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BackgroundThe success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation.MethodsWe did a multicentre, randomised controlled trial in eight hospitals in the UK, Belgium, Italy, and the Czech Republic. We recruited women younger than 38 years who had normal ultrasound of the uterine cavity and history of two to four unsuccessful IVF cycles. We used an independent web-based trial management system to randomly assign (1:1) women to receive outpatient hysteroscopy (hysteroscopy group) or no hysteroscopy (control group) in the month before starting a treatment cycle of IVF (with or without intracytoplasmic sperm injection). A computer-based algorithm minimised for key prognostic variables: age, body-mass index, basal follicle-stimulating hormone concentration, and the number of previous failed IVF cycles. The order of group assignment was masked to the researchers at the time of recruitment and randomisation. Embryologists involved in the embryo transfer were masked to group allocation, but physicians doing the procedure knew of group assignment and had hysteroscopy findings accessible. Participants were not masked to their group assignment. The primary outcome was the livebirth rate (proportion of women who had a live baby beyond 24 weeks of gestation) in the intention-to-treat population. The trial was registered with the ISRCTN Registry, ISRCTN35859078.FindingsBetween Jan 1, 2010, and Dec 31, 2013, we randomly assigned 350 women to the hysteroscopy group and 352 women to the control group. 102 (29%) of women in the hysteroscopy group had a livebirth after IVF compared with 102 (29%) women in the control group (risk ratio 1·0, 95% CI 0·79–1·25; p=0·96). No hysteroscopy-related adverse events were reported.InterpretationOutpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the livebirth rate. Further research into the effectiveness of surgical correction of specific uterine cavity abnormalities before IVF is warranted.FundingEuropean Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Study Objective To describe safety, tolerability, and effectiveness results through a minimum 2-year follow-up of patients who underwent permanent sterilization with the Essure insert. Design A retrospective multicenter study (Canadian Task Force classification II2). Setting Seven general hospitals and 4 clinical teaching centers in Italy. Patients A total of 1968 women, mean age 39.5 years (range, 23–48 years) who underwent office hysteroscopic sterilization using the Essure insert between April 1, 2003, and December 30, 2014. Intervention The women underwent office hysteroscopic bilateral Essure insert placement, with satisfactory device location and tube occlusion based on hysterosalpingography or hysterosalpingo-contrast sonography (HyCoSy). Measurements and Main Results Placement rate, successful bilateral tubal occlusion, perioperative adverse events, early postoperative (during the first 3 months of follow-up), and late complications were evaluated. Satisfactory insertion was accomplished in 97.2% of women and, in 4, perforation and 1 expulsion were detected during hysterosalpingography. Three unintended pregnancies occurred before the 3-month confirmation test. Two pregnancies were reported among women relying on the Essure inserts. Postprocedure pain was minimal and brief; in 9 women, pelvic pain became intractable, necessitating removal of the devices via laparoscopy. On telephone interviews, overall satisfaction was rated as “very satisfied” by the majority of women (97.6%), and no long-term adverse events were reported. Conclusion The findings from this extended Italian survey further support the effectiveness, tolerability, and satisfaction of Essure hysteroscopic sterilization when motivated women are selected and well informed of the potential risks of the device. Moreover, the results do not demonstrate an increased incidence of complications and pregnancies associated with long-term Essure use. Patients with a known hypersensitivity to nickel may be less suitable candidates for the Essure insert.

La crioconservazione del tessuto ovarico e una tecnica innovativa per preservare la fertilita delle giovani pazienti a rischio di insufficienza ovarica a causa di trattamenti oncostatici gonadotossici oppure per cause benigne quali patologie genetiche, autoimmuni od ovariche. Il tessuto ovarico crioconservato, dopo scongelamento, puo essere reimpiantato orto elo eterotopicamente oppure posto in coltura per ottenere la maturazione in vitro dei follicoli primordiali. Ad oggi nel mondo sono nati 17 bambini da ritrapianto ortotopico di tessuto ovarico. Il primo e unico caso di bambino nato con questa tecnica in Italia e stato recentemente ottenuto dalla nostra equipe.

Study Question Can endometrial mesenchymal stromal cells (E-MSCs) differentiate into endothelial cells in an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs)? Summary Answer E-MSCs can acquire endothelial markers and function in a direct co-culture system with HUVECs. What is Known Already E-MSCs have been identified in the human endometrium as well as in endometriotic lesions. E-MSCs appear to be involved in formation of the endometrial stromal vascular tissue and the support of tissue growth and vascularization. The use of anti-angiogenic drugs appears as a possible therapeutic strategy against endometriosis. Study Design, Size, Duration This is an in vitro study comprising patients receiving surgical treatment of ovarian endometriosis (n = 9). Participants/Materials, Setting, Methods E-MSCs were isolated from eutopic and ectopic endometrial tissue and were characterized for the expression of mesenchymal and endothelial markers by FACS analysis and Real-Time PCR. CD31 acquisition was evaluated by FACS analysis and immunofluorescence after a 48 h-direct co-culture with green fluorescent protein +-HUVECs. A tube-forming assay was set up in order to analyze the functional potential of their interaction. Finally, co-cultures were treated with the anti-angiogenic agent Cabergoline. Main Results and the Role of Chance A subpopulation of E-MSCs acquired CD31 expression and integrated into tube-like structures when directly in contact with HUVECs, as observed by both FACS analysis and immunofluorescence. The isolation of CD31+ E-MSCs revealed significant increases in CD31, vascular endothelial growth factor receptor 2, TEK receptor tyrosine kinase and vascular endothelial-Cadherin mRNA expression levels with respect to basal and to CD31neg cells (P < 0.05). On the other hand, the expression of mesenchymal genes such as c-Myc, Vimentin, neuronal-Cadherin and sushi domain containing 2 remained unchanged. Cabergoline treatment induced a significant reduction of the E-MSC angiogenic potential (P < 0.05 versus control). Large Scale Data Not applicable. Limitations, Reasons for Caution Further studies are necessary to investigate the cellular and molecular mechanisms underlying the endothelial cell differentiation. Wider Implications of the Findings E-MSCs may undergo endothelial differentiation, and be potentially involved in the development of endometriotic implants. Cell culture systems that more closely mimic the cellular complexity typical of endometriotic tissues in vivo are required to develop novel strategies for treatment. Study Funding/Competing Interest(s) This study was supported by the 'Research Fund ex-60%', University of Turin, Turin, Italy. All authors declare that their participation in the study did not involve actual or potential conflicts of interests.

Laparoscopic sacropexy (LSP) is associated with obstructed defecation syndrome (ODS) in 10-50% of cases. An anatomoclinical study was carried out to investigate whether there is any correlation between iatrogenic denervation during LSP and ODS.Five female cadavers were dissected to identify possible sites of nerve injury during LSP. Subsequently, the videos of 18 LSP were blindly reviewed to assess the location of sacral dissection and tacks, the position and depth of the peritoneal tunnel, and another 4 variables. An anatomical triangle was defined on the right lumbosacral spine so as to clearly describe the sites of the surgical variables, which were then statistically correlated with the patients' postoperative outcome.The only variable associated with postsurgical ODS was dissection in the 90° angle of the anatomical triangle, where the superior hypogastric plexus was observed in all cadavers.Medial and midline dissection over the sacral promontory might be associated with postoperative ODS.

Objective To describe a live birth obtained in Italy after autologous orthotopic transplantation of cryopreserved ovarian cortical tissue. Design Case report. Setting University department of gynecology and obstetrics, reproductive medicine and IVF unit. Patient(s) A 29-year-old patient affected by β-thalassemia (intermedia phenotype) who underwent chemotherapy and bone marrow transplantation at age 21 years, resulting in a complete precocious ovarian failure. Intervention(s) Before being treated with chemotherapy (busulfan, cyclophosphamide, and cyclosporine) for bone marrow transplantation, the patient underwent laparoscopic sampling of ovarian cortical tissue that was frozen and cryopreserved in liquid nitrogen. Eight years later, the ovarian tissue was thawed and grafted during laparoscopy at an orthotopic site. Main Outcome Measure(s) Ultrasound and endocrine monitoring of the postgrafting restoration of ovarian function; conception, pregnancy, and live birth. Result(s) Three months after grafting, the decrease of circulating FSH levels and the parallel increase of E 2 levels demonstrated ovarian function restoration, which was confirmed by bidimensional ultrasound and color Doppler examinations. After some ovulatory cycles, the patient spontaneously conceived 16 months after transplantation. After 39 weeks of uneventful gestation, a healthy girl weighing 3,970 g was born. Conclusion(s) Autologous grafting of cryopreserved ovarian cortex at an orthotopic site may allow ovarian function restoration, spontaneous conception, and birth of a healthy baby.

In order to estimate the impact of laparoscopic stripping of endometriomas on the ovarian follicular reserve, 43 normo-ovulatory women were studied by endocrine (anti-Mullerian hormone (AMH), FSH, LH, inhibin B, oestradiol) and ultrasonographic (antral follicle count (AFC)) methods before surgery, and 3 and 9 months after surgery. The operation was performed by experienced laparoscopists, particularly aware of the need to avoid damaging the healthy part of the ovary. Serum AMH concentrations significantly decreased after the operation (1.4±0.2 ng/ml after 3 months and 1.3±0.3 ng/ml after 9 months versus 3.0±0.4 ng/ml before surgery; P

Study Objective To evaluate the correlation between salpingoscopic and laparoscopic findings and their relation to reproductive outcomes. Design Prospective study (Canadian Task Force classification II-2). Setting University-affiliated hospital. Patients Ninety-one infertile women. Intervention Salpingoscopy and laparoscopy. Measurements and Main Results Salpingoscopic findings were expressed according to a widely used classification. Tubal morphology at laparoscopy was defined as regular (normal morphology), convoluted (any kind of distortion or adhesion), or hydrosalpinx. Laparoscopic and salpingoscopic findings did not correlate. Seventeen pregnancies occurred within 1 year from the procedures. According to life table analysis, the cumulative pregnancy rate was significantly higher in women with endotubal morphology showing minimal or no tubal damage, than in women with higher grades of endotubal damage. Conversely, tubal morphology at laparoscopy was not able to predict pregnancy outcome. Conclusion Laparoscopy alone might not be sufficient to predict tubal integrity. Performing salpingoscopy with laparoscopy could significantly increase accuracy in predicting short-term fertility outcome. Given its low complication rate and brief duration, salpingoscopy should have a primary role in management of infertility.

The role of laparoscopy as the gold standard for the diagnosis of pelvic endometriosis is questioned. An accurate histologic analysis fails to confirm the presence of endometriosis in a substantial proportion of patients diagnosed at laparoscopy.