Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo.

Embryonic implantation requires synchrony between the endometrium and the embryo. When analyzed in isolation, competent embryos may be unsuccessful when placed on a nonreceptive endometrium or vice versa, contributing to the "black box" of implantation failure. It is when the two are assessed together that dyssynchrony becomes evident, due to premature progesterone stimulus on the endometrium, physiologic displacement of the window of implantation or late blastulation of the embryo, or all combined.

Aging and the environment affect gamete and embryo potential: can we intervene?

Optimal maturation of the oocyte depends on its environment and determines embryo competence, because the embryonic genome is not active until the cleavage stage and new mitochondria are not produced until blastulation. Adverse environmental factors include aging, andropause, oxidative stress, obesity, smoking, alcohol, and psychologic stress, whereas androgen supplementation, a prudent diet, exercise, nutritional supplements, and psychologic interventions have beneficial effects. Mitochondrial function and energy production deteriorate with age, adversely affecting ovarian reserve, chromosome segregation, and embryo competence.

Distribution patterns of segmental aneuploidies in human blastocysts identified by next-generation sequencing.

Objective: To evaluate the ability of next-generation sequencing (NGS) to detect pure and mosaic segmental aneuploidies in trophectoderm biopsies and to identify distribution patterns in whole blastocysts.

Design: Validation study.

Setting: Reference laboratory.

Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of leiomyoma.

Objective: To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pIC(PEI)] in xenografted human leiomyomas.

Design: Heterologous leiomyoma mouse model.

Setting: University-affiliated infertility center.

Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome.

During embryo implantation, the blastocyst interacts with and regulates the endometrium, and endometrial fluid secreted by the endometrial epithelium nurtures the embryo. Here, we propose that maternal microRNAs (miRNAs) might act as transcriptomic modifier of the pre-implantation embryo. Microarray profiling revealed that six of 27 specific, maternal miRNAs were differentially expressed in the human endometrial epithelium during the window of implantation--a brief phase of endometrial receptivity to the blastocyst--and were released into the endometrial fluid.

Is endometrial receptivity transcriptomics affected in women with endometriosis? A pilot study.

Endometrial receptivity is still questioned today in women with endometriosis. The aim of this study was to assess the endometrial receptivity gene signature in patients with different stages of endometriosis by investigating transcriptomic modifications of their endometrium using the endometrial receptivity array (ERA) test. A prospective, interventional multicentre pilot trial was designed and implemented in two university-affiliated infertility units from Belgium and Spain.

Human CD133(+) bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome.

Objective: To investigate the engraftment and proliferation of superparamagnetic iron oxide nanoparticles (SPIOs)-labeled human CD133(+) bone marrow-derived stem cells (BMDSCs) in an animal model of Asherman syndrome (AS).

Design: Prospective experimental animal study.

Setting: University research laboratories.

Dopamine agonist inhibits vascular endothelial growth factor protein production and secretion in granulosa cells.

Background: Dopamine receptor 2 agonists (D2-ags) inhibit vascular endothelial growth factor (VEGF) secretion in luteinized granulosa cells (LGCs) both in vitro and in vivo. However, the mechanism of D2 regulation of the VEGF/VEGF Receptor 2 (VEGFR-2) pathway remains to be elucidated. We sought to determine the effects of D2 signaling on VEGF transcription and translation in LGCs, with the expectation of identifying potential D2-ag-based therapies for ovarian hyperstimulation syndrome (OHSS).

Comprehensive carrier genetic test using next-generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology.

Objective: To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assisted reproductive technology (ART) patients and donors.

Design: Retrospective analysis of results obtained from 2,570 analyses.

Setting: Reproductive genetic laboratory.

Evaluation of the potential therapeutic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of endometriosis.

Objective: To assess the therapeutic potential of polyinosine-polycytidylic acid, a double-stranded RNA molecule with selective proapoptotic and antiangiogenic activity, complexed with polyethyleneimine (pIC(PEI)) in treating endometriosis.

Design: A heterologous mouse model of endometriosis was created by injecting human endometrial fragments into the peritoneum. Endometrial fragments were engineered to express the fluorescent protein mCherry as a reporter to monitor status over the course of the 4-week study.

Cell Therapy and Tissue Engineering from and toward the Uterus.

Regenerative medicine offers the potential for replacement or repair of different types of cells within damaged tissues or the tissues themselves, typically through cell therapy or tissue engineering. Stem cells are critical to these approaches; indeed, the involvement of bone marrow in the differentiation of stem cells to nonhematopoietic cells is well demonstrated. Further, the contribution of bone marrow-derived stem cells in promoting neoangiogenesis has been demonstrated not only in animal models, but also in human clinical trials with an excellent safety profile.

Follicular fluid and mural granulosa cells microRNA profiles vary in in vitro fertilization patients depending on their age and oocyte maturation stage.

Objective: To determine whether there is any difference in the follicular fluid (FF) microRNA (miRNA) profiles from in vitro fertilization (IVF) patients according to their age and oocyte maturation stage.

Design: Observational prospective study.

Setting: IVF clinic/hospital facilities.

Circulating miR-200-family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time.

Objective: To determine whether circulating micro-RNA (miR) 200a, miR-200b, and miR-141 have altered levels in patients with endometriosis compared with control individuals.

Design: Experimental laboratory study.

Setting: University.

New strategy for diagnosing embryo implantation potential by combining proteomics and time-lapse technologies.

Objective: To develop a diagnostic tool for embryo implantation potential with the use of proteomic fingerprinting combined with time-lapse morphokinetic analysis.

Design: Retrospective cohort study.

Setting: University-affiliated private in vitro fertilization center.

Mitochondrial DNA content as a viability score in human euploid embryos: less is better.

Objective: To investigate the clinical relevance of mitochondrial DNA (mtDNA) content as a viability score in human euploid embryos.

Design: Retrospective analysis of mtDNA content of transferred euploid embryos.

Setting: Reproductive genetics laboratory.

Stro-1/CD44 as putative human myometrial and fibroid stem cell markers.

Objective: To identify and characterize myometrial/fibroid stem cells by specific stem cell markers in human myometrium, and to better understand the stem cell contribution in the development of uterine fibroids.

Design: Prospective, experimental human and animal study.

Setting: University research laboratory.

Converting a Problem into an Opportunity: mtDNA Heteroplasmy Shift.

The transmission of mitochondrial DNA (mtDNA) disease from a mother with a heteroplasmic mtDNA mutation to her children is unpredictable. In a recent issue of Cell, Reddy et al. (2015) present the potential for mitochondrial-targeted nucleases to remove mutated mtDNA through the induction of heteroplasmy shift in oocytes and zygotes.

Antral Follicle Priming Before Intracytoplasmic Sperm Injection in Previously Diagnosed Low Responders: A Randomized Controlled Trial (FOLLPRIM).

Context: A low response to controlled ovarian hyperstimulation implies a reduced number of embryos and impaired pregnancy rate. Follicular priming with steroids before controlled ovarian hyperstimulation has been suggested to improve the subsequent ovarian response.

Objective: The purpose of this study was to determine the best follicular priming protocol in low responders and to investigate the intrafollicular mechanisms triggered by steroid hormone priming.

Trends in clinical reproductive medicine research: 10 years of growth.

Objective: To study the most important metrics of publication in the field of reproductive medicine over the decade 2003-2012 to aid in discerning the clinical, social, and epidemiologic implications of this relatively new but rapidly emerging area in medical sciences.

Design: Bibliometric analysis of most-cited publications from Web of Science databases.

Setting: Not applicable.

Understanding and improving endometrial receptivity.

Purpose Of The Review: For a successful pregnancy, the synchronic coordination between the embryonic development and the endometrial status is crucial. The endometrium is a hormonally regulated organ that is nonadhesive to embryos throughout most of the menstrual cycle in humans. Endometrial receptivity refers to a hormone-limited period in which the endometrial tissue acquires a functional and transient ovarian steroid-dependent status allowing blastocyst implantation and therefore pregnancy initiation.

Human Endometrial Transcriptomics: Implications for Embryonic Implantation.

Human endometrium has been extensively investigated in the search for markers capable of predicting its receptive status. The completion of the Human Genome Project has triggered a rapid development of new fields in molecular biology, the "transcriptomics" being a major turning point in the knowledge acquisition of endometrial receptivity. Based on this, a customized Endometrial Receptivity Array (ERA) has been developed, which is capable of identifying the genomic signature of receptivity.

Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model.

Objective: To study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation.

Design: Prospective experimental animal study.

Setting: University research laboratories.