Different Dosages of Progesterone in Luteal Phase Support Reflect Varying Endometrial microRNA Expression in Frozen Embryo Transfer Cycles.

Despite serum progesterone being a widely accepted method for luteal phase support during embryo transfer cycles, debates persist regarding the optimal strategy for guiding clinical decisions on progesterone dosages to maximize reproductive outcomes. This retrospective study explored the utility of microRNA (miRNA) biomarkers in guiding personalized progesterone dosage adjustments for frozen embryo transfer (FET) cycles in 22 in vitro fertilization (IVF) patients undergoing hormone replacement therapy. Utilizing MIRA, an miRNA-based endometrial receptivity test, we analyzed patients' miRNA expression profiles before and after progesterone dosage adjustments to determine suitable dosages and assess endometrial status. Despite patients receiving identical progesterone dosages, variations in miRNA profiles were observed in the initial cycle, and all patients presented a displaced window of implantation. Following dosage adjustments based on their miRNA profiles, 91% of patients successfully transitioned their endometrium towards the receptive stages. However, two patients continued to exhibit persistent displaced receptivity despite the adjustments. Given the evident variation in endometrial status and serum progesterone levels among individuals, analyzing miRNA expression profiles may address the challenge of inter-personal variation in serum progesterone levels, to deliver more personalized dosage adjustments and facilitate personalized luteal phase support in IVF.

Association of angiotensin II and receptors in peri-implantation endometrium with microvessel density and pregnancy outcomes of women with recurrent implantation failure after embryo transfer.

Purpose: Investigate whether local angiotensin II (AngII) and its AngII type 1 and 2 receptors (AT1R, AT2R) in the endometrium are different and correlate with microvessel density in women with reproductive failure and pregnancy outcomes. Methods: Endometrium during the window of implantation from 40 women with recurrent miscarriage (RM) and 40 with recurrent implantation failure (RIF) were compared with 27 fertile women. Peri-implantation endometrium from 54 women prior to euploid embryo transfer were collected and compared in women with successful pregnancy and unsuccessful pregnancy. Results: Compared with fertile women, expression of AT2R was significantly lower, while AT1R/AT2R expression ratio was significantly higher in the stroma of the RIF group. Endometrium arteriole MVD was significantly lower and negatively correlated with the AT1R/AT2R expression ratio in the stroma of the RIF group. No significant differences and correlations were found in the RM group. Compared with the pregnancy group, expression of AT1R and AT2R were significantly lower in all compartments, but only AT1R/AT2R ratio was significantly higher in the stroma of the non-pregnancy group. Similarly, endometrium arteriole MVD was also significantly lower and negatively correlated with the AT1R/AT2R ratio in the stroma of the non-pregnancy group. Conclusion: Local renin-angiotensin system is dysregulated in peri-implantation endometrium and associated with abnormal angiogenesis in RIF and poor implantation outcome after embryo transfer.

Development of a Predictive Model for Optimization of Embryo Transfer Timing Using Blood-Based microRNA Expression Profile.

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

A novel platform for discovery of differentially expressed microRNAs in patients with repeated implantation failure.

OBJECTIVE: To identify predictor microRNAs (miRNAs) from patients with repeated implantation failure (RIF). DESIGN: Systemic analysis of miRNA profiles from the endometrium of patients undergoing in vitro fertilization (IVF). SETTING: University research institute, private IVF center, and molecular testing laboratory. PATIENT(S): Twenty five infertile patients in the discovery cohort and 11 patients in the validation cohort. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): A signature set of miRNA associated with the risk of RIF. RESULT(S): We designed a reproductive disease-related PanelChip to access endometrium miRNA profiles in patients undergoing IVF. Three major miRNA signatures, including hsa-miR-20b-5p, hsa-miR-155-5p, and hsa-miR-718, were identified using infinite combination signature search algorithm analysis from 25 patients in the discovery cohort undergoing IVF. These miRNAs were used as biomarkers in the validation cohort of 11 patients. Finally, the 3-miRNA signature was capable of predicting patients with RIF with an accuracy >90%. CONCLUSION(S): Our findings indicated that specific endometrial miRNAs can be applied as diagnostic biomarkers to predict RIF. Such information will definitely help to increase the success rate of implantation practice.

Is routine single-incision laparoscopic cholecystectomy feasible? A retrospective observational study.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) has been shown to be safe for uncomplicated gallbladder diseases. Routinely applying SILC is debatable. METHODS: Two hundred SILCs were performed with single-incision multiple-port longitudinal-array and self-camera techniques. RESULTS: Eighty-eight (44%) procedures were scheduled for complicated diseases. The routine group had a higher comorbidity rate, a lower preoperative endoscopic retrograde cholangiopancreatography rate, a higher intraoperative cholangiography rate, a higher proportion of complicated gallbladder diseases, shorter operative time, more intraoperative blood loss, and lower postoperative pethidine dose than the selective group (the first 73 patients). The conversion and complication rates showed no statistical difference. It took fewer cases but longer time to pass the learning phase of SILC for complicated gallbladder diseases. The multivariate analysis showed that male sex and complicated gallbladder diseases were associated with a higher procedure conversion rate, and increased patient age was related to a higher complication rate. CONCLUSIONS: Routine SILC for benign gallbladder diseases is feasible in the experienced phase. Practicing SILC for uncomplicated gallbladder diseases helps to achieve competence in this technique for complicated diseases.

Embryonic early-cleavage rate is decreased with aging in GnRH agonist but not inantagonist protocols.

PURPOSE: The aim of this study was to evaluate the correlation between embryonic early-cleavage status and the age of patients receiving either a GnRH agonist long protocol or a GnRH antagonist protocol. METHODS: This retrospective study included 534 patients undergoing a fresh cycle of oocyte retrieval and day-3 embryo transfer. Of the 534 patients treated, 331 received a GnRH agonist long stimulation protocol (GnRH agonist group) for ovarian stimulation and 203 patients received a GnRH antagonist protocol (GnRH antagonist group). RESULTS: By logistic regression analysis, the rate of embryonic early-cleavage was significantly decreased with increasing age of women in the agonist (P < 0.001) but not in antagonist groups (P = 0.61). Based on the results of this study, maternal age is a critical factor for embryonic early-cleavage in agonist protocol but not in antagonist protocol. The results also showed that early-cleavage embryos were of better quality and resulted in a higher pregnancy rate than late-cleavage embryos in the GnRH agonist group. However, embryo quality and pregnancy rate was not significantly different between early and late cleavage embryos in the GnRH antagonist group. CONCLUSIONS: We conclude that embryonic early-cleavage status is negatively correlated with aging in women receiving GnRH agonist long down-regulation but not in GnRH antagonist protocols. We also conclude that early cleavage of the zygote is not a reliable predictor for pregnancy potential using the GnRH antagonist protocol.

Early-cleavage is a reliable predictor for embryo implantation in the GnRH agonist protocols but not in the GnRH antagonist protocols.

BACKGROUND: To test if early-cleavage was a strong predictor of pregnancy in patients receiving either a GnRH agonist long protocol or a GnRH antagonist protocol for in-vitro fertilization treatment (IVF) and intracytoplasmic sperm injection (ICSI). METHODS: This retrospective study included 534 patients undergoing a fresh cycle of oocyte retrieval and the day-3 embryo transfer (from 22 to 46 years old). Of the 534 patients treated, 331 received a GnRH agonist long stimulation protocol (GnRH agonist group) for ovarian stimulation and 203 patients received a GnRH antagonist protocol (GnRH antagonist group). In each group, patients who had at least one early-cleavage embryo transferred were designated as the 'early-cleavage' subgroup. Patients who had no early-cleavage embryos transferred were designated as the 'late-cleavage' subgroup. RESULTS: The early cleavage rate was significantly lower in the GnRH antagonist group compared with that in the GnRH agonist group (IVF cycles: 34% versus 20%; ICSI cycles: 50% versus 37.8%, respectively, P < 0.0001). In the GnRH agonist group, the pregnancy rates were significantly higher in the early-cleavage subgroup than those in the late-cleavage subgroup (53.7% vs 33.9%, P < 0.0001). In the GnRH antagonist group, the pregnancy rates were not significantly different between the early-cleavage and late-cleavage subgroups (45.9% vs 43.8%, P > 0.05). CONCLUSION: Early cleavage of zygote is not a reliable predictor for embryo implantation potential in using the GnRH antagonist protocol. Furthermore, the implantation rates between the GnRH agonist and GnRH antagonist groups were comparable.

Early cleavage does not predict treatment outcome following the use of GnRH antagonists in women older than 35.

OBJECTIVE: To compare the early-cleavage rates and the implantation potential of embryos between the GnRH antagonist and agonist long stimulation protocols in women older than 35 years. DESIGN: Retrospective analysis. SETTING: Academic medical center. PATIENTS: Two hundred twenty patients older than 35 years old underwent IVF. INTERVENTION(S): Sixty-eight patients received GnRH antagonist protocol (GnRH antagonist group) and 152 patients received GnRH agonist long stimulation protocol (GnRH agonist group). MAIN OUTCOME MEASURE(S): Early-cleavage rate of zygotes, implantation rate, and pregnancy rate. RESULT(S): Early-cleavage rate of zygotes was significantly lower in the GnRH antagonist group than agonist group (21.8% vs. 32.6%, P<.0001). In the GnRH antagonist group, the pregnancy rate was not significantly different between the early-cleavage and late-cleavage subgroups (40.0% vs. 47.4%). In the GnRH agonist group, the pregnancy rate was significantly higher in the early-cleavage subgroup than in the late-cleavage subgroup (61.0% vs. 29.8%, P<.0001). CONCLUSION(S): In women older than 35 years, the early-cleavage rate of zygotes is significantly lower in the GnRH antagonist group than the agonist group. Early-cleavage status of zygotes is not a reliable predictor for embryo implantation in patients receiving the GnRH antagonist protocol.