Surgery For Benign Gynaecological Conditions Research Articles

Distribution of endometriosis phenotypes according to patients' age in adult women with surgical evaluation.

What is the distribution of endometriosis phenotypes according to age in adult women undergoing surgery? The phenotype of endometriosis did not significantly vary after 24 years old. The phenotypic evolution of endometriosis over time remains unclear. While adolescents can exhibit any type of endometriosis lesions, ovarian endometriosis (OMA) and/or deep-infiltrating endometriosis (DIE) tend to increase with age in young adults. In adulthood, understanding the evolution of lesions is crucial for disease management, but the literature on this subject is limited. This study aims to examine the distribution of endometriosis phenotypes in relation to age among adult patients requiring surgical treatment. This observational cohort study included patients aged between ≥18 and ≤42 years, who underwent surgery for benign gynecological conditions at our institution between January 2004 and December 2022. A standardized questionnaire was completed for each patient during a face-to-face interview conducted by the surgeon in the month preceding surgery. Women with histologically proven endometriosis were included. The distribution of endometriosis phenotypes (isolated superficial (SUP) endometriosis, OMA ± SUP, DIE ± SUP/OMA) was compared between young adults (≤24 years) and adults (>24 years) and among adults (25-28 years, 29-33 years, 34-38 years, 39 to ≤42 years) using univariate and multivariate analysis. The distribution of different subtypes of DIE (uterosacral ligament(s), vagina, bladder, intestine, and ureter), OMA size, and intensity of pain symptoms were also examined. A total of 1311 adult women with histologically proven endometriosis were included. In women aged 24 years or younger (n = 116), the distribution of endometriosis phenotypes differed significantly from women older than 24 years (n = 1195): The frequency of the DIE ± SUP/OMA phenotype was lower (41.4% versus 56.1%, respectively), while the rate of isolated superficial lesions was higher (from 32.0% versus 25.9%) (P = 0.001). In the group of women aged >24 years, a significantly higher proportion of vaginal DIE lesions (P = 0.012) and a lower proportion of uterosacral ligament DIE lesions (P = 0.004) were found compared to women aged ≤24years. No significant differences were observed in terms of endometrioma size. Between the ages of 25 and 42years, there were no significant changes in the distribution of endometriosis phenotypes after univariate and multivariate analysis. The distribution of subtype of DIE lesions did not significantly change with age between 25 and 42 years. Concerning pain symptom scores, there was a significant decrease with age for dysmenorrhea and dyspareunia. Inclusion of only surgical patients may have introduced a selection bias. Women referred to our center may have suffered from particularly severe clinical forms of endometriosis. This study highlights that endometriosis presentation did not change with age in adult women. Further research on endometriosis phenotype evolution is necessary to assist practitioners in clinical decisions and treatment strategies. None declared. N/A.

Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer.

Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage, and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.

Alterations in mitochondria isolated from peripheral blood mononuclear cells and tumors of patients with epithelial ovarian cancers

Metabolic alterations play an essential role in ovarian carcinogenesis. The flexibility of mitochondrial functions facilitates cellular adaptation to the tough environment associated with carcinogenesis. An understanding of the differences in mitochondrial functions in normal ovaries and cancers could provide a basis for further exploration of future mitochondria-based screening, diagnosis, prognostic prediction, and targeted therapy for epithelial ovarian cancers. The main objective of this study was to assess mitochondrial function profiles measured from PBMCs and ovarian tissues of epithelial ovarian cancers in comparison with normal ovaries. A total of 36 patients were recruited for the study, all of whom underwent primary surgical treatment for malignant epithelial ovarian neoplasm. Of these, 20 patients were in the early stage and 16 patients were in the advanced stage. Additionally, 21 patients who had pelvic surgery for benign gynecologic conditions, with normal ovaries incidentally removed, were recruited as controls. At the time of surgery, a blood sample was collected from each participant for PBMC isolation, and ovarian tissue was retained for molecular studies. These studies included the examination of oxidative stress, mitochondrial mass, mitochondrial respiration, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes, and mitochondrial swelling. Clinical and histopathological data were also collected and compared between different stages of epithelial ovarian cancers: early-stage (group 1), advanced-stage (group 2), and normal ovaries (group 3). The levels of cellular oxidative stress, mitochondrial mass, and mitochondrial biogenesis in the peripheral blood mononuclear cells (PBMCs) of participants with ovarian cancer were significantly lower than those of the control group. However, the mitochondrial respiratory parameters measured from the PBMCs were similar across all three groups. Furthermore, mitochondrial membrane depolarization and mitochondrial swelling were observed in ovarian tissues of both early-stage and advanced-stage cancer groups. We demonstrated the dynamic nature of mitochondrial ROS production, biogenesis, and respiratory function in response to epithelial ovarian carcinogenesis. The flexibility of mitochondrial functions under diverse conditions may make it a challenging therapeutic target for ovarian cancer.

Single centre experience in India for benign gynecological robotic surgery with da Vinci Si system: A real world data analysis of one decade

Objective: To analyse real time data over a decade of robotic surgery for benign Gynecological conditions using the da Vinci Si system.Methods: This is a retrospective analysis of prospectively collected data of da Vinci Si robotic surgery between August 2012 and July 2021 at single medical centre by a single surgeon.Results: Of the total 452 cases, the procedures were broadly categorised into myomectomy (RM-204), hysterectomy (RH-150), endometriosis excision (RE-80). The mean age of 46.12±6.77 and the mean BMI 28.89±5.02 kg/m2 in RH group was higher in RH group when compared to RM and RE groups. The mean docking time over 10 years was 10.59 minutes and mean console time was 96.35±47.77 minutes and both were significantly lower in the last 5 years when compared to first 5 years. 49.9% patients did not require intravenous analgesics beyond 24 hours and only 7.2% needed beyond 48 hours. 44.7% had less than 24 hours of hospital stay and 1.1% stayed beyond 48 hours. The mean hemoglobin drop was 1.109±0.7531 g%, significantly higher in RM group. The mean specimen weight in RM group was 323.8 g (200–1,372 g) and 84 cases had multiple leiomyomas. The commonest indication of robotic surgery was fibroid uterus.Conclusion: Robotic surgery for benign gynecologic surgery feasible and safe. It has equivalent outcomes when compared to laparoscopic surgery and superior when compared with laparotomy. Using robots to reduce open and repeat surgery for injury corrections could translate to reductions in the over-all economic burden of treatment.

A Double-blinded, Randomized, Placebo-controlled Trial of Antibiotic Prophylaxis in Elective Non-hysterectomy Laparoscopic Surgery for Benign Gynecologic Conditions: A Pilot Study

To determine the feasibility of a double-blinded randomized, placebo-controlled study in determining the efficacy of antibiotic prophylaxis in preventing postoperative infections (POIs) in elective nonhysterectomy laparoscopic procedures for benign gynecologic conditions. Double-blinded, randomized, placebo-controlled trial. University-affiliated tertiary referral hospital in Sydney, Australia. Women older than 18 years undergoing elective nonhysterectomy laparoscopic procedures for benign gynecologic conditions were eligible for the study and approached. Before surgery, participants were randomized to receive either 2-g cephazolin or placebo (10-mL normal saline) administered by the anesthetist. Participants and other research staff were blinded to group allocation. The primary outcome was study feasibility measured by recruitment rates, compliance rates of drug administration, compliance rates of delivery, maintenance of double blinding, and follow-up rates. Secondary outcomes included rate of POIs, length of hospitalization, readmission to hospital, unscheduled presentations to healthcare facilities, and antibiotic-related reactions. Between February 2019 and March 2021, 170 patients were approached with 117 participants (68.8%) recruited and randomized. The study had a high compliance rate of trial drug delivery (95.7%) and a high follow-up rate (99.1%). This pilot study has demonstrated feasibility of a large-scale study with a recruitment rate of 68% of patients approached and excellent trial drug delivery and follow-up rates. As anticipated, it is underpowered for identifying clinically significant findings for POI rates. A large-scale study is appropriate and essential to determine the health-related risks of antibiotic prophylaxis with an emphasis on antimicrobial stewardship. The sample size for a large-scale study is 1678 participants based on infection rates in this pilot study.

Mental health in women undergoing gynecological surgery at risk of infertility

Surgery for benign gynecologic conditions may lead to infertility complications. In a cross-sectional study we investigated depressive and anxiety symptoms, Quality of Life (QoL), and coping strategies in women with benign gynecologic conditions undergoing surgical treatment (G1, N = 45) compared with women that did not need surgery (G2, N = 43), through the Patient’s Health Questionnaire, the Short Form Health Survey-12 items, the Self-Rating Anxiety State, and the Brief COPE. Statistical analyses showed that women in G1 had significant higher depressive (p=.04) and anxiety (p=.03) symptoms, and lower QoL (p=.01), than did those in G2. Moreover, women with more depressive or anxiety symptoms in both groups were more likely to present maladaptive coping modalities. A careful evaluation of the mental health of women undergoing gynecological surgery at risk of infertility should be included in the care for benign gynecologic conditions, in order to prevent psychosocial distress and alleviate the burden on QoL.

Residents' Participation in Robotic Surgery and Operative Time: Does Attending Surgeons’ Volume Influence This Relationship?

Objective: This research assessed if attending surgical volume impacted the relationship between resident participation and operative time in robotic surgery for benign gynecologic conditions. Mate...

Peritoneal HPV-DNA test in cervical cancer (PIONEER study): A proof of concept.

The aim of this study was to investigate the prevalence of peritoneal human papillomavirus (HPV) infection in different clinical cervical cancer (CC) settings, and its association with potential clinical and/or histological factors. This is a single-center, prospective, observational study. Consecutive patients with newly diagnosed or recurrent/persistent CC, between March 2019 and April 2020, were included. A group of patients undergoing surgery for benign gynecological conditions was included as control group. All patients underwent HPV-DNA test in the cervix and in the peritoneal cavity simultaneously at time of surgery. Two-hundred seventy-two patients had cervical and peritoneal HPV test analyzed. Cervical and peritoneal HPV positivity (PHP) was found in 235 (88.0%) and 78 (28.7%) patients, respectively; the prevalence of PHP was 17.7% in early stage, 28.8% in locally advanced cervical cancer (LACC) and 46.6% in the metastatic/persistent/recurrent setting (P = .001). No control patient was found to have peritoneal HPV infection. Higher frequency of PHP was documented in patients with larger tumor size (P = .003), presence of cervical HPV 16/18 genotypes (P < .001), higher number of cervical high-risk (HR)-HPV per patient (P = .018) and peritoneal carcinomatosis (P < .001). Multivariate analysis demonstrated that lack of preoperative cervical conization in early stages (P = .030), while higher International Federation of Gynecology and Obstetrics (FIGO) stage (P = .021) and presence of cervical HPV 16/18 (P = .001) in LACC, was associated with PHP. This is a proof-of-concept study. A number of potential clinical implications, including prognosis, could be obtained by further studies.

The frequency of endometriosis in the general and selected populations: A systematic review

Background: In this article, we have reviewed available data on the frequency of endometriosis considering separately the incidence and the prevalence of the disease using data from papers published from 2000 to June 2019. Study design: Systematic review and meta-analysis. PubMed and EMBASE were searched for observational studies reporting data on the incidence or prevalence rates or ratios for the following pre-specified populations: general population, infertile women, women reporting pelvic pain, women who underwent pelvic surgical procedures unrelated with endometriosis. Results: A total of 42 papers were included in this review. Considering the 11 studies that have analysed the prevalence of endometriosis in the general population, the reported prevalence ranged from 0.8% to 28.6% with an overall estimated of 4.4% (95% CI 3.6–5.2). When we considered separately the estimates reported in each study according to geographic area, the pooled estimate was lower in the European studies (1.4%), increased to 5.7% in the US studies and was 15.4% in the Asian ones. The pooled estimated prevalence of endometriosis was 33.5% (95% CI 24.3–42.8, Figure 2(c)) in women who underwent surgery for benign gynaecological conditions, 23.8% (95% CI 16.1–31.5, Figure 2(d)) in infertile women, and 49.7 % (95% CI 14.4–85.0) in women with chronic pelvic pain. Conclusion: This review offers an overview of the available data on the frequency of endometriosis in the general population and in selected population, in particular among infertile women and women with chronic pelvic pain.

Less is more: clinical impact of decreasing pneumoperitoneum pressures during robotic surgery.

The objective of this study was to investigate the effects of decreasing insufflation pressure during robotic gynecologic surgery. The primary outcomes were patient-reported postoperative pain scores and length of stay. Secondary outcomes include surgical time, blood loss, and intraoperative respiratory parameters. This is a retrospective cohort study of patients undergoing robotic surgery for benign gynecologic conditions by a single minimally invasive surgeon at an academic hospital between 2014 and 2017. Patients were categorized by the maximum insufflation pressure reached during the surgery as either 15, 12, 10, or 8mmHg. Continuous variables were compared using analysis of variance and χ2 test was used for categorical variables. 598 patients were included in this study with no differences in age, BMI, race, prior abdominal surgeries, or specimen weight between the four cohorts. When comparing cohorts, each decrease in insufflation pressure correlated with a significant decrease in initial pain scores (5.9 vs 5.4 vs 4.4 vs. 3.8, p ≤ 0.001), and hospital length of stay (449 vs 467 vs 351 vs. 317min, p ≤ 0.001). There were no differences in duration of surgery (p = 0.31) or blood loss (p = 0.09). Lower operating pressures were correlated with significantly lower peak inspiratory pressures (p < 0.001) and tidal volumes (p < 0.001). Surgery performed at lower-pressure pneumoperitoneum (≤ 10mmHg) is associated with lower postoperative pain scores, shorter length of stay, and improved intraoperative respiratory parameters without increased duration of surgery or blood loss. Operating at lower insufflation pressures is a low-cost, reversible intervention that should be implemented during robotic surgery as it results in the improved pain scores and shorter hospital stays.

Migraine in relation with endometriosis phenotypes: Results from a French case-control study.

Studies have shown a significant association between migraine and endometriosis, but no study has explored the relationship between migraine and endometriosis phenotypes: Superficial peritoneal endometriosis, ovarian endometrioma, and deep infiltrating endometriosis. We conducted a case-control study using data collected from 314 women aged 18 to 42 years who had undergone surgery for benign gynecological conditions between January 2013 and December 2015. All women completed a self-administered headache questionnaire according to the IHS classification. Cases (n = 182) are women with histologically proven endometriosis and controls are women (n = 132) without endometriosis. Occurrence of migraine was studied according to endometriosis phenotypes. Migraine prevalence in cases was significantly higher compared with controls (35.2% vs. 17.4%, p = 0.003). The risk of endometriosis was significantly higher in migrainous women (OR = 2.62; 95% CI = 1.43-4.79). When we take into account endometriosis phenotypes, the risk of ovarian endometrioma and deep infiltrating endometriosis were significant (OR = 2.78; 95% CI = 1.11-6.98 and OR = 2.51; 95% CI = 1.25-5.07, respectively). In women with endometriosis, the intensity of chronic non-cyclical pelvic pain was significantly greater for those with migraine (visual analogic scale (VAS) = 3.6 ± 2.9) compared with the women without headache (VAS = 2.3 ± 2.8, p = 0.0065). Our study shows a significant association between migraine and endometriosis. In clinical practice, women of reproductive age who suffer from migraine should be screened for endometriosis criteria in order to optimise the medical and therapeutic care of this condition.

Occult Uterine Malignancy at the Time of Surgery for Benign Gynecologic Indications: An Updated Systematic Review

Study Objective To conduct an updated systematic review to estimate the prevalence of occult uterine malignancy, of any subtype, among women undergoing surgery for benign gynecologic conditions. Design Systematic review. Setting N/A Patients or Participants Women undergoing surgery for presumed benign gynecologic conditions. Interventions Hysterectomy or Myomectomy. Measurements and Main Results The PRISMA guidelines were followed in this systematic review. The search terms used were “occult malignancy” or “occult uterine pathology” paired with “morcellation” or “hysterectomy.” March 25, 2019 was the last date that articles were searched. We did not restrict articles based on language or publication date. Inclusion criteria included any peer-reviewed journal articles reporting occult uterine malignancy rates at the time of surgery for benign conditions, regardless of whether morcellation was used or not. We excluded articles that were reported exclusively on women with pre-operatively diagnosed or suspected uterine malignancies. Our search yielded a total of 233 journal articles, of which 53 met the criteria for a full-text review and 27 were included in the final systematic review. There were 339,420 patients across 9 countries that were included in these 27 studies. As a comparison, the previous systematic review done by the Agency for Healthcare Research and Quality (AHRQ) only included a total of 136,195 patients. There were a total 2,479 occult uterine malignancies (all subtypes combined) among these 339,420 patients. The crude unadjusted occult uterine malignancy rate was 0.73% (95% CI 0.70 – 0.76%). When we examined a subset of the included studies that reported specific data on women undergoing morcellation, there were 82 occult malignancies among a total of 25,422 patients (Crude proportion = 0.32% [95% CI 0.25 – 0.39%]). Conclusion Based on this systematic review, incorporating over 300,000 patients, the overall prevalence of occult uterine malignancy at the time of surgery for benign gynecologic indications is approximately 0.73%.

1960 The Impact of Resident Participation on Operating Time in Robotic Surgery for Benign Gynecological Conditions

Study Objective To assess the association between resident participation and operative time in robotic surgery for benign gynecological conditions. Design A retrospective cohort study. Setting Two hospitals in Las Vegas, Nevada (one is a teaching hospital and one is not). Patients or Participants A total of 329 patients who underwent robotic surgery for benign gynecologic conditions from January 2018 to March 2019. All cases were performed by a single high volume robotic surgeon. Interventions Resident participation (versus non-participation) in 41.6% of 329 robotic cases. Measurements and Main Results The primary outcome was the total operative time. The primary exposure was resident participation versus non-participation in the robotic case. In our primary analysis we compared the mean and median operative times for cases with versus without resident participation. We then constructed a regression model to adjust for potential confounders including age, body mass index (BMI), specimen weight (in grams) and whether the surgery was a hysterectomy or not. There were no baseline differences in patient characteristics between cases involving residents and those not involving residents. In unadjusted analysis, the mean operative time was longer for cases involving residents (130.3 minutes [95% CI 122.8-137.7 minutes] vs 109.6 minutes [95% CI 104.0-115.3 minutes], p Conclusion Consistent with a prior study looking at trainee participation in gynecologic oncology cases performed robotically, we found that resident participation in robotic cases for benign gynecologic surgical conditions was associated with an increased operative time of approximately 20 minutes, even adjusting for age, BMI, type of surgery (hysterectomy vs. other type) and specimen weight.

Transition from multiport to single-site surgery: A single institution experience in robotic supracervical hysterectomy for benign gynecological diseases

ObjectiveTo share our experience of transition from multiport to single-site robotic surgery for benign gynecological conditions as well as to assess the selection criteria of candidates for robotic single-site supracervical hysterectomy (RSSH). Materials and methodsA retrospective review was conducted on patients undergoing robotic supracervical hysterectomy by a single surgeon in a single institute between June 2014 and December 2017. Patients who underwent additional procedures along with supracervical hysterectomy and who had unexpectant corpus malignancy proved pathologically were excluded from comparisons between patients undergoing RSSH and robotic multiport supracervical hysterectomy (RMSH). ResultsBetween June 2014 and December 2017, we accomplished 26 RSSH and 57 RMSH. There were no conversions, intraoperative complications, and readmissions within 30 days after surgery. In the RSSH group, the mean uterine weight was 264.6 ± 140.9 g with mean docking time of 15.8 ± 5.5 min, mean console time of 61.1 ± 35.6 min and mean operative time of 140.3 ± 34.4 min. In comparison to the RMSH group, the percentage of overweight/obese patients was lower (p = 0.018) and the uterine size was smaller (p < 0.001) with adenomyosis diagnosed more frequently (p = 0.002) in the RSSH group. While the operative time in the RSSH group was significantly shorter (p = 0.002), the RSSH group took longer time in docking (p < 0.001) and comparable time in console (p = 0.254). In view of chronological change, docking time and console time in the RMSH group remained steady, whereas steep decreases were observed in the RSSH group. The intraoperative blood loss and hemoglobin drop were comparable. The length of hospital stay was significantly shorter in the RSSH group (p = 0.005). ConclusionTransition from multiport to single-site surgery can be smooth for a surgical team experienced in the conventional multiport robotic system. RSSH is safe and feasible in properly selected patients.

The role of appendectomy at the time of laparoscopic surgery for benign gynecologic conditions.

The risk-benefit ratio of concurrent appendectomy at the time of gynecologic surgery has long been debated and remains controversial. However, emerging data on the appendix's role in chronic pain syndromes point to a previously unrecognized link between gynecologic disorders and appendicular pathology. In this article, we review the indications for appendectomy at the time of laparoscopic gynecologic surgery for the treatment of endometriosis and chronic pelvic pain. The incidence of appendiceal endometriosis is highly variable depending on the patient population selected. Although rare in patients undergoing appendectomy for acute appendicitis, women with endometriosis may experience rates as high as 9.3-39.0%, especially when suffering from deep infiltrative endometriosis. Appendectomy may also significantly reduce pain in women with unexplained chronic pelvic pain. Despite lack of prospective data, retrospective studies suggest that appendectomy during gynecologic procedures for chronic pelvic pain and severe endometriosis may be beneficial and necessary to fully address the treatment of these complex gynecologic conditions. In these clinical scenarios, the benefits of laparoscopic appendectomy at the time of the primary gynecologic procedure may outweigh the risks and cost, and should be discussed with patients preoperatively.

Light element distribution in fresh and frozen-thawed human ovarian tissues: a preliminary study.

Does synchrotron X-ray fluorescence (XRF) provide novel chemical information for the evaluation of human ovarian tissue cryopreservation protocols? Tissues from five patients undergoing laparoscopic surgery for benign gynaecological conditions were fixed for microscopic analysis either immediately or after cryopreservation. After fixation, fresh and slowly frozen samples were selected by light microscopy and transmission electron microscopy, and subsequently analysed with synchrotron XRF microscopy at different incident energies. The distributions of elements detected at 7.3 keV (S, P, K, Cl, Fe, and Os) and 1.5 keV (Na and Mg) were related to the changes revealed by light microscopy and transmission electron microscopy analyses. The light elements showed highly informative findings. The S distribution was found to be an indicator of extracellular component changes in the stromal tissues of the freeze-stored samples, further revealed by the transmission electron microscopy analyses. Low-quality follicles, frequent in the freeze-thawed tissues, showed a high Na level in the ooplasm. On the contrary, good-quality follicles were detected by a homogeneous Cl distribution. The occurrence of vacuolated follicles increased after cryopreservation, and the XRF analyses showed that the vacuolar structures contained mainly Cl and Na. The study demonstrates that elemental imaging techniques, particularly revealing the distribution of light elements, could be useful in establishing new cryopreservation protocols.

Dysregulation of the ADAM17/Notch signalling pathways in endometriosis: from oxidative stress to fibrosis.

Is oxidative stress associated with the A disintegrin and metalloproteases (ADAM) metallopeptidase domain 17 (ADAM17)/Notch signalling pathway and fibrosis in the development of endometriosis? Oxidative stress is correlated with hyperactivation of the ADAM17/Notch signalling pathway and a consequent increase in fibrosis in patients with endometriosis. It is nowadays accepted that oxidative stress plays an important role in the onset and progression of endometriosis. Oxidative stress is able to induce the synthesis of some members of the 'ADAM' family, such as ADAM17. ADAM17/Notch signalling is dysregulated in other profibrotic and inflammatory diseases. This was a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n = 202) during surgery for a benign gynaecological condition. After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free control women were enrolled. Peritoneal fluid (PF) samples were obtained from all the study participants during surgery in order to detect advanced oxidation protein products (AOPPs) and metalloproteinase activity of ADAM17. Stromal cells from endometrial specimens (n = 8) were obtained from endometrium of control patients (Cs), and from eutopic (Es) and ectopic (Ps) endometrium of patients with deep infiltrating endometriosis (DIE) (n = 8). ADAM17, Notch and the fibrosis markers α-smooth muscle actin (α-SMA) and type-I collagen were assessed using immunoblotting in all the endometrial samples obtained. Additionally, fibrosis was assessed after using Notch cleavage inhibitors (DAPT and FLI-06). Notch and fibrosis were also evaluated after stimulation of stromal endometrial cells with ADAM17 purified protein, increasing concentrations of H2O2 and primary cell culture supernatants. Patients with DIE presented higher PF AOPP and ADAM17 protein levels than controls (P < 0.01 and P < 0.05, respectively). In addition, these two markers were positively correlated (r = 0.614; P < 0.001). At the cellular level, ADAM17 activity was increased in Es and Ps compared to Cs (P < 0.001 and P < 0.01, respectively). Furthermore, Ps presented hyperactivation of Notch signalling (P < 0.05) and augmentation of fibrosis markers (P = 0.009 for α-SMA and P = 0.015 for type-I collagen) compared to controls. The use of DAPT and FLI-06 reduced both fibrosis markers in Ps but not in Cs. Stimulation with ADAM17, H2O2 and Ps supernatant culture significantly increased Notch and fibrosis in both Ps and Cs. N/A. The control group consisted of women who underwent surgery for benign gynaecological conditions, which could lead to biases because some of these conditions may cause alterations in oxidative stress and the ADAM17/Notch pathways. The small sample size of endometrial biopsies used for each group of patients (n = 8) is a limitation of the study, and results should be interpreted with caution. We propose a novel pathway in endometriosis pathogenesis that correlates oxidative stress, hyperactivation of ADAM17/Notch signalling and a consequent increase in fibrosis. This study suggests that Notch signalling plays a key role in the fibrotic processes that take place in ectopic lesions of patients with DIE, as already observed in other pro-fibrotic diseases. This work was supported by grants from University Paris Descartes, INSERM and Fundación Alfonso Martín Escudero. The authors have no competing interests to declare.

Vitamin D Storage in Adipose Tissue of Obese and Normal Weight Women.

Although vitamin D deficiency is prevalent among obese individuals, its cause is poorly understood. Few studies have measured vitamin D concentrations in adipose of obese (OB) subjects, and none have included normal weight controls (C). The goal of this study was to investigate whether the relationship between body composition, serum 25-hydroxyvitamin D (25OHD), vitamin D in subcutaneous (SQ) and omental (OM) adipose, and total adipose stores of vitamin D differ among OB and C. Obese women undergoing bariatric surgery and normal-weight women undergoing abdominal surgery for benign gynecologic conditions were enrolled. Subjects had measurements of serum 25OHD by high-performance liquid chromatography (HPLC) and body composition by dual-energy X-ray absorptiometry (DXA). Vitamin D concentrations in SQ and OM adipose were measured by mass spectroscopy. Thirty-six women were enrolled. Serum 25OHD was similar between groups (OB 27 ± 2 versus C 26 ± 2 ng/mL; p = 0.71). Adipose vitamin D concentrations were not significantly different in either SQ (OB 34 ± 9 versus C 26 ± 12 ng/g; p = 0.63) or OM compartments (OB 51 ± 13 versus C 30 ± 18 ng/g; p = 0.37). The distribution of vitamin D between SQ and OM compartments was similar between groups. Serum 25OHD was directly related to adipose vitamin D in both groups. Total body vitamin D stores were significantly greater in OB than in C (2.3 ± 0.6 versus 0.4 ± 0.8 mg, respectively; p < 0.01). In summary, although OB had significantly greater total vitamin D stores than C, the relationship between serum 25OHD and fat vitamin D and the overall pattern of distribution of vitamin D between the OM and SQ fat compartments was similar. Our data demonstrate that obese subjects have greater adipose stores of vitamin D. They support the hypotheses that the enlarged adipose mass in obese individuals serves as a reservoir for vitamin D and that the increased amount of vitamin D required to saturate this depot may predispose obese individuals to inadequate serum 25OHD. © 2016 American Society for Bone and Mineral Research.

Increased rate of spontaneous miscarriages in endometriosis-affected women.

Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls? Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls. The association between endometriosis and miscarriages has long been debated without reaching a consensus. We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosis group and 466 in the control group. Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification). Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted IRR: 1.70, 95% confidence interval: 1.34-2.16). There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented. This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates. No external funding was used for this study. The authors have no conflicts of interest to declare.

Successful slush nitrogen vitrification of human ovarian tissue

To study whether slush nitrogen vitrification improves the preservation of human ovarian tissue. Control vs. treatment study. University research laboratory. Ovarian biopsies collected from nine women (aged 14-35years) during laparoscopic surgery for benign gynecologic conditions. None. Ovarian cortical strips of 2 × 5 × 1mm were vitrified with liquid or slush nitrogen. Fresh and vitrified cortical strips were analyzed for cryodamage and viability under light, confocal, and transmission electron microscopy. Compared with liquid nitrogen, vitrification with slush nitrogen preserves [1] follicle quality (grade 1 follicles: fresh control, 50%; liquid nitrogen, 27%; slush nitrogen, 48%); [2] granulosa cell ultrastructure (intact cells: fresh control, 92%; liquid nitrogen, 45%; slush nitrogen, 73%), stromal cell ultrastructure (intact cells: fresh control, 59.8%; liquid nitrogen, 24%; slush nitrogen, 48.7%), and DNA integrity (TUNEL-positive cells: fresh control, 0.5%; liquid nitrogen, 2.3%; slush nitrogen, 0.4%); and [3] oocyte, granulosa, and stromal cell viability (oocyte: fresh control, 90%; liquid nitrogen, 63%; slush nitrogen, 87%; granulosa cells: fresh control, 93%; liquid nitrogen, 53%; slush nitrogen, 81%; stromal cells: fresh control, 63%; liquid nitrogen, 30%; slush nitrogen, 52%). The histology, ultrastructure, and viability of follicles and stromal cells are better preserved after vitrification with slush nitrogen compared with liquid nitrogen.