One week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid1. Here we show that naive human pluripotent stem cells cultured in PXGL medium2 and triply inhibited for the Hippo, TGF-β and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development3,4.

Integrated pseudotime analysis of human preimplantation embryo single-cell transcriptomes reveals the dynamics of lineage specification Graphical abstract Highlights d Distinct trophectoderm/epiblast signatures arise at the B2-B3 blastocyst stages d IFI16 is broadly expressed in the ICM and then restricted to epiblast after implantation d NR2F2 arises from the polar TE in late blastocysts and then spreads to all TE cells

Highlights d Reprogramming of patient somatic cells to induced hTSCs with OSKM d Conversion of naive and extended hPSCs to hTSCs d Comparison of models of the human trophoblast lineage d h(i/c)TSCs are akin to day 8 trophoblasts of the human embryo

Induced pluripotent stem cells (iPSCs) have considerably impacted human developmental biology and regenerative medicine, notably because they circumvent the use of cells of embryonic origin and offer the potential to generate patient-specific pluripotent stem cells. However, conventional reprogramming protocols produce developmentally advanced, or primed, human iPSCs (hiPSCs), restricting their use to post-implantation human development modeling. Hence, there is a need for hiPSCs resembling preimplantation naive epiblast. Here, we develop a method to generate naive hiPSCs directly from somatic cells, using OKMS overexpression and specific culture conditions, further enabling parallel generation of their isogenic primed counterparts. We benchmark naive hiPSCs against human preimplantation epiblast and reveal remarkable concordance in their transcriptome, dependency on mitochondrial respiration and X-chromosome status. Collectively, our results are essential for the understanding of pluripotency regulation throughout preimplantation development and generate new opportunities for disease modeling and regenerative medicine.

BACKGROUND A worldwide increase in the prevalence of obesity has been observed in the past three decades, particularly in women of reproductive age. Female obesity has been clearly associated with impaired spontaneous fertility, as well as adverse pregnancy outcomes. Increasing evidence in the literature shows that obesity also contributes to adverse clinical outcomes following in vitro fertilization (IVF) procedures. However, the heterogeneity of the available studies in terms of populations, group definition and outcomes prevents drawing firm conclusions. A previous meta-analysis published in 2011 identified a marginal but significant negative effect of increased female body mass index (BMI) on IVF results, but numerous studies have been published since then, including large cohort studies from national registries, highlighting the need for an updated review and meta-analysis. OBJECTIVE AND RATIONALE Our systematic review and meta-analysis of the available literature aims to evaluate the association of female obesity with the probability of live birth following IVF. Subgroup analyses according to ovulatory status, oocyte origin, fresh or frozen-embryo transfer and cycle rank were performed. SEARCH METHODS A systematic review was performed using the following key words: (‘obesity’, ‘body mass index’, ‘live birth’, ‘IVF’, ‘ICSI’). Searches were conducted in MEDLINE, EMBASE, Cochrane Library, Eudract and clinicaltrial.gov from 01 January 2007 to 30 November 2017. Study selection was based on title and abstract. Full texts of potentially relevant articles were retrieved and assessed for inclusion by two reviewers. Subsequently, quality was assessed using the Newcastle-Ottawa Quality Assessment Scales for patient selection, comparability and assessment of outcomes. Two independent reviewers carried out study selection and data extraction according to Cochrane methods. Random-effect meta-analysis was performed using Review Manager software on all data (overall analysis), followed by subgroup analyses. OUTCOMES A total of 21 studies were included in the meta-analysis. A decreased probability of live birth following IVF was observed in obese (BMI ≥ 30 kg/m2) women when compared with normal weight (BMI 18.5–24.9 kg/m2) women: risk ratio (RR) (95% CI) 0.85 (0.82–0.87). Subgroups analyses demonstrated that prognosis was poorer when obesity was associated with polycystic ovary syndrome, while the oocyte origin (donor or non-donor) did not modify the overall interpretation. WIDER IMPLICATIONS Our meta-analysis clearly demonstrates that female obesity negatively and significantly impacts live birth rates following IVF. Whether weight loss can reverse this deleterious effect through lifestyle modifications or bariatric surgery should be further evaluated.

The current Zika virus outbreak and its potential severe health consequences, especially congenital fetal syndrome, have led to increased concern about sexual transmission, especially in pregnant women and women of reproductive age. Here we report a case of Zika virus sexual transmission, likely male-to-female, in a totally asymptomatic couple.

This work was supported by the Proteomics Core Facility at Biogenouest and was funded by Conseil Régional de Bretagne, IBiSA and Agence de la Biomédecine grants. The authors declare that there exists a competing financial interest in this work that is related to a patent application on the use of identified germ cell-specific proteins in an antibody-based assay (Fertichip™) to predict the successful testicular biopsy outcomes in human non-obstructive azoospermia.

Although the association between smoking and female infertility is now largely demonstrated, the proportion of smokers in women of reproductive age remains important. Tobacco contains numerous toxicants that could affect ovarian reserve and lead to poor prognosis in assisted reproductive techniques. To investigate the effect of female active smoking on ovarian reserve and IVF outcome, smoking status, hormonal status, i.e. serum FSH, oestradiol and anti-Müllerian hormone (AMH), ovarian response to hyperstimulation, i.e. mature oocytes retrieved, and IVF outcome, i.e. clinical pregnancy, were retrospectively analysed in 111 women undergoing IVF-embryo transfer cycles. Compared with non-smokers (n = 71), active smoking women (n = 40) had decreased ovarian response (12.12 +/- 5 versus 8.62 +/- 4 mature oocytes retrieved) to hyperstimulation and lower clinical pregnancy rate (29.6 versus 10.0%). Serum AMH concentrations were lower in the smoker group (3.86 +/- 1.92 versus 3.06 +/- 1.68 mug/l) and had no predictive value for ovarian response, inversely to non-smokers. In conclusion, active smoking is associated with poor prognosis in assisted reproduction cycles, i.e. ovarian response and pregnancy, and leads to altered ovarian reserve, as reflected by decreased serum AMH concentrations.