Ovarian 25OH-vitamin D production in young women affected by polycystic ovary syndrome.

INTRODUCTION: Vitamin D is involved in the regulatory mechanisms of ovarian function and is frequently low in PCOS patients. Since obesity and hyperinsulinemic state negatively influenced vitamin D levels, therefore, we evaluated the production of vitamin D at the ovarian level only in lean and normoinsulinemic PCOS subjects. Basal, GnRH analogue-induced ovarian production of 25OH-vitamin D (VitD) and a direct sampling at ovarian vein level were investigated. METHODS: Basal and GnRH analogue-induced hormone levels were evaluated at peripheral level in 45 subjects, aged 18-39 years, and in 22 healthy women with age- and BMI-matched as controls. In 12 PCOS patients, undergoing laparoscopy, a venous sampling at both peripheral and ovarian level was further done. All subjects presented low VitD levels, appropriate to the season and with no difference between PCOS and control subjects. RESULTS: GnRH analogue significantly stimulated plasma LH, FSH, 17-OHP and estradiol secretion (p from < 0.05 to < 0.001 vs basal levels), whereas no effect was observed on both serum AMH and VitD concentrations in all groups. A significant difference (p < 0.006), between peripheral and ovarian veins, was observed in both AMH and estradiol levels in PCOS subjects, while no gradient of VitD was detected. CONCLUSIONS: All patients presented with low VitD levels. The absence of any VitD variation, both at basal and after GnRH analogue administration, or at peripheral-ovarian vein gradient, suggests no pituitary-ovarian axis involvement in VitD production or its direct ovarian production in lean and normoinsulinemic PCOS subjects.

Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. OBJECTIVE: The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. SEARCH STRATEGY: Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. SELECTION CRITERIA: Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. DATA COLLECTION AND ANALYSIS: The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. MAIN RESULTS: Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. CONCLUSION: Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. TWEETABLE ABSTRACT: Pituitary block with GnRH antagonists does not improve the success of IUI cycles.

Uterine rupture in pregnancy: two case reports and review of literature.

Rupture of a gravid uterus is an obstetric emergency. Risks factors include a scarred uterus but also spontaneous rupture of an un- scarred uterus during pregnancy is possible. The authors present two cases of a spontaneous complete uterine rupture during pregnancy. The first case had only a past history of dilatation and curettage for abortion; the second case had a past history of dilatation and curettage for abortion and a monolateral laparoscopic salpingectomy for ectopic pregnancy. They presented with abdominal pain and after ultrasound scan, uterine ruptures were diagnosed. These cases show that there should be a high index of suspicious of uterine rupture in a gravid woman with a history of curettage for the possible presence of misunderstood uterine scar and in women with a past history of salpingectomy with or without corneal resection. Appropriate counseling and close follow-up might help to avoid such obstetrical catastrophes. To provide more insight into the possible risk factors for prelabor uterine rupture in pregnancy, a literature review was performed.

Management of bladder endometriosis with combined transurethral and laparoscopic approach. Follow-up of pain control, quality of life, and sexual function at 12 months after surgery.

To describe the pre-surgical and post-surgical outcomes at one year in terms of recurrence of lower urinary tract symptoms, quality of life, and sexual function of a transurethral and laparoscopic combined approach in the treatment of bladder endometriosis. The au- thors performed a prospective observational study of 16 women affected by symptomatic bladder endometriosis at the University Hos- pitals of Cagliari, Padua, and Foggia. In all patients bladder nodule was excised with a transurethral and laparoscopic combined approach technique. Intensity of lower urinary tract symptoms (VAS score) were assessed pre- and post-operatively at one, six, and 12 months after surgery; quality of life (SF-36) and sexual functions (FSFI) were collected preoperatively and one year postoperatively. Operative time was 120.18 ± 15.77 minutes and mean blood loss was 65.12 ± 44.74. No intraoperative and postoperative complications and conversion laparotomy occurred. Intensity of lower urinary tract symptoms evaluated with VAS score were significantly lower after one, six, and 12 months postsurgery vs. presurgery (p < 0.001). The authors observed a significantly improvement in the quality of life and sexual functions in all patients at one year after surgery. This surgical approach is safe and simple in the treatment of bladder en- dometriosis, with low risks and optimal resolution of symptoms, and improvement of quality of life and sexual function.

Sertoli-Leydig cell tumors: hormonal profile after dynamic test with GnRH analogue: triptorelin represents a useful tool to evaluate tumoral hyperandrogenism.

We report the case of a 15-year-old woman with signs of hyperandrogenism affected by a Sertoli-Leydig cell tumor (SLCT). In our patient, blood analysis showed a high testosterone (T) level (T: 8.53 nmol/L; nv < 1.87 nmol/L) while the GnRH-analogue test demonstrated an exaggerated secretion of 17-hydroxyprogesterone (OHP), T, and androstenedione (A) by the ovary after stimulation. We compared the GnRH-analogue test of our patient with that obtained in a group of normal and healthy women (no. 8 subjects, 16-26 years old), men (no. 4 subjects, 18-28 years old), and in a group of PCOS patients with age and body weight compared. We found in our patient a value of OHP, 17-beta estradiol (E2) and T, from 2 to 18 times higher than healthy women. When we compared our patient with healthy men, we differently observed a comparable response of T. The response of our patient was also comparable with that observed in the PCOS group for E2. During the post-surgical follow up, the GnRH-analogue test of our patient showed a response of OHP, T, and E2 comparable with that of the PCOS group. The GnRH-analogue test is a useful tool to characterize steroidogenesis in SLCT.

Predictors of malignancy in endometrial polyps: a multi-institutional cohort study.

PURPOSE OF INVESTIGATION: The risk of endometrial cancer in women with endometrial polyps (EPs) has been reported to vary between 0.3% and 4.8%. There is a lack of data about the management of asymptomatic women with incidental diagnosis of EPs. In the present study the authors correlated demographic and clinical characteristics with histopathological features of the EPs hysteroscopically removed. MATERIALS AND METHODS: An observational multi-institutional cohort study was conducted from February 2010 to December 2012 to identify all the premenopausal and postmenopausal women consecutively undergoing hysteroscopic polypectomy. The data of women were reviewed and clinical features were related to histopathologic results. RESULTS: The patients recruited were 813. The mean age was 52.5 years (range 22-87). The results showed a correlation between older age, high body mass index (BMI) and obesity, postmenopausal state, abnormal uterine bleeding (AUB), hypertension, and risk of malignant EPs. On multivariable analysis, the correlation remained only for age (OR 1.08, 95% CI 1.03 - 1.14) and AUB (OR 3.53, 95% CI 1.87 - 6.65). CONCLUSION: Older patients in postmenopausal status with AUB, a high BMI, and hypertension are at higher risk for premalignant and malignant polyps. In these patients a surgical approach should be used, consisting in hysteroscopical removing of the polyp.

Risk of recurrent menorrhagia after hydrothermoablation: role of GnRH analogues neoadjuvant treatment in long-term successful rate.

OBJECTIVE: To evaluate the long-term effectiveness of presurgical therapy with GnRH analogues in patients who underwenthydrothermal endometrial ablation (HTA) for menorrhagia and assess the relationship between sonographically measured myometrium thickness and pelvic pain. MATERIALS AND METHODS: A prospective randomized control study comparing 15 women (Group A) with presurgical subcutaneous triptorelin depot injection before HTA with controls (Group B, n = 15). Inclusion criteria were: recurrent menorrhagia, uterus length < 12 cm, no previous hormonal therapy for at least six month, and family plan completed. Student's t test was applied, as appropriate, to compare continuous variables. Proportion were compared with chi-squared. RESULTS: After 12 months of follow-up, Group A showed a significantly lower (0% vs 20%; p = 0.03) failure rate after hydrothermoablation than the Group B and a generally higher successful rate at 24 and 48 months. The discomfort, evaluated with VAS, showed a mean value of 47.6 +/- 15.9 +/- SD); 96.7% of women reported a mild-moderate postoperative pain. No perioperative and late complications were recorded. CONCLUSIONS: Presurgical treatment with GnRH analogues seems to improve long-term efficacy of HTA. Perioperative pelvic pain seems to not be affected by myometrium thickness.

Monopolar versus bipolar device: safety, feasibility, limits and perioperative complications in performing hysteroscopic myomectomy.

PURPOSE OF INVESTIGATION: The authors' aim is to compare surgical outcome of hysteroscopic G1 and G2 submucous myomectomy using bipolar resectoscope to those performed by monopolar device. MATERIALS AND METHODS: a multicenter-observational-case-control study was conducted on premenopausal women affected by menorrhagia, pelvic pain or infertility because of submucous uterine myoma. The authors considered eligible: single G1 or G2 submucous uterine myoma, at least 0.5 cm ultrasound 'myometrial-free-margin' and two months GnRH pre-surgical treatment (myoma > three cm). Goup A patients were treated b y bipolar resectoscope and Group B by monopolar resectoscope. Primary endpoint was to compare the groups in term of complete or incomplete myomas resection ("second-step-procedure" rate). Secondary endpoint was to compare two treatments in term of surgical time and intraoperative complications rate. RESULTS: Group A (60 patients) and Group B (216 patients) were homogeneous for general features and myomas location but they differed for G2 type prevalence (73.3% vs 50.5%), mean myomas diameter (33.17 +/- 11.93 vs 29.45 +/- 9.63), and surgical time (29.43 +/- 12.6 vs 23.2 +/- 8.2 minutes). In Group A patients both G1 and G2 myomas were completely removed in single step without intraoperative/postoperative complications; in Group B surgical outcomes of G1 myomas were similar to those of Group A, while G2 myomas required procedure termination in 12% of cases because of light electrolyte disturbance (22 cases) and severe iponatremia in four cases. All intraoperative complications occurred when procedure time exceeded 30 minutes and when myomas diameter was greater than 37.5 millimeters. CONCLUSION: in the era ofmini-invasive surgery, hysteroscopic approach by bipolar device should be considered as a useful, safe, and large scale feasible procedure for submucosal myoma treatment, particularly when G2.

Accuracy of hysteroscopy made by young residents in detecting endometrial pathologies in postmenopausal women.

PURPOSE OF INVESTIGATION: The aim of the study was to analyze the diagnostic value of hysteroscopy made by young residents in evaluating uterine cavity compared to experienced hysteroscopists with histological diagnosis as reference in postmenopausal women, with particular attention to endometrial hyperplasia and cancer. MATERIALS AND METHODS: A total of 600 postmenopausal women that underwent diagnostic hysteroscopy (DH) between January 2011 and December 2013 were evaluated. The authors compared the first 200 hysteroscopic findings of each young resident with those of seniors that supervised all the procedures, regarding the same patients. Subsequent histological evaluation was obtained by operative hysteroscopy or endometrial biopsy. Residents' and seniors' data were compared with the final histological diagnosis established by anatomopathologist. RESULTS: No adverse effects such as vaso-vagal reactions or uterine perforations in DH neither in operative hysteroscopic procedures were reported. Hysteroscopy made by residents had 60%, 9.09%, and 70.4% sensitivity (SE) and 97.1%, 98.8%, and 99.1% specificity (SP) in detecting hyperplasia without atypia, hyperplasia with atypia, and endometrial cancer, respectively. On the other hand, DH made by seniors resulted in 85%, 72.7%, and 96.3% SE and 99.8%, 99.8%, and 100% SP, in detecting the same three histological findings. CONCLUSION: Outpatient hysteroscopy made by residents at their endoscopic experience beginning has good accuracy in detecting clear endometrial malignant lesions, unlike in detecting premalignant lesion as hyperplasia with atypia. This could signify that more than 200 hysteroscopies are necessary for a resident to well recognize premalignant and malignant lesions.

Laparoscopic surgical staging of endometrial cancer: does obesity influence feasibility and perioperative outcome?

AIM: Laparoscopic treatment of early-stage endometrial cancer is the gold standard to reduce perioperative morbidity. Obesity is a well-known risk factor for endometrial cancer and anesthesiological and surgical complications. The authors' aim was to examine the effect of body mass index (BMI) on perioperative parameters and complications in laparoscopically-treated patients with endometrial cancer. MATERIALS AND METHODS: A consecutive series of patients affected by endometrial cancer and their demographic and clinicopathological data were collected. Patients were divided in 41 non-obese (BMI or= 30) groups. All patients had been preoperatively evaluated with hysteroscopic procedures and toraco-abdominal computed tomography (CT) and had been submitted to laparoscopic radical hysterectomy according to Querleu-Morrow, pelvic lymphadenectomy, peritoneal washing, and bilateral adnexectomy. RESULTS: There was no statistically significant difference in blood loss, number of lymph nodes removed, and hospital stay between the groups, but there was a trend towards a lengthening of surgical time in the obese women. There were no major intraoperative and postoperative complications. DISCUSSION: This study demonstrates that laparoscopic approach is feasible and safe in obese women evaluating the anesthesiological risk.

Morular endometrial metaplasia: review of the literature and proposal of the management.

PURPOSE OF INVESTIGATION: Morular endometrial metaplasia is a rare condition that can be often misdiagnosed and overtreated, because it can be mistaken for a malignant disease. The aim of this review was to update the current opinion on the significance of this pathology and its risk for potential malignancies. MATERIALS AND METHODS: The authors report their experience of two cases of morular metaplasia involving very young women managed conservatively with hysteroscopic resection of the affected areas. RESULTS: Hysteroscopic resection of these lesions can be an adequate and fertility-sparing treatment of morular metaplasia in women of childbearing age. CONCLUSIONS: Morular metaplasia has indeed a mutational origin but it is a benign and hormonally inert condition. The risk to develop cancer is closely associated with premalignant or malignant endometrioid glandular proliferations that are often associated with hysthological finding of morules rather than with morules themselves. Management of this condition requires trained pathologists and gynecologists and should be adapted to the age of the patient.

Evaluation of adhesions after laparoscopic myomectomy using the Harmonic Ace and the auto-crosslinked hyaluronan gel vs Ringer's lactate solution.

OBJECTIVE: To evaluate the efficacy of a crosslinked hyaluronic acid (HA) for the prevention of postsurgical adhesions after laparoscopic myomectomy using the Harmonic Ace. MATERIALS AND METHODS: Women 23-42 years of age who wished to conceive underwent laparoscopic myomectomy. As adhesion preventing agents, crosslinked HA gel was applied on the myometrial scar at the end of the surgery in Group A, whereas in Group B a Ringer's lactate solution was used in a prospective, observational study. Second-look mini-laparoscopy was performed 45-60 days after surgery and the adhesions were assessed according to a site-specific modified scoring. RESULTS: The incidence of postoperative adhesions was the same in both groups, but anatomically significant adhesions and site-specific modified score was significantly reduced in Group A compared to Group B control group (31.8% vs 54.6% and 1.05 +/- 1 vs 2.27 +/- 2.5, respectively). CONCLUSION: The use of auto-cross-linked HA gel confirms a protection on adhesion formation on myometrial wounds, although the degree of this effect appears to be weak. The absence of adnexa adhesions using the HA and a different uterine incision appear remarkable, although a larger number of patients is required to confirm the present findings.

Atypical endometrial lesions: hysteroscopic resection as an alternative to hysterectomy.

BACKGROUND: Endometrial hyperplasia is a precursor to endometrial carcinoma: the risk of progression to invasive endometrial cancer is increased in postmenopausal women and much more in cases of atypical endometrial hyperplasia (25%-30%). In addition, in 12.7% to 42.6% of cases according to various studies, endometrial cancer coexists in patients with diagnosis of atypical endometrial hyperplasia. The aim of this study was to evaluate the correlation between radical hysteroscopic resection of atypical endometrial lesions and the histopathological examination of the uterus. MATERIALS AND METHODS: The authors collected 25 patients referring to the Department of Woman and Child Health, in the University of Padua (Italy) from January 2008 to June 2012, undergoing hysteroscopic resection for atypical polyps and focal atypical endometrial hyperplasia, and following hysterectomy within 30 days. Average age, menopausal status, hormone replacement therapy, body mass index (BMI), presence of hypertension and diabetes, and taking tamoxifen were reported. RESULTS: After hysteroscopic resection in all patients atypical polyps and focal endometrial hyperplasia were confirmed. The hystopathologic evaluation of the uterus reported: in only two (8%) cases, the persistence of atypical endometrial lesion, whereas in 23 (92%) cases the endometrial tissue was negative for atypia or malignancy. CONCLUSIONS: Radical endometrial resection by hysteroscopy may serve as an alternative to hysterectomy in selected patients with atypical focal endometrial lesions, not only in fertile women, but also in patients who refuse hysterectomy or present high anesthesiologic and surgical risks, regardless of the risk of recurrence, and with the necessity of undergoing hysteroscopic close follow-up.

Steroid hormones and BDNF.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin abundantly expressed in several areas of the central nervous system (CNS) and is known to induce a lasting potentiation of synaptic efficacy, to enhance specific learning and memory processes. BDNF is one of the key molecules modulating brain plasticity and it affects cognitive deficit associated with aging and neurodegenerative disease. Several studies have shown an altered BDNF production and secretion in a variety of neurodegenerative diseases like Alzheimer's and Parkinson's diseases but also in mood disorders like depression, eating disorders and schizophrenia. Plasma BDNF is also a biomarker of impaired memory and general cognitive function in aging women. Gonadal steroids are involved in the regulation of several CNS processes, specifically mood, affective and cognitive functions during fertile life and reproductive aging. These observations lead many scientists to investigate a putative co-regulation between BDNF and gonadal and/or adrenal steroids and their relationship with gender difference in the incidence of mental diseases. This overview aims to summarize the current knowledge on the correlation between BDNF expression/function and both gonadal (progesterone, estrogens, and testosterone) and adrenal hormones (mainly cortisol and dehydroepiandrosterone (DHEA)) with relevance in clinical application.

Comparison between transvaginal sonography, saline contrast sonovaginography and magnetic resonance imaging in the diagnosis of posterior deep infiltrating endometriosis.

OBJECTIVE: To compare clinical evaluation, transvaginal sonography (TVS), saline contrast sonovaginography (SCSV) and magnetic resonance imaging (MRI) in the diagnosis of posterior deep pelvic endometriosis (DPE). METHODS: Women suspected of having posterior DPE on the basis of subjective symptoms and clinical evaluation underwent digital vaginal and rectal examination, TVS, SCSV and MRI. Laparoscopy was performed and specimens were sent for histological examination. Sensitivity, specificity, positive and negative predictive value, as well as positive and negative likelihood ratios were analyzed for each diagnostic method. RESULTS: Fifty-four out of 102 women suspected of having posterior DPE underwent laparoscopic surgery. Among these, in 46 (85.2%) cases DPE was confirmed at laparoscopic and histological examination. SCSV correctly identified 43 (93.5%) cases, presenting higher accuracy than did the other procedures. SCSV and MRI were more accurate in diagnosing and discriminating between the different locations of endometriotic lesions, with respective sensitivities of 94.7 and 73.1% for vaginal fornix, 88.9 and 66.7% for the uterosacral ligaments and 80.6 and 83.3% for involvement of the rectovaginal septum. The specificity of SCSV and MRI, respectively, was 97.1 and 94.3% for vaginal fornix, 95.6 and 95.6% for uterosacral ligaments and 100 and 77.8% for involvement of the rectovaginal septum. In the diagnosis of rectal endometriosis, we found a sensitivity of 66.7% for both techniques and specificity of 93.8% for SCSV and 95.8% for MRI. CONCLUSION: TVS should be used as the first-line diagnostic technique and SCSV and/or MRI as second-line methods in the diagnosis of posterior DPE.

Preterm premature rupture of membranes, chorioamnion inflammatory scores and neonatal respiratory outcome.

OBJECTIVE: To evaluate whether histological chorioamnionitis (HCA), in the setting of preterm premature rupture of membranes (PPROM), affects infant respiratory outcome. DESIGN: A prospective histological study on 287 consecutive placentas was performed in preterm infants (

Reduction of postoperative adhesions with an auto-crosslinked hyaluronan gel in gynaecological laparoscopic surgery: a blinded, controlled, randomized, multicentre study.

BACKGROUND: Following myomectomy, postoperative adhesions occur in many patients with adverse effects on fertility. This study investigated the applicability, safety and efficacy of an auto-crosslinked hyaluronan gel in preventing adhesion formation after laparoscopic myomectomy. METHODS: Fifty-two patients aged 22-42 years, undergoing surgery at four centres, were randomly allocated to receive either the gel or no adhesion prevention. The incidence and severity of postoperative adhesions were assessed laparoscopically after 12-14 weeks in a blinded, scored fashion. The primary efficacy variable was the presence/absence of postoperative adhesions at second-look. RESULTS: A nonsignificantly higher proportion of patients receiving the gel were free from adhesions (13 of 21; 62%) compared with control patients (9 of 22; 41%), with a statistically significant difference between the severity of uterine adhesions at baseline and at second-look (0.3 +/- 0.9 versus 0.8 +/- 1.0, P < 0.05). In subjects undergoing myomectomy without concomitant surgery, the proportion of adhesion-free patients was 8 of 12 (67%) and 4 of 11 (36%) (not significant) in the gel and control groups, respectively, with a significant difference in the mean severity scores (P < 0.05). In subjects without uterine adhesions before myomectomy, 12 of 18 (67%) and 8 of 20 (40%) patients in the gel and control groups, respectively were adhesion-free (not significant), with a significant difference in the severity of uterine adhesions (P = 0.05). CONCLUSIONS: Our results suggest that the auto-crosslinked hyaluronan gel may have a favourable safety profile and efficacious antiadhesive action following laparoscopic myomectomy.

Hysteroscopic permanent tubal sterilization using a nitinol-dacron intratubal device without anaesthesia in the outpatient setting: procedure feasibility and effectiveness.

BACKGROUND: Hysteroscopic permanent tubal sterilization has recently been introduced, resulting in a non-invasive, safe and effective technique. The aim of this study was to assess the feasibility of outpatient hysteroscopic tubal sterilization using a nitinol-dacron intratubal device without anaesthesia and to assess patient procedure compliance. MATERIALS AND METHODS: We untertook a prospective study of 36 consecutive cases of outpatient hysteroscopic tubal sterilization using a nitinol-dacron intratubal device without anaesthesia. Tubal sterilization was performed by placing the device with the aid of a 5.2-mm continuous-flow operative hysteroscope. At the end of the procedure women were asked to rate the pain experienced on a visual analogue scale (VAS) (0, no discomfort to 100, severe discomfort). Successful device placement was assessed after 3 months by hysterosalpingography and diagnostic hysteroscopy. RESULTS: Successful bilateral placement was obtained in 32 patients (88.9%); in one (2.8%) the placement was monolateral; and in three (8.3%) the procedure failed. Mean operating time was 8.6 +/- 5.3 min. A mean VAS of 36.1 +/- 23.9 was recorded. CONCLUSIONS: The nitinol-dacron intratubal device is safe, appears to be effective long-term, is non-invasive and can be used in the outpatient setting without anaesthesia. Low-level discomfort was experienced by the patients. Limitations of its use include that it is not effective immediately, it is irreversible, it requires special equipment and training, and it is difficult to use in cases of uterine anomalies. We conclude that this method may be offered to all woman asking for permanent tubal sterilization, particularly those who refuse or have contraindications for anaesthesia.