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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. [ABSTRACT FROM AUTHOR]

Objective: To study whether intrauterine application of auto-crosslinked polymers of hyaluronic acid (ACP) gel after dilation and curettage (D&C) improves reproductive outcomes.Design: Follow-up of a prospective randomized trial.Setting: University and university-affiliated teaching hospitals.Patient(s): Women with a miscarriage at <14 weeks' gestation with at least one previous D&C were randomized to D&C plus ACP gel (intervention) or D&C alone (control). A hysteroscopy was performed after 8-12 weeks, and if intrauterine adhesion (IUAs) were encountered, adhesiolysis was executed.Intervention(s): Participants received a questionnaire 30 months after treatment.Main Outcome Measure(s): Ongoing pregnancy and outcome of subsequent pregnancies.Result(s): Ongoing pregnancies were recorded in 74.6% (50/67) of the intervention group versus 67.2% (43/64) of the control group, and in, respectively, 94.3% (50/53) versus 71.7% (43/60) in the women wishing to conceive. The median times to conception leading to a live birth were, respectively, 21.9 versus 36.1 months. Reduced menstrual blood loss was reported in 7.5% (5/67) versus 20.3% (13/64) and dysmenorrhea in 14.9% (10/67) versus 34.4% (22/64), respectively.Conclusion(s): Application of ACP gel following D&C performed after miscarriage seems to have a favorable effect on subsequent reproductive outcomes in women with at least one previous D&C. Given the fact that the study was not powered for reproductive outcomes, the data should be interpreted with caution. The effect may be underestimated due to routine removal of IUAs.Dutch Clinical Trial Registry Number: NTR 3120. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate a unique presentation and surgical treatment of a posterior uteroperitoneal fistula with excision of the fistula tract and repair in multiple layers.Design: Illustrative video presentation. A case report is used to describe potential causes of an uteroperitoneal fistula found in a patient during evaluation of secondary infertility and to highlight surgical technique and management using the principles of fistula repair through a minimally invasive approach. The Institutional Review Board reviewed this video article and it was deemed "not human subject research."Setting: Tertiary medical center.Patient(s): A 33-year-old G1P1001 woman with a history of a cesarean section presented with secondary infertility, pelvic pain, and dysmenorrhea and was found to have a posterior uteroperitoneal fistula at the time of hysterosalpingography.Intervention(s): The patient underwent an uncomplicated robot-assisted laparoscopic excision of a posterior uteroperitoneal fistula with the use of careful dissection of the fistula tract, continuous reassessment, and tension-free closure in layers.Main Outcome Measure(s): Preoperative diagnosis and surgical management displaying intraoperative techniques for robot-assisted excision of fistula tract and repair of defect.Result(s): The patient underwent robot-assisted operative laparoscopy that revealed a 4-cm mass on the right posterior aspect of the uterus independent from her adnexa. Concomitant hysteroscopy revealed normal endometrium without an evident fistula. During chromopertubation, extravasation was seen into the peritoneal cavity from this mass. The mass and fistula tract were excised without a connection found from her cesarean scar, and reconstruction was performed in multiple layers. Endometriotic lesions were noted intraperitoneally in locations distant from the mass. The patient had significant improvement in her symptoms after surgery.Conclusion(s): We present a unique case of a suspected spontaneous posterior uteroperitoneal fistula in the presence of endometriosis without evidence of a connection to her prior hysterotomy scar. Possible etiologies include an undiagnosed, unrepaired hysterotomy extension or a result of chronic inflammation from deep infiltrating endometriosis. Adverse effects on fertility from uteroperitoneal fistulas may be due to disruption of sperm function or endometrial quality secondary to presence of old blood products sequestered in the fistula or due to resultant inflammation from the same. As in this video case, successful treatment of symptoms resulting from an uteroperitoneal fistula requires removal of the fistula tract. The constellation of pelvic pain, dysmenorrhea, postmenstrual bleeding, and infertility should raise suspicion for an uteroperitoneal fistula. [ABSTRACT FROM AUTHOR]

Objective: To assess the international agreement on the hysteroscopic diagnosis of septate uterus. Design: Interobserver study. Setting: Eight hysteroscopy recordings were put online on the website of the European Society of Gynaecological Endoscopy. Patient(s): Asymptomatic, infertile women indicated for a first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycle. Intervention(s): Office hysteroscopy. Main Outcome Measure(s): The interobserver agreement on the uterine shape and necessity to correct the abnormality found. Result(s): Seventy-eight observers from 24 different countries assessed 8 hysteroscopy recordings. The interobserver agreement on uterine shape variations septate and arcuate was fair (intraclass correlation coefficient = 0.27). Observers from the same country reached a significantly higher level of agreement. The agreement on the necessity of correction was poor (intraclass correlation coefficient = 0.17). The most distinct features for diagnosing a septate uterus judged to be the extent of endocavitary bulging and the angle of the bulging structure from the fundal area. Conclusion(s): The agreement among international experts on the hysteroscopic diagnosis of the septate uterus was found to be poor. This may have implications for the accuracy of screening hysteroscopy for diagnosing uterine cavity abnormalities in infertile patients. Development of consented definitions for the hysteroscopic diagnosis of septate and arcuate uterus is recommended. [ABSTRACT FROM AUTHOR]

Objective: To identify potential novel biomarkers that differ between subjects with and without endometriosis and that might aid in developing a noninvasive, serum-based diagnostic test.Design: Case-control evaluation of a diagnostic test.Setting: University medical center.Patient(s): Consenting women of reproductive age undergoing laparoscopy for indications of pain, infertility, elective tubal ligation, tubal reanastomosis, or other benign indication.Intervention(s): Diagnostic laparoscopy and peripheral venipuncture.Main Outcome Measure(s): Concentrations of low-molecular-weight proteins in serum; surgical staging of endometriosis.Result(s): Six proteins were found that were differentially expressed between those with and without disease and that had good diagnostic properties. Taken together in a two-step diagnostic algorithm, we were able to diagnose 55% of subjects, with 99% accuracy as to the status of disease. Further combining this algorithm with that derived by our previous study of serum putative markers (monocyte chemoattractant protein-1, migration inhibitory factor, leptin, and CA-125) improved our diagnostic capability to 73% of subjects, with 94% overall accuracy.Conclusion(s): This study is the critical first step in the identification of potential novel biomarkers of endometriosis. Future identification of the proteins and further validation in a second population is needed before applying these findings in clinical practice. [ABSTRACT FROM AUTHOR]

: ObjectiveTo assess the reliability, feasibility, and safety of lens-based minihysteroscopy.: DesignRetrospective comparative study.: SettingAcademic research environment.: Patient(s)Women with different indications for hysteroscopy.: Intervention(s)Six thousand seventeen outpatient diagnostic hysteroscopies with a minihysteroscope (2.7-mm outer diameter [OD] telescope with 3.5-mm OD single-flow diagnostic sheath) and 4,204 with traditional hysteroscope (4-mm OD telescope with 5-mm OD single-flow diagnostic sheath). All hysteroscopies were performed using a vaginoscopic approach and saline to distend the uterus.: Main outcome measure(s)Rate of successful introduction of the hysteroscope, rate of satisfactory examinations, pain intensity experienced using an arbitrary pain scale (0 = no pain; 1 = low pain; 2 = moderate pain; 3 = severe pain), and number of side effects and complications.: Result(s)In the minihysteroscopy, group rates of successful introduction and satisfactory examinations were significantly higher than in the traditional hysteroscope group (99.52% vs.72.53% and 98.53% vs. 92.33%, respectively), while pain and vagal reactions were significantly lower (0.10 ± 0.34 vs.1.09 ± 0.53 and 2.25% vs.17.12%, respectively).: Conclusion(s)Hysteroscopy with lens-based minihysteroscopes was easier, less painful, more reliable, and safer than with 5-mm hysteroscopes. Minihysteroscopy with a vaginoscopic approach is a very well tolerated, effective, and safe outpatient procedure. [Copyright &y& Elsevier]

Objective: To study the value of virtual hysterosalpingography (VHSG) in the diagnosis of bicornuate vs. septate uterus. Design: Retrospective study of all cases with bicornuate or septate uterus that had VHSG during the last 3 years at our center. Setting: Private fertility center and radiology institute with university affiliations. Patient(s): A total of 47 patients (from more than 1,000 studies) with bicornuate uterus (n = 15) or septate uterus (n = 32) were analyzed to determine the ability of VHSG to distinguish both entities. Intervention(s): Virtual hysterosalpingography was performed in patients with bicornuate or septate uterus. Main Outcome Measure(s): Procedure length, discomfort, amount of radiation, and ability to outline the uterine fundus. Result(s): We were able to clearly distinguish bicornuate from septate uterus. In all patients who underwent septoplasty the VHSG diagnosis of septate uterus was confirmed. Virtual hysterosalpingography was well tolerated by all patients; scanning took 5 seconds per patient, and the average radiation was very low (0.9 ± 0.7 mSv). Conclusion(s): Virtual hysterosalpingography seems to be a valuable tool in the diagnosis of common uterine anomalies. [ABSTRACT FROM AUTHOR]

Based on a recent review of the medical literature, a clinical diagnosis of infertility may not agree with strict criteria. Standardized definitions of diagnostic categories are essential for accurate patient prognosis and future research. [Copyright &y& Elsevier]

Objective: To examine the long-term complications and reproductive outcomes after the management of retained products of conception (RPOC).Design: Systematic review.Setting: Not applicable.Patient(s): Women suspected of RPOC who were subjected to medical therapy with misoprostol or surgical treatment.Intervention(s): An electronic literature search was conducted in June 2015 using MEDLINE, EMBASE, and the Cochrane library. We included clinical trials in which women were consecutively included, independent of their symptoms.Main Outcome Measure(s): The prevalence of intrauterine adhesions (IUAs) and reproductive outcomes.Result(s): No studies reporting on IUAs or reproductive indicators after medical management with misoprostol were found. We included 10 cohort studies with poor to average methodological quality. Five cohort studies (n = 339) reported IUAs in 22.4% (95% confidence interval, 18.3%-27%) of women hysteroscopically evaluated. Significantly more IUAs were encountered after dilation and curettage (D&C) compared with after hysteroscopic resection (HR): 30% vs. 13%. Incomplete evacuation was encountered in, respectively, 29% and 1% of the D&C and HR cases. Similar conception, ongoing pregnancy, live-birth, and miscarriage rates were reported after D&C and HR in six cohort studies (n = 380), and there was a tendency toward earlier conception after HR. The reproductive outcomes were not reported in relation to IUAs.Conclusion(s): HR may be a preferable surgical treatment in women suspected of RPOC; fewer IUAs and incomplete evacuations are encountered, while similar reproductive outcomes were reported compared with D&C. Confirmation of the observed effects is required, and trials evaluating medical treatment with misoprostol as well as expectant management are urgently needed. [ABSTRACT FROM AUTHOR]

Objective: To study the success rate of hysteroscopic adhesiolysis and the spontaneous recurrence rate of intrauterine adhesions (IUAs) in patients with Asherman syndrome.Design: Cohort study.Setting: University-affiliated hospitals.Patient(s): A total of 638 women with Asherman syndrome were included, all diagnosed using hysteroscopy, and operated on between 2003 and 2013.Intervention(s): Hysteroscopic adhesiolysis.Main Outcome Measure(s): Hysteroscopic adhesiolysis was classified as successful if a normalization of menstrual blood flow occurred, along with a restored, healthy, cavity anatomy, free of adhesions, with hysteroscopic visualization of ≥ 1 tubal ostium. Recurrences of adhesions were diagnosed using hysteroscopy after an initial successful procedure.Result(s): A first-trimester procedure preceded Asherman syndrome in 371 women (58.2%) and caused adhesions of grades 1-2A. In 243 (38.1%) women, a postpartum procedure caused IUAs of grades 3-5. The procedure was successful in 606 women (95%), and restoration of menstrual blood flow occurred in 97.8%; IUAs spontaneously recurred in 174 (27.3%) of these cases. High grades of adhesions were predictive of a higher chance of spontaneous recurrence of adhesions.Conclusion(s): In 95% of women with Asherman syndrome, a healthy uterine cavity was restored with hysteroscopic adhesiolysis, in 1-3 attempts, with a 28.7% recurrence rate of spontaneous IUAs. [ABSTRACT FROM AUTHOR]