Objective: To characterize the effect of ulipristal acetate (UPA) treatment on transforming growth factor (TGF) canonical and noncanonical signaling pathways in uterine leiomyoma tissue and cells. UPA decreased extracellular matrix in surgical specimens; we characterize the mechanism in this study. Design: Laboratory study. Setting: University. Intervention(s): Exposure of leiomyoma cell lines to UPA. Main Outcome Measure(s): RNAseq was performed on matched myometrium and leiomyoma surgical specimens of placebo- and UPA-treated patients. Changes in gene expression and protein were measured using quantitative polymerase chain reaction and western immunoblot analysis, respectively. Result(s): In surgical specimen, mRNA for TGF-beta 3 was elevated 3.75-fold and TGFR2 was decreased 0.50-fold in placebo leiomyomas compared with myometrium. Analysis of leiomyomas from UPA-treated women by western blot revealed significant reductions of active TGF-beta 3 (0.64 +/- 0.12-fold), p-TGFR2 (0.56 +/- 0.23-fold), pSmad 2 (0.54 +/- 0.04-fold), and pSmad 3 (0.65 +/- 0.09-fold) compared with untreated leiomyomas. UPA treatment demonstrated statistically significant reduction in collagen 1, fibronectin, and versican proteins. Notably, there was a statistically significant increase of the extracellular matrix protein fibrillin in leiomyoma treated with UPA (1.48 +/- 0.41-fold). Data from in vitro assays with physiologic concentrations of UPA supported the in vivo findings. Conclusion(s): TGF-beta pathway is highly up-regulated in leiomyoma and is directly responsible for development of the fibrotic phenotype. UPAattenuates this pathway by reducingTGF-beta 3 message and protein expression, resulting in a reduction inTGF-beta canonical signaling. In addition, UPA significantly increased fibrillin protein expression, which can serve to bind inactive TGF-beta complexes. Therefore, UPA inhibits leiomyoma fibrosis by decreasing active TGF-beta 3 and diminishing signaling through the canonical pathway. (C) 2019 by American Society for Reproductive Medicine.
Objectives: to determine the ability of pre-surgical markers to predict the ability to retrieve sperm in non-obstructive azoospermia (NOA) undergoing surgical sperm retrieval. Methods: a cross-sectional descriptive analysis of 136 infertile patients with azoospermia, examined in the Hue Center for Reproductive Endocrinology and Infertility (HUECREI), Hue University Hospital from August 2014 to July 2018. Patients underwent surgical sperm retrieval in a stepwise manner via percutaneous epididymal sperm aspiration (PESA), testicular sperm aspiration (TESA) then testicular sperm extraction (TESE) until sperm were detected. Patient age, duration of infertility, body mass index (BMI), hormonal profile (FSH, LH & testosterone), and testicular volume were analyzed to determine the predictor of successful sperm retrieval. Analysis was done by univariate & multivariate generalized estimating equation modeling where the primary outcome was sperm retrieved at surgery. Results: In total of 136 infertile men with azoospermia, beside 45 cases with OA, surgical sperm retrieval was successful in 22/91 patients with NOA (24.2%). The group of men with successful sperm retrieval were more likely to live in urban area (P=0.012), higher proportion of normal testicular density (P<0.05), lower serum FSH and serum LH (P<0.001). By multiple logistic regression model, total testicular volume was found to be a only considerable predictor of sperm retrieval in NOA group (OR 1.09, 95%CI 1.013-1.178, P=0.022). Conclusions: The measurement of total testicular volume can be helpful for predicting the successful result of surgical sperm retrieval in Vietnamese infertile men with non-obstructive azoospermia. Key words: testicular ultrasound; endocrine profile; surgical sperm retrieval; non-obstructive; azoospermia.
Objective: To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI).Design: An updated systematic review and meta-analysis.Setting: Not applicable.Patient(s): Patients undergoing OI-IUI for infertility.Intervention(s): Exogenous P luteal support after OI-IUI.Main Outcome Measure(s): Live birth.Result(s): Eleven trials were identified that met inclusion criteria and constituted 2,842 patients undergoing 4,065 cycles, more than doubling the sample size from the previous meta-analysis. In patients receiving gonadotropins for OI, clinical pregnancy (relative risk [RR] 1.56, 95% confidence interval [CI] 1.21-2.02) and live birth (RR 1.77, 95% CI 1.30-2.42) were more likely in P supplemented patients. These findings persisted in analysis of live birth per IUI cycle (RR 1.59, 95% CI 1.24-2.04). There were no data on live birth in clomiphene citrate or clomiphene plus gonadotropin cycles. There was no benefit on clinical pregnancy with P support for patients who underwent OI with clomiphene (RR 0.85, 95% CI 0.52-1.41) or clomiphene plus gonadotropins (RR 1.26, 95% CI 0.90-1.76).Conclusion(s): Progesterone luteal phase support is beneficial to patients undergoing ovulation induction with gonadotropins in IUI cycles. The number needed to treat is 11 patients to have one additional live birth. Progesterone support did not benefit patients undergoing ovulation induction with clomiphene citrate or clomiphene plus gonadotropins. (C) 2017 by American Society for Reproductive Medicine.
The fact remains that regardless of the environmental "hardware" in place, the laboratory environment must be maintained as cleanly as possible in order to provide optimal growing conditions for the oocytes, sperm, and embryos. This involves containing or even eliminating possible sources of contamination to promote successful embryonic development and patient outcomes.
Objective: To evaluate the effect of luteal phase P support after ovulation induction IUI.Design: A systematic review and meta-analysis.Setting: Not applicable.Patient(s): Undergoing ovulation induction IUI.Intervention(s): Any form of exogenous P in ovulation induction IUI cycles.Main Outcome Measure(s): Clinical pregnancy and live birth.Result(s): Five trials were identified that met inclusion criteria and comprised 1,298 patients undergoing 1,938 cycles. Clinical pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.15-1.98) and live birth (OR 2.11, 95% CI 1.21-3.67) were more likely in P-supplemented patients. These findings persisted in analyses evaluating per IUI cycle, per patient, and first cycle only data. In subgroup analysis, patients receiving gonadotropins for ovulation induction had the most increase in clinical pregnancy with P support (OR 1.77, 95% CI 1.20-2.6). Conversely, patients receiving clomiphene citrate (CC) for ovulation induction showed no difference in clinical pregnancy with P support (OR 0.89, 95% CI 0.47-1.67).Conclusion(s): Progesterone luteal phase support may be of benefit to patients undergoing ovulation induction with gonadotropins in IUI cycles. Progesterone support did not benefit patients undergoing ovulation induction with CC, suggesting a potential difference in endogenous luteal phase function depending on the method of ovulation induction. (C) 2013 by American Society for Reproductive Medicine.