shape of the enhancer can regulate gene expression from millions of base pairs away will be discussed. Additionally, translational implications of these discoveries and potential roadblocks in leiomyoma treatment will be addressed.</p><p><strong>Search methods: </strong>A comprehensive PubMed search was performed to identify published articles containing keywords relevant to the focus of the review, such as: uterine leiomyoma, uterine fibroids, epigenetic alterations, epigenomics, stem cells, chromatin modifications, extracellular matrix [ECM] organization, DNA methylation, enhancer, histone post-translational modifications and dysregulated gene expression. Articles until September 2021 were explored and evaluated to identify relevant updates in the field. Most of the articles focused on in the discussion were published between 2015 and 2021, although some key discoveries made before 2015 were included for background information and foundational purposes. We apologize to the authors whose work was not included because of space restrictions or inadvertent omission.</p><p><strong>Outcomes: </strong>Chemical alterations to the DNA structure and of nucleosomal histones, without changing the underlying DNA sequence, have now been implicated in the phenotypic manifestation of uterine leiomyomas. Genome-wide DNA methylation analysis has revealed subsets of either suppressed or overexpressed genes accompanied by aberrant promoter methylation. Furthermore, differential promoter access resulting from altered 3D chromatin structure and histone modifications plays a role in regulating transcription of key genes thought to be involved in leiomyoma etiology. The dysregulated genes function in tumor suppression, apoptosis, angiogenesis, ECM formation, a variety o","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 4","pages":"518-547"},"PeriodicalIF":13.3,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247409/pdf/dmac008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ee Von Woon, Orene Greer, Nishel Shah, Dimitrios Nikolaou, Mark Johnson, Victoria Male
<p><strong>Background: </strong>Uterine natural killer cells (uNK) are the most abundant lymphocytes found in the decidua during implantation and in first trimester pregnancy. They are important for early placental development, especially trophoblast invasion and transformation of the spiral arteries. However, inappropriate uNK function has been implicated in reproductive failure, such as recurrent miscarriage (RM) or recurrent implantation failure (RIF). Previous studies have mainly focussed on peripheral NK cells (pNK), despite the well-documented differences in pNK and uNK phenotype and function. In recent years, there has been an explosion of studies conducted on uNK, providing a more suitable representation of the immune environment at the maternal-foetal interface. Here, we summarize the evidence from studies published on uNK in women with RM/RIF compared with controls.</p><p><strong>Objective and rationale: </strong>The objectives of this systematic review and meta-analysis are to evaluate: differences in uNK level in women with RM/RIF compared with controls; pregnancy outcome in women with RM/RIF stratified by high and normal uNK levels; correlation between uNK and pNK in women with RM/RIF; and differences in uNK activity in women with RM/RIF compared with controls.</p><p><strong>Search methods: </strong>MEDLINE, EMBASE, Web of Science and Cochrane Trials Registry were searched from inception up to December 2020 and studies were selected in accordance with PRISMA guidelines. Meta-analyses were performed for uNK level, pregnancy outcome and uNK/pNK correlation. Narrative synthesis was conducted for uNK activity. Risk of bias was assessed by ROBINS-I and publication bias by Egger's test.</p><p><strong>Outcomes: </strong>Our initial search yielded 4636 articles, of which 60 articles were included in our systematic review. Meta-analysis of CD56+ uNK level in women with RM compared with controls showed significantly higher levels in women with RM in subgroup analysis of endometrial samples (standardized mean difference (SMD) 0.49, CI 0.08, 0.90; P = 0.02; I2 88%; 1100 women). Meta-analysis of CD56+ uNK level in endometrium of women with RIF compared with controls showed significantly higher levels in women with RIF (SMD 0.49, CI 0.01, 0.98; P = 0.046; I2 84%; 604 women). There was no difference in pregnancy outcome in women with RM/RIF stratified by uNK level, and no significant correlation between pNK and uNK levels in women with RM/RIF. There was wide variation in studies conducted on uNK activity, which can be broadly divided into regulation and receptors, uNK cytotoxicity, cytokine secretion and effect of uNK on angiogenesis. These studies were largely equivocal in their results on cytokine secretion, but most studies found lower expression of inhibitory receptors and increased expression of angiogenic factors in women with RM.</p><p><strong>Wider implications: </strong>The observation of significantly increased uNK level in endometrium of
{"title":"Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis.","authors":"Ee Von Woon, Orene Greer, Nishel Shah, Dimitrios Nikolaou, Mark Johnson, Victoria Male","doi":"10.1093/humupd/dmac006","DOIUrl":"10.1093/humupd/dmac006","url":null,"abstract":"<p><strong>Background: </strong>Uterine natural killer cells (uNK) are the most abundant lymphocytes found in the decidua during implantation and in first trimester pregnancy. They are important for early placental development, especially trophoblast invasion and transformation of the spiral arteries. However, inappropriate uNK function has been implicated in reproductive failure, such as recurrent miscarriage (RM) or recurrent implantation failure (RIF). Previous studies have mainly focussed on peripheral NK cells (pNK), despite the well-documented differences in pNK and uNK phenotype and function. In recent years, there has been an explosion of studies conducted on uNK, providing a more suitable representation of the immune environment at the maternal-foetal interface. Here, we summarize the evidence from studies published on uNK in women with RM/RIF compared with controls.</p><p><strong>Objective and rationale: </strong>The objectives of this systematic review and meta-analysis are to evaluate: differences in uNK level in women with RM/RIF compared with controls; pregnancy outcome in women with RM/RIF stratified by high and normal uNK levels; correlation between uNK and pNK in women with RM/RIF; and differences in uNK activity in women with RM/RIF compared with controls.</p><p><strong>Search methods: </strong>MEDLINE, EMBASE, Web of Science and Cochrane Trials Registry were searched from inception up to December 2020 and studies were selected in accordance with PRISMA guidelines. Meta-analyses were performed for uNK level, pregnancy outcome and uNK/pNK correlation. Narrative synthesis was conducted for uNK activity. Risk of bias was assessed by ROBINS-I and publication bias by Egger's test.</p><p><strong>Outcomes: </strong>Our initial search yielded 4636 articles, of which 60 articles were included in our systematic review. Meta-analysis of CD56+ uNK level in women with RM compared with controls showed significantly higher levels in women with RM in subgroup analysis of endometrial samples (standardized mean difference (SMD) 0.49, CI 0.08, 0.90; P = 0.02; I2 88%; 1100 women). Meta-analysis of CD56+ uNK level in endometrium of women with RIF compared with controls showed significantly higher levels in women with RIF (SMD 0.49, CI 0.01, 0.98; P = 0.046; I2 84%; 604 women). There was no difference in pregnancy outcome in women with RM/RIF stratified by uNK level, and no significant correlation between pNK and uNK levels in women with RM/RIF. There was wide variation in studies conducted on uNK activity, which can be broadly divided into regulation and receptors, uNK cytotoxicity, cytokine secretion and effect of uNK on angiogenesis. These studies were largely equivocal in their results on cytokine secretion, but most studies found lower expression of inhibitory receptors and increased expression of angiogenic factors in women with RM.</p><p><strong>Wider implications: </strong>The observation of significantly increased uNK level in endometrium of","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 4","pages":"548-582"},"PeriodicalIF":14.8,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/f9/dmac006.PMC9247428.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10250456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bede Tyler, Hugo Walford, Jennifer Tamblyn, Stephen D Keay, Dimitrios Mavrelos, Ephia Yasmin, Bassel H Al Wattar
<p><strong>Background: </strong>Several interventions and techniques are suggested to improve the outcome of embryo transfer (ET) in assisted conception. However, there remains no consensus on the optimal practice, with high variations among fertility specialists.</p><p><strong>Objective and rationale: </strong>We conducted a comprehensive systematic review and meta-analyses of randomized controlled trials (RCTs) aiming to identify effective interventions that could be introduced around the time of ET to improve reproductive outcomes.</p><p><strong>Search methods: </strong>We searched the electronic databases (MEDLINE, EMBASE and Cochrane CENTRAL) from inception until March 2021 using a multi-stage search strategy of MeSH terms and keywords, and included all RCTs that evaluated an intervention in the 24-h period before/after ET in women undergoing IVF/ICSI. Our primary outcome was clinical pregnancy rate post-ET confirmed as viable pregnancy on ultrasound scan. We assessed the risk of bias in included trials and extracted data in duplicate. We pooled data using a random-effect meta-analysis and reported using risk ratio (RR) with 95% CI. We explored publication bias and effect modifiers using subgroup analyses.</p><p><strong>Outcomes: </strong>Our search yielded 3685 citations of which we included 188 RCTs (38 interventions, 59 530 participants) with a median sample size of 200 (range 26-1761). The quality of included RCTs was moderate with most showing a low risk of bias for randomization (118/188, 62.8%) and attrition (105/188, 55.8%) but there was a significant risk of publication bias (Egger's test P = 0.001). Performing ET with ultrasound guidance versus clinical touch (n = 24, RR 1.265, 95% CI 1.151-1.391, I2 = 38.53%), hyaluronic acid versus routine care (n = 9, RR 1.457, 95% CI 1.197-1.261, I2 = 46.48%) and the use of a soft versus hard catheter (n = 27, RR 1.122, 95% CI 1.028-1.224, I2 = 57.66%) led to higher clinical pregnancy rates. Other pharmacological add-ons also showed a beneficial effect including granulocyte colony-stimulating factor (G-CSF: n = 4, RR 1.774, 95% CI 1.252-2.512, I2 = 0), Atosiban (n = 7, RR 1.493, 95% CI 1.184-1.882, I2 = 68.27%) and hCG (n = 17, RR 1.232, 95% CI 1.099-1.382, I2 = 57.76%). Bed rest following ET was associated with a reduction in clinical pregnancy (n = 6, RR 0.857, 95% CI 0.741-0.991, I2 = 0.01%). Other commonly used interventions, such as non-steroidal anti-inflammatory drugs, prophylactic antibiotics, acupuncture and cervical mucus removal, did not show a significant benefit on reproductive outcomes. Our effect estimates for other important outcomes, including miscarriage and live birth, were limited by the varied reporting across included RCTs.</p><p><strong>Wider implications: </strong>Using ultrasound guidance, soft catheters and hyaluronic acid at the time of ET appears to increase clinical pregnancy rates. The use of Atosiban, G-CSF and hCG showed a trend towards increased clinical pregnan
背景:提出了几种干预措施和技术来改善辅助受孕胚胎移植(ET)的结果。然而，在最佳实践上仍然没有达成共识，生育专家之间存在很大差异。目的和理由:我们对随机对照试验(rct)进行了全面的系统回顾和荟萃分析，旨在确定可在ET前后引入的有效干预措施，以改善生殖结果。检索方法:我们使用MeSH术语和关键词的多阶段检索策略检索了从初始到2021年3月的电子数据库(MEDLINE、EMBASE和Cochrane CENTRAL)，并纳入了所有评估体外受精/ICSI妇女体外受精前后24小时内干预措施的随机对照试验。我们的主要结局是临床妊娠率，经超声扫描确认为妊娠。我们评估了纳入试验的偏倚风险，并提取了重复的数据。我们使用随机效应荟萃分析合并数据，并使用95% CI的风险比(RR)进行报告。我们使用亚组分析探讨了发表偏倚和效应修饰因子。结果:我们的检索获得了3685条引用，其中包括188项随机对照试验(38项干预措施，59530名受试者)，中位样本量为200(范围26-1761)。纳入的rct质量为中等，大多数随机化偏倚风险较低(118/188,62.8%)，磨耗风险较低(105/188,55.8%)，但发表偏倚风险显著(Egger检验P = 0.001)。超声引导与临床触摸进行ET (n = 24, RR 1.265, 95% CI 1.151-1.391, I2 = 38.53%)、透明质酸与常规护理(n = 9, RR 1.457, 95% CI 1.197-1.261, I2 = 46.48%)、软导管与硬导管的使用(n = 27, RR 1.122, 95% CI 1.028-1.224, I2 = 57.66%)导致临床妊娠率较高。其他附加药物包括粒细胞集落刺激因子(G-CSF: n = 4, RR 1.774, 95% CI 1.252-2.512, I2 = 0)、阿托西班(n = 7, RR 1.493, 95% CI 1.184-1.882, I2 = 68.27%)和hCG (n = 17, RR 1.232, 95% CI 1.099-1.382, I2 = 57.76%)也显示出有益的效果。ET后卧床休息与临床妊娠减少相关(n = 6, RR 0.857, 95% CI 0.741-0.991, I2 = 0.01%)。其他常用的干预措施，如非甾体抗炎药、预防性抗生素、针灸和宫颈粘液清除，对生殖结果没有显着的好处。我们对其他重要结局(包括流产和活产)的效果估计受到纳入随机对照试验中不同报告的限制。更广泛的意义:在ET时使用超声引导、软导管和透明质酸似乎可以增加临床妊娠率。阿托西班、G-CSF和hCG的使用有增加临床妊娠率的趋势，但在临床实践中采用这些干预措施之前，需要进行更大规模的试验。et后卧床休息与临床妊娠减少有关，不应推荐。
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Emilio Francés-Herrero, Rosalba Lopez, M. Hellström, L. de Miguel-Gómez, S. Herraiz, M. Brännström, A. Pellicer, I. Cervelló
Abstract BACKGROUND To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field. OBJECTIVE AND RATIONALE This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman’s syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases. OUTCOMES Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather t
{"title":"Bioengineering trends in female reproduction: a systematic review","authors":"Emilio Francés-Herrero, Rosalba Lopez, M. Hellström, L. de Miguel-Gómez, S. Herraiz, M. Brännström, A. Pellicer, I. Cervelló","doi":"10.1093/humupd/dmac025","DOIUrl":"https://doi.org/10.1093/humupd/dmac025","url":null,"abstract":"Abstract BACKGROUND To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field. OBJECTIVE AND RATIONALE This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman’s syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases. OUTCOMES Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather t","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 1","pages":"798 - 837"},"PeriodicalIF":13.3,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60910529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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