Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy.

Endometrial cancer is one the most prevalent gynecological cancers and, unfortunately, has a poor prognosis due to low response rates to traditional treatments. However, the progress in molecular biology and understanding the genetic mechanisms involved in tumor processes offers valuable information that has led to the current classification that describes four molecular subtypes of endometrial cancer. This review focuses on the molecular mechanisms involved in the pathogenesis of endometrial cancers, such as genetic mutations, defects in the DNA mismatch repair pathway, epigenetic changes, or dysregulation in angiogenic or hormonal signaling pathways. The preclinical genomic and molecular investigations presented allowed for the identification of some molecules that could be used as biomarkers to diagnose, predict, and monitor the progression of endometrial cancer. Besides the therapies known in clinical practice, targeted therapy is described as a new cancer treatment that involves identifying specific molecular targets in tumor cells. By selectively inhibiting these targets, key signaling pathways involved in cancer progression can be disrupted while normal cells are protected. The connection between molecular biomarkers and targeted therapy is vital in the fight against cancer. Ongoing research and clinical trials are exploring the use of standard therapy agents in combination with other treatment strategies like immunotherapy and anti-angiogenesis therapy to improve outcomes and personalize treatment for patients with endometrial cancer. This approach has the potential to transform the management of cancer patients. In conclusion, enhancing molecular tools is essential for stratifying the risk and guiding surgery, adjuvant therapy, and cancer treatment for women with endometrial cancer. In addition, the information from this review may have an essential value in the personalized therapy approach for endometrial cancer to improve the patient's life.

The Artificial Ovary: the Next Step in Fertility Preservation in Cancer Patients.

The cryopreservation procedure of ovarian tissue is used for subsequent transplantation to preserve fertility in cancer patients. In the case of cancers with possible ovarian damage, due to the increased risk of transmission of malignant cells in the cryopreserved ovarian tissue, after remission of the disease, the transplant cannot be performed due to the high rate of recurrence. Thus, to resolve fertility preservation in these cancer patients, making an artificial ovary that could be transplanted under maximum safety conditions was necessary. This was not easy to achieve because it was essential to develop a porous and rigid matrix that could encapsulate and protect the ovarian follicles and, at the same time, create an optimal neuroendocrine environment. The present article analyzes the technological progress in creating an artificial ovary, the opportunity for transplantation, the proper counseling of these patients, and the prognosis regarding using this modern technique to preserve fertility.

Sucrosomial® iron effectiveness in recovering from mild and moderate iron-deficiency anemia in the postpartum period.

BACKGROUND: Postpartum iron deficiency anemia (PPIDA) is highly prevalent in developing countries where it constitutes an important cause of maternal morbidity and mortality. Potential determinants of PPIDA are prepartum iron deficiency or iron deficiency anemia in association with severe blood loss during delivery. We investigated the efficacy of oral Sucrosomial® iron for recover from mild-to-moderate PPIDA. METHODS: This pilot study was conducted in three medical centers in Romania. Adult women (≥ 18y) with mild (hemoglobin [Hb] 9-11 g/dL) or moderate (Hb 7-9 g/dL) PPIDA diagnosed at screening (2-24 h after delivery) were eligible. Women with mild PPIDA received oral Sucrosomial® iron (Pharmanutra, S.p.A, Italy) once daily (30 mg elemental iron per capsule) for 60 days. Those with moderate PPIDA received oral Sucrosomial® iron twice daily (60 mg elemental iron) for 10 days, followed by a 50-day course of oral Sucrosomial® iron once daily (30 mg elemental iron). Laboratory parameters, as well as subjective clinical symptoms using a 3-point Likert Scale, were assessed at baseline and on study days 10, 30 and 60. RESULTS: Sixty anemic women entered the study, but three were missed during follow-up. At day 60, a Hb rise was observed in both groups (+ 3.6 ± 1.5 g/dL; p < 0.01), 81% experienced correction of anemia (Hb ≥ 12 g/dL), 36% achieved a ferritin concentration ≥ 30 ng/mL (p < 0.05), and 54% a transferrin saturation (TSAT) ≥ 20% (p < 0.01). For women still anemic at day 60, mean Hb was close to normality (11.3 ± 0.8 g/dL). Resolution of IDA-associated clinical symptoms was already observed just 10 days after treatment initiation. No patient discontinued treatment due to gastrointestinal adverse events. CONCLUSIONS: Sucrosomial® iron was shown to be potentially effective and well tolerated at treating mild and moderate PPIDA. These results encourage the use of oral Sucrosomial® iron as a treatment option for PPIDA, but larger studies with longer follow-up are warrant.

The Current Strategy in Hormonal and Non-Hormonal Therapies in Menopause-A Comprehensive Review.

Menopause is a natural stage of hormonal aging in women, accompanied by a series of symptoms that reduce the quality of life of a fully active person. As no therapy is entirely satisfactory, the race for a better option is in full swing. Our study objective is to investigate the most recent menopause studies on pharmacological resources, emerging therapies, and the particularities of hormonal replacement therapy (HRT). For this purpose, a comprehensive search was conducted in two main databases (PubMed and Web of Science) guided by the specific keywords "menopause" and "therapy" or "estrogen" or "progesterone" or "hormone replacement" during the last ten years period. Studies were eligible if they met certain criteria: randomized controlled trials (RCT) in adult women with menopause and hormonal or non-hormonal therapies. We selected 62 RCTs, which are focused on four main topics: (a) epidemiology of menopause-related symptoms, (b) hormonal replacement therapy (HRT) selective estrogen receptor modulators, (c) emerging therapies, and (d) menopause. HRT has proven a real health benefit for menopausal women; besides, complementary interventions must be considered. Further studies are needed on menopause and menopause-related therapies. The continuous updating of clinical experience will strengthen the therapeutic benefit and the decision to treat patients safely. This goal will fully access all therapeutic resources to address an unresolved health issue of active adult women.

Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women.

Polycystic ovary syndrome (PCOS) is a disorder with an unknown etiology that features a wide range of endocrine and metabolic abnormalities that hamper fertility. PCOS women experience difficulties getting pregnant, and if pregnant, they are prone to miscarriage, gestational diabetes, pregnancy-induced hypertension and preeclampsia, high fetal morbidity, and perinatal mortality. Insulin, the pancreatic hormone best known for its important role in glucose metabolism, has an underrated position in reproduction. PCOS women who have associated insulin resistance (with consequent hyperinsulinemia) have fertility issues and adverse pregnancy outcomes. Lowering the endogen insulin levels and insulin resistance appears to be a target to improve fertility and pregnancy outcomes in those women. Berberine is an alkaloid with a high concentration in various medicinal herbs that exhibits a hypoglycaemic effect alongside a broad range of other therapeutic activities. Its medical benefits may stand up for treating different conditions, including diabetes mellitus. So far, a small number of pharmacological/clinical trials available in the English language draw attention towards the good results of berberine's use in PCOS women with insulin resistance for improving fertility and pregnancy outcomes. Our study aims to uncover how berberine can counteract the negative effect of insulin resistance in PCOS women and improve fertility and pregnancy outcomes.

New Entity-Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement.

Beta-thalassemia (BTH), a recessively inherited haemoglobin (Hb) disorder, causes iron overload (IO), extra-medullary haematopoiesis and bone marrow expansion with major clinical impact. The main objective of this review is to address endocrine components (including aspects of reproductive health as fertility potential and pregnancy outcome) in major beta-thalassemia patients, a complex panel known as thalassemic endocrine disease (TED). We included English, full-text articles based on PubMed research (January 2017-June 2022). TED includes hypogonadism (hypoGn), anomalies of GH/IGF1 axes with growth retardation, hypothyroidism (hypoT), hypoparathyroidism (hypoPT), glucose profile anomalies, adrenal insufficiency, reduced bone mineral density (BMD), and deterioration of microarchitecture with increased fracture risk (FR). The prevalence of each ED varies with population, criteria of definition, etc. At least one out of every three to four children below the age of 12 y have one ED. ED correlates with ferritin and poor compliance to therapy, but not all studies agree. Up to 86% of the adult population is affected by an ED. Age is a positive linear predictor for ED. Low IGF1 is found in 95% of the population with GH deficiency (GHD), but also in 93.6% of persons without GHD. HypoT is mostly pituitary-related; it is not clinically manifested in the majority of cases, hence the importance of TSH/FT4 screening. HypoT is found at any age, with the prevalence varying between 8.3% and 30%. Non-compliance to chelation increases the risk of hypoT, yet not all studies confirmed the correlation with chelation history (reversible hypoT under chelation is reported). The pitfalls of TSH interpretation due to hypophyseal IO should be taken into consideration. HypoPT prevalence varies from 6.66% (below the age of 12) to a maximum of 40% (depending on the study). Serum ferritin might act as a stimulator of FGF23. Associated hypocalcaemia transitions from asymptomatic to severe manifestations. HypoPT is mostly found in association with growth retardation and hypoGn. TED-associated adrenal dysfunction is typically mild; an index of suspicion should be considered due to potential life-threatening complications. Periodic check-up by ACTH stimulation test is advised. Adrenal insufficiency/hypocortisolism status is the rarest ED (but some reported a prevalence of up to one third of patients). Significantly, many studies did not routinely perform a dynamic test. Atypical EM sites might be found in adrenals, mimicking an incidentaloma. Between 7.5-10% of children with major BTH have DM; screening starts by the age of 10, and ferritin correlated with glycaemia. Larger studies found DM in up to 34%of cases. Many studies do not take into consideration IGF, IGT, or do not routinely include OGTT. Glucose anomalies are time dependent. Emerging new markers represent promising alternatives, such as insulin secretion-sensitivity index-2. The pitfalls of glucose profile interpretation include the levels of HbA1c and the particular risk of gestational DM. Thalassemia bone disease (TBD) is related to hypoGn-related osteoporosis, renal function anomalies, DM, GHD, malnutrition, chronic hypoxia-induced calcium malabsorption, and transplant-associated protocols. Low BMD was identified in both paediatric and adult population; the prevalence of osteoporosis/TBD in major BTH patients varies; the highest rate is 40-72% depending on age, studied parameters, DXA evaluation and corrections, and screening thoracic-lumbar spine X-ray. Lower TBS and abnormal dynamics of bone turnover markers are reported. The largest cohorts on transfusion-dependent BTH identified the prevalence of hypoGn to be between 44.5% and 82%. Ferritin positively correlates with pubertal delay, and negatively with pituitary volume. Some authors appreciate hypoGn as the most frequent ED below the age of 15. Long-term untreated hypoGn induces a high cardiovascular risk and increased FR. Hormonal replacement therapy is necessary in addition to specific BTH therapy. Infertility underlines TED-related hormonal elements (primary and secondary hypoGn) and IO-induced gonadal toxicity. Males with BTH are at risk of infertility due to germ cell loss. IO induces an excessive amount of free radicals which impair the quality of sperm, iron being a local catalyser of ROS. Adequate chelation might improve fertility issues. Due to the advances in current therapies, the reproductive health of females with major BTH is improving; a low level of statistical significance reflects the pregnancy status in major BTH (limited data on spontaneous pregnancies and growing evidence of the induction of ovulation/assisted reproductive techniques). Pregnancy outcome also depends on TED approach, including factors such as DM control, adequate replacement of hypoT and hypoPT, and vitamin D supplementation for bone health. Asymptomatic TED elements such as subclinical hypothyroidism or IFG/IGT might become overt during pregnancy. Endocrine glands are particularly sensitive to iron deposits, hence TED includes a complicated puzzle of EDs which massively impacts on the overall picture, including the quality of life in major BTH. The BTH prognostic has registered progress in the last decades due to modern therapy, but the medical and social burden remains elevated. Genetic counselling represents a major step in approaching TH individuals, including as part of the pre-conception assessment. A multidisciplinary surveillance team is mandatory.

Diagnostic Pitfall in Atypical Febrile Presentation in a Patient with a Pregnancy-Specific Dermatosis-Case Report and Literature Review.

Pruritic urticarial papules and plaques of pregnancy (PUPPP) usually occurs in the third trimester of pregnancy in primiparous women. It is a self-limiting inflammatory disorder with a still unknown pathogenic mechanism. The abdominal wall overdistension, with a subsequent inflammatory response due to damage to the connective tissue, represents a pathogenesis explanation. Clinical features involve intensely pruritic urticarial rash with edematous, erythematous papules and plaques. The clinical picture and dermal biopsy establish the diagnosis. Topical corticosteroids and oral antihistamines are usually sufficient, but sometimes systemic corticosteroids are necessary. Maternal and fetal prognosis is excellent, and the lesions resolve after birth with no scarring or pigmentary change. We present a case of a 36-year-old patient with a 32-week pregnancy who was admitted with a generalized pruritic rash accompanied by fever. The final diagnosis was decided after multiple pathology exclusions. Treatment consisted of systemic corticoid therapy. The patient gave birth by cesarean section to a healthy newborn without dermatological lesions or other conditions. Adding more PUPPP cases to the literature portfolio will bring more awareness to this under-recognized and under-reported skin disorder. We trust this case will encourage other physicians to publish more cases of pregnancy-specific dermatoses.

The Role of Programmed Cell Death Receptor 1 in Lung Cancer.

BACKGROUND/AIM: Lung cancer is the most common cancer worldwide. Cancer immunotherapy is the activation of the immune system against cancer. The latest method of immunotherapy involves immune checkpoint inhibitors. Increased levels of programmed death ligand 1 (PD-L1) expression were observed on non-small-cell lung cancer. The association between PD-L1 expression and clinicopathological characteristics in lung cancer is still unclear. PATIENTS AND METHODS: This is a cross-sectional, observational study that evaluated a sample of 41 lung cancer patients diagnosed between March 2019 and December 2020. PD-L1 tumor expression is described as a percentage. RESULTS: Patients were diagnosed with non-microcellular lung cancer and aged 37 to 87 years. Most patients were diagnosed with adenocarcinoma. According to the analysis, the average age of patients with negative PD-L1 tumors was 65.6 years, and of those with positive PD-L1 tumors was 63.6 years. The average value of the tumor proportion score for males was 26.97%, and for females 25.55%. CONCLUSION: No correlation was found between PD-L1 tumor expression and the age and sex of patients.

New approaches in predicting and diagnosing preeclampsia: Congo Red Dot Paper Test (Review).

Preeclampsia (PE), a complication of pregnancy that is characterized by de novo hypertension and proteinuria, remains a leading cause of morbidity and mortality during pregnancy, influencing 2.5-7% of singleton and 7-21% of twin pregnancies. At present, diagnosis is based on traditional but unreliable and nonspecific clinical markers, and treatment of PE is suboptimal, with minimal effect on maternal and fetal mortality and morbidity. With the hope of developing an affordable and simple procedure for PE prediction for developing countries, a previous study examined the use of Congo red staining of misfolded and damaged proteins in the urine of women with PE. This feature has diagnostic and prognostic potential since it precedes the onset of clinical manifestations and correlates with disease severity. The test is inexpensive, popular within the medical staff, easy to use, and identifies women with PE in only 3 min. Obstetrical providers benefit from the Congo Red Dot Paper Test analysis, since a negative result promotes lesser waiting times in triage, prevents unneeded admissions, and diminishes the health costs associated per case.

A Challenging Diagnosis: Placental Mesenchymal Dysplasia-Literature Review and Case Report.

We describe a 22-year-old woman (2-gravid) case who was referred to our clinic at 18 weeks of gestation for a placenta with vesicular lesions discovered on prenatal examination routine. An ultrasound exam at 31 weeks of gestation showed numerous vesicular lesions, which gradually augmented as the pregnancy advanced. A live normal-appearing fetus was confirmed by intrauterine growth restriction (IUGR). The maternal serum ß-human chorionic gonadotropin level remained in normal ranges. At some point, a multidisciplinary medical consensus considered the termination of the pregnancy, but the patient refused to comply. At 33 weeks of gestation, preterm premature rupture of membranes (pPROM) occurred, and she spontaneously delivered a 1600 g healthy female baby with a good long-term outcome. Placental mesenchymal dysplasia (PMD) was retrospectively diagnosed after confronting the data from ultrasound, chorionic villus sampling (CVS), amniocentesis, pathological examination, and immunohistochemical stain. The lack of sufficient reports of PMD determines doctors to be cautious and reserved, approaching these cases more radically than necessary. We reviewed this disease and searched for all cases of PMD associated with healthy, live newborns.

The Effects of SARS-CoV-2 Infection on Female Fertility: A Review of the Literature.

As the coronavirus pandemic is far from ending, more questions regarding the female reproductive system, particularly fertility issues, arise. The purpose of this paper is to bring light upon the possible link between COVID-19 and women's reproductive health. This review emphasizes the effect of SARS-CoV-2 on the hormones, endometrium and menstrual cycle, ovarian reserve, follicular fluid, oocytes, and embryos. The results showed that endometrial samples did not express SARS-CoV-2 RNA. Regarding the menstrual cycle, there is a large range of alterations, but they were all reversible within the following months. The ovarian reserve was not significantly affected in patients recovering from both mild and severe infection in most cases, except one, where the levels of AMH were significantly lower and basal follicle-stimulating hormone (FSH) levels were increased. All COVID-19 recovered patients had positive levels of SARS-CoV-2 IgG in the follicular fluid. The amount of retrieved and mature oocytes and the fertilization rate were unharmed in three studies, except for one study, where the quantity of retrieved and mature oocytes was reduced in patients with higher levels of SARS-CoV-2 antibodies. The numbers of blastocysts, top-quality embryos, and euploid embryos were affected in most of the studies reviewed.

Difference between Preterm Birth in Adolescent and Adult Patients.

Background: Preterm delivery represents an important public health problem due to its neonatal outcomes. There are numerous complications that occur due to prematurity, but the most significant one is represented by neonatal death. Even if the certain mechanism of prematurity is elusive, there are various risk factors known to be involved in the etiology of preterm birth, among which one is young age. Objectives: The present study aims to find whether preterm delivery has a higher rate in adolescent patients and if neonatal outcomes are different in adolescent and adult patients. Patients and methods:We performed an observational retrospective study about preterm infants from adolescent and adult patients. Thus, we analyzed 96 patients aged between 13 and 38 years who delivered in our unit between October 1st 2018 and December 31st 2021. Patients were divided into two groups: a study group (n=59), which included adolescents who delivered preterm, and a control group (n=37), which comprised adult patients who delivered preterm. We evaluated the rate of prematurity of all births and among patients enrolled in the present study and the neonatal outcome by newborn's weight, one-minute newborn's Apgar score and Neonatal Intensive Care Unit (NICU) admission. Results:In our study, the rate of prematurity was higher in adolescent patients, with a rate of 61.46%. The newborns' outcomes, analyzed by newborn's weight and one-minute Apgar score, were better in adolescent patients compared to adult ones. Therefore, newborns from adult patients needed neonatal intensive care more often, with a rate of 62.16%, while in the study group the percentage was 38.98%. The rate of antenatal care was higher in adult patients compared to adolescent ones (32.43% versus 27.12%). Conclusion:Adolescents have a higher risk of preterm delivery; however, their newborns have better outcomes than those of adult patients. The lack of antenatal care represents a risk factor for preterm delivery.

A Warning Call for Fertility Preservation Methods for Women Undergoing Gonadotoxic Cancer Treatment.

Malignant hematological conditions have recognized an increased incidence and require aggressive treatments. Targeted chemotherapy, accompanied or not by radiotherapy, raises the chance of defeating the disease, yet cancer protocols often associate long-term gonadal consequences, for instance, diminished or damaged ovarian reserve. The negative effect is directly proportional to the types, doses, time of administration of chemotherapy, and irradiation. Additionally, follicle damage depends on characteristics of the disease and patient, such as age, concomitant diseases, previous gynecological conditions, and ovarian reserve. Patients should be adequately informed when proceeding to gonadotoxic therapies; hence, fertility preservation should be eventually regarded as a first-intention procedure. This procedure is most beneficial when performed before the onset of cancer treatment, with the recommendation for embryos or oocytes' cryopreservation. If not feasible or acceptable, several options can be available during or after the cancer treatment. Although not approved by medical practice, promising results after in vitro studies increase the chances of future patients to protect their fertility. This review aims to emphasize the mechanism of action and impact of chemotherapy, especially the one proven to be gonadotoxic, upon ovarian reserve and future fertility. Reduced fertility or infertility, as long-term consequences of chemotherapy and, particularly, following bone marrow transplantation, is often associated with a negative impact of recovery, social and personal life, as well as highly decreased quality of life.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

Postoperative Assessment of the Quality of Life in Patients with Colorectal Endometriosis.

Morbidity and mortality alone are not comprehensive measures of evaluating the benefits of surgical interventions in endometriosis patients, thus, subjective patient-reported instruments are required. The 36-tem Short Form Survey (SF-36) is a Health-Related Quality of Life (HRQoL) instrument that has not been validated yet for women with endometriosis. The aims of this study are to evaluate the validity and reliability of the SF-36 in patients with colorectal endometriosis and to compare the HRQoL before and after surgery, using different Quality of Life (QoL) instruments: the Gastrointestinal QoL Index (GIQLI) and Knowles-Eccersley-Scott Symptom Questionnaire (KESS). We conducted a retrospective study using prospectively recorded data in the North-West Inter-Regional Female Cohort for Patients with Endometriosis (CIRENDO) database. The assessment was performed on four hundred and eighty-eight patients before and 12 months after the surgery. Preoperative and postoperative item-internal consistency and Cronbach's α proved evidence for good reliability showing that SF-36 is a useful instrument for endometriosis patients' QoL. The domains of Role (limitation) physical, Bodily pain and Role (limitation) emotional showed the most remarkable improvements (difference before vs. one year after surgery) with p < 0.001. Our data show that SF-36 has validity and reliability and can be used in patients with endometriosis. Surgery improved the QoL and digestive function.

Maternal-Fetal Outcomes in Women with Endometriosis and Shared Pathogenic Mechanisms.

The connection between endometriosis and pregnancy outcomes is trending among the research topics. Until recently, endometriosis and its painful symptomatology were considered to be alleviated by pregnancy. However, these beliefs have shifted, as emerging literature has demonstrated the role of this condition in affecting pregnancy evolution. The underlying pathogenesis of endometriosis is still poorly understood, all the more when pregnancy complications are involved. Debatable opinions on endometriosis associated with obstetric complications exist because of the potential bias resulting from the heterogeneity of preceding evidence. This review aims to evaluate the connection between endometriosis and adverse pregnancy outcomes and their shared pathogenic mechanisms. We searched PubMed and EMBASE and focused on the studies that include placenta praevia, premature rupture of membranes, spontaneous preterm birth, gestational hypertension, preeclampsia, obstetric hemorrhages (ante- and postpartum bleeding, abruptio placentae), miscarriage, stillbirth, neonatal death, gestational diabetes mellitus, gestational cholestasis, small for gestational age, and their association with endometriosis. Not only the risks of emergence were highlighted, but also the pathogenic connections. Epigenetic alterations of some genes were found to be mirrored both in endometriosis and obstetric complications. This review issues a warning for providing increased attention to pregnant women with endometriosis and newborns as higher risks of preeclampsia, placental issues, and preterm deliveries are associated.

Social Freezing: Pressing Pause on Fertility.

Increasing numbers of women are undergoing oocyte or tissue cryopreservation for medical or social reasons to increase their chances of having genetic children. Social egg freezing (SEF) allows women to preserve their fertility in anticipation of age-related fertility decline and ineffective fertility treatments at older ages. The purpose of this study was to summarize recent findings focusing on the challenges of elective egg freezing. We performed a systematic literature review on social egg freezing published during the last ten years. From the systematically screened literature, we identified and analyzed five main topics of interest during the last decade: (a) different fertility preservation techniques, (b) safety of freezing, (c) usage rate of frozen oocytes, (d) ethical considerations, and (e) cost-effectiveness of SEF. Fertility can be preserved for non-medical reasons through oocyte, embryos, or ovarian tissue cryopreservation, with oocyte vitrification being a new and optimal approach. Elective oocyte cryopreservation is better accepted, supports social gender equality, and enhances women's reproductive autonomy. Despite controversies, planned oocyte cryopreservation appears as a chosen strategy against age-related infertility and may allow women to feel that they are more socially, psychologically, and financially stable before motherhood.

The prevalence of SARS-CoV-2 antibodies in triage-negative patients and staff of a fertility setting from lockdown release throughout 2020.

STUDY QUESTION: What is the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in triage-negative patients undergoing ART and fertility care providers after lockdown release and throughout 2020? SUMMARY ANSWER: Out of the triage-negative patients whose blood samples were assessed for SARS-CoV-2 antibodies over 6 months, 5.2% yielded positive results with a significantly higher rate in health care workers (HCWs) and a significant month-by-month increase in those with evidence of antibodies. WHAT IS KNOWN ALREADY: Patients of reproductive age are more prone to asymptomatic or minimal forms of coronavirus disease 2019 (COVID-19) as compared to older age groups, and the identification of those with active infection and those already exposed (and probably immunized) is important for safety and cost-effective use of testing resources in the fertility setting. Data on the prevalence of SARS-CoV-2 in ART patients are limited and encompass short time frames; current rates are unknown. There is also no consensus on the optimal way of screening triage-negative ART patients in moderate/high-risk areas. STUDY DESIGN SIZE DURATION: A prospective longitudinal unicentric study on triage negative ART patients (n = 516) and clinical staff (n = 30) was carried out. We analyzed 705 serological tests for SARS-CoV-2 sampled between 17 May 2020 (the first working day after lockdown release) up to 1 December 2020, to assess the positivity rates for SARS-CoV-2 antibodies. PARTICIPANTS/MATERIALS SETTING METHODS: We collected data on the serological status for IgM and IgG antibodies against SARS-CoV-2 in 516 triage-negative men (n = 123) and women (n = 393) undergoing ART at a private fertility center and 30 HCWs that were at work during the study period. Antibodies were detected with a capture chemiluminescence assay (CLIA) targeting the highly Immunogenic S1 and S2 domains on the virus spike protein. We also analyzed the molecular test results of the cases exhibiting a positive serology. MAIN RESULTS AND THE ROLE OF CHANCE: The data showed that 5.2% of the triage-negative ART patients had a positive serological result for SARS-CoV-2, with an overall conversion rate of 2.1% for IgG and 4.6% for IgM. There was no significant difference in seroprevalence between sexes. The small cohort (n = 30) of HCWs had a markedly increased seroprevalence (12.9% for Ig M and 22.6% for IgG). The highest seropositivity in our cohort was recorded in November (16.2%). The IgM positivity rates revealed significant monthly increments, paralleling official prevalence rates based on nasopharyngeal swabs. No positive molecular tests were identified in cases exhibiting a solitary positive IgG result. We show that despite a 6-fold increase in the number of ART patients with a positive serology between May and December 2020, most of our patients remain unexposed to the virus. The study was undertaken in a high-risk area for COVID-19, with a 20-times increase in the active cases across the study period. LIMITATIONS REASONS FOR CAUTION: The geographical restriction, alongside the lack of running a second, differently-targeted immunoassay (orthogonal testing), could limit the generalizability and translation of our results to other fertility settings or other immunoassays. WIDER IMPLICATIONS OF THE FINDINGS: The low positivity rates for IgG against the SARS-CoV-2 spike protein seen at the end of 2020 imply that most of the fertility patients are still at risk for SARS-CoV-2 infection. Until mass vaccination and other measures effectively diminish the pandemic, risk mitigation strategies must be maintained in the fertility units in the foreseeable future. Patients with a solitary IgG+ status are most likely 'non-infectious' and can elude further testing without giving up the strict use of universal protective measures. With increasing seroprevalences owing to infection or vaccination, and with the consecutive increase in test performance, it is possible that serological screening of ART patients might be more cost-effective than PCR testing, especially for the many patients with repeat treatments/procedures in a time-frame of months. STUDY FUNDING/COMPETING INTERESTS: This research received no external funding. All authors declare having no conflict of interest with regard to this trial.

Long-term Response After Stopping Immunotherapy in a Patient With Metastatic Renal Cancer.

BACKGROUND/AIM: Kidney cancers account for about 2% of human malignancies. In recent decades, the incidence of this cancer type has gradually increased, mainly due to advances in imaging. The metastatic potential of these cancers is significant: a quarter of patients will immediately present with metastases and more than one third of patients treated with nephrectomy for a localized disease will develop metastases during their course. In total, more than half of patients will suffer from the consequences of metastasis. The median survival at this stage is only thirteen months, so the therapeutic challenge is immense. CASE REPORT: The present case report describes a case of left renal clear cell carcinoma with brain, lung, right adrenal, bone and lymph node metastases in a 55-year-old male. The patient received only one line of anticancer treatment with sunitinib, which could not be continued due to haemorrhagic manifestations in brain metastases. The treatment was changed with immunotherapy which showed its effect even if it was stopped due to the patient wishes in the context of the COVID-19 epidemic. CONCLUSION: Immunotherapy opens the doors to a new era in treatment of metastatic renal cancer and shows efficiency even after it has been stopped.

Long-term oncological outcome in patients with cervical cancer after 3 trimodality treatment (radiotherapy, platinum-based chemotherapy, and robotic surgery).

ABSTRACT: Cervical cancer represents a general health issue spread all over the globe, which prompts the surge of scientific survey toward the rise of survival and condition of life of these patients. American and European guidelines suggest the open surgery, laparoscopic, and robotic surgery are the main therapeutic approaches for radical hysterectomy for patients with cervical cancer. This is the first survey to analyze the long-term oncological outcome of an extensive series of subjects cared for with multimodality treatment, here comprising robotic surgery.This study intents to evaluate the long-term oncological result in patients diagnosed with cervical cancer treated with radiotherapy (±chemotherapy) and robotic surgery compared with open surgery. Medical files of 56 patients diagnosed with cervical cancer who underwent a robotic hysterectomy and radiotherapy ± chemotherapy were retrospectively analyzed.The median age at diagnosis was 50.5 (range: 23-70). Eleven patients (19.6%) presented in an early stage (IB-IIA) and 80.4% advanced stage (IIB-IVA). Overall response rate after radiotherapy and chemoradiotherapy was 96.2%. Pathologic complete response was obtained in 64% of patients. After a median follow-up of 60 months (range: 6-105 months), 8 patients (14.2%) presented local recurrence or distant metastases. Disease-free survival (DFS) was 92% at 2 years and 84% at 3 and 5 years. Overall survival (OS) rates at 2, 3, and 5 years for patients with robotic surgery were 91%, 78%, and 73%, median OS not reached. OS was lower in the arm of open surgery (2, 3, and 5 years 87%, 71%, and 61%, respectively; median OS was 72 months P = .054). The multivariate analysis regarding the outcome of patients revealed an advantage for complete versus partial response (P < .002), for early versus advanced stages (P = .014) and a 10% gained in DFS at 3 years for patients in whom chemoradiotherapy was administered (DFS at 3 years 75% vs 85%) in patients with advanced stages.Robotic surgery has a favorable oncological outcome when associated with multimodal therapy.