Epithelial ovarian cancer is infiltrated by activated effector T cells co-expressing CD39, PD-1, TIM-3, CD137 and interacting with cancer cells and myeloid cells.

Introduction: Despite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity. Methods: In this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs). Results: Activated T cells showing features of partial exhaustion with a CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ signature. Conclusion: These data demonstrate that EOC is enriched in CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches.

Endometriosis-Related Ovarian Cancers: Evidence for a Dichotomy in the Histogenesis of the Two Associated Histotypes.

Evidence indicates that different pathways of malignant degeneration underlie the development of endometriosis-associated ovarian tumors of endometrioid and clear cell histotypes. The aim of this study was to compare data from patients affected by these two histotypes to investigate the hypothesis of a dichotomy in the histogenesis of these tumors. Clinical data and tumor characteristics of 48 patients who were diagnosed with either pure clear cell ovarian cancer and mixed endometrioid-clear cell ovarian cancer arising from endometriosis (ECC, n = 22) or endometriosis-associated endometrioid ovarian cancer (EAEOC, n = 26) were compared. A previous diagnosis of endometriosis was detected more frequently in the ECC group (32% vs. 4%, p = 0.01). The incidence of bilaterality was significantly higher in the EAOEC group (35% vs. 5%, p = 0.01) as well as a solid/cystic rate at gross pathology (57.7 ± 7.9% vs. 30.9 ± 7.5%, p = 0.02). Patients with ECC had a more advanced disease stage (41% vs. 15%; p = 0.04). A synchronous endometrial carcinoma was detected in 38% of EAEOC patients. A comparison of the International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis showed a significantly decreasing trend for ECC compared to EAEOC (p = 0.02). These findings support the hypothesis that the origin, clinical behavior and relationship with endometriosis might be different for these histotypes. ECC, unlike EAEOC, seems to develop within an endometriotic cyst, thus representing a window of possibility for ultrasound-based early diagnosis.

Role of Machine Learning (ML)-Based Classification Using Conventional 18F-FDG PET Parameters in Predicting Postsurgical Features of Endometrial Cancer Aggressiveness.

PURPOSE: to investigate the preoperative role of ML-based classification using conventional 18F-FDG PET parameters and clinical data in predicting features of EC aggressiveness. METHODS: retrospective study, including 123 EC patients who underwent 18F-FDG PET (2009-2021) for preoperative staging. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were computed on the primary tumour. Age and BMI were collected. Histotype, myometrial invasion (MI), risk group, lymph-nodal involvement (LN), and p53 expression were retrieved from histology. The population was split into a train and a validation set (80-20%). The train set was used to select relevant parameters (Mann-Whitney U test; ROC analysis) and implement ML models, while the validation set was used to test prediction abilities. RESULTS: on the validation set, the best accuracies obtained with individual parameters and ML were: 61% (TLG) and 87% (ML) for MI; 71% (SUVmax) and 79% (ML) for risk groups; 72% (TLG) and 83% (ML) for LN; 45% (SUVmax; SUVmean) and 73% (ML) for p53 expression. CONCLUSIONS: ML-based classification using conventional 18F-FDG PET parameters and clinical data demonstrated ability to characterize the investigated features of EC aggressiveness, providing a non-invasive way to support preoperative stratification of EC patients.

Experimental drugs for fallopian cancer: promising agents in the clinical trials and key stumbling blocks for researchers.

INTRODUCTION: Fallopian tube carcinoma (FC) as a single entity is a rare disease. Although its diagnosis is increasing thanks to the widespread use of prophylactic salpingectomy, there are no clinical trials exclusively designed for FC. AREAS COVERED: This review aims at identifying the most promising trials and future therapeutic pathways in the setting of FC. EXPERT OPINION: Hot topics in FC treatment include the consequences of using PARP inhibitors (PARPi) as first-line therapy, ways to overcome platinum resistance, and the role of immunotherapy. Patient selection is a key point for future development of target therapies. Next-generation sequencing (NGS) is one of the most investigated technologies both for drug discovery and identification of reverse mutations, involved in resistance to PARPi and platinum. New, promising molecular targets are emerging. Notwithstanding the disappointing outcomes when used by itself, immunotherapy in FC treatment could still have a role in combination with other agents, exploiting synergistic effects at the molecular level. The development of cancer vaccines is currently hampered by the high variability of tumor neoantigens in FC. Genomic profiling could be a solution, allowing the synthesis of individualized vaccines.

Current Evidence on Immunotherapy for Gestational Trophoblastic Neoplasia (GTN).

BACKGROUND: Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy. METHODS: Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed. RESULTS: Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses. CONCLUSIONS: Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.

Prognostic Significance of Neutrophil/Lymphocytes Ratio (NLR) in Predicting Recurrence of Cervical Dysplasia.

Objective: The objective of the present study was to investigate the potential prognostic role of neutrophil-lymphocyte ratio (NLR) in comparison with known parameters of prediction for the detection of recurrences of cervical intraepithelial neoplasia (CIN) after treatment. Methods: We retrospectively evaluated patients who underwent surgical treatment for CIN2, CIN3, and carcinoma in situ (CIN2+) between 2010 and 2019. NLR was recorded before surgery, and the follow-up records of patients were analyzed. Cases were splitted into two subgroups according to baseline NLR-low-NLR for <2 and high-NLR for ≥2 values of the index-and correlated with recurrences. Results: 428 cases fulfilled the criteria and were included in the study. Recurrence rate in patients with NLR <2.0 and NLR ≥2.0 was 15.2% and 27.3%, respectively, being the odd ratio for recurrence significantly higher in patients with NLR ≥2 (OR = 2.09; 95% CI 1.28-3.41; p = 0.003). A highly significant statistical difference in recurrence rate was demonstrated, in both univariate and multivariate, for surgical margins, follow-up HPV-DNA status, and NLR values. Conclusion: Preoperative NLR categorization is a strong independent prognostic factor for recurrences after surgical excision of CIN. NLR evaluation is a simple, reproducible, and cost-effective clinical instrument that could optimally be introduced in clinical practice in every setting.

Hybrid PET/MRI in Staging Endometrial Cancer: Diagnostic and Predictive Value in a Prospective Cohort.

AIM: The assessment of deep myometrial invasion (MI) and lymph node involvement is of utmost importance in the preoperative staging of endometrial cancer (EC). Imaging parameters derived respectively from MRI and PET have shown good predictive value. The main aim of the present study is to assess the diagnostic performance of hybrid 18F-FDG PET/MRI in EC staging, with particular focus on MI and lymphnodal involvement detection. PATIENTS AND METHODS: Prospective monocentric study including 35 patients with biopsy-proven EC undergoing preoperative 18F-FDG PET/MRI (December 2018-March 2021) for staging purpose. Histological examination was the reference standard. PET (SUVmax, SUVmean with a threshold of 40% of SUVmax-SUVmean40, metabolic tumor volume, total lesion glycolysis) and MRI (volume index [VI], total tumor volume, tumor volume ratio [TVR], mean apparent diffusion coefficient, minimum apparent diffusion coefficient) parameters were calculated on the primary tumor, and their role in predicting EC risk group, the presence of lymphovascular space invasion (LVSI), and MI was assessed. Receiver operating characteristics analysis was used to assess the predictive value of PET and MRI parameters on EC characteristics. RESULTS: Patients' median age was 66.57 years (SD, 10.21 years). 18F-FDG PET/MRI identified the primary tumor in all patients. Twenty-two of 35 patients had high-risk EC and 13/35 low-risk disease; 13/35 presented LVSI, 22/35 had deep MI at histological examination, and 13/35 had p53 hyperexpression.PET/MRI was able to detect lymphnodal involvement with high accuracy and high specificity (sensitivity of 0.8571, specificity of 0.9286, accuracy of 0.9143), also showing a high negative predictive value (NPV) for lymphnodal involvement (NPV of 0.9630, positive predictive value [PPV] of 0.7500).The assessment of deep MI using PET/MRI correctly staged 27 patients (77.1%; sensitivity of 0.7273, specificity of 0.8462, accuracy of 0.7714), with also a good PPV (PPV of 0.8889, NPV of 0.647).MRI-derived total tumor volume, VI, and TVR were significant in predicting EC groups (high-risk vs low-risk patients) (P = 0.0059, 0.0235, 0.0181, respectively). MRI-derived volume, VI, TVR, and PET-derived metabolic tumor volume and total lesion glycolysis were able to predict LVSI (P = 0.0023, 0.0068, 0.0068, 0.0027, 0.01394, respectively). Imaging was not able to predict grading, presence of deep MI, nor hyperexpression of p53. CONCLUSIONS: 18F-FDG PET/MRI has good accuracy in preoperative staging of EC; PET and MRI parameters have synergic role in preoperatively predicting LVSI, with MRI parameters being also predictive for EC risk group.

Ovarian Cancer Radiosensitivity: What Have We Understood So Far?

Radiotherapy has been increasingly considered as an active treatment to combine with other approaches (i.e., surgery, chemotherapy, and novel target-based drugs) in ovarian cancers to palliate symptoms and/or to prolong chemotherapy-free intervals. This narrative review aimed to summarize the current knowledge of the radiosensitivity/radioresistance of ovarian cancer which remains the most lethal gynecological cancer worldwide. Indeed, considering the high rate of recurrence in and out of the radiotherapy fields, in the era of patient-tailored oncology, elucidating the mechanisms of radiosensitivity and identifying potential radioresistance biomarkers could be crucial in guiding clinical decision-making.

Impact of COVID-19 on medical treatment patterns in gynecologic oncology: a MITO group survey.

OBJECTIVE: COVID-19 is a global public health emergency. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological tumors. The Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) performed a survey to evaluate the impact of the COVID-19 pandemic on medical treatment of gynecological cancer, with a focus on chemotherapy and oral treatment with poly(ADP)-ribose polymerase inhibitors (PARP-i). METHODS: The survey consisted of a self-administered online questionnaire, sent via email between November 2020 and January 2021 to all members of MITO group. RESULTS: Forty-nine centers completed the questionnaire. The majority of respondents (83%) use screening tests to determine COVID-19 status in patients who were to undergo chemotherapy or oral medications. All respondents to our survey continued cancer therapy in patients who tested negative for COVID-19 during the pandemic. Seventy-three percent of respondents declared they stopped treatment with chemotherapy or PARP-i only after a positive swab and resumed therapy when negative tests were confirmed. CONCLUSIONS: COVID-19 positivity impacted patterns of treatment in patients diagnosed with ovarian cancer within the MITO group. Further investigations are needed to evaluate whether these modifications influence oncological clinical outcomes.

Stage I juvenile granulosa cell tumors of the ovary: A multicentre analysis from the MITO-9 study.

OBJECTIVE: Juvenile type granulosa cell tumor (JGCTs) are extremely rare, mainly diagnosed in young women and pre-pubertal girls at stage I disease. Literature is scanty and guidelines regarding the optimal management are still controversial. The aim of this study is to add on the experience of the MITO group (Multicenter Italian Trials in Ovarian Cancer). METHODS: Clinicopathological data from patients with stage I JGCTs were retrospectively collected. Descriptive statistics were used to characterize the patient population. Clinicopathological features and treatment variables were evaluated for association with relapse. RESULTS: Seventeen patients were identified. Surgical approach was laparoscopic and open for 7 (41%) and 10 (59%) patients, respectively. Fertility sparing surgery (FSS) was performed in 15 patients (88%): unilateral salpingo-oophorectomy (USO) in 11 patients, cystectomy with subsequent USO in 2 patients and cystectomy alone in the remaining 2. Adjuvant chemotherapy was given in 2 cases. After a median follow up time of 80 months, no recurrences were registered. CONCLUSIONS: Given the available data, minimally invasive surgery is safe in stage I JGCTs. Because of the good prognosis and of the young age of patients, FSS can be chosen in most of the cases. The role of cystectomy deserves further validation. The need of adjuvant chemotherapy in stage I disease is still unclear, even if available data does not seem to support treatment over surveillance.

Endometriosis and spontaneous hemoperitoneum in pregnancy: evaluation of the magnitude of the risk in women becoming pregnant via in vitro fertilization.

OBJECTIVE: To estimate the frequency of spontaneous hemoperitoneum in pregnancy (SHiP) in women with endometriosis achieving pregnancy with in vitro fertilization (IVF). DESIGN: Retrospective case series. SETTING: Referral academic assisted reproductive technology (ART) center. PATIENT(S): Three hundred and forty-eight women with a history of surgery for endometriosis and women with ovarian endometriomas or deep endometriotic nodules detected at basal transvaginal ultrasound performed before IVF cycle. INTERVENTION(S): Information obtained from patients' charts on basal characteristics, IVF cycle, and pregnancy outcomes, and binomial distribution model created to determine the 95% confidence interval (CI) of the proportion of SHiP. MAIN OUTCOME MEASURE(S): Rate of SHiP. RESULT(S): Overall, 362 pregnancies were included, among which 238 (66%) had a history of previous surgery for endometriosis and 231 (64%) had endometriosis detected at ultrasound (107 women, 30%, had both). Pregnancies were achieved after fresh and frozen cycles in 244 (67%) and 118 (33%) women, respectively. One case of SHiP was recorded, corresponding to a rate of 0.3%. CONCLUSION(S): In the general population of women with endometriosis undergoing IVF, SHiP is uncommon. Future studies should better identify the risk factors for SHiP to disentangle the subgroups of women at higher risk.

Synergic role of preoperative 18F-fluorodeoxyglucose PET and MRI parameters in predicting histopathological features of endometrial cancer.

BACKGROUND: The aim of the present study is to explore the correlation between PET and MRI parameters of primary tumour and clinicopathological features and to determine their synergic predictive role in patients with endometrial cancer candidate to surgery. METHODS: Retrospective study including 27 patients with endometrial cancer and preoperative 18F-fluorodeoxyglucose (18F-FDG)-PET and MRI scan. The following parameters, calculated on the primary tumour, were used for analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for PET scans; mean apparent diffusion coefficient (ADCmean) and volume index for MRI scans. FIGO stage, grade, histotype, lymphovascular space invasion (LVSI) and myometrial invasion were the considered clinicopathological features. RESULTS: MRI volume index was a good predictor for deep myometrial invasion [area under the curve (AUC) = 0.85; P = 0.003] and for LVSI (AUC = 0.74; P = 0.039). A cutoff value of 9.555 for MRI volume index was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%); a cutoff of 12.165 was predictive for LVSI (sensitivity = 69.2%; specificity = 83.3%). A TLG cutoff value of 26.03 was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%). A high-direct correlation was found with MRI volume index (rho = 0.722; P < 0.001); low-direct correlation with SUVmax (rho = 0.484; P = 0.012), SUVmean (rho = 0.47; P = 0.015) and TLG (rho = 0.482; P = 0.013) were identified. The SUVmax/ADCmean ratio showed a low-direct correlation with percentage of myometrial invasion (rho = 0.467; P = 0.016). CONCLUSION: Volume index, TLG and SUVmax/ADCmean ratio are associated with deep myometrial invasion. As myometrial invasion is the index used to predict lymph node involvement in endometrial cancer, the synergic use of these imaging parameters may be suggested to predict lymphnodal metastases.

Chemotherapy-induced nausea in a sample of gynaecological cancer patients: assessment issues and personal risk factors evaluation.

PURPOSE: Chemotherapy-induced nausea (CIN) is a relevant problem for gynaecological cancer patients. The evaluation of CIN is a key aspect in its management, along with the identification of associated risk factors. The objective of the study was to compare different measurements of nausea and to investigate personal risk factors in CIN development. METHOD: Eighty-one women treated for gynaecological cancers took part. The presence of CIN was evaluated using the MASCC Antiemesis Tool (MAT) and a patient's report to clinicians at the subsequent chemotherapy cycle. Personal risk factors were assessed using the State-Trait Anxiety Inventory and a self-report questionnaire. RESULTS: The study shows that the agreement between patients' assessment of CIN with MAT and what they referred to clinicians was only moderate for acute nausea (Cohen's Kappa = 0.55; p < 0.001), while good for delayed nausea (Cohen's Kappa = 0.68; p < 0.001). At multiple logistic regression analysis, younger age, anticipatory nausea, patient medium-high expectations of CIN, and parity emerged as risk factors for the development of acute nausea (p = 0.0087, 0.0080, 0.0122 and 0.0021, respectively). Patient medium-high expectations of CIN and being single resulted to be risk factors for delayed nausea (p = 0.0397 and 0.0024, respectively). CONCLUSIONS: Our findings confirm that personal factors contribute to individual differences in the development of CIN; moreover, we highlight the importance of CIN evaluation by clinicians, underlining the need to use reliable instruments.

Feasibility of hand-assisted laparoscopic sentinel node biopsy in open endometrial cancer surgery.

Background: The aim of this preliminary retrospective study was to assess the feasibility and accuracy of Indocyanine Green (ICG) sentinel node (SLN) sampling using a laparoscopic camera during open endometrial cancer surgery.Material and methods: Retrospective study. Fourteen women with endometrial cancer, not fit for a complete laparoscopic staging, underwent SLN mapping using the IMAGE1 camera during open surgery.Results: The median age of patients was 67 (range 33-86) years. Median BMI was 31 (range 23-58). Mean operative time 157.5 minutes and hospital stay three days. The overall detection rate of SLN mapping was 93%. Bilateral detection was 86%. No post-operative short or long-term complications were observed.Conclusions: Real-time NIR technology supported by the IMAGE1 S is a reliable system and represents a promising method for SLN mapping in selected cases with EC and severe surgical risks, during 48 traditional open approaches. The use of laparoscopy ICG in open surgery seems to be a feasible and useful tool for the detection of SLN in endometrial cancer patients with intraoperative and/or postoperative high morbidity risk. It represents a valid alternative to robotic surgery, particularly in countries and centers where the robotic platform or SPY system for open surgery are not available.

What women want: Fertility sparing surgery in Borderline ovarian tumours patients and pregnancy outcome.

OBJECTIVE: Borderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS. MATERIALS AND METHODS: Patients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes. RESULTS: 85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate. CONCLUSIONS: Conservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT.

New Keystone flap application in vulvo-perineal reconstructive surgery: A case series.

OBJECTIVE: This study aimed to evaluate the application of the Keystone flap technique and the long-term results of vulvovaginal reconstruction after vulvar surgery. METHODS: This is the first case series describing the application of the Keystone perforator island flaps (KPIF) technique to close a wide defect after radical vulvectomy. We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients. The benefits, cosmetic results and satisfaction of patients were analyzed in the follow up. RESULTS: Five patients were selected for the study: four underwent radical vulvectomy for squamous cell vulvar cancer, and one underwent vulvar wide excision for Paget disease followed by reconstruction with the Keystone flap technique. The defects were successfully covered by the Keystone flap technique in all patients. CONCLUSIONS: Keystone flaps seem to be easy to design and elevate, and it offers rapid fasciocutaneous closure in wide vulvo-perineal defects with excellent long-term results.

Flexible CO2 laser fiber: first look at the learning curve required in gynecological laparoscopy training.

BACKGROUND: The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible. METHODS: Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant. RESULTS: Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser. CONCLUSIONS: Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery.

Pregnancy outcome in women with endometriosis achieving pregnancy with IVF.

STUDY QUESTION: Are women with endometriosis who conceive with IVF at increased risk of preterm birth? SUMMARY ANSWER: Women with endometriosis who conceive with IVF do not face an increased risk of preterm birth. WHAT IS KNOWN ALREADY: The eutopic endometrium of women with endometriosis has been repeatedly shown to present molecular and cellular alterations. On this basis, it has been hypothesized that pregnancy outcome may be altered in affected women. However, to date, available evidence from epidemiological studies is scanty and conflicting. Data tended to be partly consistent only for an increased risk of preterm birth and placenta previa. STUDY DESIGN, SIZE, DURATION: Retrospective matched case-control study of women achieving an IVF singleton pregnancy progressing beyond 12 weeks' gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women achieving IVF singleton pregnancies that progressed beyond 12 weeks' gestation at two infertility units were reviewed. Cases were women with a history of surgery for endometriosis and/or with a sonographic diagnosis of the disease at the time of the IVF cycle. Controls were women without current or past evidence of endometriosis who were matched to cases by age (± 6 months), type of cycle (fresh or frozen cycle) and study period. Male factor and unexplained infertility were the most common diagnoses in the control group. Two hundred and thirty-nine women with endometriosis and 239 controls were selected. The main outcome of the study was the rate of preterm birth (birth < 37 weeks' gestation) regardless of the cause. Secondary analyses were performed for the most common obstetrical complications. MAIN RESULTS AND THE ROLE OF CHANCE: The rate of preterm birth was similar in the two study groups (14% and 14%, respectively, p = 0.89). The rate of live birth and the incidence of hypertensive disorders, gestational diabetes, small and large for gestational age newborns and neonatal problems also did not differ. In contrast, placenta previa was more common in women with endometriosis than controls (6% versus 1%, respectively; p = 0.006): The adjusted odds ratio was 4.8 (95% confidence interval: 1.4-17.2). LIMITATIONS, REASONS FOR CAUTION: As for all observational studies, confounders cannot be totally excluded. Moreover, the retrospective study design exposes the findings to some inaccuracies. For example, the independent role of adenomyosis could not be reliably assessed because this diagnosis is complex and would necessitate a prospective recruitment. Second, the selection of controls may also be a matter of concern because some affected women may have been erroneously included in this group. Third, even if the sample size is significant, it is insufficient for robust subgroup analyses. Finally, it is mandatory to point out that our conclusions are valid for IVF pregnancies only, and specific data from properly designed studies are required to support any inference for natural pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: The results of our study suggest that women with endometriosis conceiving with IVF can be reassured regarding the risk of preterm birth. The observed association with placenta previa requires further investigation and may open a new avenue of research. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. None of the authors have any conflict of interest to declare.