MRAP2 regulates endometrial receptivity and function.

A successful embryo implantation depends on the synchronization between a competent blastocyst and a receptive endometrium. Recently, potential modulators of endometrial receptivity (OVGP1, MRAP2, ZCCHC12, and HAP1) have been reported likely with a functional role during embryo implantation. The aim of this study was to evaluate the gene expression of these genes in the endometrium of infertile women. Eighteen endometrial biopsies, during secretory lutheal phase, were recruited from women with unexplained infertility and women who cannot conceive due to their partners' fertility problems. qRT-PCR was carried out to evaluate MRAP2, OVGP1, ZCCHC12 and HAP1 gene expression. MRAP2 expression was also detected by western blot and it was localized by immunohistochemistry. Morphological analysis was performed by light microscopy. MRAP2 was significantly up-regulated in study vs. control group. Western blot analysis confirmed the observed MRAP2 up-expression. MRAP2 resulted mainly localized in the epithelial cells of uterine glands. Morphological analysis displayed that the epithelium of the uterine glands undergo hypertrophy in women with unexplained infertility in respect to women with male infertility factor. MRAP2 could be considered a mediator of endometrial receptivity likely acting on endometrial stability by binding to MCRs and PKR1.

Human Mesenchymal Stem Cells Reendothelialize Porcine Heart Valve Scaffolds: Novel Perspectives in Heart Valve Tissue Engineering.

Heart valve diseases are usually treated by surgical intervention addressed for the replacement of the damaged valve with a biosynthetic or mechanical prosthesis. Although this approach guarantees a good quality of life for patients, it is not free from drawbacks (structural deterioration, nonstructural dysfunction, and reintervention). To overcome these limitations, the heart valve tissue engineering (HVTE) is developing new strategies to synthesize novel types of valve substitutes, by identifying efficient sources of both ideal scaffolds and cells. In particular, a natural matrix, able to interact with cellular components, appears to be a suitable solution. On the other hand, the well-known Wharton's jelly mesenchymal stem cells (WJ-MSCs) plasticity, regenerative abilities, and their immunomodulatory capacities make them highly promising for HVTE applications. In the present study, we investigated the possibility to use porcine valve matrix to regenerate in vitro the valve endothelium by WJ-MSCs differentiated along the endothelial lineage, paralleled with human umbilical vein endothelial cells (HUVECs), used as positive control. Here, we were able to successfully decellularize porcine heart valves, which were then recellularized with both differentiated-WJ-MSCs and HUVECs. Data demonstrated that both cell types were able to reconstitute a cellular monolayer. Cells were able to positively interact with the natural matrix and demonstrated the surface expression of typical endothelial markers. Altogether, these data suggest that the interaction between a biological scaffold and WJ-MSCs allows the regeneration of a morphologically well-structured endothelium, opening new perspectives in the field of HVTE.

Extrapituitary actions of GnRH antagonists: prospects for in vitro fertilization programs.

Gonadotropin-releasing hormone antagonists (GnRH-ant) are routinely used to prevent premature luteinizing hormone (LH) surges in women undergoing in vitro fertilization (IVF) programs. GnRH-ant act by competitively binding GnRH receptors (GnRHr), leading to rapid pituitary suppression. GnRH-ant can also block extrapituitary GnRHr, including those present in ovary, placenta, and endometrium. A full understanding of the functional roles played by extrapitutary GnRHr, along with a better characterization of the possible reproductive consequences of their blockage may aid the refinement of controlled ovarian stimulation (COS) protocols using GnRHant. This review summarizes current research in the area, especially focusing on the possible impact of GnRH-ant on steroidogenesis, folliculogenesis and endometrial receptivity.

Ovulation inducing agents and cancer risk: review of literature.

Over the past decades, the use of ovulation inducing drugs has been increasing. A possible causal link between fertility treatments (especially clomiphene citrate and gonadotrophins) and various types of malignancies, including cancers of female reproductive system, thyroid cancer and melanoma, has been postulated. The majority of the available studies on this subject suffers from methodological limitations, including the small number of outcomes, short and incomplete follow-up, and inability to control for potential confounders. Concerning ovarian cancer, while early studies led to the suggestion of an association between ovulation inducing agents and increased risk of malignancies, the majority of data do not support a causal link. An increased risk was recently observed in women giving birth after in vitro fertilization (IVF), but it appeared to be consequential to the infertile status rather than the effect of fertility drugs. More controversial are the results concerning breast cancer with some investigations suggesting an increased risk after exposure to ovulation inducing agents, especially clomiphene citrate, whereas others not supporting this concept. A possible trend towards an increased risk has been reported by some authors for endometrial cancer. Altogether, current data should be thus regarded as a signal for the need of further studies rather than being definitive in them.

Impact of a single endometrial injury on assisted reproductive technology outcome: a preliminary observational study.

OBJECTIVE: To find a more acceptable strategy for our patients to improve endometrial receptivity in assisted reproductive technologies (ART) and to study the impact of a single endometrial sampling performed on day 21 of the spontaneous menstrual cycle. STUDY DESIGN: In this preliminary study, the possible beneficial effects on ART outcome of a single biopsy performed on the midluteal phase (day 21) of the spontaneous menstrual cycle preceding controlled ovarian stimulation was tested in a group of patients with 3 or more implantation failures. RESULTS: After endometrial biopsy 45.94% of patients with more than two failed ART cycles obtained clinical pregnancy. CONCLUSION: Although these preliminary results are encouraging, further investigation is needed to validate the study.

Cytogenetic findings and reproductive outcome of infertile couples referred to an assisted reproduction program.

It is still undefined whether all the couples entering an assisted reproduction program should undergo to karyotype analysis. The present study was conducted to determine the prevalence of chromosomal abnormalities in a non-selected sample of 1,146 couples referred to assisted reproduction technologies (ART), and to analyze the outcome of pregnancies from couples in whom cytogenetic anomalies were detected. Irrespective of the infertility factor, fertilization was achieved by intracytoplasmic sperm injection (ICSI). A total number of 35 karyotype anomalies were diagnosed, corresponding to an abnormality frequency of 1.52% (1.83% for men and 1.22% for women). As could be expected, the majority of men presenting karyotype anomalies had a low sperm count. Among women, the majority of cytogenetic anomalies were detected in individual not presenting risk factors for aberrant karyotype. Around 41% of pregnancies achieved in couples presenting chromosomal anomalies ended in spontaneous abortion. Information on fetal karyotype was limited. No major malformations were observed among newborns from parents with abnormal karyotype. In consideration of the elevated frequency of pregnancy loss, it seems advisable to recommend that chromosomal analysis be performed in all couples undergoing ART. This with the aim of identifying patients that would possibly benefit from pre-implantation genetic diagnosis.