Search Results (157)

Purpose: To review parental pre-pregnancy and pregnancy exposures in relation to pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 17 March 2021. Results: Strong evidence links increased risk of childhood cancer with maternal diabetes, age, and alcohol and coffee consumption during pregnancy. Both paternal and maternal cigarette smoking before and during pregnancy are associated with childhood cancers. Diethylstilbestrol (DES) exposure in utero has long been known to be causally associated with increased risk of vaginal/cervical cancers in adolescent girls. More recent evidence implicates in utero DES exposure to testicular cancer in young men and possible intergenerational effects on ovarian cancer in the granddaughters of women exposed to DES during pregnancy. There is strong evidence that childhood cancer risk is also associated with both high and very low birth weight and with gestational age. Evidence is also strong for the protective effects of maternal vitamin consumption and a healthy diet during pregnancy. Unlike early studies, those reviewed here show no association between in utero exposure to medical ionizing radiation, which may be explained by reductions over time in radiation doses, avoidance of radiation during pregnancy, and/or by inadequate statistical power to detect small increases in risk, rather than a lack of causal association. Evidence is mixed or conflicting for an association between childhood cancer and maternal obesity, birth order, cesarean/instrumental delivery, and prenatal exposure to diagnostic medical radiation. Evidence is weak or absent for associations between childhood cancer and multiple gestations or assisted reproductive therapies, as well as prenatal exposure to hormones other than DES, and medications. Full article

Background and Objectives: Epithelial ovarian cancer (EOC) remains the deadliest gynecologic malignancy, yet the psychosocial dynamics of early survivorship are inadequately described. We prospectively quantified six-month trajectories in the quality of life in a consecutive cohort of 88 women newly diagnosed with EOC and explored clinical moderators of change. Methods: Eighty-eight consecutive patients (mean age 59.1 ± 10.7 years) completed the SF-36, WHOQOL-BREF, EORTC QLQ-C30, and 10-item Perceived Stress Scale (PSS-10) at baseline (pre-therapy) and six months after cytoreductive surgery ± platinum-based chemotherapy. Stage (FIGO I–II vs. III–IV) and treatment pathway (primary debulking surgery, neoadjuvant chemotherapy plus interval debulking, chemotherapy only) data were recorded. Results: Global QoL improved significantly (EORTC Global Health +5.9 ± 7.7 points; p < 0.001) while perceived stress declined (ΔPSS −3.6 ± 5.1; p < 0.001). SF-36 Physical Functioning rose 4.7 ± 7.9 points (p < 0.001) and Mental Health 4.4 ± 7.9 points (p = 0.004). The WHOQOL Physical and Psychological domains gained 4.7 ± 7.1 and 4.3 ± 7.4 points, respectively (both p < 0.01). Advanced-stage patients experienced larger stress reductions than early-stage patients (−4.1 ± 2.7 vs. −2.9 ± 2.2; p = 0.028) but comparable QoL gains. Greater stress relief correlated with greater mental-health improvement (r = −0.51) and global-health gains (r = −0.45) (all p < 0.001). Treatment pathway did not significantly influence trajectories. Conclusions: Early survivorship after first-line ovarian-cancer therapy was characterized by the clinically meaningful recovery of physical and emotional functioning together with the moderate alleviation of perceived stress. Improvements were observed irrespective of stage and treatment strategy, suggesting that contemporary multimodal regimens do not inevitably compromise patient-reported outcomes. Our estimates provide preliminary effect sizes that should be validated in multi-center cohorts with longer follow-up. Full article

Introduction: Fetal ovarian cysts are known to be a common form of fetal abdominal masses in female fetuses, often resulting from hormonal stimulation in utero. Although many resolve spontaneously without sequelae, others can develop into more complex pathologies, such as intracystic hemorrhage or torsion, which can compromise ovarian integrity and long-term reproductive outcomes. Early detection and appropriate follow-up evaluation are therefore crucial for optimal perinatal management. Materials and Methods: We conducted a retrospective study of 12 cases of fetal ovarian cysts diagnosed by routine prenatal ultrasound examinations over a two-year period at our institution. Inclusion criteria were the presence of a cystic adnexal lesion detected in utero, detailed prenatal ultrasound documentation, and a comprehensive postnatal examination. Sonographic features such as cyst size, internal echogenicity, and signs of vascular compromise were recorded. The mother’s clinical variables, including gestational age at diagnosis and relevant medical conditions, were noted. Postnatal follow-up evaluation consisted of ultrasound examinations and, if indicated, pediatric surgical consultation. Results: Of the 12 cases, 9 were characterized by a simple cystic morphology. All spontaneously regressed postnatally and did not require surgical intervention. Three were defined as complex cysts showing septations or echogenic deposits; one of these cysts required immediate surgical exploration for suspected torsion. No cases with a malignant background were identified. All infants showed a favorable course with normal growth and development until follow-up evaluation. Conclusions: This series emphasizes that most fetal ovarian cysts are benign and often resolve without intervention, highlighting the benefit of systematic prenatal imaging. Nevertheless, complex or large cysts require close prenatal and neonatal monitoring to diagnose complications such as torsion. Full article

Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in childhood, its reproductive implications are underrecognized. This study reports a case of successful fertility preservation in an adult woman with APECED and reviews the relevant literature. Methods: We describe the clinical course of a 37-year-old woman with genetically confirmed APECED who underwent ovarian stimulation for fertility preservation. A comprehensive PubMed search was also conducted to identify English-language case reports on fertility preservation in APECED-associated POI. Results: The patient experienced menarche at age 13, adrenal insufficiency at 14, and menstrual irregularities from age 18. Genetic analysis confirmed an AIRE mutation (NM_000383: exon 11: c.1400+1G>A). Given her relatively high anti-Müllerian hormone level, she opted for fertility preservation and underwent six cycles of ovarian stimulation, resulting in the cryopreservation of 17 mature oocytes. During ovarian stimulation, multiple follicular developments were observed, but serum E2 levels remained low. The literature review identified fewer than 20 reported cases addressing fertility preservation in APECED, highlighting its rarity and the lack of standardized management. Conclusions: Although APECED frequently leads to early POI due to impaired steroidogenesis, residual ovarian function may persist. Early assessment of ovarian reserve and timely fertility counseling are crucial, even in asymptomatic patients or those diagnosed in childhood. Reproductive planning should be integrated into the long-term care of women with APECED. Full article

Background: The national guidelines, informed by evidence from the National Institutes of Health (NIH), define the criteria for genetic testing of BRCA1/2 and other genes associated with Hereditary Breast and Ovarian Cancer (HBOC) and Lynch Syndrome (LS). When a germline pathogenic variant (PV) is identified in an index case, clinical recommendations advise informing at-risk relatives about the availability of predictive genetic testing, as early identification of carriers allows for timely implementation of preventive measures. Methods: This retrospective observational study examined data collected between 2017 and 2024 at the Medical Genetics Unit of the “Renato Dulbecco” University Hospital in Catanzaro, Italy. The analysis focused on trends in the identification of individuals carrying PVs in cancer predisposition genes (CPGs) and the subsequent uptake of cascade genetic testing (CGT) among their family members. Results: Over the study period, from 116 probands were performed 257 CGTs on 251 relatives. A notable reduction of approximately ten years in median age was observed, 39% were found to carry familial mutation and were referred to personalized cancer prevention programs. Among these, 62% accessed Oncological Genetic Counselling (CGO) within one year of the proband’s diagnosis, suggesting effective communication and outreach. Conclusions: The findings highlight the critical role of effective CGO and intrafamilial communication in hereditary cancer prevention. The identification of PVs, followed by timely CGTs and implementation of preventive strategies, significantly contributes to early cancer risk management. Periodic monitoring of CGT uptake and outcome trends, as demonstrated in this study, is essential to refine and optimize genetic services and public health strategies. Full article

Background: Ovarian cancer remains the deadliest and leading cause of gynecological cancer-associated mortality in the US. The aim of this study was to characterize the trends in the incidence of ovarian cancer between premenopausal and postmenopausal women to inform future targeted interventions. Methods: This population-based cross-sectional study analyzed data from the US Cancer Statistics (USCS) database, which covered the whole of the US population between 2001 and 2021. Joinpoint regression was used to compute the average annual percentage change (APC) with 95% confidence interval (CI) and age-standardized incidence rates per 1,000,000 population. Results: The results showed that the IR of ovarian cancer declined between 2001 and 2021. Postmenopausal women had greater decreases in the IR of ovarian cancer compared to premenopausal women who showed a small decline. When stratified by race/ethnicity, non-Hispanic American Indian/Alaska Native women aged 20–49 years experienced an increase in the IR of ovarian cancer (APC = 2.4; 95% CI 0.9 to 4.1) compared to other racial/ethnic groups which showed a decline. Joinpoint trend analyses identified one inflection point in localized ovarian cancer incidence trends among all three age groups: an initial decline from 2001 to 2011 among women 20–49 years old and 65+ years old, and from 2001 to 2012 among women 50–64 years old, followed by an upward trend thereafter to 2021. Similarly, there was one inflection point in the IR of ovarian cancer for the clear cell and endometrioid types among women aged 20–49 years old. Conclusions: The IR of ovarian cancer in the US declined significantly among postmenopausal compared to premenopausal women, for whom the IR of ovarian cancer decreased only slightly. Although encouraging, these findings show a need for continued efforts to improve early detection and prevention strategies to mitigate the burden of this deadly disease. Full article

Background: Wolfram syndrome (WFS), also known as DIDMOAD, is a rare monogenic neurodegenerative disorder characterized by four key components: non-autoimmune insulin-dependent diabetes mellitus (DM), optic atrophy, sensorineural hearing loss, and diabetes insipidus. Although it significantly affects quality of life, gonadal dysfunction, particularly hypogonadism, remains underrecognized. Methods: In total, 45 patients (25 men, 20 women) with genetically confirmed WFS from a single tertiary-care center were prospectively followed to assess gonadal function. Men underwent hormonal evaluations, semen analysis, imaging tests, and testicular biopsies. In women, data on age at menarche, menstrual irregularities, and age at menopause were recorded. Hormonal analyses, including anti-Müllerian hormone (AMH) levels, and imaging tests were also conducted. Results: Hypogonadism was identified in 19 men (76.0%), of whom 17 (68.0%) had hypergonadotropic hypogonadism and 2 (8.0%) had hypogonadotropic hypogonadism. Testicular biopsies showed seminiferous tubule damage, Sertoli cell predominance, and reduced Leydig cells. Azoospermia was observed in 12 patients, whereas others presented with oligozoospermia, teratozoospermia, or asthenozoospermia. Most patients exhibited low testosterone levels along with elevated LH and FSH, suggesting primary testicular failure, except for two cases of hypogonadotropic hypogonadism. Correlations between biomarkers, onset age and severity have been analyzed and provide important insights regarding medical treatment. In women, menstrual irregularities were universal, with 20% experiencing premature menopause. Four patients had low AMH levels, with ovarian atrophy in three and a postmenopausal uterus in two, indicating early hypogonadism risk. Conclusions: Gonadal dysfunction is a significant yet overlooked feature of WFS, requiring systematic evaluation during puberty and beyond. Proper management is essential to mitigate metabolic disturbances and psychological impacts, including infertility distress, relationship challenges, and quality of life concerns. Addressing sexual health is crucial as WFS patients live longer and aspire to establish relationships or start families. Full article

Background/Objectives: Premature ovarian insufficiency (POI) is a leading cause of hypoestrogenism in women under the age of 40 years and is associated with an increased risk of impaired bone health. Early diagnosis and timely hormonal intervention are essential to prevent irreversible bone loss. However, diagnostic delay is not uncommon in clinical practice. Methods: We conducted a retrospective analysis of 168 women diagnosed with POI or early menopause (EM) between 2017 and 2024 at a tertiary gynecological endocrinology unit. Bone mineral density (BMD) and T-score were assessed by dual-energy X-ray absorptiometry (DXA) at the time of diagnosis in 125 patients, of whom 116 had secondary amenorrhea. The interval between the last menstrual period (LMP) and diagnosis was used to assess the impact of diagnostic delay. The patients were further stratified by serum estradiol (E2) levels and body mass index (BMI). Results: At the time of diagnosis, 43.1% of patients had osteopenia, and 10.3% had osteoporosis. A statistically significant negative correlation was observed between time to diagnosis and BMD (r = −0.225, p = 0.022), with a similar trend seen for T-score (r = −0.211, p = 0.031). In patients with E2 ≤ 5 ng/L, the association was stronger (BMD: r = −0.401, p = 0.026). Lower E2 levels tended to be associated with poorer bone health in women with a BMI < 25 kg/m², whereas no such trend was observed in those with a higher BMI. Conclusions: Our findings indicate that diagnostic delay in POI is associated with deterioration in bone health, particularly in lean patients and those with severe hypoestrogenism. These results underscore the importance of early recognition and timely initiation of hormone therapy to preserve bone mass and reduce long-term skeletal complications. Full article

Endometriosis, a complex inflammatory disease, affects a significant proportion of women of reproductive age, approximately 10–15%. The disease involves the growth of endometrial glands and stroma outside the uterine cavity, leading to tissue remodeling and fibrosis. Hormonal imbalances, accompanied by local and general inflammation and pain, are key features of endometriosis. Endometriotic lesions are associated with the overproduction of cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, and extracellular vesicles. Genetic predisposition and cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast cells, Th1 in the early phase, Th2 in the late phase, and T regulatory cells play a crucial role in endometriosis. Reduced NK cell function and impaired immune vigilance contribute to endometrial growth. The strong inflammatory condition of the endometrium poses a barrier to the proper implantation of the zygote, contributing to the infertility of these patients. Cytokines from various cell types vary with the severity of the disease. The role of microbiota in endometriosis is still under study. Endometriosis is associated with autoimmunity and ovarian cancer. Hormonal treatments and surgery are commonly used; however, recent interest focuses on anti-inflammatory and immunomodulatory therapies, including cytokine and anti-cytokine antibodies. Modulating the immune response has proven critical; however, more research is needed to optimize treatment for these patients. Full article

Gynecological cancers pose a significant threat to women’s health. This study aimed to investigate the disease burden of cervical, uterine, and ovarian cancers in Asia from 1980 to 2021. The Global Burden of Disease 2021 database (GBD 2021) was used to conduct a cross-sectional study. The incidence, mortality rates, and disability-adjusted life years (DALYs) were obtained as indicators to estimate the burden. The effects of age, period, and cohort on the incidence of gynecological cancers were analyzed via the age-period-cohort web tool (APC-Web). The future trends of the gynecological cancer burden in Asia from 2025 to 2050 were predicted via a Bayesian age-period-cohort model. In 2021, cervical cancer exhibited the highest age-standardized mortality burden (3.1 deaths per 100,000; 95% UI: 2.7–3.4), whereas uterine cancer had the lowest (0.7 deaths per 100,000; 95% UI: 0.6–0.9). Geographically, South Asia has experienced the highest cervical cancer burden, with Seychelles, Mongolia, Cambodia, and Nepal ranking among the most affected nations. In contrast, Central Asia had the highest ovarian cancer burden, led by Georgia, followed by the United Arab Emirates, Seychelles, and Brunei Darussalam. Similarly, the uterine cancer burden was most pronounced in Central Asia, with Georgia, Armenia, Mauritius, and the United Arab Emirates exhibiting elevated rates. Finally, increasing trends in the burden of gynecological cancers were predicted across all age groups from 2025 to 2050, with women aged 60 to 64 years being the most affected. In conclusion, gynecological cancers are significant contributors to the disease burden in Asia. Improved early screening methods are essential to mitigate this increasing burden. Full article

Selective serotonin reuptake inhibitors (SSRIs), like fluoxetine, are increasingly used by women of a reproductive age, raising concerns about their impact on oocyte quality and early embryonic development. This study investigated the effects of chronic fluoxetine exposure on oocyte maturation, ovulation, and embryonic development in a mouse model. Female mice were administered fluoxetine via drinking water, and their reproductive outcomes were compared to those of control mice. Oocyte quantity and quality were assessed following superovulation, including the analysis of spindle morphology, chromatin configuration, and maturation markers. In vitro maturation assays were conducted to evaluate the developmental competence of oocytes exposed to fluoxetine. Finally, the impact of fluoxetine on blastocyst formation, litter size, offspring growth, and ovarian reserve was examined. The results show that fluoxetine treatment reduced the number of ovulated oocytes but did not significantly affect oocyte quality or meiotic spindle formation. Fluoxetine exposure impaired cytoplasmic maturation at the germinal vesicle stage, resulting in a lower proportion of fully mature oocytes and reduced in vitro maturation efficiency. While blastocyst numbers were modestly reduced in fluoxetine-treated mice, litter size and offspring ovarian reserve were unaffected. Unexpectedly, offspring of fluoxetine-treated mothers exhibited increased body weight. These findings suggest that while fluoxetine may impair oocyte developmental competence through disruptions in cytoplasmic maturation, it does not severely compromise overall reproductive outcomes or offspring fertility. Full article

Introduction: Previous studies have suggested an additional increased risk for types of malignancies other than breast and ovarian cancer for female BRCA1/2 GPV carriers, but risk estimates vary widely. The aim of this study was to investigate if female BRCA1/2 GPV carriers have an increased risk of malignancies other than breast and tubal/ovarian cancer at an early age. Methods: Prospectively collected data from female BRCA1/2 GPV carriers in our hospital-based data/biobank were linked to the PALGA Dutch Pathology Database. Incidences of malignancies occurring before 60 years of age were compared to crude rates/100.000 person-years in the Netherlands, stratified by age and calendar time. Standardized incidence ratios (SIRs) were calculated with 95% confidence intervals (95%CIs). Results: In 1347 women, 82 malignancies other than breast and tubal/ovarian cancer were detected in patients under 60 years of age in 37,068 person-years. An increased risk of cancer in general (SIR:2.25, 95%CI:1.78–2.80, p < 0.001), head and neck cancer (SIR:3.17, 95%CI:1.03–7.39, p < 0.05), gastrointestinal cancer (SIR:1.96, 95%CI:1.14–3.13, p < 0.05), and female genital cancer (SIR:2.48, 95%CI:1.61–3.65, p < 0.001) was found. Conclusions: If confirmed in larger, prospective studies that include the role of bias and previous cancer treatment, awareness of the possible increased risks of head and neck, gastrointestinal, and female genital cancer may be used to tailor clinical guidelines for female BRCA1/2 GPV carriers. Full article

Background: Thyroid autoimmunity (TAI) has been widely associated with reduced fertility; however, its impact on assisted reproductive technology (ART) outcomes in euthyroid women remains controversial. Ovarian reserve (OR) and anti-Müllerian hormone (AMH) are considered to be the most reliable predictors of controlled ovarian hyperstimulation (COH) and ART outcome. This study aims to evaluate whether TAI affects COH outcomes depending on the OR, or if TAI is an independent negative factor affecting COH outcomes. Methods: This study includes 341 infertile euthyroid participants under 38 years old undergoing ART at a single reproductive medicine center. The serum concentrations of sex hormones, thyrotropin (TSH), AMH, and antithyroid antibodies (ATAbs) were measured before COH. Ovarian response to COH, assessed by oocyte number and maturation (percentage of mature MII oocytes), fertilization rate (FR), and early embryo development (cleavage and blastocyst rate), were assessed in 191 participants with TAI and 150 TAI negative age-matched controls with normal ORs. The TAI group was further divided into two subgroups: the TAI1 group with normal OR (n = 120) and the TAI2 group with diminished ORs (n = 71). Results: The mean of the retrieved oocytes was significantly lower in TAI1 (p = 0.015) and expectedly significantly lower in TAI2 (p < 0.001) compared to the control. The percentage of MII oocytes was significantly lower in the TAI1 (p < 0.001) and TAI2 (p = 0.009) groups compared to the control group. We observed significantly lower FR (p = 0.002), cleavage rate (p = 0.020), and blastocyst rate (p < 0.001) in the TAI1 group compared to control. In the TAI2 group, there was a lower cleavage rate (p < 0.001) and blastocyst rate (p < 0.001) compared to the control. There was no difference in the mean percentage of MII oocytes, FR, and cleavage rate between the TAI1 and TAI2 groups, but the blastocyst rate was significantly lower (p < 0.001) in the TAI2 group. Conclusions: TAI may represent a negative predictor of in vitro fertilization outcomes by impairing oocyte maturation, fertilization rate, and embryo development in ART cycles, regardless of ORs. Full article

Background: Adult granulosa cell tumours (AGCT) of the ovary account for 2–5% of ovarian tumours, with 30% occurring in women of childbearing age. Despite a good prognosis, up to 25% recur. There is a paucity of high-quality evidence to guide management. Objective: To describe management of AGCT across multiple gynaecological cancer centres. Methods: Retrospective analysis of electronic patient records from six gynaecological cancer centres in Southwest England between 2000 and 2021 (n = 119). Results: We included 107 patients with a median follow-up of 60 months (0–261 months). Most (97/107; 90.7%) were diagnosed with stage I disease (31.8% stage Ic). Primary management was staging surgery in 33/107 (30.8%), hysterectomy and bilateral salpingo-oophorectomy (BSO) (28/107; 26.2%), or conservation of an ovary (17/107; 15.9%). Three had a subsequent pregnancy. A quarter (27/107; 25.2%) were diagnosed with recurrent disease. Fifteen patients (15/107; 14%) had multiple recurrences. Recurrence was more likely if cyst rupture was reported at surgery (38.7%) compared with no rupture (14.3%; p < 0.001). The recurrence rate was higher with ovarian conservation (6/17; 35.3%) compared with BSO (21/90; 23.3%; p < 0.01), and all recurrences involved the residual ovary. Of the 11 deaths, 6 (54.5%) were attributed to progressive disease. Conclusions: Although survival with early-stage disease is good, ovarian cystectomy or unilateral ovarian conservation was associated with increased risk of recurrence. There is no conclusive evidence to support a contralateral oophorectomy in pre-menopausal women, but completion surgery should at least be considered, either immediately or after childbearing/assisted reproductive treatment. Full article

Background: Endometriosis is a benign gynecologic condition that has the risk of malignant transformation in approximately 0.5–1% of cases, most of which develop into endometriosis-associated ovarian cancers (EAOCs), such as clear cell and endometrioid adenocarcinomas. The current systematic review aims to condense recent information on the genetic and molecular mechanisms, clinical risk factors, and possible therapeutic targets of the malignant transformation of endometriosis. Methods: A systematic literature search of PubMed, Europe PMC, and Google Scholar was carried out according to PRISMA guidelines for articles published until December 2024. Following a screening of 44,629 titles, 43 full articles were included after meeting inclusion criteria. No case reports or reviews were included, and articles had to mention a malignant transformation of endometriosis and not just a diagnosis of cancer. The quality and risk of bias of studies were evaluated using ROBINS-I. Results: Malignant transformation of endometriosis is associated with genetic alterations, including ARID1A mutations, microsatellite instability, and abnormal PI3K/Akt and mTOR pathway activation. Increased oxidative stress, inflammation-driven mismatch repair deficiency, and epigenetic alterations like RUNX3 and RASSF2 hypermethylation are implicated in carcinogenesis. Clinical risk factors are advanced age (40–60 years), large ovarian endometriomas (>9 cm), postmenopausal status, and prolonged estrogen exposure. Imaging techniques like MR relaxometry and risk models based on machine learning are highly predictive for early detection. Conclusions: Endometriosis carcinogenesis is a multifactorial process driven by genetic changes, oxidative stress, and inflammatory mechanisms. Identification of high-risk individuals through molecular and imaging biomarkers may result in early detection and personalized therapy. Further research should aim at the development of more precise predictive models and exploration of precision medicine approaches to inhibit the emergence of EAOC. Full article