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Objective: To optimize a method of isolating extracellular vesicles (EVs) from uterine fluid and to characterize small non-coding RNAs (sncRNAs) from the EVs, with the goal of identifying novel receptivity-associated biomarkers., Design: Longitudinal study comparing sncRNA expression profiles from endometrial EVs., Setting: University-affiliated, hospital-based fertility clinic., Patient(s): Healthy volunteers with no history of infertility (Group A) and women receiving controlled ovarian stimulation (COS)-in vitro fertilization treatment (Group B)., Interventions(s): In Group A, EVs were isolated from uterine fluid obtained on luteinizing hormone (LH)+2 and LH+7 in one natural menstrual cycle. In Group B, EVs were isolated from uterine fluid obtained on human chorionic gonadotropin (hCG)+2 and hCG+7 in one COS cycle. RNAs extracted from EVs were profiled using next-generation sequencing., Main Outcome Measure(s): Differential EV-sncRNAs between LH+2 and LH+7 (Group A), between hCG+2 and hCG+7 (Group B), and between pregnant and nonpregnant in vitro fertilization cycles (Group B)., Result(s): Ultracentrifugation was validated as the most efficient method to isolate EVs from uterine fluid. We identified 12 endometrial EV-sncRNAs (11 microRNAs and 1 piwi-interacting RNA) as receptivity-associated transcripts conserved in both natural and COS cycles. These sncRNAs were associated strongly with biological functions related to immune response, extracellular matrix, and cell junction. Within COS cycles, we also identified a group of EV-sncRNAs that exhibited differential expression in patients who conceived versus those who did not, with hsa-miR-362-3p most robustly overexpressed in the nonpregnant patients., Conclusion(s): This study is the first to profile comprehensively sncRNAs in endometrial EVs from uterine fluid and identify sncRNA biomarkers of endometrial receptivity and implantation success., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether a minimally invasive approach to sampling endometrial cells that can be applied during an active conception cycle can generate robust biomarker candidates for endometrial receptivity by genomewide gene expression profiling., Design: Longitudinal study comparing gene expression profiles of cells isolated from uterine aspirates collected during the prereceptive and receptive phases of a natural cycle., Setting: University-affiliated hospital., Patient(s): Healthy volunteers, ≤40 years of age, with regular menstrual cycles and no history of infertility., Intervention(s): One menstrual cycle monitored with urinary kits to identify the luteinizing hormone (LH) surge; uterine aspirations collected at LH + 2 days (LH + 2) and at LH + 7; endometrial biopsy obtained on LH + 7; RNA extraction from the cellular material for gene expression profiling, and differential gene expression validated by NanoString assay and cross-validated against a publically available data set., Main Outcome Measure(s): Differentially expressed genes between LH + 2 and LH + 7 samples., Result(s): NanoString assay validated 96% of the 245 genes found differentially expressed at LH + 7. Unsupervised hierarchical clustering of aspiration and biopsy samples demonstrated the concordance of the sampling methods. A predictor gene cassette derived by a shrunken centroid class prediction technique correctly classified the receptive phase within an external data set., Conclusion(s): Uterine aspiration, which can be performed during an active conception cycle, identified robust candidate biomarkers of endometrial receptivity, and will enable their validation by direct correlation with clinical outcomes., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the day 3 FSH/LH ratio as a predictor of prognosis in IVF cycles., Design: A retrospective cohort study., Setting: An academic hospital-based fertility center., Patient(s): Two hundred ninety-seven women younger than 40 years old with day 3 FSH levels or=2)., Main Outcome Measure(s): Pregnancy and cancellation rates., Result(s): One-third of patients had a day 3 FSH/LH ratio >or=2.0. Patients with an elevated FSH/LH ratio were more likely to have been placed on an aggressive protocol and had higher starting (257 vs. 232 IU) and total (2484 vs. 2136 IU) FSH doses. Patients with an elevated FSH/LH ratio were more likely to have their cycles cancelled before retrieval (19.6% vs. 8.5%). Although there was a trend toward lower pregnancy rates (24.7% vs. 33.5%), this result was not statistically significant. No clinical pregnancies occurred in 16 women with an FSH/LH ratio >or=3.5., Conclusion(s): An increased FSH/LH ratio of >or=2.0 was associated with poorer IVF cycle outcomes and higher rates of cycle cancellation.

Objective: Comparison of two transfer catheters in an IVF program., Design: Prospective, randomized clinical study., Setting: A private tertiary care center for ART., Patient(s): 66 patients < 38 years of age undergoing IVF and/or ICSI., Intervention(s): Patients were randomly assigned to undergo ET using the Tomcat catheter (n = 32) or the TDT catheter (n = 34)., Main Outcome Measure(s): Primary outcome measures were implantation and pregnancy rates. Secondary outcome measures were contamination with blood and/or mucus on the tip of the catheter, cramping or patient discomfort, and time required to complete ET., Result(s): Use of the Tomcat catheter resulted in significantly higher implantation (25.2% vs. 8.4%) and clinical pregnancy rates (47% vs. 14.7%) compared with the TDT catheter. All secondary outcome measures were similar for both catheters., Conclusion(s): The choice of ET catheter may affect the success of IVF-ET cycles. Use of the Tomcat catheter compared with the TDT catheter seems to result in significantly better efficiency of the ET procedure and is more cost effective.

Objective: To compare oocyte maturity, fertilization rate and cleavage rate after a short and long GnRH agonist (GnRH-a) stimulation protocol and intracytoplasmic sperm injection (ICSI)., Design: Retrospective study of 34 sequential ICSI cycles stimulated with a short or long GnRH-a protocol., Setting: A university-based tertiary care center for assisted reproductive treatment., Results: Significantly more oocytes were mature (metaphase II) after a long GnRH-a protocol then after a short GnRH-a protocol (25.6% and 80.8%, respectively). The long protocol resulted in more cleaving embryos (36/152 versus 9/132) and more cycles of ET (12/17 versus 5/17) than the short group., Conclusion: A greater percentage of mature oocytes results from ovarian stimulation with a long GnRH-a protocol than a short GnRH-a protocol. Maturity could be assessed accurately after cumulus stripping that is required before ICSI. Fertilization rate and cleavage rate with ICSI was superior after a long GnRH-a stimulation protocol for superovulation.

Objective: To explore the pulsatile-release characteristics of LH and P in women with premenstrual syndrome (PMS) compared with age-matched phase-matched controls., Design: Prospective, repeated measures, two-group study., Setting: Human volunteers in an academic research environment., Participants: Six women with rigorously defined prospectively determined PMS; six age-matched phase-matched controls., Main Outcome Measures: Frequency, amplitude, concentration, and coincident pulsatile release characteristics of LH and P at three symptom-related points of the luteal phase., Results: No significant between-group differences in frequency, amplitude, or concentration were found. In pooled data, significant coincident pulsing between LH and P was demonstrated. The length of time between LH and P pulses systematically increased across the luteal phase, a finding not previously reported. In the PMS group only, significant coincident pulsing occurred at an unexpected zero time lag on the symptom-onset sampling day., Conclusion: A progressively increasing coupling interval may reflect the gradual decline of the corpus luteum. Presence of a zero time lag between LH and P at symptom onset in women with PMS may indicate an aberrance in corpus luteum response to LH stimulation.

Objective: To assess the outcome of standard IVF treatment (nonmicromanipulated) with respect to total motile sperm number recovered by swim-up, particularly for couples with severe male factor infertility defined as total motile sperm number < 0.5 x 10(6)., Design: Retrospective study of patients who underwent successful oocyte retrieval in an IVF program from August 10, 1992 to December 31, 1993., Setting: A university-based tertiary referral center (The Toronto Hospital)., Patients: All cycles (n = 672) were divided into four groups according to total motile sperm number recovered using standard swim-up: group 1, total motile sperm number < or = 0.50 x 10(6); group 2, total motile sperm number between 0.51 and 1.00 x 10(6); group 3, total motile sperm number between 1.01 and 1.50 x 10(6); and group 4, total motile sperm number > or = 1.51 x 10(6). All patients received the same controlled ovarian hyperstimulation protocol, which consisted of a GnRH analog flare-up followed by parenteral menotropins. Clinical and cycle characteristics in the four groups were analyzed and outcome was evaluated., Results: There was no significant difference in clinical and cycle characteristics between the groups. The uniformity of the groups justified analysis of their outcome. A fertilization rate of 21.5% was achieved in couples with severe male factor (group 1). Fertilization rate and number of embryos transferred increased directly with the total motile sperm number. There was no significant difference in implantation rate per embryo between the groups., Conclusions: The results in couples with severe male factor infertility compare favorably with monospermic fertilization rates reported in the literature using partial zona dissection and subzonal insertion but is lower than with intracytoplasmic sperm injection. Therefore, we believe that couples with severe male factor infertility should be considered for standard IVF, as long as adequate total motile sperm can be recovered (100 x 10(3) per dish). If intracytoplasmic sperm injection is available, it should be offered to these couples.

Objective: To assess adhesion formation after laparoscopic ovarian cautery in women with polycystic ovarian syndrome (PCOS) and the efficacy of Interceed Adhesion Barrier (Ethicon, Summerville, NJ) in their prevention., Design: Prospective, randomized, blinded, clinical study of laparoscopic ovarian cautery with application of Interceed to one ovary, followed by short interval second-look laparoscopy, scoring of adhesions, and clinical follow-up., Setting: Tertiary care clinic at a University teaching hospital., Patients: Eight infertile women with PCOS who failed to conceive with previous clomiphene citrate (CC) therapy., Results: Periovarian adhesions of varying severity developed in all women after laparoscopic ovarian cautery. Interceed showed no protective effect. Despite this finding, all women initiated regular menses after laparoscopic ovarian cautery and seven of eight women spontaneously conceived eight singleton pregnancies without any further therapy., Conclusion: Laparoscopic ovarian cautery should be considered in infertile women with PCOS who fail to respond to CC therapy. These women must be counseled with respect to the possible complication of postoperative adhesion formation.