Currently, the world is in the seventh month of the COVID-19 pandemic. Globally, infections with novel SARS-CoV-2 virus are continuously rising with mounting numbers of deaths. International and local public health responses, almost in synchrony, imposed restrictions to minimize spread of the virus, overload of health system capacity, and deficit of personal protective equipment (PPE). Although in most cases the symptoms are mild or absent, SARS-CoV-2 infection can lead to serious acute respiratory disease and multisystem failure. The research community responded to this new disease with a high level of transparency and data sharing; with the aim to better understand the origin, pathophysiology, epidemiology and clinical manifestations. The ultimate goal of this research is to develop vaccines for prevention, mitigation strategies, as well as potential therapeutics.The aim of this review is to summarize current knowledge regarding the novel SARS CoV-2, including its pathophysiology and epidemiology, as well as, what is known about the potential impact of COVID-19 on reproduction, fertility care, pregnancy and neonatal outcome. This summary also evaluates the effects of this pandemic on reproductive care and research, from Canadian perspective, and discusses future implications.In summary, reported data on pregnant women is limited, suggesting that COVID-19 symptoms and severity of the disease during pregnancy are similar to those in non-pregnant women, with pregnancy outcomes closely related to severity of maternal disease. Evidence of SARS-CoV-2 effects on gametes is limited. Human reproduction societies have issued guidelines for practice during COVID-19 pandemic that include implementation of mitigation practices and infection control protocols in fertility care units. In Canada, imposed restrictions at the beginning of the pandemic were successful in containing spread of the infection, allowing for eventual resumption of assisted reproductive treatments under new guidelines for practice. Canada dedicated funds to support COVID-19 research including a surveillance study to monitor outcomes of COVID-19 during pregnancy and assisted reproduction. Continuous evaluation of new evidence must be in place to carefully adjust recommendations on patient management during assisted reproductive technologies (ART) and in pregnancy.
Pregnancy-associated listeriosis should be considered as a cause of fever during pregnancy and appropriate treatment should be initiated preemptively. Prevention remains the best way to control listeriosis and should be reinforced among patients, health care professionals, and regulatory agencies.
BACKGROUND Delayed parenthood, by both women and men, has become more common in developed countries. The adverse effect of advanced maternal age on embryo aneuploidy and reproductive outcomes is well known. However, whether there is an association between paternal age (PA) and embryonic chromosomal aberrations remains controversial. Oocyte donation (OD) is often utilized to minimize maternal age effects on oocyte and embryo aneuploidy, thus providing an optimal model to assess the effect of PA. Several studies have revealed a higher than expected rate of aneuploidy in embryos derived from young oocyte donors, which warrants examination as to whether this may be attributed to advanced PA (APA). OBJECTIVE AND RATIONALE The objective of this systematic review and individual patient data (IPD) meta-analysis is to evaluate existing evidence regarding an association between PA and chromosomal aberrations in an OD model. SEARCH METHODS This review was conducted according to PRISMA guidelines for systematic reviews and meta-analyses. Medline, Embase and Cochrane databases were searched from inception through March 2020 using the (MeSH) terms: chromosome aberrations, preimplantation genetic screening and IVF. Original research articles, reporting on the types and/or frequency of chromosomal aberrations in embryos derived from donor oocytes, including data regarding PA, were included. Studies reporting results of IVF cycles using only autologous oocytes were excluded. Quality appraisal of included studies was conducted independently by two reviewers using a modified Newcastle-Ottawa Assessment Scale. A one-stage IPD meta-analysis was performed to evaluate whether an association exists between PA and aneuploidy. Meta-analysis was performed using a generalized linear mixed model to account for clustering of embryos within patients and clustering of patients within studies. OUTCOMES The search identified 13 032 references, independently screened by 2 reviewers, yielding 6 studies encompassing a total of 2637 IVF-OD cycles (n = 20 024 embryos). Two ‘low’ quality studies using FISH to screen 12 chromosomes on Day 3 embryos (n = 649) reported higher total aneuploidy rates and specifically higher rates of trisomy 21, 18 and 13 in men ≥50 years. One ‘moderate’ and three ‘high’ quality studies, which used 24-chromosome screening, found no association between PA and aneuploidy in Day 5/6 embryos (n = 12 559). The IPD meta-analysis, which included three ‘high’ quality studies (n = 10 830 Day 5/6 embryos), found no significant effect of PA on the rate of aneuploidy (odds ratio (OR) 0.97 per decade of age, 95% CI 0.91–1.03), which was robust to sensitivity analyses. There was no association between PA and individual chromosome aneuploidy or segmental aberrations, including for chromosomes X and Y (OR 1.06 per decade of age, 95% CI 0.92–1.21). Monosomy was most frequent for chromosome 16 (217/10802, 2.01%, 95% CI 1.76–2.29%) and trisomy was also most frequent for chromosome 16 (194/10802, 1.80%, 95% CI 1.56–2.06%). WIDER IMPLICATIONS We conclude, based on the available evidence, that APA is not associated with higher rates of aneuploidy in embryos derived from OD. These results will help fertility practitioners when providing preconception counselling, particularly to older men who desire to have a child.
Meiotic recombination is a fundamental source of human genetic diversity and is also critical for ensuring the accuracy of chromosome segregation. Understanding the landscape of meiotic recombination, its variation across individuals, and the processes by which it goes awry are long-standing goals in human genetics. Current approaches for inferring the landscape of recombination either rely on population genetic patterns of linkage disequilibrium (LD)—capturing a time-averaged view—or direct detection of crossovers in gametes or multi-generation pedigrees, limiting the scale and availability of relevant datasets. Here, we introduce an approach for inferring sex-specific landscapes of recombination from retrospective analysis of data from preimplantation genetic testing for aneuploidy (PGT-A) based on low-coverage (<0.05×) whole-genome sequencing of biopsies from in vitro fertilized (IVF) embryos. To overcome the sparsity of these data, our method exploits its inherent relatedness structure, knowledge of haplotypes from external population reference panels, as well as the frequent occurrence of chromosome loss in embryos, whereby the remaining chromosome is phased by default. Based on extensive simulation, we show that our method retains high accuracy down to coverages as low as 0.02×. Applying this method to low-coverage PGT-A data from 18,967 embryos, we mapped 70,660 recombination events at an average resolution of ~150 kbp, replicating key features of sex-specific recombination maps from the literature. We observed that the total length of the female genetic map is reduced for trisomies compared to disomies, while the genomic distribution of crossovers is also altered in a chromosome-specific manner. Based on haplotype configurations detected in regions surrounding the centromeres, our data additionally indicate that individual chromosomes possess unique propensities for different mechanisms of meiotic error. Together, our results provide a detailed view of the role of aberrant meiotic recombination in the origins of human aneuploidies, as well as a flexible tool for mapping crossovers in low-coverage sequencing data from multiple siblings.
of the placenta, and thus pregnancy and neonatal outcomes, is understudied. This is one of the largest studies performed in a U.S. patient population to evaluate obstetric outcomes after transfer of biopsied and frozen embryos. This provides reassurance to the ongoing use of blastocyst biopsy for PGT.
OBJECTIVE: Serum AMH levels are routinely used to predict an individual's response to controlled ovarian stimulation. The association between AMH and live birth is controversial, however, particularly in older women e234
Study question Does repeated intravenous administration of human umbilical cord perivascular cells (HUCPVC) during the period of ovarian aging prevent age-related fertility decline in a mouse model? Summary answer Repeated administration of first trimester and term HUCPVC improved pregnancy rates and reduced ovarian fibrosis in a mouse model of natural ovarian aging. What is known already Mesenchymal stromal cells (MSC), such as first trimester (FTM) and term human umbilical cord perivascular cells (HUCPVC), may be good cell candidates to mitigate side-effects of oncotherapy, including infertility, and are also gaining interest in ovarian rejuvenation strategies. The intraovarian or systemic administration of various sources of mesenchymal stromal cells in animal models of advanced reproductive age have been previously reported to improve ovarian reserve, follicle activation and function, via multiple proposed mechanisms. However, mating studies have not previously been performed to demonstrate fertility preservation. In addition, the optimal dose regimen and timing of treatment has not been established. Study design, size, duration Pre-clinical randomized controlled study in a mouse model of natural ovarian aging from 6 months to 12 months, including a negative control group (vehicle-treated), a cell control group (fibroblast-treated) and 3 experimental groups (HUCPVC, 2 sources and 2 dose regimens; n = 10-15 per group). All parameters were compared with young control female mice (6-8 weeks, 6 months). Cell injections and all assessments were blinded. Participants/materials, setting, methods 6-month-old ICR mice randomized into 4 groups received 6 monthly tail vein injections of 1x106 HUCPVC (FTM or term), fibroblast cells or HBSS (vehicle control). A 5th group received a single injection of FTM HUCPVC at 11M (n = 5). Pregnancy and litter size data were collected after breeding trials. The total number of follicles per ovary and picrosirius red (PSR) staining were quantified. Serum anti-Mullerian hormone (AMH) and C-reactive protein (CRP) were analyzed by ELISA. Main results and the role of chance No differences in mortality rates (P = 0.2) and animal weights were observed. The weight gain in FTM and term HUCPVC treated animals was significantly greater than in the other groups, over the duration of the study (P = 0.04). Animals that received 6 injections of FTM and term HUCPVC showed significantly higher pregnancy rates at 12M (100%, 80%) (P = 0.007; P = 0.048, respectively), when compared to animals that received HBSS (40%) and were similar to pregnancy rates of 6-8weeks (100%) and 6M (77%) groups. Fibroblast-treated and 1x FTM HUCPVC-treated groups showed 60% pregnancy rates. Age-associated declines in litter sizes and ovarian reserve indicators were observed as expected, but not rescued by cell treatments, except for levels of AMH which were increased in the group that received 1x FTM HUCPVC injections when compared to HBSS controls (P = 0.04). Age-associated increases in ovarian stroma fibrosis were observed with aging in the control groups (P < 0.0001), and were significantly reduced in 6x FTM HUPCVC, 6x term HUCPVC and 1x FTM HUCPVC groups, when compared to HBSS and fibroblast controls (P < 0.0001; P = 0.01 and P < 0.0001, respectively). An age-associated increase in CRP (P = 0.01) was significantly decreased in 6x FTM HUCPVC-treated groups, when compared to HBSS (P = 0.04). Limitations, reasons for caution Pregnancy rate (the main outcome measured in this study) may confound some of the secondary outcomes analyzed (CRP levels). Use of ovarian tissue for histological analysis and limited serum samples precluded further molecular analyses to assess potential mechanisms for the effects of HUCPVC. Wider implications of the findings FTM HUCPVC have anti-inflammatory and anti-fibrotic effects, and represent a promising source of MSC to prevent fertility decline in women of advanced reproductive age. Trial registration number Not Applicable
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