Human Reproduction Update最新文献

{"title":"DNA damage in preimplantation embryos and gametes: specification, clinical relevance and repair strategies.","authors":"Richard Musson,&nbsp;Łukasz Gąsior,&nbsp;Simona Bisogno,&nbsp;Grażyna Ewa Ptak","doi":"10.1093/humupd/dmab046","DOIUrl":"https://doi.org/10.1093/humupd/dmab046","url":null,"abstract":"<p><strong>Background: </strong>DNA damage is a hazard that affects all cells of the body. DNA-damage repair (DDR) mechanisms are in place to repair damage and restore cellular function, as are other damage-induced processes such as apoptosis, autophagy and senescence. The resilience of germ cells and embryos in response to DNA damage is less well studied compared with other cell types. Given that recent studies have described links between embryonic handling techniques and an increased likelihood of disease in post-natal life, an update is needed to summarize the sources of DNA damage in embryos and their capacity to repair it. In addition, numerous recent publications have detailed novel techniques for detecting and repairing DNA damage in embryos. This information is of interest to medical or scientific personnel who wish to obtain undamaged embryos for use in offspring generation by ART.</p><p><strong>Objective and rationale: </strong>This review aims to thoroughly discuss sources of DNA damage in male and female gametes and preimplantation embryos. Special consideration is given to current knowledge and limits in DNA damage detection and screening strategies. Finally, obstacles and future perspectives in clinical diagnosis and treatment (repair) of DNA damaged embryos are discussed.</p><p><strong>Search methods: </strong>Using PubMed and Google Scholar until May 2021, a comprehensive search for peer-reviewed original English-language articles was carried out using keywords relevant to the topic with no limits placed on time. Keywords included 'DNA damage repair', 'gametes', 'sperm', 'oocyte', 'zygote', 'blastocyst' and 'embryo'. References from retrieved articles were also used to obtain additional articles. Literature on the sources and consequences of DNA damage on germ cells and embryos was also searched. Additional papers cited by primary references were included. Results from our own studies were included where relevant.</p><p><strong>Outcomes: </strong>DNA damage in gametes and embryos can differ greatly based on the source and severity. This damage affects the development of the embryo and can lead to long-term health effects on offspring. DDR mechanisms can repair damage to a certain extent, but the factors that play a role in this process are numerous and altogether not well characterized. In this review, we describe the multifactorial origin of DNA damage in male and female gametes and in the embryo, and suggest screening strategies for the selection of healthy gametes and embryos. Furthermore, possible therapeutic solutions to decrease the frequency of DNA damaged gametes and embryos and eventually to repair DNA and increase mitochondrial quality in embryos before their implantation is discussed.</p><p><strong>Wider implications: </strong>Understanding DNA damage in gametes and embryos is essential for the improvement of techniques that could enhance embryo implantation and pregnancy success. While our knowledge about DNA damage f","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dc/9b/dmab046.PMC9071077.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39814646","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}

{"title":"Early programming of reproductive health and fertility: novel neuroendocrine mechanisms and implications in reproductive medicine.","authors":"Miguel Angel Sánchez-Garrido,&nbsp;David García-Galiano,&nbsp;Manuel Tena-Sempere","doi":"10.1093/humupd/dmac005","DOIUrl":"10.1093/humupd/dmac005","url":null,"abstract":"<p><strong>Background: </strong>According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, environmental changes taking place during early maturational periods may alter normal development and predispose to the occurrence of diverse pathologies later in life. Indeed, adverse conditions during these critical developmental windows of high plasticity have been reported to alter the offspring developmental trajectory, causing permanent functional and structural perturbations that in the long term may enhance disease susceptibility. However, while solid evidence has documented that fluctuations in environmental factors, ranging from nutrient availability to chemicals, in early developmental stages (including the peri-conceptional period) have discernible programming effects that increase vulnerability to develop metabolic perturbations, the impact and eventual mechanisms involved, of such developmental alterations on the reproductive phenotype of offspring have received less attention.</p><p><strong>Objective and rationale: </strong>This review will summarize recent advances in basic and clinical research that support the concept of DOHaD in the context of the impact of nutritional and hormonal perturbations, occurring during the periconceptional, fetal and early postnatal stages, on different aspects of reproductive function in both sexes. Special emphasis will be given to the effects of early nutritional stress on the timing of puberty and adult gonadotropic function, and to address the underlying neuroendocrine pathways, with particular attention to involvement of the Kiss1 system in these reproductive perturbations. The implications of such phenomena in terms of reproductive medicine will also be considered.</p><p><strong>Search methods: </strong>A comprehensive MEDLINE search, using PubMed as main interface, of research articles and reviews, published mainly between 2006 and 2021, has been carried out. Search was implemented using multiple terms, focusing on clinical and preclinical data from DOHaD studies, addressing periconceptional, gestational and perinatal programming of reproduction. Selected studies addressing early programming of metabolic function have also been considered, when relevant.</p><p><strong>Outcomes: </strong>A solid body of evidence, from clinical and preclinical studies, has documented the impact of nutritional and hormonal fluctuations during the periconceptional, prenatal and early postnatal periods on pubertal maturation, as well as adult gonadotropic function and fertility. Furthermore, exposure to environmental chemicals, such as bisphenol A, and maternal stress has been shown to negatively influence pubertal development and gonadotropic function in adulthood. The underlying neuroendocrine pathways and mechanisms involved have been also addressed, mainly by preclinical studies, which have identified an, as yet incomplete, array of molecular and neurohormonal effectors. These include, prominently, ","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/31/c2/dmac005.PMC9071071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39637367","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}

{"title":"Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis.","authors":"Hajra Khattak, Rosamund Malhas, Laurentiu Craciunas, Yousri Afifi, Christiani A Amorim, Simon Fishel, Sherman Silber, Debra Gook, Isabelle Demeestere, Olga Bystrova, Alla Lisyanskaya, Georgy Manikhas, Laura Lotz, Ralf Dittrich, Lotte Berdiin Colmorn, Kirsten Tryde Macklon, Ina Marie Dueholm Hjorth, Stine Gry Kristensen, Ioannis Gallos, Arri Coomarasamy","doi":"10.1093/humupd/dmac003","DOIUrl":"10.1093/humupd/dmac003","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ovarian tissue cryopreservation involves freezing and storing of surgically retrieved ovarian tissue in liquid or vapour nitrogen below -190°C. The tissue can be thawed and transplanted back with the aim of restoring fertility or ovarian endocrine function. The techniques for human ovarian tissue freezing and transplantation have evolved over the last 20 years, particularly in the context of fertility preservation in pre-pubertal cancer patients. Fresh ovarian tissue transplantation, using an autograft or donor tissue, is a more recent development; it has the potential to preserve fertility and hormonal function in women who have their ovaries removed for benign gynaecological conditions. The techniques of ovarian tissue cryopreservation and transplantation have progressed rapidly since inception; however, the evidence on the success of this intervention is largely based on case reports and case series.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;The aim of this study was to systematically review the current evidence by incorporating study-level and individual patient-level meta-analyses of women who received ovarian transplants, including frozen-thawed transplant, fresh or donor graft.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;The review protocol was registered with PROSPERO (CRD42018115233). A comprehensive literature search was performed using MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials from database inception to October 2020. Authors were also contacted for individual patient data if relevant outcomes were not reported in the published manuscripts. Meta-analysis was performed using inverse-variance weighting to calculate summary estimates using a fixed-effects model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;The review included 87 studies (735 women). Twenty studies reported on ≥5 cases of ovarian transplants and were included in the meta-analysis (568 women). Fertility outcomes included pregnancy, live birth and miscarriage rates, and endocrine outcomes included oestrogen, FSH and LH levels. The pooled rates were 37% (95% CI: 32-43%) for pregnancy, 28% (95% CI: 24-34%) for live birth and 37% (95% CI: 30-46%) for miscarriage following frozen ovarian tissue transplantation. Pooled mean for pre-transplant oestrogen was 101.6 pmol/l (95% CI: 47.9-155.3), which increased post-transplant to 522.4 pmol/l (95% CI: 315.4-729; mean difference: 228.24; 95% CI: 180.5-276). Pooled mean of pre-transplant FSH was 66.4 IU/l (95% CI: 52.8-84), which decreased post-transplant to 14.1 IU/l (95% CI: 10.9-17.3; mean difference 61.8; 95% CI: 57-66.6). The median time to return of FSH to a value &lt;25 IU/l was 19 weeks (interquartile range: 15-26 weeks; range: 0.4-208 weeks). The median duration of graft function was 2.5 years (interquartile range: 1.4-3.4 years; range: 0.7-5 years). The analysis demonstrated that ovarian tissue cryopreservation and transplantation could restore reproductive and hormonal functio","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9733829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10490871","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}

{"title":"Anti-Müllerian hormone as a marker of ovarian reserve and premature ovarian insufficiency in children and women with cancer: a systematic review.","authors":"Richard A Anderson,&nbsp;David Cameron,&nbsp;Florian Clatot,&nbsp;Isabelle Demeestere,&nbsp;Matteo Lambertini,&nbsp;Scott M Nelson,&nbsp;Fedro Peccatori","doi":"10.1093/humupd/dmac004","DOIUrl":"https://doi.org/10.1093/humupd/dmac004","url":null,"abstract":"<p><strong>Background: </strong>Female patients undergoing anticancer treatment are at elevated risk of adverse ovarian outcomes including infertility and premature ovarian insufficiency (POI), which is associated with short- and long-term health risks. Anti-Müllerian hormone (AMH) is a key biomarker of ovarian reserve, but its role prior to and after cancer treatment is less well understood.</p><p><strong>Objective and rationale: </strong>To conduct a systematic review evaluating AMH as a biomarker of ovarian reserve and POI before and after anticancer treatment, which has become a pressing clinical issue in reproductive medicine. There are a large number of observational studies, but differences in patient groups, cancer diagnoses and study design make this a confusing field that will benefit from a thorough and robust review.</p><p><strong>Search methods: </strong>A systematic literature search for AMH in women with cancer was conducted in PubMed, Embase and Cochrane Central Register of Controlled Trials up to 1 April 2021. Bias review was conducted using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) protocol along with qualitative assessment of quality. Exploratory subgroups were established based on age, cancer type and length of follow-up.</p><p><strong>Outcomes: </strong>Ninety-two publications (N = 9183 patients) were included in this analysis after quality and bias review. Reduced/undetectable AMH was consistently identified in 69/75 studies (92%) following chemotherapy or radiotherapy, with reductions ranging from 42% to concentrations below the limit of detection, and many reporting mean or median declines of ≥90%. Where longitudinal data were analysed (42 studies), a majority (33/42 (79%)) of studies reported at least partial recovery of AMH at follow-up, however, effect estimates were highly variable, reflecting that AMH levels were strongly impacted by anticancer treatment (i.e. the chemotherapy regimen used and the number of treatment cycles need), with recovery and its degree determined by treatment regimen, age and pre-treatment AMH level. In 16/31 (52%) publications, oligo/amenorrhoea was associated with lower post-treatment AMH consistent with impending POI, although menstruation and/or pregnancy were reported in patients with low or undetectable AMH. Long-term (>5 years) follow-up of paediatric patients following cancer treatment also found significantly lower AMH compared with control groups in 14/20 (70%) of studies, with very variable effect sizes from complete loss of AMH to full recovery depending on treatment exposure, as in adult patients.</p><p><strong>Wider implications: </strong>AMH can be used to identify the damaging effect of cancer treatments on ovarian function. This can be applied to individual women, including pre-pubertal and adolescent girls, as well as comparing different treatment regimens, ages and pre-treatment AMH levels in populations of women. While there was evidence for its ","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/fe/dmac004.PMC9071067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9668381","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}

{"title":"IVF and human evolution.","authors":"H. I. Hanevik, D. Hessen","doi":"10.1093/humupd/dmac014","DOIUrl":"https://doi.org/10.1093/humupd/dmac014","url":null,"abstract":"Humans are shaped by evolution through natural selection, as are all species. While evolution is central to all biological processes, the key stage for competition and selection is reproduction, which encompasses various events from courtship and mating to fertilization and pregnancy. In humans, IVF is used to aid the intrinsically inefficient reproduction by coitus, and in several countries, the proportion of children born after IVF is increasing. While IVF is an enabling technology for infertile patients, it also circumvents reproductive barriers and changes selection pressures. This grand theme review describes the systematic differences between IVF and coitus in selection pressures on reproducing cells, individuals and populations. At the cellular unit of selection, for example, IVF favours different traits in spermatozoa (fast swimmers over short distances) than coitus does (forward mobility over longer distances). Similarly, a male with low sperm quality and a female who decides to delay her first birth to an advanced age, can both increase their reproductive fitness by IVF compared to if reproduction by coitus is their only option. In as much as delayed reproduction is a cultural trait, IVF thus enables cultural practices that may in their turn affect human evolution. A main point in this review is to discuss the interactive effects of biological and cultural traits in the context of IVF, and how they act in concert as drivers towards increased demand for IVF. It is not the aim of this review to argue against IVF, which no doubt is a major medical advancement, but rather to examine IVF and human evolution from a broad perspective, including potential longer-term impacts. Since IVF is a young technology, the empirical data indicative of evolutionary effects of IVF in humans are sparse. In general, we argue that IVF facilitates the redirection of resources away from reproduction in humans, since reproduction by IVF bypasses some of the resource-demanding processes that reproduction by coitus entails. Hence, IVF sets the evolutionary stage for a human species increasingly reliant on, and adapted to, technological means of reproduction.","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60910490","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}

{"title":"Transcriptional control of human gametogenesis","authors":"Fang Fang,Phillip J Iaquinta,Ninuo Xia,Lei Liu,Lei Diao,Renee A Reijo Pera","doi":"10.1093/humupd/dmac002","DOIUrl":"https://doi.org/10.1093/humupd/dmac002","url":null,"abstract":"ABSTRACT The pathways of gametogenesis encompass elaborate cellular specialization accompanied by precise partitioning of the genome content in order to produce fully matured spermatozoa and oocytes. Transcription factors are an important class of molecules that function in gametogenesis to regulate intrinsic gene expression programs, play essential roles in specifying (or determining) germ cell fate and assist in guiding full maturation of germ cells and maintenance of their populations. Moreover, in order to reinforce or redirect cell fate in vitro, it is transcription factors that are most frequently induced, over-expressed or activated. Many reviews have focused on the molecular development and genetics of gametogenesis, in vivo and in vitro, in model organisms and in humans, including several recent comprehensive reviews: here, we focus specifically on the role of transcription factors. Recent advances in stem cell biology and multi-omic studies have enabled deeper investigation into the unique transcriptional mechanisms of human reproductive development. Moreover, as methods continually improve, in vitro differentiation of germ cells can provide the platform for robust gain- and loss-of-function genetic analyses. These analyses are delineating unique and shared human germ cell transcriptional network components that, together with somatic lineage specifiers and pluripotency transcription factors, function in transitions from pluripotent stem cells to gametes. This grand theme review offers additional insight into human infertility and reproductive disorders that are linked predominantly to defects in the transcription factor networks and thus may potentially contribute to the development of novel treatments for infertility.","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138506303","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}

{"title":"HLA Class Ib-receptor interactions during embryo implantation and early pregnancy.","authors":"L. L. Nilsson, T. Hviid","doi":"10.1093/humupd/dmac007","DOIUrl":"https://doi.org/10.1093/humupd/dmac007","url":null,"abstract":"BACKGROUND\u0000Although the immune system intuitively must have an important role in embryo implantation and in the achievement of a pregnancy, the molecular details have for long been controversial. The role of the human leukocyte antigen (HLA) system has been debated. The unique HLA expression profile of the HLA Class Ia molecule HLA-C and the HLA Class Ib molecules HLA-E, HLA-F and HLA-G at the feto-maternal interface is now recognized. However, HLA Class Ib molecules may also have a role in embryo implantation and pregnancy success.\u0000\u0000\u0000OBJECTIVE AND RATIONALE\u0000The aim of this review was to evaluate the literature and recent discoveries on the role of the non-polymorphic HLA Class Ib molecules with a focus on HLA-F and HLA-G molecules at the time of implantation, including the interaction with uterine immune cells through the specific receptors immunoglobulin-like transcript 2 (ILT2), ILT4 and a number of killer cell immunoglobulin-like receptors (KIRs), and the importance of HLA-F and HLA-G genetic variation that influences fertility and time-to-pregnancy.\u0000\u0000\u0000SEARCH METHODS\u0000Drawing on recent advances in basic and clinical studies, we performed a narrative review of the scientific literature to provide a timely update on the role of HLA Class Ib in embryo implantation, fertility and infertility. Pertinent studies were searched in PubMed/Medline using relevant key words.\u0000\u0000\u0000OUTCOMES\u0000Both HLA-F and HLA-G interact with inhibitory or activating ILT2 or ILT4 receptors and KIRs on uterine immune cells, especially uterine natural killer (NK) cells that are highly abundant in the mid-secretory endometrium and in early pregnancy. The binding of HLA-G to ILT2 stimulates the secretion of growth-promoting factors from decidual NK cells. However, functional aspects of a HLA-F-receptor interaction remain to be clarified. Recent studies indicate that HLA-F and HLA-G are expressed in mid-secretory endometrium and HLA-G is expressed in the blastocyst. HLA-F fluctuates during the menstrual cycle with high levels during the implantation window. The level of HLA-F protein expression correlates with the number of CD56-positive NK cells in the mid-secretory endometrium. HLA-F and HLA-G gene polymorphisms, including a single nucleotide polymorphism (SNP) in a progesterone-responsive element, are associated with time-to-pregnancy. Depending on the SNP genotype, the effect of progesterone varies resulting in differences in HLA-F expression and thereby the interaction with receptors on the uterine NK cells. Studies suggest that the expression of HLA-G and HLA-F, both by the embryonic-derived trophoblast cells and by cells in the endometrium and decidua, and the interaction between HLA-G and HLA-F with specific receptors on uterine immune cells, stimulate and facilitate embryo implantation and placentation by secretion of growth factors, cytokines and angiogenic factors.\u0000\u0000\u0000WIDER IMPLICATIONS\u0000A detailed understanding of the molecular mechanisms controlling the expression of HLA-","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49260235","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}

{"title":"Barriers and facilitators for the inclusion of fertility care in reproductive health policies in Africa: a qualitative evidence synthesis.","authors":"Anna Afferri,&nbsp;Haddijatou Allen,&nbsp;Andrew Booth,&nbsp;Susan Dierickx,&nbsp;Allan Pacey,&nbsp;Julie Balen","doi":"10.1093/humupd/dmab040","DOIUrl":"https://doi.org/10.1093/humupd/dmab040","url":null,"abstract":"<p><strong>Background: </strong>Infertility affects over 50 million couples worldwide and impacts people's social and emotional wellbeing. In low- and middle-income countries, particularly across Africa, the inclusion of fertility care into reproductive health (RH) policies remains fragmented or non-existent.</p><p><strong>Objective and rationale: </strong>This review aims to provide a framework for understanding the inclusion (or lack thereof) of fertility care in RH policies in African settings. It synthesizes the barriers and facilitators to such inclusion, with a view to uncovering the positioning of fertility care in broader health systems and on the agendas of key stakeholders such as health policymakers and practitioners.</p><p><strong>Search methods: </strong>A qualitative evidence synthesis was performed, systematically searching papers and grey literature. Searches were conducted in MEDLINE, EMBASE, CINAHL, Web of Science and Scopus between February and April 2020. No date restrictions were applied. Language was limited to publications written in English and French. Two reviewers independently screened titles and abstracts, and extracted data, applying thematic coding. The quality of the included papers was evaluated using The Joanna Briggs Institute Checklist for Text and Opinion Papers.</p><p><strong>Outcomes: </strong>The search identified 744 papers, of which 20 were included. Findings were organized under four cross-cutting categories, namely: perceived importance of infertility; influence of policy context; resource availability and access; and perceived quality of care. Across these categories, key barriers to the inclusion of fertility care in RH policies were limited political commitment, under-recognition of the burden of infertility and high costs associated with ART. Conversely, facilitators comprised specialized training on infertility for healthcare providers, standard procedures for ART safety and guidelines and North-South/South-South collaborations.</p><p><strong>Wider implications: </strong>The inclusion of fertility care in African RH policies depends upon factors that include the recognition of infertility as a disease, strong political engagement and proactivity and affordability of ART through opportunities for partnership with the private sector, which ease costs on the public health system. Further qualitative and quantitative research, including context-specific analysis and in-depth comparative approaches across diverse African countries, will help to delineate differential impacts of local and global factors on fertility care to address this neglected RH issue.</p>","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39710620","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}

{"title":"Obstetric and perinatal outcomes of singleton pregnancies after blastocyst-stage embryo transfer compared with those after cleavage-stage embryo transfer: a systematic review and cumulative meta-analysis.","authors":"Nicola Marconi,&nbsp;Christopher Patrick Allen,&nbsp;Siladitya Bhattacharya,&nbsp;Abha Maheshwari","doi":"10.1093/humupd/dmab042","DOIUrl":"https://doi.org/10.1093/humupd/dmab042","url":null,"abstract":"<p><strong>Background: </strong>Extended embryo culture to blastocyst stage is widely used in IVF and is the default strategy in most clinics. The last decade has witnessed a growing interest in obstetric-perinatal outcomes following blastocyst transfer. Recent studies have challenged the conclusions of systematic reviews that associate risks of preterm birth (PTB) and large for gestational age (LGA) babies with blastocyst transfer. A higher proportion of blastocysts is transferred as frozen-thawed embryos, which may also have added implications.</p><p><strong>Objective and rationale: </strong>The aim of this study was to conduct an updated systematic review of the obstetric-perinatal outcomes in singleton pregnancies following blastocyst-stage transfer compared to cleavage-stage transfer in IVF/ICSI cycles. Where deemed appropriate, data were combined in cumulative meta-analyses.</p><p><strong>Search methods: </strong>Data sources from Medline, EMBASE, CINAHL, Web of Science, the Cochrane Central Register of Clinical Trials and the International Clinical Trials Registry Platform (ICTRP) (1980-2020) were searched using combinations of relevant keywords. Searches had no language restrictions and were limited to human studies. Observational studies and randomized controlled trials comparing obstetric-perinatal outcomes between singleton pregnancies after blastocyst-stage transfer and those after cleavage-stage transfer in IVF/ICSI cycles were sought. Two independent reviewers extracted data in 2 × 2 tables and assessed the methodological quality of the relevant studies using the Critical Appraisal Skills Programme scoring. Cumulative meta-analyses were carried out with independent analysis of pregnancies after fresh and frozen embryo transfers, using the Comprehensive Meta-Analysis software. If provided by included studies, adjusted effect sizes were combined in a sensitivity analysis.</p><p><strong>Outcomes: </strong>A total of 35 studies were included (n = 520 769 singleton pregnancies). Outcome data suggest singleton pregnancies following fresh blastocyst transfer were associated with higher risk of LGA (risk ratio (RR) 1.14; 95% CI 1.05-1.24) and very PTB (RR 1.17; 95% CI 1.08-1.26) compared to fresh cleavage-stage transfer. Singleton pregnancies following frozen blastocyst transfer were associated with higher risks of LGA (RR 1.17; 95% CI 1.08-1.27), PTB (RR 1.13; 95% CI 1.03-1.24) and caesarean section (RR 1.08; 95% CI 1.03-1.13) but lower risks of small for gestational age (RR 0.84, 95% CI 0.74-0.95) and perinatal mortality (RR 0.70; 95% CI 0.58-0.86). Increased risks of LGA and PTB after frozen blastocyst transfer persisted in the sensitivity analysis, which also showed a significantly increased risk of PTB after fresh blastocyst transfer. Cumulative meta-analyses revealed consistency in prevalence and magnitude of risks for a number of years. Data on other perinatal outcomes are still evolving.</p><p><strong>Wider implications: </strong>Wh","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9933133","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}

{"title":"The putative roles of FSH and AMH in the regulation of oocyte developmental competence: from fertility prognosis to mechanisms underlying age-related subfertility.","authors":"Jose Buratini,&nbsp;Thaisy Tino Dellaqua,&nbsp;Mariabeatrice Dal Canto,&nbsp;Antonio La Marca,&nbsp;Domenico Carone,&nbsp;Mario Mignini Renzini,&nbsp;Robert Webb","doi":"10.1093/humupd/dmab044","DOIUrl":"https://doi.org/10.1093/humupd/dmab044","url":null,"abstract":"<p><strong>Background: </strong>Fertility loss during female ageing is associated with increasing basal FSH and decreasing anti-Müllerian hormone (AMH) concentrations, together with compromised oocyte quality, presumably due to increased oxidative stress (OS) and DNA damage, as well as reduced metabolic and meiotic competences. Basal FSH and AMH circulatory concentrations have been broadly utilized as IVF success predictors, regardless of fluctuations in prognostic accuracy; basal FSH and AMH perform better in pre-advanced maternal age (AMA: >35 years) and AMA patients, respectively. The relationships between FSH and AMH intrafollicular levels and IVF outcomes suggest, nevertheless, that both hormones regulate oocyte competence, supporting the hypothesis that changes in FSH/AMH levels cause, at least in part, oocyte quality degradation during ageing. To understand the reasons behind the fluctuations in FSH and AMH prognostic accuracies and to clarify their participation in mechanisms determining oocyte competence and age-related subfertility, a deeper knowledge of the regulation of FSH and AMH intrafollicular signalling during the female reproductive lifespan, and of their effects on the cumulus-oocyte complex, is required.</p><p><strong>Objective and rationale: </strong>An extensive body of information on the regulation of FSH and AMH intrafollicular availability and signalling, as well as on the control of folliculogenesis and oocyte metabolism, has been accumulated. However, these datasets have been explored within the relatively narrow boundaries of their specific subjects. Given the aforementioned gaps in knowledge and their clinical relevance, herein we integrate clinical and basic data, within a wide biological perspective, aiming to shed light on (i) the reasons for the variability in the accuracy of serum FSH and AMH as fertility markers, and on (ii) the potential roles of these hormones in mechanisms regulating oocyte quality, particularly those associated with ageing.</p><p><strong>Search methods: </strong>The PubMed database encompassing the period between 1960 and 2021 was searched. Principal search terms were FSH, FSH receptor, AMH, oocyte, maternal age, cumulus, transzonal projections (TZPs), actin, OS, redox, reactive oxygen species, mitochondria, DNA damage, DNA repair, aneuploidy, spindle, meiosis, gene expression, transcription, translation, oocyte secreted factors (OSFs), cAMP, cyclic guanosine monophosphate, natriuretic peptide C, growth differentiation factor 9, bone morphogenetic protein 15 and fibroblast growth factor.</p><p><strong>Outcomes: </strong>Our analysis suggests that variations in the accuracy of fertility prognosis reflect a modest association between circulatory AMH levels and oocyte quality as well as increasing basal FSH inter-cycle variability with age. In addition, the basic and clinical data articulated herein support the hypothesis that increased intrafollicular FSH levels, as maternal age advances, may ","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":null,"pages":null},"PeriodicalIF":13.3,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39774320","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}