Long-term storage does not impact the quality of cryopreserved human ovarian tissue

Background: Ovarian tissue cryopreservation is an emerging technique, also addressed to very young cancer patients, for whom it is not possible to perform an ovarian stimulation for oocytes freezing, before gonadotoxic treatment. In this cases, ovarian tissue must be cryopreserved for a long period of time and it is very important to know if it maintains fertility function after a long period of storage. Here we aimed to assess the effect of long-term storage on preservation and viability of cryopreserved human ovarian tissue. Methods: Descriptive study of three cases of cancer patients whose cryopreserved ovarian tissue remained stored for 18 years. Long-term stored tissue was examined by histological and immunohistochemical analysis, transmission electron microscopy, TUNEL assay and LIVE/DEAD viability/citotoxicity test. Results: Ovarian tissue stored for 18 years showed a good morphology. Follicles presented negative staining for estrogen and progesterone receptors, positive staining for ki67 in granulosa cells and/or oocytes and for bcl2 in granulosa cells. Regarding stroma, patch/focal positive expression was found for estrogen receptor and ki67, diffusely positive expression for progesterone receptor and bcl2. After long-term storage, ultrastructural examination showed sub-cellular integrity of follicles and interstitial oedema foci. No apoptosis was observable by TUNEL assay. Stromal cell viability remained >97 % during the culture period. Conclusion: The evaluation of different aspects o f the tissue provides evidence that the storage time does not impact on tissue quality and gives hope especially to cancer girls, whose tissues could remain cryopreserved for a very long time

Impact of the COVID-19 pandemic on ovarian tissue cryopreservation planning in the Bologna clinical center

Introduction: Treatment of patients with COVID-19 has been a priority by competing with the treatment of any other disease due to limited hospital resources. The current pandemic situation has focused the attention of healthcare providers around the world away from all other non-emergency health problems, including oncofertility. The aim of the study was to evaluate the repercussions of the COVID-19 pandemic on the activity levels of ovarian tissue cryopreservation (OTC) in the our center. Methods: The study analyzed the number of patients treated for OTC in our center during three periods: pre-pandemic period: March 2019-February 2020, pandemic period: March 2020-February 2021 and post-pandemic period: March 2021-February 2022. Results: In our center routine hospital operation was completely reorganized, allowing only urgent interventions. Continuing to urgently preserve fertility during the pandemic required rapid changes to our standard practices for the care of these vulnerable patients. Despite the modifications, there was no difference in the number of OTC performed among the periods analyzed. Similarly, the number of patients who did not perform OTC was the same over the three years analyzed. Discussion: Despite the local and national restructuring of care to conserve resources and protect the community, it is significant to continue offering fertility-sparing treatment to cancer patients. This emphasis on the importance of preserving fertility despite the pandemic further highlights the essential and urgent nature of this procedure

Epigallocatechin-3-gallate inhibits doxorubicin-induced inflammation on human ovarian tissue

Chemotherapy protocol can destroy the reproductive potential of young cancer patients. Doxorubicin (DOX) is a potent anthracycline commonly used in the treatment of numerous malignancies. The purpose of the study was to evaluate the ovarian toxicity of DOX via inflammation and the possible protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG). Ovarian tissue of three patients was cultured with 1 \ub5g/ml DOX and/or 10 \ub5g/ml EGCG for 24 and 48 h. Levels of inflammatory factors were determined by quantitative Real-Time PCR, western blot, zimography, and multiplex bead-based immunoassay. Morphological evaluation, damaged follicle count and TUNEL assay were also performed. DOX influenced inflammatory responses by inducing a significant increase in the expression of pro-inflammatory cytokines, such as tumor necrosis factor-\u3b1 (TNF-\u3b1) and cyclooxigenase-2 (COX-2), of inflammatory interleukins (IL), such as interleukin-6 (IL-6) and interleukin-8 (IL-8), and the inflammatory proteins mediators metalloproteinase-2 and metalloproteinase-9 (MMP2 and MMP9). IL-8 secretion in the culture supernatants and MMP9 activity also significantly raised after DOX treatment. Moreover, a histological evaluation of the ovarian tissue showed morphological damage to follicles and stroma after DOX exposure. EGCG significantly reduced DOX-induced inflammatory responses and improved the preservation of follicles. DOX-induced inflammation could be responsible for the ovarian function impairment of chemotherapy. EGCG could have a protective role in reducing DOX-mediated inflammatory responses in human ovarian tissue

Integration of Molecular Data in the Prognostic Stratification and Management of Endometrial Carcinoma

In the last years, the TCGA-based molecular classifier have been progressively integrated in the management of endometrial carcinoma. While molecular assays are increasingly available across pathology laboratories, the additional costs will expectedly be compensated by a reduction in overtreatments and a prevention of recurrences. The additional time might be shortened by assessing molecular markers on biopsy specimens. Retrospective data suggest that the molecular classifier will have a major impact of on the risk stratification, with many patients having their risk class down- or upstaged based on POLE mutations or p53 abnormalities, respectively. However, there are still several issues to be resolved, such as the prognostic value of the TCGA classifier in each FIGO stage, or the type of adjuvant treatment most suitable for each molecular group. Other issues regard the prognostic stratification of the mismatch repair-deficient and “no specific molecular profile” groups, which currently follows the same criteria; however, the former seems to be prognostically consistent regardless of FIGO grade and histotype, whereas the latter appears highly heterogeneous. Numerous clinical, histological, immunohistochemical and molecular markers have been proposed to refine the TCGA classification, but their prognostic value is still undefined. Hopefully, prospective data collected in the next years will help resolving these issues

Robotic Surgery and Deep Infiltrating Endometriosis Treatment: The State of Art

Objective: Surgical treatment of endometriosis, when indicated, has demonstrated to be effective in reducing painful symptoms and improve quality of life of patients affected with endometriosis. The minimally invasive approach via laparoscopy is the preferred method when compared with laparotomy but in the last two decades another minimally invasive approach has become available, the robotically assisted laparoscopic surgery. Robotic technology is widely used in different surgical branches, such as general surgery and urology. Moreover, the use of robotic surgery is already accepted for different gynecological procedures either for benign and for oncological diseases. The advantages of robotic surgery such as improve dexterity of movements, avoided tremor, increased magnification of 3-dimensional vision seem strategic in the context of a complex surgery as is deep endometriosis eradication. However, to date there is no unanimous consensus on whether robotically assisted procedures are a valid and safe alternative to laparoscopy in the treatment of endometriosis. Mechanism: In this narrative review we analyze the available literature assessesing the robotic treatment of all types of endometriosis and specifically deep infiltrating endometriosis, compared to the outcomes of conventional laparoscopy. Findings in Brief: Indeed, the evidence of safety and effectiveness of robotically assisted laparoscopy in endometriosis treatment is strong and almost unanimous. There is no clear superiority of one approach to the other but robotic-related advantages and future prospective are promising to be able to improve operative outcomes, reduce surgeon’s fatigue and provide a technology easy to implement with a fast learning curve. Conclusions: Robotic technology applied to laparoscopy in the treatment of endometriosis could be seen as an effective and safe alternative to the conventional laparoscopic treatment

Controversies in Surgical Staging of Endometrial Cancer

Endometrial cancer is the most common gynaecological malignancy and its incidence is increasing. In 1998, international federation of gynaecologists and obstetricians (FIGO) required a change from clinical to surgical staging in endometrial cancer, introducing pelvic and paraaortic lymphadenectomy. This staging requirement raised controversies around the importance of determining nodal status and impact of lymphadenectomy on outcomes. There is agreement about the prognostic value of lymphadenectomy, but its extent, therapeutic value, and benefits in terms of survival are still matter of debate, especially in early stages. Accurate preoperative risk stratification can guide to the appropriate type of surgery by selecting patients who benefit of lymphadenectomy. However, available preoperative and intraoperative investigations are not highly accurate methods to detect lymph nodes and a complete surgical staging remains the most precise method to evaluate extrauterine spread of the disease. Laparotomy has always been considered the standard approach for endometrial cancer surgical staging. Traditional and robotic-assisted laparoscopic techniques seem to provide equivalent results in terms of disease-free survival and overall survival compared to laparotomy. These minimally invasive approaches demonstrated additional benefits as shorter hospital stay, less use of pain killers, lower rate of complications and improved quality of life

The use of near-infrared imaging with indocyanine green in the ovarian tissue transplantation: a case report

The request for fertility preservation has consistently increased in recent years. To our knowledge this case report is the first to describe the application of near-infrared intraoperative imaging using indocyanine green (NIR-ICG) during ovarian tissue transplantation (OTT), to assist surgeon choosing the site of implantation of ovarian fragments. OTT was performed in a 42-year-old woman using NIR-ICG to evaluate the vascularisation of peritoneal area as the site of implantation for the ovarian graft. we believe this new approach could be useful in identifying the best reimplantation site

When Two Coincidences are a Clue: A Retrospective Cohort Study Regarding the Incidence of Ruptured Tubal Pregnancies in a Northern Italy Hospital During the COVID-19 Pandemic

Background: Undiagnosed ectopic pregnancies are among the main gynecological emergencies, and hemorrhage from an ectopic pregnancy is still the leading cause of maternal mortality in the first trimester. During the first lockdown period in Italy (March–April 2020) and in March 2021 restrictive measures were issued by the Italian government, but their impact on the incidence of ruptured tubal pregnancies remains unknown. Methods: The purpose of this study was to evaluate the impact of restrictive measures for the COVID-19 outbreak on the incidence of ruptured tubal pregnancies at our referral center for endoscopic gynecologic surgery. In particular, the primary outcome was the comparison of the incidence of ruptured tubal pregnancies between the lockdown phases and the other months of the pandemic. For this retrospective cohort study we considered all women examined for tubal ectopic pregnancy at our emergency unit from 1 January 2019 to 30 April 2021. We divided patients into three groups according to the period they were referred to our center: 10 March 2019–10 March 2020 (Pre-Covid period); 11 March–4 May 2020 and 6 March–30 April 2021 (Lockdown periods); 5 May 2020–5 March 2021 (COVID-19 pandemic period without restrictive policies). We compared data acquired during the lockdown phases with data collected both before the COVID-19 pandemic and during the restriction-free COVID-19 period. Results: 31 of 85 women were diagnosed with a ruptured tubal pregnancy. The proportion of ruptured ectopic pregnancies was higher during the lockdown period than the other two periods combined (62.5% vs 30.4%, p = 0.016). Mean gestational age and beta-HCG levels showed the same tendency (7.31 ± 1.25 weeks vs 5.99 ± 1.28 weeks, p < 0.0001; 7392.56 ± 4337.50 mUI/mL vs 4188.36 ± 3235.95 mUI/mL, p = 0.001). There were no differences between the proportion of ruptured pregnancies during the whole COVID-19 pandemic and the months preceding it (45.7% vs 25.6%, p = 0.07). Conclusions: Our study demonstrated that restrictive lockdown policies for the containment of the COVID-19 outbreak are associated with an increased rate of ruptured extrauterine tubal pregnancies