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 INTEREST(s) No external funding was used for this study. None of the authors have any conflict of interest to declare.

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.

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.