Background The disease caused by the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) was named Coronavirus Disease 19 (COVID-19) and classified as a global public health emergency. The evidence related to the impact of COVID-19 on pregnancy are limited to the second and the third trimester of pregnancy, while data on the first trimester are scant. Many viral infections can be harmful to the fetus during the first trimester of pregnancy, and whether SARS-CoV-2 is one of them is still unknown. Objective(s) With this study we evaluated SARS-CoV-2 infection as a risk factor for early pregnancy loss in first trimester of pregnancy. Furthermore, COVID-19 course in the first trimester was assessed. Study design Between February 22 and May 21, 2020, we conducted a case-control study at S. Anna Hospital, Turin, among first trimester pregnant women, paired for last menstruation. The cumulative incidence of COVID-19 was compared between women with spontaneous abortion (case group, n=100) and those with ongoing pregnancy (control group, n=125). Current or past infection was determined by detection of SARS-CoV-2 from nasopharingeal swab and SARS-CoV-2 IgG/IgM antibodies in blood sample. Patient demographics, COVID-19-related symptoms, and the main risk factors for abortion were collected. Results Twenty-three of the 225 women (23/225, 10.2%) tested positive for COVID-19 infection. There was no difference in the cumulative incidence of COVID-19 between the cases (11/100, 11%) and the controls (12/125, 9.6%) (p=0.73). Logistic regression analysis confirmed that COVID-19 was not an independent predictor of early pregnancy loss (Odd Ratio 1.28, confidence interval 0.53-3.08). COVID-19 related symptoms in the first trimester were fever, anosmia, ageusia, cough, arthralgia and diarrhea; no pneumonia or Hospital admission due to COVID-19-related symptoms were recorded. No difference in the incidence of symptoms was noted between the two groups. Conclusion(s) SARS-CoV-2 infection during the first trimester of pregnancy does not appear to predispose to early pregnancy loss; its cumulative incidence did not differ between women with spontaneous abortion and women with ongoing pregnancy. COVID-19 appears to have a favorable maternal course at the beginning of pregnancy, consistent with what has been observed during the second and the third trimester.

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Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers. Despite improvements in medical treatments, the prognosis for EOC remains poor, and there is an urgent need for new therapeutic strategies. Immune checkpoint inhibitors (CPIs) have dramatically improved survival of several cancers and are under evaluation in OC. Unfortunately, CPIs have shown globally unsatisfactory results. The aim of this manuscript is to critically review the results from early-phase trials with CPIs in terms of safety and activity, discuss the possible reasons for disappointing results and the new therapeutic approaches to improve patient outcomes. However, despite the success of immunotherapy in other malignancies such as in melanoma, non-small cell lung cancer (NSCLC) and urothelial cancers [25,26], the use of antibodies inhibiting the immune checkpoint programmed cell death (PD-1) or its ligand (PD-L1) obtained modest results in EOC so far, with median response rates of 10% up to 15% [18][19][20]27].Interestingly, the combination of the anti-PD1 nivolumab and the anti-lymphocyte-associated protein 4 (anti-CTLA4) ipilimumab showed promising results in platinum-resistant EOC at six-month interim analyses with an overall response rate (ORR) of 34% (doubling the results of nivolumab monotherapy). However, final results are still awaited [28].As a consequence, no immunotherapeutic agent has obtained regulatory approval for EOC thus far. PD1/PD-L1

Congenitally‐ or perinatally‐acquired viral infections can be harmful to the fetus but data are limited about prevalence and outcomes of COVID‐19 disease during the first trimester of pregnancy. We report epidemiologic data from a study investigating a cohort of women who became pregnant just before or during the COVID‐19 pandemic. We recruited 138 consecutive pregnant women attending for first trimester screening (11‐13 weeks of gestation) at Sant'Anna Hospital, Turin, Piedmont, Italy, during the plateau and the falling phase of the COVID‐19 epidemic curve. Patients were tested for SARS‐CoV‐2 IgM/IgG antibody levels and SARS‐CoV‐2 detection in sera and nasopharyngeal swab samples. COVID‐19 cumulative incidence during the first trimester was of 10.1% with high prevalence of asymptomatic patients (42.8%). Similar to the course of the disease in non pregnant adults, 80‐90% of infections were not severe. The prevalence of reported symptoms was four‐fold higher in SARS‐CoV‐2 positive patients (57%) than in those negative (13%) (p<0.001), suggesting that direct self‐testing should open doors to confirmatory testing for COVID‐19. Our findings support the need for COVID‐19 screening in early pregnancy in epidemic areas to plan materno‐fetal health surveillance programs. This article is protected by copyright. All rights reserved.

BackgroundOsteomyelitis of the pubic symphysis is a rare cause of pelvic pain after delivery, mainly caused by Staphylococcus aureus and Pseudomonas aeruginosa.The clinical context is the same as the more common diastasis of the pubic bone, but the presence of intense local pain in association with fever should prompt further clinical work-up based on blood chemistry, microbiology and diagnostic imaging. We report the first case of methicillin-resistant Staphylococcus aureus osteomyelitis of the pubic symphysis occuring after the delivery.Case presentationA 39-year-old woman developed pain over the pubic bone 12 h after the delivery. After 72 h fever rose and laboratory examination showed elevation of C-reactive protein and procalcitonin levels. Pelvic x-rays and magnetic resonance showed pubic diastasis, joint effusion, tiny irregularities of articular surfaces and, severe bone edema. The patient was started on broad spectrum intravenous (IV) antibiotics (piperacillin-tazobactam) and then replaced to IV vancomycin and oral levofloxacin based on antibiogram result. She was then discharged with oral antibiotic therapy and fully recovered.ConclusionsDue to the rarity of this disease, we compared our experience with the other cases of osteomyelitis of pubic symphysis occurring in peri-postpartum reported in the literature. The course of osteomyelitis was favourable in all patients, and only in one case an additional orthopedic procedure for symphysis fixation was necessary. Knowledge of this rare condition is important to enable prompt diagnosis and treatment.

Purpose Does controlled ovarian stimulation (COS) and progesterone (P) luteal supplementation modify the vaginal and endometrial microbiota of women undergoing in vitro fertilization? Methods Fifteen women underwent microbiota analysis at two time points: during a mock transfer performed in the luteal phase of the cycle preceding COS, and at the time of fresh embryo transfer (ET). A vaginal swab and the distal extremity of the ET catheter tip were analyzed using next-generation 16SrRNA gene sequencing. Heterogeneity of the bacterial microbiota was assessed according to both the Bray-Curtis similarity index and the Shannon diversity index. Results Lactobacillus was the most prevalent genus in the vaginal samples, although its relative proportion was reduced by COS plus P supplementation (71.5 ± 40.6% vs. 61.1 ± 44.2%). In the vagina, an increase in pathogenic species was observed, involving Prevotella (3.5 ± 8.9% vs. 12.0 ± 19.4%), and Escherichia coli-Shigella spp. (1.4 ± 5.6% vs. 2.0 ± 7.8%). In the endometrium, the proportion of Lactobacilli slightly decreased (27.4 ± 34.5% vs. 25.0 ± 29.9%); differently, both Prevotella and Atopobium increased (3.4 ± 9.5% vs. 4.7 ± 7.4% and 0.7 ± 1.5% vs. 5.8 ± 12.0%). In both sites, biodiversity was greater after COS (p < 0.05), particularly in the endometrial microbiota, as confirmed by Bray-Curtis analysis of the phylogenetic distance among bacteria genera. Bray-Curtis analysis confirmed significant differences also for the paired endometrium-vagina samples at each time point. Conclusions Our findings suggest that COS and P supplementation significantly change the composition of vaginal and endometrial microbiota. The greater instability could affect both endometrial receptivity and placentation. If our findings are confirmed, they may provide a further reason to encourage the freeze-all strategy.

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

Infection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an involvement of the fetal-maternal unit could be expected, but, so far, the histopathological evaluation of placentas delivered by women with SARS-CoV-2 infection did not show distinct hallmarks. A consecutive series of 11 placentas, delivered by 10 women with COVID-19 admitted to our Obstetrics and Gynecology clinic have been investigated and compared to a control cohort of 58 pre-COVID-19 placentas and 28 placentas delivered by women who had a previous cesarean section. Four out of eleven placentas showed changes consistent with chronic villitis/villitis of unknown etiology (VUE), while in one case, chronic histiocytic intervillositis was diagnosed. Thrombo-hemorrhagic alterations were observed in a subset of cases. Compared to the control cohort, chronic villitis/VUE (p < 0.001), chronic deciduitis (p = 0.023), microvascular thrombosis (p = 0.003), presence of infarction areas (p = 0.047) and of accelerated villous maturation (p = 0.005) showed higher frequencies in placentas delivered by women with COVID-19. Chronic villitis/VUE (p = 0.003) and accelerated villous maturation (p = 0.019) remained statistically significant by restricting the analysis to placentas delivered after a previous cesarean section. The observed differences in terms of pathological findings could be consistent with SARS-CoV-2 pathogenesis, but just a subset of alterations remained statistically significant after adjusting for a previous cesarean section. A careful consideration of potential confounders is warranted in future studies exploring the relationship between COVID-19 and pregnancy.