Project description:Endometrial receptivity on genomic level is one of the major cause of implantation failure in IVF patients with unexlained infertility and is a main obstacle in success of IVF. Gene expression profiles of implantation failure cases of unexplained infertility were compared with proven healthy oocyte donors as controls, both undergoing ovarian stimulation. The results provide additional information about gene expression profile related to endometrial receptivity in implantation failure cases especially under the influence of ovarian stimulation during IVF cycle.
Project description:Endometrial receptivity on genomic level is one of the major cause of implantation failure in IVF patients with unexplained infertility and is a main obstacle in success of IVF. Gene expression profiles of implantation failure cases of unexplained infertility were compared with proven healthy oocyte donors as controls, both undergoing ovarian stimulation. The results provide additional information about gene expression profile related to endometrial receptivity in implantation failure cases especially under the influence of ovarian stimulation during IVF cycle.
Project description:CONTEXT Nowadays, the molecular mechanisms involved in endometrial receptivity and implantation are still not clear. OBJECTIVE The gene expression of human endometrium of patients undergoing an IVF treatment with GnRH antagonists/rec-FSH was studied. CONCLUSIONS COX-2 has been extensively studied as a crucial fertility element in both knock-out mice and human. It appears that increased expression of COX-2 and/or SCGB1D2 on the day of oocyte retrieval in GnRH antagonist/rec-FSH stimulated cycles coincides with a lower probability of achieving a clinical pregnancy in this cycle. Keywords: gene expression analysis, clinical pregnancy in IVF stimulated cycles Endometrial biopsies taken from patients on day of oocyte retrieval in stimulated IVF cycles with 1 or 2 embryos replaced in the same cycle. Gene expression of pregnant patients (n=4) was compared with matched non-pregnant patients (n=4)
Project description:Inner uterine lining or endometrium is a unique constantly self-renewed adult tissue that is vital for embryo implantation. As the footrace for universal endometrial receptivity markers continues, RNA-seq remains the most powerful tool for transcriptomic marker discovery. In this study, we aimed to elucidate endometrial maturation mechanisms at transcriptomic level and identify novel robust biomarker candidates for endometrial receptivity in a multicentre study. Additionally, we compared mid-secretory transcriptome profiles from healthy women with profiles of women with repeated IVF failure to find transcriptome changes related to problems with endometrial receptivity.
Project description:Embryo implantation is a key step in establishing pregnancy and a major limiting factor in IVF. Implantation requires the endometrium, the inner lining of the uterus, to transform from a non-receptive to a receptive state, to allow embryos to attach to the surface and enter into the tissue. However, the fundamental mechanisms governing receptivity are not well understood. Here we show that transmembrane protein podocalyxin is a major and clinically significant factor regulating human endometrial receptivity. Podocalyxin is expressed in all endometrial epithelial cells in the non-receptive state but is selectively down-regulated in the luminal epithelium at receptivity. We present evidence that podocalyxin critically governs the barrier function of the endometrial epithelium, likely as an intrinsic protective mechanism, rendering it non-receptive to an embryo. In addition, podocalyxin suppresses genes promoting receptivity (eg LIF, CSF1) but stimulates those inhibiting implantation (eg WNT7A, LEFTY2). Down-regulation of podocalyxin in the luminal epithelium, likely mediated by progesterone, selectively converts the endometrial surface to a more adhesive state that facilitates embryo attachment and penetration. Furthermore, inadequate down-regulation of podocalyxin in the endometrial luminal epithelium is associated with poorer implantation rates in IVF. We thus propose that podocalyxin promotes the barrier function of human endometrial epithelial cells and critically regulates receptivity for embryo implantation.
Project description:CONTEXT Nowadays, the molecular mechanisms involved in endometrial receptivity and implantation are still not clear. OBJECTIVE The gene expression of human endometrium of patients undergoing an IVF treatment with GnRH antagonists/rec-FSH was studied. CONCLUSIONS COX-2 has been extensively studied as a crucial fertility element in both knock-out mice and human. It appears that increased expression of COX-2 and/or SCGB1D2 on the day of oocyte retrieval in GnRH antagonist/rec-FSH stimulated cycles coincides with a lower probability of achieving a clinical pregnancy in this cycle. Keywords: gene expression analysis, clinical pregnancy in IVF stimulated cycles
Project description:Administration of GnRH antagonist in IVF has several advantages. However, studies have shown that GnRH antagonist protocol cycles have lower implantation and clinical pregnancy rates than GnRH agonist long protocol cycles. Endometrial receptivity rather than embryo quality is thought to account for this phenomenon, however the mechanism is still largely unknown. This microarray analysed human endometrium during ‘implantation window phase’ between three groups: 1) untreated control, 2) GnRH agonist long protocol, and 3) GnRH antagonist protocol. The differential gene between groups uncovered the molecular mechanism occurred in endometrium affected by the intake of GnRH agonist or GnRH antagonist. Further study of these differential gene promises to find the reasons for lower endometrial receptivity in patients treated with GnRH antagonist and to improve the implantation rate in GnRH antagonist protocols in IVF.
Project description:microRNAs profiling of human serum comparing control fertile women with women who had experienced repeated implantation failure after ovarian stimulation and IVF-ET. Repeated implantation failure was defined as women who had undergone≥3 failed cycles with high-grade embryos were transferred.
Project description:Intrauterine BoTA treatment has a beneficial effect on vascular reconstruction of functional endometrium prior to embryo implantation by increasing endometrial blood flow near the uterine cavity suggesting BoTA treatment as a potential therapeutic strategy for patients who are suffering from repeated implantation failure with the problems with endometrial receptivity.