LncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes.

Accumulating evidence has shown an abnormal expression of several non-coding RNAs in ovarian tissues which might be closely linked with the pathogenesis of PCOS. The aim of this study was to identify competing endogenous (ce) RNA network: long non-coding RNA (lncRNA), microRNA (miRNA) and their target genes: androgen receptor (AR), follistatin (FST) and insulin receptor substrate-2 (IRS-2), which are relevant to PCOS, to underline the molecular pathogenesis of PCOS and assist in early diagnosis and treatment. Bioinformatic analysis was performed to retrieve a ceRNA network: [lncRNA (NEAT1 and MALAT1) - miRNA (miR-30a-5p and miR-30d-5p) - mRNA (AR, FST and IRS-2)] linked to PCOS. Expression of the selected RNAs was examined by qPCR in peripheral blood leukocytes obtained from 73 PCOS patients (41 obese and 32 non-obese) and 31 healthy controls. PCOS patients showed significantly higher expression levels of NEAT1, miR-30a-5p, AR, FST and IRS-2, with significantly lower expression levels of MALAT1 and miR-30d-5p relative to controls especially in obese versus non-obese patients. Receiver operating characteristic (ROC) curve analysis indicated that most of the selected RNAs could serve as potential early diagnostic markers for PCOS with the highest efficiency obtained upon combining NEAT1 and miR-30d-5p or MALAT1 and miR-30a-5p with either of PCOS target genes. Moreover, all addressed RNAs had been proved as potential predictors of PCOS. The obtained data of ceRNA network raised the possibility that NEAT1 overexpression may increase the expression levels of AR, FST and IRS-2 by sponging miR-30d-5p, while low expression of MALAT1 may allow higher expression of the above genes via increasing miR-30a-5p, suggesting their involvement in PCOS pathogenesis and promising role for future diagnosis and targeted therapy.

Barbed sutures versus conventional sutures for uterine closure at cesarean section; a randomized controlled trial.

INTRODUCTION: The aim of this randomized control trial was to compare the operative data and the early postoperative outcomes of cesarean sections in which the uterine incision was closed with a barbed suture (STRATAFIX™ Spiral PDO Knotless Tissue Control Device, SXPD2B405, Ethicon Inc.) with those of cesarean sections in which the uterine incision was closed with a conventional smooth suture (VICRYL™; Ethicon Inc.). MATERIALS AND METHODS: One hundred pregnant patients were randomized in a 1:1 ratio to the Stratafix group or the Vicryl group. The uterine incision was closed by two layers of sutures in both groups. In the Vicryl group, the first layer was continuous and the second layer was interrupted. In the Stratafix group, both layers were continuous. RESULTS: The uterine closure time was significantly lower in the Stratafix group (224 ± 46 versus 343 ± 75 s, p < .001). Operative time was comparable between both groups. Twelve patients in the Vicryl group and two patients in the Stratafix group required additional sutures to achieve hemostasis (p value = .009). The mean blood loss during closure of uterine incision and mean hospital stay were lower in the Stratafix group but these differences failed to reach statistical significance. CONCLUSION: The use of barbed suture for uterine incision closure at cesarean section is associated with shorter uterine closure time and similar early perioperative complications compared with conventional smooth suture. The difference between both groups in the technique of suturing the second layer of the uterine incision may be the cause of the reduction in the uterine closure time and the need for additional sutures to achieve hemostasis during suturing the uterine incision with a barbed suture. Further, well designed randomized controlled trials should be conducted to investigate the association between the type of suture (barbed or conventional smooth) and remote complications of cesarean section (infertility, pelvic pain, abnormal placentation and rupture uterus).

Misoprostol Prior to Diagnostic Office Hysteroscopy in the Subgroup of Patients with No Risk Factors for Cervical Stenosis: A Randomized Double Blind Placebo-Controlled Trial.

AIMS: To assess the effectiveness of vaginal misoprostol in minimizing the pain perceived by patients with no risk factors for cervical stenosis (i.e., parous women of reproductive age who have no history of cesarean section or cervical surgery) during diagnostic office hysteroscopy. METHODS: A total of 100 patients with no risk factors for cervical stenosis were randomized to the misoprostol group (n = 50) or the placebo group (n = 50). In the misoprostol group, 2 misoprostol tablets (400 µg) were administered vaginally 12 h before office hysteroscopy. In the placebo group, 2 placebo tablets were administered. The patients rated the intensity of pain perceived during the procedure and at 30 min after the procedure with the use of a 100 mm visual analog scale (VAS). The hysteroscopists also scored the difficulty of hysteroscope insertion into the uterine cavity with the use of a 100 mm VAS. RESULTS: There were no significant differences between both groups in the VAS pain scores during or at 30 min after the procedure (28.3 ± 13.58 vs. 30.42 ± 15.13 and 11.1 ± 10.23 vs. 13.32 ± 11.12, respectively). The difficulty of hysteroscope insertion into the uterine cavity was comparable between both groups. CONCLUSION: Misoprostol administration prior to diagnostic office hysteroscopy appears to have no beneficial role in the subgroup of patients with no risk factors for cervical stenosis.

Misoprostol versus uterine straightening by bladder distension for pain relief in postmenopausal patients undergoing diagnostic office hysteroscopy: a randomised controlled non-inferiority trial.

OBJECTIVE: To compare the effectiveness of misoprostol with uterine straightening by bladder distension in minimising the pain experienced by postmenopausal patients during diagnostic office hysteroscopy. STUDY DESIGN: Seventy-six postmenopausal patients were randomly allocated in a 1:1 ratio to the misoprostol group or to the bladder distension group. Patients in the misoprostol group were instructed to insert two misoprostol tablets (400µg) in the vagina 12h before office hysteroscopy. Patients in the bladder distension group were instructed to drink one litre of water and to avoid urination during a period of 2h before office hysteroscopy. The severity of pain experienced by the patients during and at 30min after the procedure was measured using a 100-mm visual analogue scale (VAS). The ease of passing the hysteroscope through the cervical canal was assessed by the hysteroscopists using a 100-mm VAS. RESULTS: The passage of the hysteroscope through the cervical canal was easier in the misoprostol group [60.37±15.78 vs. 50.05±19.88, p=0.015]. The mean VAS pain score during the procedure was significantly lower in the misoprostol group [39.47±13.96 vs. 50.18±15.44, p=0.002]. The mean VAS pain score 30min post-procedure was comparable between both groups [11.82±3.71 vs. 12.61±4.06, p=0.379]. CONCLUSION: Vaginal misoprostol is more effective than uterine straightening by bladder distension in relieving the pain experienced by postmenopausal patients during office hysteroscopy. TRIAL REGISTRATION: Clinicaltrials.gov [NCT02328495]. https://clinicaltrials.gov/ct2/show/NCT02328495.

Barbed Versus Conventional Suture: A Randomized Trial for Suturing the Endometrioma Bed After Laparoscopic Excision of Ovarian Endometrioma.

OBJECTIVES: To determine whether the unidirectional knotless barbed suture can be used to control bleeding from the endometrioma bed after laparoscopic excision of ovarian endometrioma, and to detect whether the use of the unidirectional barbed suture is associated with shorter suturing time of the endometrioma bed compared with the continuous conventional smooth suture with intracorporeal knot tying. DESIGN: Randomized clinical trial (Canadian Task Force classification I). SETTING: Tertiary hospital. PATIENTS: Forty patients with unilateral ovarian endometrioma (mean diameter, 3-10 cm) were randomized in a 1:1 ratio to the barbed suture group or the conventional suture group. INTERVENTIONS: The endometrioma bed was sutured either with unidirectional barbed suture (V-Loc 180; Covidien, Mansfield, MA) or conventional suture (Vicryl; Ethicon, Somerville, NJ). Two layers of continuous sutures were used to control bleeding from the endometrioma bed and to reapproximate the ovarian edges. MEASUREMENTS AND MAIN RESULTS: The degree of suturing difficulty was evaluated by the surgeons using a visual analog scale (VAS) ranging from 1 (least difficult suturing) to 10 (most difficult suturing). Operating time and suturing time were significantly shorter in the barbed suture group (43.3 ± 10.54 vs 52.8 ± 9.69 minutes; p = .005 and 8.85 ± 2.52 vs 15.7 ± 4.12 minutes; p < .001, respectively). Suturing with barbed suture was less difficult than suturing with conventional suture (3.68 ± 1.37 vs 4.77 ± 1.56; p = .025). Intraoperative blood loss was similar in the 2 groups. No perioperative complications were reported in either group. A nonsignificant decrease in serum anti-mullerian hormone (AMH) levels was observed after the operation in the barbed suture group and the conventional suture group (3.04 ± 1.5 vs 2.52 ± 1.31 ng/mL; p = .252 and 2.76 ± 1.48 vs 2.13 ± 1.14 ng/mL; p = .139, respectively). The rate of decline in serum AMH levels after the operation was 18.32% in the barbed suture group and 22.84% in the conventional suture group. CONCLUSION: The unidirectional knotless barbed suture (V-Loc) facilitates suturing of the endometrioma bed after laparoscopic excision of ovarian endometrioma. Compared with conventional smooth suture (Vicryl), the unidirectional barbed suture reduces the time needed to suture the endometrioma bed and the total operating time.

Antagonist protocol versus clomiphene in unexplained infertility: A randomized controlled study.

OBJECTIVE: The primary purpose of this randomized controlled trial study was to compare clinical pregnancy rates and ovulation parameters in female patients of unexplained infertility undergoing intrauterine insemination (IUI) using an antagonist protocol versus a conventional clomiphene citrate protocol. MATERIALS AND METHODS: This was a multicenter parallel randomized controlled, open-label trial. A central randomization center used computer generated tables to allocate treatments. We conducted the study in two centers: Saudi Center and Samir Abbas and Assisted Reproductive Techniques Center of Cairo University, Cairo, Egypt between January 2011 and January 2014. Six hundred and twenty-two couples with unexplained infertility were randomized into two equal groups with 27 excluded after randomization: the antagonist protocol group and the clomiphene group. Antagonist protocol: human menopausal gonadotropins were given to 298 patients from Day 2 to reach a dominant follicle of 18-22 mm, intramuscularly. Then, orgalutrone (0.25 mg) was subcutaneously started from Day 6 or Day 7 until the day of human chorionic gonadotropins (hCG; that was given in the dose of 10,000 IU, intramuscularly) when follicles reached 18-22 mm. Afterward, the IUI of 0.5 mL was done from 34 hours to 36 hours using IUI catheter without guidance of ultrasonography and with an empty urinary bladder. The clomiphene citrate protocol was clomiphene citrate given 100 mg/d to 297 patients from Day 2 to Day 6 and follow up until day of hCG. The clinical pregnancy rate detected with ultrasound confirmed fetal heart pulsations at 6-weeks' gestation (4 weeks after IUI). The number of dominant follicles, level of serum estradiol, and luteinizing hormone at the day of hCG injection and the incidence of twin or triplet pregnancies in both groups were secondary outcome measures. RESULTS: The clinical pregnancy rate in the antagonist protocol group was significantly (p < 0.001) higher than in the clomiphene group. It was 80 patients (27%) in the antagonist protocol group versus 41 patients (14%) in the clomiphene group. The mean number of dominant follicles was significantly (p < 0.001) greater in the antagonist protocol group (4.36 ± 1.36 dominant follicles) compared with the clomiphene group (2.71 ± 0.96 dominant follicles). In addition, the rate of twin pregnancies was 15 cases in the antagonist protocol group versus six cases only in the clomiphene group (p = 0.047). The luteinizing hormone also was significantly lower in the antagonist group (2.1 ± 1.3) compared with that in the clomiphene group (9.5 ± 3.6). CONCLUSION: IUI clinical pregnancy rates were significantly higher by antagonist protocol.

GnRH antagonist rescue protocol combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS. METHODS: Two hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation. RESULTS: The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129-0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups. CONCLUSION: GnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS. TRIAL REGISTRATION: Clinical trial.gov ( NCT02461875 ).

Diclofenac plus lidocaine gel for pain relief during intrauterine device insertion. A randomized, double-blinded, placebo-controlled study.

OBJECTIVE: To determine the effectiveness of diclofenac potassium combined with 2% lidocaine gel in reducing the pain of intrauterine device (IUD) insertion. STUDY DESIGN: We randomized 90 parous women requesting copper T380A IUD insertion in a 1:1 ratio to active or placebo treatment. Active treatment included administration of two 50-mg diclofenac potassium tablets 1h before IUD insertion, application of 3mL of 2% lidocaine gel on the anterior cervical lip 3min before IUD insertion and placement of a cotton swab soaked in 2% lidocaine gel in the cervical canal 3min before IUD insertion. Women in the placebo group received placebo tablets and gel. Participants assessed pain intensity using a 10-cm visual analog scale (VAS). We considered a 2-cm difference in VAS pain score between both groups during IUD insertion to be a clinically significant difference. RESULTS: Subjects receiving active treatment, as compared to placebo, experienced less pain during tenaculum placement (1.66±0.85 vs. 2.33±1.19, p=.003) and IUD insertion (3.14±0.92 vs. 3.94±1.3, p=.001). Women who delivered only by cesarean section had higher pain scores with IUD insertion compared with women with previous vaginal deliveries (4.41±1.24 vs. 3.29±1.05, p=.001). CONCLUSION: Diclofenac potassium combined with 2% lidocaine gel slightly reduced pain scores during tenaculum application and copper IUD insertion in parous women; however, the reduction in pain scores lacked clinical significance. IMPLICATIONS: Although we found a statistically significant lowering of pain scores with pretreatment with diclofenac potassium and lidocaine gel in parous women having copper IUD placement, the reduction is not clinically relevant. These findings may be more relevant for nulliparous women who experience more pain than parous women with IUD insertion and support studies of diclofenac potassium and lidocaine gel in this population.

Hysteroscopic Myomectomy of Large Submucous Myomas in a 1-Step Procedure Using Multiple Slicing Sessions Technique.

OBJECTIVE: To evaluate the feasibility and efficacy of our technique for resectoscopic removal of large symptomatic submucous myomas. DESIGN: Prospective study (Canadian Task Force classification II-3). SETTING: A university teaching hospital and a private hospital. PATIENTS: Forty-nine patients with submucous myomas ≥ 4 cm in diameter complaining of abnormal uterine bleeding. Seventeen patients were also complaining of infertility. INTERVENTIONS: The intrauterine portion of submucous myomas was resected using the slicing technique. Slicing started at the site of the maximum bulge of the myoma and was continued down to the level of the endometrial surface. Each slicing session lasted for 5 to 10 minutes. After each slicing session, saline infusion was discontinued and restarted alternatively several times to induce rapid changes in the intrauterine pressure (hydromassage) to stimulate uterine contractions. The resectoscope was removed, and ovum forceps was used to extract the myoma fragments. Bimanual massage of the uterus was performed to induce extrusion of the intramural portion of the myoma into the uterine cavity. The same steps (slicing session lasting for 5-10 minutes to excise the portion of the myoma extruded into the uterine cavity, hydromassage, and uterine massage) were repeated several times until complete removal of the myoma. MEASUREMENTS AND MAIN RESULTS: The mean diameter of the principle myomas was 51.94 ± 5.58 mm. The rate of 1-step complete resection of myomas was 91.84% (45/49). Improvement of bleeding symptoms was observed in all patients with complete resection of myomas. Nine of the 17 infertile women conceived after hysteroscopic myomectomy. One-step complete resection of myomas was more frequent in patients with myomas < 6 cm (43/44 [97.73%] vs 2/5 [40%], risk ratio [RR] = 2.44, p = .002), single myomas (39/40 [97.5%] vs 6/9 [66.67%], RR = 1.46, p = .016), principle myomas with a Lasmar score < 7 (32/32 [100%] vs 13/17 [76.47%], RR = 1.31, p = .011), and myomas with less than 50% extension into the myometrium (26/26 [100%] vs 19/23 [82.61%], RR = 1.21, p = .042). The rate of 1-step complete removal of myomas was 95% (19/20) for type II myomas < 6 cm and 0% (0/3) for type II myomas ≥ 6 cm. CONCLUSION: Our technique of hysteroscopic myomectomy is a safe and effective management for submucous myomas up to 6 cm in diameter.

Ultrasound guided aspiration of hydrosalpinx fluid versus salpingectomy in the management of patients with ultrasound visible hydrosalpinx undergoing IVF-ET: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the efficacy of ultrasound guided aspiration of hydrosalpinx fluid at the time of oocyte retrieval with salpingectomy in the management of patients with ultrasound visible hydrosalpinx undergoing IVF-ET. METHODS: One hundred and sixty patients with ultrasound visible hydrosalpinx were randomized into salpingectomy group and aspiration group using computer generated randomization list and sequentially numbered sealed envelopes containing allocation information written on a card. RESULTS: The clinical pregnancy rate per started cycle and the implantation rate were non- significantly higher in the salpingectomy group compared with the aspiration group [40% vs. 27.5% (p value = 0.132) and 18.95% vs. 12.82% (p value =0.124), respectively]. In the aspiration group, 34.21% of patients had rapid re-accumulation of the hydrosalpinx fluid (i.e. within first two weeks after embryo transfer). Whereas, the clinical pregnancy rate per transfer cycle and the implantation rate were significantly higher in salpingectomy group compared with the subgroup of patients with rapid re-accumulation of hydrosalpinx fluid [42.67% vs. 19.23% (p value = 0.036) and 18.95% vs. 7.58% (p value = 0.032), respectively], no significant differences were detected between the salpingectomy group and the subgroup of patients with no re-accumulation of hydrosalpinx fluid (42.67% vs. 34% (p value = 0.356) and 18.95% vs. 15.5% (p value = 0.457), respectively). CONCLUSION: The small sample size could be the cause of failure of detecting significant increase in implantation and pregnancy rates in salpingectomy group compared with aspiration group. Further larger randomized controlled trials are needed to determine whether salpingectomy is more effective than aspiration of hydrosalpinx fluid or not. Moreover, the data presented in this study suggested that rapid re-accumulation of hydrosalpinx fluid is an obstacle against successful implantation and the cause of lower success rate with ultrasound guided aspiration of hydrosalpinx fluid compared with salpingectomy. TRIAL REGISTRATION: Clinical trials.gov ( NCT02008240 ), registered 8 December 2013.

Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.