Recent research has shown that environmental and lifestyle factors play a significant role in the development of cancer, and can include carcinogenic agents in soil, water, air, and food. Modifiable factors such as these are imperative to understand and address to optimize cancer prevention. This article is a review focusing on the impact of environmental exposures and lifestyle behaviors on cancer in women and aiming to identify the role of risk factors in gynecologic cancer risk and progression. Environmental and lifestyle factors play a role in many gynecologic cancers. Ovarian cancer has one of the highest mortality rates of any gynecologic cancer and is influenced by factors including high body mass index (BMI) and dietary habits such as a lack of fruits and vegetables. Less modifiable risk factors include multiparity and long-term use of contraceptives, which can lower ovarian cancer risk, and air pollution that increases the risk. Uterine cancer is one of the most prevalent gynecologic cancers in high-income countries, and is associated with obesity, physical inactivity, and diets high in animal fat and low in fiber. Pesticides have also been implicated due to an association with hormonal disruption and systemic inflammation. Cervical cancer, on the other hand, is primarily related to sexual behaviors, as it is directly associated with HPV infection. Other risk factors include tobacco use, nutritional deficiencies such as folate and antioxidants, and an imbalance of the vaginal microbiome. Less common cancers, such as vulvar and vaginal cancers, are also strongly influenced by lifestyle and environmental factors, such as obesity, smoking, and exposure to carcinogens. Genetic and environmental factors interact in a nuanced way in the development of gynecologic cancer, and some risk factors are modifiable while some are not. Certain genetic mutations have been associated with an increased risk of several types of cancers, and this is outside of an individual’s control; however, the risk of gynecologic cancer can be reduced via a healthy diet and activity level and can mitigate some of the increased genetic risk. Polygenic risk scores (PRSs) have been developed as a tool to estimate individual risk of certain diseases, including gynecologic cancers, and calculate a score based on genetic factors that are present and their association with each disease based on genome-wide association studies (GWAS). Genetic factors with the highest relevance for gynecologic cancers include BRCA mutation carriers, aberrant DNA methylation, abnormal histone acetylation and methylation, and dysregulation of noncoding RNAs such as microRNAs. Evidence has shown that modifying risk factors even after diagnosis of gynecologic cancer can improve long-term outcomes; these can include smoking cessation, increased physical activity, diet, and body weight. These factors can improve both cancer survival and quality of life. Interplay between genetic and environmental factors is nuanced but imperative for understanding individualized gynecologic cancer risk. Some nuances of modifiable and nonmodifiable factors include cultural context and sociodemographic factors that can influence the ability of individuals to adhere to health recommendations, such as physical activity and dietary habits, as well as influence their access to health care and education. These disparities must be acknowledged when determining individual cancer risk. Future studies and interventions should include education and information dissemination, public health initiatives, regular cancer screenings, and supporting cancer survivors. (Summarized from Farina S, Sabatelli A, Boccia S, et al. Environment, lifestyle, and cancer in women. Int J Gynaecol Obstet. 2025;171 Suppl 1(Suppl 1):138-146. doi: https://doi.org/10.1002/ijgo.70156)

Sex chromosome trisomies (SCTs), caused by the presence of an extra X or Y chromosome, are among the most common chromosomal abnormalities but remain substantially underrecognized. Klinefelter syndrome (47,XXY) is the most frequently diagnosed SCT and, as a result, has been the primary focus of research on associated comorbidities, while individuals with 47,XYY and 47,XXX are typically undiagnosed and understudied. This reliance on clinically identified cases introduces bias and limits understanding of the full spectrum of SCT-associated disease, particularly for physical health outcomes. Large-scale biobanks that link genetic data with medical records offer a unique opportunity to study both diagnosed and undiagnosed SCTs across subtypes. This retrospective cohort study uses biobank data to examine the risk of physical comorbidities across all three SCTs, including both diagnosed and undiagnosed individuals. Data were compiled from three large population-based biobanks: the Million Veteran Program (MVP), FinnGen, and the UK Biobank, each of which includes genotyped blood-derived DNA linked to detailed electronic health records. The MVP cohort was started in 2011 and includes ~650,000 veterans in the VA health care system, while FinnGen includes 500,000 Finns across varied national health registries, with records beginning at or before 1969. The UK Biobank is a prospective cohort of ~500,000 volunteers in the United Kingdom aged 40 to 70 that began recruitment in 2006. To determine the presence of an SCT, the researchers analyzed SNP array data for the relative signal strength of X and Y chromosomes present, from which the copy number was inferred. The number of these patients who were officially diagnosed was abstracted from ICD-9 or ICD-10 codes. Disease outcome rates were captured using phecodes, which are clinically meaningful groups of International Classification of Diseases (ICD) codes, and were grouped into system-based categories. Associations between SCT subtypes and lifetime disease risk were evaluated using a matched case-control design, with each SCT carrier matched to five control individuals by genetic sex, birth year, and genetic ancestry. Among the 1.5 million individuals included, 2769 (0.19%) were found to have an SCT, the large majority of which (86.2%) were undiagnosed. Diagnosis rates differed by subtype, with 26.2% of 47,XXY patients, 1.4% of those with 47,XYY and 6.4% of those with 47,XXX carrying a clinical diagnosis. Phenome-wide association analyses identified hundreds of disease associations spanning nearly all organ systems, with 43 conditions shared across all three SCTs, most of which were categorized as cardiovascular, respiratory, and metabolic diseases. Vascular conditions, including venous thromboembolism, atherosclerosis, and cerebrovascular disease, showed strong associations across SCT subtypes. Metabolic and respiratory conditions, such as obesity, type 2 diabetes, asthma, and sleep apnea, were also more prevalent across SCT subtypes. Subtype-specific associations were also identified, with reproductive and bone disorders concentrated in 47,XXY, select renal and infectious conditions concentrated in 47,XXX, and no distinct phenotype unique to 47,XYY. The findings show that most individuals with SCTs remain undiagnosed into adulthood and experience an increase in a wide range of chronic diseases that are shared across SCT subtypes. Despite the historical attribution of many of these phenotypes to hypogonadism, particularly in cases of 47,XXY, the commonalities found across karyotypes, genetic sexes, and cohorts suggests that increased sex chromosome gene dosage plays a central role in SCT pathophysiology. The vascular phenotypes that were frequently observed across all three SCTs, including venous thromboembolism and chronic venous disease, are consistent with previous studies, and future research should investigate possible underlying etiologies. Limitations of the study include reliance on EHR-based phenotyping, potential homogeneity between biobanks, and limited power to assess phenotype severity or differences across ancestral groups. (Abstracted from Am J Hum Genet. 2025;112:2088–2101. doi:10.1016/j.ajhg.2025.07.017)

The sex chromosome trisomies (SCT), including XXY, XYY, and XXX, are common chromosomal aneuploidies associated with increased risk for early developmental delays and later neurodevelopmental disorders. Precise data on the timing and variability of early milestones in this population remain limited, so despite rising rates of prenatal SCT diagnosis, clinicians and families lack clear, evidence-based expectations for early motor and language development. This study aims to quantify the spectrum of early developmental milestones in infants with SCT and compare their timing with well-established standards for unaffected children to better contextualize early developmental risk. This analysis used data from the eXtraordinarY Babies Natural History Study, a prospective cohort of prenatally identified infants with SCT followed from infancy through early childhood. Between 2 and 36 months of life, parents reported easily observable gross motor and expressive language milestones, and clinicians validated these findings at regularly scheduled study visits as part of a broader assessment of development and health trajectories. A total of 12 milestones were collected for each participant: 8 gross motor skills and 4 expressive communication milestones. To compare these values with a normative reference group, data were retrieved from the Denver II Scales, the WHO Motor Development Study, and the Primitive Reflex Profile. Analyses assessed the median age of acquisition, variance, and differences across SCT karyotypes, as well as the proportion of children who fell outside CDC milestone expectations. Among 298 infants with SCT (174 with XXY, 50 with XYY, and 74 with XXX), results showed a later median age of acquisition for 9 of the 12 milestones evaluated, including rolling front to back, sitting, cruising, walking, running, cooing, babbling, first words, and 2-word phrases. There was also greater variance in milestone timing for the SCT group compared with the reference population, with extended upper percentiles across most skills indicating a wider range of typical achievement. While these delays were statistically significant, there was considerable overlap between the SCT group and the general pediatric population, and only a minority of infants met the CDC criteria for developmental delay. Differences across SCT karyotypes were small and generally not significant, although children with XXY achieved several skills slightly earlier than those with XYY or XXX. These findings provide an evidence-based schedule for early motor and language milestones in infants with SCT to aid early childhood surveillance and counseling. The later median age of acquisition and greater variability observed across all SCT conditions support the need for periodic developmental assessment beyond guidelines for the general population to identify children requiring additional support earlier. Although many infants with SCT will experience developmental trajectories similar to unaffected peers, this study shows that they remain at higher developmental risk and may benefit from increased monitoring, clearer parent guidance, and earlier referral for intervention when indicated.(Abstracted from Pediatrics (2025) 156 (2): e2024068773. doi: 10.1542/peds.2024-068773.).

The number of births achieved through a gestational carrier has been increasing. Yet few studies have looked at the mental health outcomes for gestational carriers. Pregnancy increases vulnerability to mental illness, and population-based data suggest that gestational carriers have higher rates of severe maternal morbidity than women in traditional pregnancies. Current guidelines emphasize selecting gestational carriers with stable family supports and requiring psychological evaluation before pregnancy, as up to half of women with prior severe mental illness relapse during pregnancy or postpartum. Risk factors for gestational carriers include emotional separation from the newborn, relationships with intended parents, and societal scrutiny. The aim of this study was to assess the risk of new-onset mental illness among gestational carriers compared with women who conceived unassisted and those who conceived using in vitro fertilization (IVF). This was a population-based study of births >20 weeks of gestation in women between 18 and 50 years of age from 2012 through 2021 in a universal health care system in Ontario, Canada. Excluded were women with a history of an infertility diagnosis or prior mental illness, and a medical condition that would preclude them from selecting a gestational carrier. The primary outcome was new-onset mental illness, such as a mood disorder, anxiety disorder, psychosis, substance use disorder, self-harm event, or other mental illness, based on ≥2 outpatient visits or ≥1emergency department visit or hospital admission. A total of 767,406 pregnancies were included in the analysis. Of these, 97.6% were conceived unassisted, 2.3% conceived by IVF, and 0.1% used a gestational carrier. Gestational carriers were more likely to be parous [91.2% vs. 57.9% (unassisted conception) and 34.1% (IVF)] and live in lower-income areas [23.4% vs. 21.9% (unassisted) and 12.1% (IVF)]. They also have a higher rate of obesity [36.1% vs. 17% (unassisted) and 17.1% (IVF)] and chronic hypertension [3.2% vs. 1.6% (unassisted) and 2.9% (IVF)]. After a median (IQR) follow-up of 4.5 (2.3 to 7.2) years, new-onset mental illness occurred in 236 gestational carriers compared with 195,022 women who conceived unassisted [6.9 vs. 5.2 per 100 person-years; incidence rate ratios (IRRs), 1.43; 95% CI, 1.26 to 1.63) and with 4704 women receiving IVF (6.9 vs. 5.0 per 100 person-years; adjusted IRR, 1.29; 95% CI, 1.13 to 1.47). The median (IQR) time from the estimated date of conception to a diagnosis of mental illness was 2.39 (1.11 to 4.19) years for gestational carriers versus 2.29 (1.02 to 4.34) years for those who conceived unassisted and 2.72 (1.11 to 4.82) years for those who used IVF. In conclusion, gestational carriers are more likely to be diagnosed with mental illness than women who conceive unassisted or use IVF. This study highlights the importance of enhanced mental health screening and support for gestational carriers.(Abstracted from: JAMA Netw Open. 2025;8(7):e2523428.).

Iron deficiency anemia (IDA) affects approximately one-third of pregnant women worldwide and is a significant contributor to adverse maternal and fetal outcomes, including preterm delivery, low birth weight, and cognitive impairment in children. Despite advancements in iron therapy, IDA remains prevalent, affecting 29.9% of women globally. This highlights a critical need for more effective management strategies during pregnancy. To provide a comprehensive review of the mechanisms governing iron absorption, current guidelines for iron therapy, and the efficacy and safety profiles of various iron salts, with the aim of improving supplementation approaches for the effective management of IDA in pregnancy. The review evaluates existing literature on intestinal iron absorption and placental transport mechanisms of different iron salts. It also analyzes international guidelines recommending daily administration of oral and intravenous iron, alongside the clinical efficacy and safety profiles. The absorption and transport of iron are complex processes influenced by intestinal uptake and placental transport, regulated by maternal and fetal iron stores and hepcidin levels. Despite the availability of various iron formulations, none have proven ideal for managing IDA during pregnancy. Clinical trials demonstrate varying efficacy and safety profiles, indicating a significant gap in current treatment strategies. Although advancements in iron therapy have been made, no single formulation has emerged as the optimal solution for managing IDA in pregnancy. This review underscores the need for a deeper understanding of iron absorption mechanisms and more effective supplementation approaches to address the ongoing burden of IDA among pregnant women worldwide. Obstetricians and gynecologists, family physicians. After participating in this activity, the learner should be better able to explain the complex mechanism of iron absorption and identify the physiological mechanisms governing the absorption of heme and nonheme iron; summarize how to diagnose IDA and apply international guidelines for iron supplementation in pregnancy; and compare the efficacy, bioavailability, and safety profiles of various oral and intravenous iron formulations to identify the most suitable options for managing IDA during pregnancy.

(Abstracted from Reprod Biomed Online 2025;51(2):104697, doi:10.1016/j.rbmo.2024.104697) Receptivity modulators control and facilitate cell differentiation and embryo development as well as inflammatory pathways and suppression of paternal alloantigens. Molecular changes driven by the microenvironment of the endometrium drive endometrial thickening that prepares the uterus for implantation.

(Abstracted from Int J Gynecol Cancer 2025;35(7):101926, doi:10.1016/j.ijgc.2025.101926) The most common gynecologic cancer in high-income countries is endometrial cancer (EC), with a global incidence of 417,000 in 2020. It is postulated that some of this rising incidence is due to the increased prevalence of risk factors such as obesity; the number of EC-related deaths has also increased, additionally with an increasing gap in survival rates between White and Black patients as well as a gap in survival rates between individuals who have experienced socioeconomic deprivation and those who have not.

(Abstracted from Obstet Gynecol 2025;146(2):223-232) Awareness of hereditary gynecologic cancer has been growing over the last few decades, and testing and prevention methods have been decreasing in cost. This means that more people who have gene mutations for these hereditary cancers more often face decisions about risk-reducing bilateral salpingo-oophorectomy (BSO).

(Abstracted from Lancet 2024;405:1743-1756) Shoulder dystocia is associated with several maternal and neonatal complications and is a common reason for litigation in obstetrics. Maternal complications include hemorrhage and third- and fourth-degree perineal severe tears; neonatal complications include fractures, brachial plexus injury, hypoxic ischemic encephalopathy, and neonatal death.

(Abstracted from N Engl J Med 2025;392:1801-1812) Automated insulin delivery (AID) systems improve outcomes in type 1 diabetes mellitus (T1DM), but their role in type 2 diabetes mellitus (T2DM) remains uncertain due to limited, small, or uncontrolled studies. Many patients achieve glycated hemoglobin (HbA1c) <7% with glucagon-like peptide 1 agonists or sodium-glucose cotransporter 2 inhibitors, but those who do not may benefit from AID.