Polyendocrine metabolic ovarian syndrome (PMOS), previously named polycystic ovary syndrome (PCOS), affects one in eight women. However, the term PCOS is inaccurate, implying pathological ovarian cysts, obscuring diverse endocrine and metabolic features, and contributing to delayed diagnosis, fragmented care, and stigma, while curtailing research and policy framing. Building on an international mandate for change, we outline an unprecedented, rigorous, multistep global consensus process for the name change. Funding and governance were established with engagement of 56 leading academic, clinical, and patient organisations. Using iterative global surveys (with responses from 14 360 people with PCOS and multidisciplinary health professionals from all world regions), modified Delphi methods, nominal group technique workshops, and marketing and implementation analyses, we identified principles prioritising scientific accuracy, clarity, stigma avoidance, cultural appropriateness, and implementation feasibility. An accurate new name was prioritised over retaining the PCOS acronym or a generic name. Implementation approaches prioritised evolution rather than transformation. Preferred terms were polyendocrine, metabolic, and ovarian, reflecting the condition's multisystem pathophysiology, and polyendocrine metabolic ovarian syndrome was the consensus new name. Accuracy was improved by omitting cysts and by capturing endocrine, metabolic, and ovarian dysfunction. A co-designed global implementation strategy, including a transition period, education, and alignment with health systems and disease classification, is under way.
Increasing numbers of children are conceived using infertility treatment; concerns remain about potential effects on child neurodevelopment. To evaluate whether infertility treatment is associated with child neurodevelopment and whether such an association may be attributable to underlying subfecundity. DESIGN, SETTING, This cohort study was conducted among mother-child dyads in the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) Cohort, with infants conceived between 1998 and 2022. Associations of subfecundity and infertility treatment with neurodevelopmental outcomes were assessed among children ages 2 to 10 years. Data were analyzed from May 14, 2025, to March 31, 2026. Subfecundity was defined as prior consultation for, treatment of, or diagnosis of infertility for either partner; at least 2 prior miscarriages; or ever having had unprotected heterosexual intercourse for 12 months without conceiving. Infertility treatment was categorized as in vitro fertilization (IVF) or non-IVF treatment. Harmonized caregiver responses to the Strengths and Difficulties Questionnaire and the Child Behavior Checklist yielded continuous raw scores for externalizing and internalizing problems. The total raw Social Responsiveness Scale (SRS) score quantified autism-like symptoms. Caregivers reported physician diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Among 15 382 mother-infant dyads, there were 14 191 unique maternal participants (mean [SD] age at delivery, 30.9 [5.33] years; 8780 parous participants [57.1%]). ASD and ADHD were diagnosed in 876 offspring (7.6%) and 819 offspring (7.1%), respectively. In generalized linear models, subfecundity was associated with higher externalizing problem and SRS scores among all pregnancies (externalizing b = 0.47 [95% CI, 0.14-0.81]; b = 1.08 [95% CI, 0.01-2.14]) and when restricted to natural conceptions (externalizing b = 0.45 [95% CI, 0.07-0.83]; b = 1.12 [95% CI, -0.09 to 2.34]). Offspring of parents with subfecundity had higher odds of ASD (overall: odds ratio [OR], 1.27 [95% CI, 1.03-1.57]; OR, 1.31 [95% CI, 1.04-1.64]). Children conceived via non-IVF treatment had higher odds of ADHD compared with those conceived via natural conception with subfecundity (OR, 1.77 [95% CI, 1.16-2.68]) or without subfecundity (OR, 1.54 [95% CI, 1.05-2.25]). There were no significant associations for IVF treatment. In this large US cohort study, subfecundity was associated with elevated scores for caregiver-reported symptoms of behavioral problems and higher odds of ASD diagnosis, independent of infertility treatment. Non-IVF treatment was associated with ADHD, warranting further research into specific indications for treatment that may increase risk of offspring neurodevelopmental problems.
Stanford JB et al., 2026·Frontiers in Reproductive Health
Background The total fertility rate (TFR) in most developed countries has been declining for decades. In the United States (U.S.), the total fertility rate has remained below replacement level since 2007. Subfertility affects at least 15% of women or couples over their reproductive lifespan and contributes to reduced TFR. Restorative reproductive medicine (RRM) is a medically based approach to subfertility care that can be delivered in primary care settings to increase live birth rates. Objective To estimate the theoretical impact of use of RRM among subfertile couples in the United States. Methods We conducted a simulation study. Model inputs included the number of women of reproductive age in the United States by 5-year age groups; current age-specific and total fertility rates; the proportion of women in each age group with subfertility; estimated spontaneous live birth rates among women with subfertility; and age-specific crude live birth rates with RRM treatment. We evaluated fifteen scenarios two different varying assumptions for spontaneous conception (25% vs. 50%), two levels of RRM utilization among subfertile women (20% vs. 50%), three different estimates of the number of subfertile women who would be potentially eligible for RRM treatment, and 4 different levels of effectiveness (live birth) from RRM treatment. Results The baseline TFR in the United States was 1.77 during 2015-2019, and 13.5% of women ages 20-44 were estimated to have subfertility. In a conservative scenario (50% spontaneous births; 20% RRM utilization; married women trying to conceive for at least 12 months, 20.7% RRM live births), the TFR increased to 1.79, representing a 1.0% relative increase (absolute +0.02). In an optimistic scenario (25% spontaneous births; 50% RRM utilization; all subfertile women), the TFR increased to 2.02, a 14.5% relative increase (absolute +0.26), approaching replacement-level fertility. Conclusion Simulation results suggest that expanding access to RRM within primary care settings could meaningfully increase the U.S. TFR, by reducing unresolved subfertility. Realizing this potential would require policy and health system changes to address workforce capacity, insurance coverage, and equitable access. These findings underscore the potential contribution of non-IVF fertility care pathways in addressing population-level fertility decline.
Anti-Müllerian hormone (AMH), produced by ovarian granulosa cells, is a key regulator of female reproduction. Traditionally seen as a local follicular brake, emerging evidence calls for a paradigm shift. We propose that AMH acts as a context-dependent signaling hub. It primarily signals via the Smad1/5/8 pathway and interacts with Wnt/β-catenin and MAPK cascades to regulate follicle growth and steroidogenesis. Beyond the ovary, AMH and its receptors are expressed in the hypothalamus, pituitary, uterus, and placenta, modulating the hypothalamic-pituitary-gonadal axis and other reproductive processes. This review provides a comprehensive framework for understanding AMH as a context-dependent signaling hub in female mammals.
Practice Committee of the American Society for Reproductive Medicine, 2026·Fertility and Sterility
Current strategies for the assessment and treatment of recurrent pregnancy loss are discussed. This replaces the previous document, titled, "Evaluation and treatment a committee opinion," last published in 2012.
De Cicco Nardone C et al., 2026·Archives of gynecology and obstetrics
Adenomyosis is a chronic uterine disorder characterised by ectopic endometrial tissue within the myometrium, frequently associated with dysmenorrhea, abnormal uterine bleeding (AUB), chronic pelvic pain (CPP), and dyspareunia. No standardised guidelines are currently available for its management, and therapeutic options remain limited for women seeking fertility preservation. This study aimed to evaluate the efficacy of intravaginal progesterone in alleviating adenomyosis-related symptoms in patients seeking fertility preservation. In this prospective monocentric observational study, 85 patients aged 22-50 years with ultrasound-confirmed symptomatic adenomyosis were enrolled between April 2020 and April 2024. Inclusion criteria were age 18-55 years, BMI 18-35, and a Visual Analogue Scale (VAS) score ≥ 7 for dysmenorrhea, AUB, CPP, or dyspareunia. All patients received 200 mg/day of intravaginal progesterone for 10 days per cycle. Symptom severity was assessed using VAS scores at baseline and at 6 months. Data were analysed using non-parametric statistical tests. Sixty-five patients completed the 6-month follow-up. Four patients conceived during treatment and were excluded from the final analysis. Statistically significant improvements were observed for all assessed symptoms (all p < 0.05). Median VAS scores decreased for dysmenorrhea (9 to 6, p < 0.001), AUB (8 to 6, p < 0.001), chronic pelvic pain (5.5 to 3.5, p < 0.001), and dyspareunia (2 to 0, p = 0.020). The overall treatment satisfaction was high, with a mean Likert score of 7.5 out of 10. Intravaginal progesterone appears to be an effective fertility-sparing treatment for symptomatic adenomyosis, providing significant relief across all primary symptoms, with high patient satisfaction. Larger controlled studies are warranted to confirm these preliminary findings and further define its role in clinical practice.
Sajjad MU et al., 2026·Archives of gynecology and obstetrics
The human placenta consumes, on average, one third of the glucose from maternal blood. However, the role of placental glucose consumption in the production of estradiol and progesterone remains unclear. We hypothesized that placental glucose consumption in humans is associated with steroid production via a non-glycolytic pathway. We included 41 healthy pregnancies at term. Blood samples were obtained from the maternal radial artery, uterine vein, and from the umbilical artery and vein during scheduled cesarean delivery. Blood flow in the uterine artery and umbilical vein was measured using Doppler ultrasound. Plasma concentrations of estradiol, progesterone, glucose, insulin, lactate, and ketones were analyzed. We calculated uteroplacental uptake and consumption of maternal glucose and ketones, and the loss of uteroplacental lactate in 6-carbon units as well as the release of steroid hormones into maternal circulation. Our data revealed a net placental release of estradiol and progesterone into maternal circulation [24.1 (5.34, 49.8) and 560.3 (61.2, 798.2) nmol/min, respectively]. The release of estradiol was positively associated with uteroplacental glucose uptake (ρ = 0.59, p < 0.001) and consumption (ρ = 0.43, p = 0.005), while progesterone exhibited similar associations (ρ = 0.61, p < 0.001; ρ = 0.43, p = 0.005). Notably, both hormones correlated positively with lactate-adjusted uteroplacental glucose consumption but not with acetate-equivalent uteroplacental ketone consumption. Placental release of estradiol and progesterone correlates with uteroplacental consumption of glucose that primarily occurs via non-glycolytic pathways in the third trimester placenta.
Parnell TA et al., 2026·Journal of Restorative Reproductive Medicine
This secondary analysis examined two independent U.S. surveys (J.L. Partners, N=1002; McLaughlin & Associates, N=1000) investigating public perspectives on fertility treatments. Initial support for IVF reached approximately 80%, though respondents demonstrated limited procedural knowledge. Conversely, only 33% initially supported restorative reproductive medicine (RRM), with 43% unfamiliar with it. After receiving detailed information, preferences 69% favored natural fertilization approaches versus 17% preferring laboratory fertilization. Respondents prioritized "baby health (74%) over cost (13%) and time to conceive (6%)." Support for IVF declined by 10% following presentation of medical risks and ethical considerations. Findings suggest the public values comprehensive assessment, diagnostic approaches addressing underlying causes, treatment transparency, and ethical sensitivity in fertility care.
This narrative review examines the evidence for medical optimization of inflammatory conditions, vitamin deficiencies, endocrine disorders, immune dysregulation, oligo-ovulation, and luteal phase factors to improve fertility outcomes in women attempting to conceive through natural or timed intercourse. Overall, there is a paucity of data with respect to these categories among patients pursuing timed intercourse, precluding our ability to draw strong recommendations. However, there is strong evidence supporting treatment of endocrine disorders, specifically overt thyroid dysfunction and hyperprolactinemia, as well as oligo-ovulation. Conversely, treatment of subclinical hypothyroidism is not recommended. The current data are insufficient to support empiric use of antiinflammatory medications, corticosteroids, thyroid hormones, or vitamins or supplements to improve chances of pregnancy in a general infertility population.
Restorative Reproductive Medicine (RRM) aims to restore fertility by diagnosing and treating the underlying causes of infertility. RRM is frequently promoted as an alternative to assisted reproductive technology (ART), despite uncertainty regarding its comparative effectiveness and safety. Where delayed childbearing and infertility are becoming more common, reliance on optimization of natural physiology alone may delay effective treatment and compromise reproductive outcomes. A systematic review of the current evidence comparing RRM to either ART or unassisted conception is, therefore, essential to inform clinical practice, guideline development, and shared decision-making for patients experiencing infertility. To assess the effectiveness and safety of RRM approaches, evaluated as a whole, rather than as individual components, compared with ART and medically unassisted conception in couples experiencing infertility. A systematic literature search of MEDLINE, Embase, CENTRAL and the Journal of Restorative Reproductive Medicine from inception to 28 November 2025. We included randomized control trials (RCTs) or nonrandomized comparative studies evaluating reproductive and safety outcomes of RRM as a unified treatment, compared with either ART or expectant management (attempted medically unassisted conception). Two reviewers independently screened titles, abstracts and full texts with disagreements resolved by a third reviewer. We retrieved 724 records, of which 16 studies underwent full-text review. No RCTs or comparative observational studies were identified. All 16 full-text studies were excluded for an ineligible study design (no control group); most were cohort studies in which all participants underwent RRM. Ten studies reported reproductive outcomes; nine of these made claims regarding the benefits or effectiveness of RRM. None of these claims were supported by the study designs used, as the lack of a comparison group precludes reliable estimation of treatment effects. Consequently, these studies cannot provide valid estimates of RRM success rates, nor permit any meaningful inference about its effectiveness relative to unassisted conception or ART. Large-scale RCTs or prospective cohort studies reporting effectiveness and safety outcomes are required to inform evidence-based fertility guidelines. There are no comparative studies to support reliable estimates of the safety and effectiveness of RRM compared with ART or medically unassisted conception for couples experiencing infertility.
Santos da Silva A et al., 2026·Reproduction (Cambridge, England)
Endometriosis is an estrogen-dependent inflammatory disorder frequently associated with infertility and characterized by progesterone resistance and impaired endometrial receptivity. While ectopic lesions define the disease, accumulating evidence indicates that molecular abnormalities within the eutopic endometrium substantially contribute to infertility. In this study, we performed transcriptomic analysis of proliferative-phase eutopic endometrium from women with and without endometriosis and identified 44 dysregulated genes, including 13 upregulated and 31 downregulated genes, in women with endometriosis compared with controls. Among the significantly altered genes, YWHAZ (14-3-3 zeta) emerged as a prominently downregulated gene. Reduced YWHAZ expression was further validated at the protein level in both epithelial and stromal compartments of the endometrium from women with endometriosis. To investigate its physiological regulation, we examined YWHAZ expression during early pregnancy in mice and observed a dynamic, stage-specific pattern during the peri-implantation period, with strong expression at gestational days 3.5 and 4.5 and robust expression at the primary decidual zone at gestational day 5.5. Notably, YWHAZ expression was nearly abolished in uteri from progesterone receptor knockout and uterine signal transducer and activator of transcription 3 conditional knockout (Pgrcre/+Stat3f/f) mice, indicating that YWHAZ is dependent on intact progesterone receptor and STAT3 signaling. Together, these findings identify YWHAZ as a hormonally and transcriptionally regulated endometrial factor that is disrupted in endometriosis and tightly linked to implantation and decidual progression. This study highlights YWHAZ as a potential molecular node connecting progesterone resistance and STAT3 dysregulation to defective endometrial function and infertility in endometriosis.
Migraine is a neurologic disorder that disproportionately affects women and undergoes important changes across the menopausal transition. Estrogen fluctuations contribute to migraine expression and underlie the 3:1 female-to-male prevalence. Perimenopause, marked by hormonal variability and rising cardiometabolic risk, presents unique diagnostic and therapeutic challenges. Despite its high prevalence, evidence specific to perimenopausal and postmenopausal women remains limited. This review synthesizes current evidence on the epidemiology, pathophysiology, and management of migraine across the menopausal transition, with attention to hormone therapy, comorbidities, and emerging treatments. We conducted a narrative review of clinical and translational studies published within the past 5 years, supplemented by seminal mechanistic, epidemiologic, and guideline-defining studies published earlier. Relevant guideline statements from neurology, gynecology, and cardiovascular societies were also incorporated. Unstable estradiol and progesterone levels during perimenopause can worsen migraine frequency and predictability. Migraine without aura often improves after menopause, whereas migraine with aura tends to persist and independently increases the risk of ischemic stroke and other vascular events. Midlife comorbidities-including vasomotor symptoms, sleep disturbance, mood disorders, and metabolic disease-further complicate management. Menopausal hormone therapy has variable effects. Oral estrogen, particularly at higher doses, may worsen migraine and elevate vascular risk, especially in women with aura. In contrast, low-dose transdermal estrogen-recommended by the North American Menopause Society-appears safer and better tolerated. Continuous progestogen regimens may reduce withdrawal-related attacks compared with cyclic regimens. Nonhormonal options, particularly selective norepinephrine reuptake inhibitors, may be considered when vasomotor symptoms coexist, whereas migraine-specific prevention should follow established evidence-based therapies. Traditional migraine therapies (triptans, NSAIDs, beta-blockers, topiramate, antidepressants) remain central but require tailoring to vascular, bone, and metabolic health. Newer agents-including calcitonin gene-related peptide monoclonal antibodies, gepants, and ditans-offer effective, non-vasoconstrictive alternatives, especially for women with cardiovascular contraindications. Migraine during the menopausal transition reflects the interplay between hormonal dynamics and systemic health. Management requires balancing efficacy with vascular and metabolic safety while incorporating patient preferences. Evidence gaps include the lack of trials stratified by menopausal stage or migraine subtype. Multidisciplinary, menopause-informed care and prospective studies are needed to optimize outcomes in this population.
Velmahos AH et al., 2026·Journal of Restorative Reproductive Medicine
To evaluate the extent to which a history of infertility is associated with adherence to specific diets among reproductive-aged females. Cross-sectional analysis. Between 2017-2023, 7,227 North American female pregnancy planners aged 21-45 years enrolled in PRESTO (Pregnancy Study Online), a preconception cohort study. Participants completed self-administered baseline questionnaires during preconception. Infertility history, 1) self-reported 12-month clinical infertility, 2) history of visiting a clinician for an infertility work-up, and/or 3) clinician-identified cause of infertility (e.g., ovulatory or tubal). Adherence to specific diets, including vegetarian, vegan, Mediterranean, Paleo, Weight Watchers, ketogenic, dairy free, gluten free, Atkins, South Beach, Zone, raw foods, or other at baseline. Multivariable log-binomial regression models estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs), adjusted for age, income, and body mass index (BMI). The percentage of participants with a history of infertility was 26% based on the 12-month clinical infertility definition, 30% based on visiting a physician for infertility evaluation, and 26% based on an infertility diagnosis following a physician visit. Overall adherence to any particular diet was low (4.6% vegetarian, 2.8% ketogenic, 1.7% Weight Watchers, 1.4% Mediterranean, 1.3% vegan, 0.8% Paleo, <0.8%); 86.6% reported not adhering to any particular diet. A history of 12-month clinical infertility was associated with lower adherence to vegetarian (PR=0.78; 95% CI: 0.60-1.03), Paleo (PR=0.43; 95% CI: 0.19-0.91) diets. An infertility history involving a medical work-up was associated with a higher prevalence of adherence to a ketogenic diet (PR=1.56; 95% CI: 1.17-2.09). Participants whose infertility was attributed to ovulatory or tubal causes were nearly two times more likely to adhere to a ketogenic diet (PR=2.01; 95% CI: 1.38-2.94; PR=2.22; 95% CI: 1.09-4.49, respectively). The cross-sectional design cannot establish temporality or causality. The ketogenic diet was more prevalent among females with an infertility history, while vegetarian, Paleo, and Weight Watchers diets were less prevalent.
Barbato M et al., 2026·Frontiers in Reproductive Health
Couple infertility is a common clinical condition that is too often treated with assisted reproductive techniques (ARTs) without a proper evaluation of both male and female factors. To improve the likelihood of natural conception, fertility awareness methods (FAMs) are widely used. We performed a multicenter prospective study enrolling couples with primary idiopathic infertility who were seeking natural conception. Participants were followed for 12 months using FAMs, and their outcomes were compared with those of couples who only used ARTs. The aim of our study was to evaluate the pregnancy rate after 12 months among couples with idiopathic infertility using FAMs compared with those who immediately pursued ARTs. We evaluated 41 couples in the FAM group and 56 couples in the ART group. In the FAM group, we reported a pregnancy rate (PR) of 51.22%. Among women aged <34 years, we reported a PR of 90.9%, while it decreased to 36.7% among women aged 35-39 years. In the ART group, 10 couples achieved pregnancy (PR 17.8%). Within this group, we reported a PR of 30% among women aged <34 years and 17.4% among women aged 35-39 years. After 12 months of unprotected intercourse without spontaneous conception in women younger than 35 years or after 6 months in women aged 35-39 years, couples should undergo a complete multidisciplinary diagnostic evaluation involving both the male and female partners. If a diagnosis of idiopathic infertility is established at the end of this process, couples (especially younger ones) may be advised to wait an additional 12 months while using FAMs, as no advantage has been observed with direct access to ARTs. They could then be referred to ART if a spontaneous pregnancy is not achieved during this period.
Survey of 1,010 adults across the United States, United Kingdom, Ireland, and Canada (March 2026) who are trying to conceive, tried in the past five years, or plan to try within five years. IVF awareness is high (89%) but only 58% would consider pursuing it, a 31-point gap, the largest of any option surveyed, driven by perceptions of cost and invasiveness. 89% of women said they would prefer to try a less invasive fertility option before pursuing IVF if supported by clinical guidance; 83% would choose lower-cost options first. Metabolic health support generated the highest patient 84% would consider it and 85% would seek more information, yet only 44% had a clinical conversation about metabolic health during their fertility journey. Mens health support showed a similar pattern (80% would consider; only 43% of men had a provider conversation). 78% said better understanding of non-IVF options would make them more likely to pursue those options first. 49% learned about their fertility options only after beginning to try to conceive; 58% wished they had received more fertility education before trying (70% among those mid-journey). 84% agreed access to multiple fertility options would increase decision confidence, the most widely endorsed statement in the survey. 80% would be more likely to stay with an employer offering comprehensive fertility coverage (85% of women); 83% said the same of insurers. mean age 34.3; 56.7% female; 36.4% reported at least one diagnosed metabolic condition; 14.7% of women reported PCOS. Recruited via CloudResearch Connect panel.
Postvasectomy pain syndrome (PVPS) is a poorly understood, chronic condition affecting up to 5% of men post vasectomy. With limited evidence guiding its management, vasectomy reversal (VR) has been referenced as a potential treatment modality. This systematic review evaluates the current literature on the efficacy of VR in relieving PVPS symptoms. A systematic search was conducted across PubMed, ScienceDirect, SCOPUS, and Web of Science databases in accordance with Preferred Peporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Eligible studies included case series and clinical reports from the last 15 years that assessed pain outcomes after VR in men diagnosed with PVPS. Primary outcomes included pain resolution or reduction postoperatively, measured through visual analogue pain scores or patient-reported outcomes. Five studies involving 123 patients were included, encompassing vasovasostomy, vasoepididymostomy, and robotic-assisted techniques. All studies reported symptomatic improvement after VR, with pain score reductions ranging from 60% to 83%. While 2 studies used validated pain scoring systems before intervention and post intervention, the remaining studies reported other subjective or percentage-based improvements. Across all studies, VR was associated with high rates of patient satisfaction and willingness to undergo the procedure again. VR seems to offer meaningful pain relief in patients suffering from PVPS. However, further high-quality prospective studies and randomized controlled trials are needed to concretely establish its efficacy, compare it with alternative treatments, and develop standardized treatment algorithms.
Background Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder characterized by reproductive, hormonal, and metabolic disturbances. This study aimed to evaluate the association between clinical features, anthropometric indices, hormonal parameters, metabolic profile, ultrasonographic findings, and the second-to-fourth digit (2D:4D) ratio in women with PCOS compared to age-matched healthy controls. Methods A case-control study was conducted, including women diagnosed with PCOS and age-matched healthy controls. Clinical features, anthropometric measurements (BMI, waist-hip ratio (WHR), waist-height ratio (WHtR)), hormonal parameters (luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH)), metabolic variables (fasting glucose, lipid profile), ultrasonographic findings, and 2D:4D digit ratio were assessed. Statistical analysis was performed using appropriate tests, and a p-value < 0.05 was considered statistically significant. Results Women with PCOS exhibited a significantly higher prevalence of menstrual irregularity, polycystic ovarian morphology, hirsutism, and acne (p < 0.001). Hormonal analysis showed significantly elevated LH, FSH, and AMH levels in PCOS cases (p < 0.001). Anthropometric indices, including BMI, WHR, and WHtR, were significantly higher among PCOS cases (p < 0.01), indicating increased general and central adiposity. In contrast, fasting glucose and lipid profile levels did not differ significantly between groups. Additionally, the 2D:4D ratio was significantly lower in PCOS cases (p < 0.01) and showed significant negative correlations with BMI, WHR, WHtR, and cholesterol levels. Conclusion The study demonstrates that PCOS is associated with significant hormonal dysregulation, central obesity, and early metabolic alterations. The lower 2D:4D ratio observed in PCOS supports the role of prenatal androgen exposure in disease pathogenesis. These findings highlight the complex interplay between developmental, metabolic, and endocrine factors in PCOS and underscore the importance of early identification and comprehensive management strategies.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, typically characterized by irregular menstrual cycles. Our study found that postpartum menstrual cycles were largely restored in PCOS patients following assisted reproductive technology (ART) therapy. However, this recovery in menstrual cycles was not associated with any specific ART procedures. Using a PCOS mouse model, we demonstrated that elevated progesterone levels during pregnancy were responsible for normalizing estrous cyclicity. Elevated levels of progesterone induce granulosa cell apoptosis and deplete large follicles, which potentially contribute to ovarian function suppression during pregnancy. Mechanistic studies indicated that progesterone decreased follicle-stimulating hormone receptor (FSHR) expression in a GATA binding protein 2 (GATA2)-dependent manner. Interestingly, the capacity of granulosa cells to convert androgens to estrogens significantly increased after progesterone withdrawal, as evidenced by elevated cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) expression in granulosa cells when stimulated with FSH. Additionally, we found that progesterone administration reduced the thickness of the uterine endometrium in PCOS mice. Our findings suggest that sustained high levels of progesterone during pregnancy can enhance ovarian reproductive endocrine capacity and improve endometrial function, thereby facilitating the recovery of postpartum menstrual cycles.
Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org et al., 2026·Fertility and sterility
Patients preparing to undergo therapies that pose a risk to their fertility or who are at risk of premature ovarian insufficiency should be provided prompt counseling regarding available options for fertility preservation. Fertility preservation can best be provided by comprehensive programs designed and equipped to confront the unique challenges facing these patients. This document replaces the document entitled "Fertility preservation in patients undergoing gonadotoxic a committee opinion," last published in 2019.
EndometriosisPhenotype and StagingCardiometabolic RiskLipid Profiles
Open Access
Schliep KC et al., 2026·J Gynecol Obstet Hum Reprod
Endometriosis has been linked to cardiometabolic alterations, but whether these associations vary by disease severity or phenotype is unclear. We examined lipid profiles across endometriosis diagnosis, stage, and typology. Data came from 476 women in the NICHD ENDO cohort. Endometriosis was confirmed laparoscopically and staged using the rASRM criteria (I-IV). Typology was categorized as superficial endometriosis (SE), ovarian endometrioma (OE), deep infiltrating endometriosis (DE), and OE+DE. We compared endometriosis status, stage (I/II vs III/IV), and typology to no endometriosis using adverse lipid thresholds (total cholesterol ≥200 mg/dL, HDL <50 mg/dL, LDL ≥100 mg/dL, triglycerides ≥175 mg/dL, non-HDL ≥130 mg/dL, VLDL ≥30 mg/dL, ApoA1 <125 mg/dL, and ApoB ≥120 mg/dL). Adjusted prevalence ratios (aPR) and 95 % CIs were estimated via generalized linear models, controlling for age, race/ethnicity, BMI, income, marital status, and serum cotinine. Endometriosis diagnosis alone was not associated with adverse lipid profiles. In contrast, moderate/severe disease showed higher prevalence of elevated triglycerides (aPR= 2.27; 95 % CI: 1.18,4.35) and VLDL (aPR= 2.41; 95 % CI: 1.50, 3.85). Typology OE and OE+DE were associated with adverse profiles across multiple markers (aPRs 1.59-4.09), particularly ApoB and triglycerides. Minimal/mild disease and SE were not associated. The metabolic signal was phenotype-driven rather than diagnosis-driven, with severe stage and OE/OE+DE showing clear associations with adverse lipid profiles. These findings suggest lipid profiles may serve as markers of phenotype severity or shared biological milieu. Replication in larger cohorts is needed.
InfertilityIVF OutcomesBirth Weight and Gestational AgeSibling Studies
To examine birth outcomes between children conceived with in vitro fertilization (IVF) or intrauterine insemination (IUI) and sibling births from unassisted conceptions. Retrospective sibling cohort. Live born children conceived via IVF, with or without intracytoplasmic sperm injection, or IUI at the Utah Center for Reproductive Medicine, 1999-2018, and sibling births from unassisted conceptions (born 1985-2018). The main analysis included singleton births (460 IVF, 666 IUI, and 1,579 unassisted siblings). In vitro fertilization, with or without intracytoplasmic sperm injection, or IUI. Preterm birth, low birth weight, small for gestational age, large for gestational age (LGA), and major congenital anomalies. Compared with unassisted siblings, singleton children conceived via IVF had gestational ages shorter by nearly half a week (95% confidence interval [CI], -0.6 to -0.3), birth weights of 72.1 g lower (95% CI, -118.8 to -25.4), and higher proportions of preterm birth (IVF, 11.1%; IUI, 8.7%; unassisted siblings, 6.8%), LGA (IVF, 9.1%; IUI, 4.5%; unassisted siblings, 5.9%), and major congenital anomalies (IVF, 3.7%; IUI, 2.0%; unassisted siblings, 1.4%). Models adjusted for maternal age, infant sex, infant birth year, previous pregnancy, and birth order showed that children conceived via IVF were more likely to be preterm (adjusted risk ratio [aRR], 1.6; 95% CI, 1.2-2.2; absolute difference, 4.3%) and LGA (aRR, 1.8; 95% CI, 1.2-2.5; absolute difference, 3.2%). Children conceived via IVF had a higher risk of major congenital anomalies than unassisted siblings adjusted for maternal age, infant sex, and birth order (aRR, 1.9; 95% CI, 1.0-3.8; absolute difference, 2.3%). Children conceived via IUI had birth weights 55.8 g lower (95% CI, -95.6 to -15.9) than unassisted siblings. We observed an increased risk of preterm birth, low birth weight, LGA, and major congenital anomalies among singleton children conceived with IVF compared with that among unassisted siblings; however, absolute differences remain small. For children conceived via IUI, lower birth weights were observed. These results suggest that treatment-related factors in addition to underlying subfertility may contribute to adverse birth outcomes.
EndometriosisFertility OutcomesEndometriosis Surgery ClaimsReproductive Treatment Access
For many patients with endometriosis, laparoscopic surgery is the most effective treatment to alleviate severe chronic pelvic pain and improve quality of life. Because endometriosis is common among individuals with infertility, surgery is often considered alongside fertility evaluation and treatment to manage symptoms, identify disease pathology, and restore pelvic anatomy. In patients who desire pregnancy, the decision of whether and when to pursue surgery should be guided by clear medical indications and shared decision making between the patient and their obstetrician-gynecologist. In recent months, however, religious and political groups have sought to reframe this medical decision as an ideologic and moral one, advocating for endometriosis surgery in nearly all patients with infertility and claiming that this can eliminate the need for assisted reproductive technologies. This framework, known as restorative reproductive medicine (RRM), aligns with efforts to promote the "personhood" of fertilized eggs, restrict access to in in vitro fertilization (IVF), and advance endometriosis surgery and lifestyle modifications as "root-cause treatment leading to natural fertility." Recent editorials and issue briefs in the obstetrics and gynecology literature have discussed the serious ethical, medical, and policy implications of RRM, yet there remains an urgent need to address specifically the unfounded claims about endometriosis surgery and its purported advantages over assisted reproductive technology. This article examines the social context of this controversy and reviews the current evidence regarding the indications, benefits, and limitations of endometriosis surgery in the management of infertility. In contrast to RRM's assertions, no evidence supports the adoption of endometriosis surgery as a replacement for IVF or as a primary treatment for infertility. Rather, the role of surgery in fertility care is highly nuanced and depends on each patient's clinical presentation, reproductive goals, and personal priorities.
Menstrual CycleHormonal phasesCycle awarenessMeta-analysis
Open Access
This systematic review and meta-analysis examined the relationship between menstrual cycle phases and the incidence of muscle injuries in female team sport athletes, following PRISMA 2020 and PERSiST guidelines. A comprehensive search was conducted in PubMed, Scopus, and SPORTDiscus from inception to mid-January 2024. Studies were included if they examined female team sport athletes of reproductive age with regular menstrual cycles and compared the occurrence of muscle injuries across at least two menstrual phases. Studies involving hormonal contraceptive use, medications affecting the menstrual cycle or musculoskeletal system, or menstrual dysfunction were excluded. Three studies met the inclusion criteria, involving 318 participants. Meta-analysis yielded a pooled Risk Ratio of 1.18 (95% CI: 0.75 to 1.86, p = 0.46) for injury risk between the luteal and follicular phases, suggesting no statistically significant association. However, the certainty of the cumulative evidence was rated as very low due to methodological limitations, including inconsistent phase classifications and reliance on imprecise methods for identifying menstrual phases. Consequently, no practical or clinical recommendations can be made at this time. Future research employing standardised, physiologically accurate methods for classifying and detecting menstrual cycle phases is necessary to better understand the potential links between hormonal fluctuations and injury risk. The online version contains supplementary material available at 10.1038/s41598-026-36763-0.
NaProTECHNOLOGYCritique of RRMAccess to Fertility TreatmentEvidence Evaluation
Infertility affects 1 in 6 people globally (and up to a third of physicians) and is recognized by the World Health Organization and the American Medical Association as a disease. Since 1978, the development of assisted reproductive technology (ART), which is defined as fertility treatments in which gametes or embryos are handled in vitro, has made it possible to overcome otherwise insurmountable barriers to conception and has led to the birth of more than 10 million children worldwide.
EndometriosisAMH and Ovarian ReserveSurgical Staging and TypologyAnti-Müllerian Hormone
Endometriosis is a chronic, gynecologic condition in which tissue similar to the lining of the uterus implants throughout the body. Women with endometriosis have a higher prevalence of infertility and a greater risk of early natural menopause compared to those without endometriosis. This study aimed to evaluate preoperative serum AMH levels among women with and without incident endometriosis and to assess whether levels differ by surgical staging and typology. The ENDO (Endometriosis: Natural History, Diagnosis, and Outcomes) study was conducted between 2007 and 2009. The ENDO study consisted of an operative and population cohort (n=600). Only those in the ENDO operative cohort from the Utah site were used for this analysis, and included women aged 18 to 44 years who were scheduled for gynecologic surgery, irrespective of clinical indication (n=476). AMH levels were measured from stored serum collected before surgery using a quantitative enzyme-linked immunosorbent assay. After excluding participants with missing outcome data (n=51), unilateral oophorectomy (n=8), or those within the population cohort (n=69), 348 participants remained for the analysis. Surgically confirmed endometriosis diagnosis, staging (American Society for Reproductive Medicine I-IV), and typology (superficial, deep, ovarian) were ascertained by the operative report. Outliers for AMH (>14.0 ng/mL) were excluded from the analyses and AMH values were log-transformed. Multivariable linear regression models adjusted for age (squared and continuous), body mass index, serum cotinine levels, and exogenous hormonal contraceptive use were conducted. Percentage differences in AMH were calculated as (exp[β]-1)×100, and 95% confidence intervals were reported. Compared with no endometriosis, incident endometriosis diagnosis was associated with lower AMH levels (-19.8%; 95% confidence interval, -37.0 to 1.0); however, this association was not statistically significant. Stage III to IV disease was associated with 40.1% lower AMH levels (95% confidence interval, -58.9 to -12.7). Ovarian endometriomas were most strongly associated with lower AMH levels (-54.3%; 95% confidence interval, -69.4 to -31.8), with a more pronounced association among those with infertility (-72.6%; 95% confidence interval, -85.4 to -48.5). Deep (-24.1%; 95% confidence interval, -48.2 to 11.0) and superficial (-15.5%; 95% confidence interval, -34.6 to 9.3) endometriosis also showed a trend toward lower AMH levels, but these findings were not statistically significant. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis was associated with 26.8% lower AMH levels (95% confidence interval, -44.6 to -3.4). Stage III to IV disease was associated with 47.8% lower AMH levels (95% confidence interval, -65.8 to -23.2), and all subtypes of endometriosis were statistically significantly associated with lower levels of AMH compared with a postoperative diagnosis of a normal pelvis (ovarian: -60.8%; 95% confidence interval, -74.4 to -39.9; -34.3%; 95% confidence interval, -56.2 to -1.4; -24.8%; 95% confidence interval, -43.9 to -0.8). Ovarian and moderate to severe (stage III-IV) endometriosis were associated with markedly lower AMH levels compared with no endometriosis. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis and moderate to severe stages (stage III-IV) were associated with statistically significantly lower AMH levels. Additionally, typology (deep, ovarian, or superficial) was associated with statistically significantly lower AMH levels. However, this association was likely driven by the presence of ovarian endometriomas across all subtypes. These findings are consistent with previous studies and demonstrate that endometriosis lesions themselves, independent of surgical intervention, influence AMH levels.
EndometriosisRecurrence After ExcisionRetrograde Menstruation TheoryFallopian Tube Patency
Neutens S et al., 2026·Journal of Minimally Invasive Gynecology
To study whether bilateral nonpatency of fallopian tubes is correlated with a lower recurrence rate of endometriosis. Retrospective 2:1 matched case-control study. University hospital with a tertiary referral center for fertility and endometriosis surgery in Leuven, Belgium. All patients undergoing complete laparoscopic excision of any revised system of the American Society of Reproductive Medicine-stage endometriosis between 2010 and 2014 (n = 896). Comparison between patients with bilateral nonpatent or absent fallopian tubes and matched controls with at least 1 patent fallopian tube. MAIN Primary outcome was the recurrence rate, which was analyzed on 4 overall recurrence, symptom recurrence, recurrence on imaging, and need for reintervention. Of 896 patients, 49 had bilateral nonpatent or absent fallopian tubes. These cases were compared with 98 matched controls with at least 1 patent fallopian tube. Symptoms recurred in 12.2% of the cases (n = 6) and 25.5% of the controls (n = 25) (p = .09). Recurrence was confirmed by imaging in 8% of the cases (n = 4) and 10.2% of the controls (n = 10) (p = .77). In 3 patients of the case group and 12 patients of the control group, there was a need for reintervention (p = .39). Within this subgroup, recurrence of endometriosis was histologically confirmed in none of the patients of the case group and 5 patients of the control group (p = .51). This study did not observe a statistically significant reduction in endometriosis recurrence in patients with bilateral occlusion/absence of the fallopian tubes after endometriosis surgery. A type II error may count for this result.
PCOSNatural CompoundsAntioxidant TherapyHyperandrogenism and Steroidogenesis
Ursolic Acid (UA), a naturally occurring pentacyclic triterpene, was isolated from Ochrosia elliptica. Polycystic Ovary Syndrome (PCOS) a prevalent endocrine disorder characterized by hyperandrogenism, insulin resistance, and chronic inflammation. In this study, we investigate the role of UA in alleviating the symptoms of PCOS, focusing on its biochemical, hormonal, and histopathological effects in a rat model. Using adult female Wistar Albino rats, PCOS was induced through letrozole administration. The rats were then treated with UA at two different doses (25 and 50 mg/kg), alongside a control group and a standard ovulation-inducing medication, clomiphene citrate (1 mg/kg). Biochemical analyses showed that PCOS induction significantly increased serum malondialdehyde (MDA) levels by approximately 1.21-fold, while markedly reducing superoxide dismutase (SOD) and catalase (CAT) activities (p ≤ 0.05) by approximately 0.48-fold, relative to negative control. Treatment with UA (50 mg/kg) dose-dependently restored oxidative balance, reducing MDA (~ 0.82-fold) and elevating SOD (~ 2.39-fold) and CAT (~ 2.11-fold) activities toward PCOS values (p ≤ 0.05). Hormonally, PCOS rats exhibited elevated luteinizing hormone (LH) and testosterone levels by approximately 1.70-fold, compared to the negative control (p ≤ 0.05). Both doses of UA significantly lowered LH and testosterone, with the 50 mg/kg dose achieving reductions comparable to clomiphene citrate (p ≤ 0.05). Histopathological examination showed improved ovarian morphology with reduced cystic follicles and increased corpus lutea in UA-treated groups. Furthermore, UA downregulated key genes involved in steroidogenesis and oxidative stress response, suggesting a multifaceted mechanism of action. The findings highlight UA's potential as a novel therapeutic option for managing PCOS symptoms, emphasizing the need for further research into its efficacy and safety in clinical applications.
Subchorionic hematoma (SCH) is a frequent cause of first-trimester bleeding, particularly in pregnancies conceived through assisted reproductive technologies (ART), and is associated with adverse pregnancy outcomes when persistent. Management is largely conservative, with limited targeted therapeutic options. This descriptive case series evaluated the effectiveness and safety of oral alpha-lipoic acid (ALA) as an adjunct therapy in three primigravida women with ART-conceived pregnancies complicated by persistent first-trimester SCH unresponsive to conventional management, including progesterone support and hemostatic agents. ALA was administered orally at a dose of 600 mg once daily, alongside continued standard therapy. Clinical symptoms and hematoma progression were monitored through serial transvaginal ultrasonography. All three patients experienced cessation of vaginal bleeding within four to seven days of initiating ALA therapy. Complete sonographic resolution of the hematoma was observed within two to four weeks in all cases. No maternal or fetal adverse effects were reported, and all pregnancies progressed uneventfully into the second trimester. These findings suggest that oral ALA may represent a safe and potentially effective adjunctive therapy for persistent first-trimester SCH in ART pregnancies, warranting further evaluation in larger prospective studies.
EndometriosisDietary and NutritionalEating DisordersProspective Design
Disordered eating behaviors may impact the gynecologic health of adolescents through effects on menstrual cycle function and body size; however, few studies have evaluated these associations. This study aimed to prospectively investigate the associations between individual disordered eating behaviors during adolescence and the risk of subsequent endometriosis diagnosis. Prospective, longitudinal cohort (1996-2021). Female participants (n = 11,773) from the Growing Up Today Study. Frequency of binge eating, laxative use, and self-induced vomiting over the past year was self-reported on repeated questionnaires during follow-up. Physician-diagnosed endometriosis was reported on repeated questionnaires during follow-up. Multivariable logistic regression models with generalized estimating equations were used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Over 25 years of follow-up, we identified 269 incident cases of endometriosis (2.3%), 190 of which were reported as laparoscopically confirmed. A total of 32% of girls reported ever binge eating, 14% reported self-induced vomiting to lose weight, and 9% reported ever using laxatives to lose weight. The odds of a laparoscopically-confirmed endometriosis diagnosis were more than three-fold higher (aOR = 3.07; 95% CI 1.74, 5.40) for girls who cumulatively reported self-induced vomiting more than monthly during follow-up, compared with girls who never reported self-induced vomiting. Cumulative exposure to binge eating during follow-up was not associated with diagnosis of laparoscopically-confirmed endometriosis; however, girls who reported the highest ever engagement in binge eating of weekly or more had 52% lower (aOR = 0.47; 95% CI 0.25, 0.90) odds of laparoscopically-confirmed endometriosis, compared with girls who reported less than weekly binge eating. Laxative use was not strongly associated with endometriosis diagnosis, although estimates were imprecise. Females with a greater frequency of self-induced vomiting were more likely to be diagnosed with endometriosis during follow-up, whereas girls with a history of frequent binge eating had a lower likelihood of endometriosis diagnosis. We found no association between laxative use and endometriosis.
Published evidence on patient experiences, perceptions, and challenges related to early breast cancer (eBC) in Italy is limited. Understanding these aspects is critical for improving diagnosis, treatment outcomes, and quality of life (QoL). This study used social media listening (SML) to explore the patient journey, treatment perceptions, QoL, and unmet needs of patients with eBC, caregivers, and health care professionals (HCPs) in Italy. This retrospective noninterventional SML study analyzed publicly available posts from December 2021 to November 2023 using breast cancer-related keywords in English and Italian through Sprinklr, a web-based aggregator tool. Posts sourced from social media platforms, such as X (formerly known as Twitter), blogs, forums, Facebook, Instagram, and YouTube, were filtered by geographic location to include only users in Italy. Posts were filtered using natural language processing (NLP) for relevance and duplicates, followed by manual review and stakeholder identification (patients, caregivers, and HCPs). Key themes of discussion were identified through thematic analysis of posts across the stages of the patient journey (symptoms, diagnosis, treatment, etc). Ethical guidelines were followed by using anonymized, publicly available data. Descriptive statistics were used to analyze the data, and posts with missing data were excluded. Consequently, denominators varied across analyses and were adjusted based on data availability for specific variables. Of the 20,008 posts initially extracted, 1580 posts were retained following NLP filtering, and 530 posts were included after manual screening. The majority (493/518, 95%) of the posts were sharing information about diagnosis and treatment journeys, emotional challenges, QoL concerns, and symptoms (eg, lumps, breast pain), while 27% (141/518) of the posts sought information on diagnostic dilemmas, treatment options, and second opinions. Patients contributed 60% (318/530) of the posts, and caregivers contributed 21% (111/530) of the posts, with over half (57/107, 53%) discussing their mothers' diagnosis and treatment struggles. HCPs contributed 16% (85/530) of the posts, primarily sharing clinical trial updates, drug approvals, and disease awareness efforts. A total of 88 posts included discussions on QoL, and eBC significantly impacted patients' emotional, physical, functional, and social well-being. Discussions revealed key unmet needs, including limited awareness of adjuvant therapy options, lack of peer support groups, suboptimal patient-HCP communication, and insufficient access to specialty care facilities. This study highlights gaps in eBC management related to patient education, HCP communication, and access to specialty care and describes an associated worsening of QoL for patients as reflected in social media posts. Within the limitations of an observational SML design, increasing patient and caregiver awareness of available adjuvant therapies to improve adherence and reduce recurrence risk, alongside expanding access to regional breast cancer centers, may help optimize patient experiences and outcomes. Further research using complementary data sources is needed to confirm and extend these findings.
PregnancySubchorionic HemorrhageProteomic and Transcriptomic AnalysisMachine Learning Biomarker Discovery
Subchorionic hemorrhage (SCH) is characterized by a fluid-filled hypoechoic area in early pregnancy. This study investigates how laminin subunit β1 (LAMB1) modulates type III collagen (COL3A1) and Rac family small GTPase 1 (RAC1) in SCH coagulation and immunity. We recruited ten early-pregnancy SCH patients and ten gestational age-matched women undergoing elective abortion as controls. Proteomic and transcriptomic analyses were performed on decidua and villous tissues to identify differentially expressed proteins (DEPs) and genes (DEGs). Key biomarkers were screened using bioinformatics and machine learning algorithms (LASSO, SVM-RFE). An in vivo SCH-like model was established via LPS induction in pregnant rats, and in vitro experiments were conducted using HTR-8/SVneo trophoblast cells. Proteomic analysis revealed enrichment in extracellular matrix and coagulation pathways, identifying LAMB1 as a central protein. Transcriptomic data confirmed upregulation of LAMB1 and COL3A1 and downregulation of RAC1 in SCH samples. Clinical blood analysis indicated coagulation abnormalities and Th1/Th2 imbalance in SCH patients. In vivo, LAMB1 knockdown alleviated inflammation, improved pregnancy outcomes, and restored Th2 cytokine expression. In vitro, LAMB1 silencing enhanced trophoblast proliferation, migration, and invasion while reducing pro-inflammatory cytokine levels. Mechanistically, LAMB1 modulated SCH progression via the COL3A1/RAC1 axis. LAMB1 promotes inflammation and coagulation dysfunction in SCH by regulating COL3A1 and RAC1 expression. Targeting LAMB1 may offer a novel strategy for early diagnosis and therapeutic intervention in SCH to improve pregnancy outcomes.
This study investigated the effects of prenatal exposure to hexafluoropropylene oxide dimer acid (HFPO-DA), a replacement for perfluorooctanoic acid (PFOA), on mammary gland development of both pregnant rats and their offspring, as well as its influence on related hormone levels. Pregnant Sprague-Dawley (SD) rats were orally exposed to HFPO-DA at doses of 0, 1, 10, and 100 mg/kg/day from gestation day (GD) 0.5 to GD 19.5. On GD 19.5, half of the pregnant rats from each dose group underwent caesarean section, while the other half gave birth naturally. The offspring from the rats that gave birth naturally were raised until they reached postnatal day (PND) 21. The serum levels of progesterone (Pg), estradiol (E2), and prolactin (PRL) in the pregnant rats and their offspring on PND 21 were detected via ELISA (enzyme-linked immunosorbent assay). Changes in mammary glands of pregnant rats, their fetuses, and PND 21 offspring were assessed by haematoxylin and eosin (H&E) staining. The development of mammary gland tissue structures in fetuses and PND 21 offspring was evaluated using whole gland staining. Immunohistochemical staining was used to assess STAT5 expression in the mammary glands of pregnant rats and Ki67 expression in the mammary glands of fetuses and PND 21 offspring. In pregnant rats, exposure to HFPO-DA significantly increased the PRL levels. The expression of STAT5 was also significantly elevated in mammary epithelial cells. The lobular and alveolar areas expanded dose-dependently, and milk secretion was observed in the high-dose group. In fetuses and PND 21 offspring exposed to HFPO-DA, we observed significant growth of secondary mammary ducts, a substantial increase in ductal coverage area, ductal buds, and primary duct length, as well as an increase in Ki67 expression in mammary epithelial cells. Collectively, these findings suggest that HFPO-DA exposure elevates serum PRL levels in pregnant rats, promotes lactation, and stimulates early-stage mammary gland development in offspring.
Body LiteracyInformed consentInformed decision-makingCounseling
Regular welfare assessments are essential for identifying and addressing the physical, behavioral, and emotional needs of shelter dogs, thereby ensuring their well-being and improving chances for adoption or long-term stability within the shelter environment. This study compared biomarkers of physiological stress [fecal glucocorticoid metabolites (fGCM)], metabolic status [serum malondialdehyde (MDA), glucose, triglycerides, low- (LDL) and high- (HDL) density lipoproteins], and fecal microbiota composition over a 1-month period in healthy and spinal-injured disabled dogs housed in a large dog rescue shelter in Thailand for over 1 year. No significant differences in fGCM concentrations were observed between groups, indicating comparable levels of physiological stress in healthy and disabled dogs under long-term shelter conditions. In contrast, disabled dogs exhibited significant metabolic and oxidative alterations, including elevated MDA and glucose, along with lower triglyceride and HDL concentrations. Microbial analyses revealed comparable alpha diversity but differences in beta diversity between groups. Notably, disabled dogs exhibited a reduced Firmicutes-to-Bacteroidetes (F/B) ratio and decreased relative abundances of beneficial taxa such as Peptostreptococcaceae. These findings suggest that, despite comparable hormonal stress indicators, disabled dogs may experience subclinical physiological shifts that warrant more nuanced welfare monitoring. A multifactorial assessment incorporating metabolic and microbial parameters is recommended to ensure comprehensive welfare evaluation for physically impaired shelter dogs.
Stanley A et al., 2026·MCN. The American journal of maternal child nursing
Postpartum depression (PPD) affects 10% to 20% of mothers, with higher rates among marginalized communities. Mental health issues contribute to 22.7% of pregnancy-related deaths. Doulas provide continuous emotional, physical, and informational support throughout the perinatal continuum. This narrative review synthesized data from articles published from 2020-2025 that examined the impact doula support had on PPD. PubMed, CINAHL, and Google Scholar were searched in February 2025. Search terms included "Depression, Postpartum," "Social Support," "Maternal Health Services," "Doula," "Birth Support," and "Perinatal Mental Health." Nine articles met inclusion criteria and were included in the review. Qualitative, quantitative, and review articles were represented in this narrative review. Women receiving doula support had lower odds of developing PPD or postpartum anxiety. Outcomes for women who had doula participation during and after pregnancy include enhanced social support, reduced stress, improved birth experiences, and increased maternal self-efficacy. Doulas show promise for PPD prevention. Barriers exist for marginalized and underresourced populations of patients in accessing doula care, yet these are the populations who report maternal mental health disorders disproportionately compared with nonmarginalized women. We recommend focusing on the protective value of doulas in preventing PPD, overcoming barriers for patient access to doulas, and standardized mental health education for doulas. Integrating doula support into maternity care requires alignment with the health care team to ensure continuity and effectiveness. Nurses are critical in this partnership through assessment and collaborative care coordination.
General OB/GYNFetal Cardiac AnomaliesChromosomal Microarray and Exome SequencingCongenital Heart Defects
Tseng JJ et al., 2026·Taiwanese journal of obstetrics & gynecology
To assess the combined role of prenatal imaging and stepwise genetic testing in diagnosing fetal congenital heart defects (CHDs) over a 30-year period, focusing on CHD subtypes, extracardiac anomalies, and diagnostic yield. This retrospective cohort study included 423 fetuses diagnosed with CHDs at Taichung Veterans General Hospital between 1995 and 2024. All underwent detailed fetal echocardiography. Genetic testing was conducted most cases underwent karyotyping, with chromosomal microarray analysis (CMA), targeted gene panels, or whole-exome sequencing (WES) added based on clinical indications. Diagnostic yields were assessed by testing modality, with subgroup analyses based on CHD type and extracardiac features. Septal defects were the most common diagnosis (18.7 %), increasing to 26.5 % when coexisting intracardiac anomalies were included. Cyanotic CHDs predominated (39.5 %), followed by miscellaneous anomalies (22.9 %), left-to-right shunts (18.9 %), obstructive lesions (11.6 %), and arrhythmias (7.1 %). Extracardiac structural problems and fetal hydrops were present in 22.2 % and 5.0 %, respectively. Chromosomal abnormalities were detected in 12.3 % (40/326), predominantly trisomies, and were significantly associated with left-to-right shunts (55 %, P < 0.001) and extracardiac problems (62.5 %, P < 0.001). Among the 181 cases with normal karyotypes, CMA identified pathogenic or likely pathogenic copy number variants in 7.7 %, including deletions at 22q11.21 (involving TBX1), 7q11.23 (involving ELN), and 16q24.2-q24.3 (involving ZFPM1), among others. With the addition of WES or targeted sequencing, the overall diagnostic yield rose to 14.1 % (27/191), with pathogenic or likely pathogenic variants detected including ANKRD11, ACVRL1, EFTUD2, TSC2, and FBN1. The diagnostic yield P was significantly higher in fetuses with extracardiac problems (51.9 %, P < 0.001). Combining prenatal imaging with tiered genetic testing enhances the diagnostic precision in fetal CHDs, particularly in cases with extracardiac anomalies and left-to-right shunts. These findings support a clinically driven, resource-sensitive approach to prenatal genetic evaluation.
Curcumin, a bioactive polyphenol derived from turmeric (Curcuma longa), has garnered substantial attention for its potent anti-inflammatory, antioxidant, and antineoplastic properties. This review explores the therapeutic potential of curcumin in gynecologic health, with a focus on its role in the management of ovarian, cervical, and endometrial cancers, as well as benign conditions such as endometriosis, polycystic ovary syndrome, premenstrual syndrome, and menopausal symptoms. A literature review was conducted on the health effects of gynecology. Relevant articles were identified through systematic searches in major biomedical databases, including PubMed, Scopus, Cochrane Library, Embase, and Web of Science databases for studies reporting the relationship between curcumin and some in gynecological diseasess as of 2025. Curcumin modulates key inflammatory signaling pathways, reduces oxidative stress, and exerts antiproliferative effects, making it a promising adjunct in the treatment of both neoplastic and inflammatory gynecologic disorders. Nevertheless, clinical translation remains limited by challenges such as poor bioavailability and a paucity of large-scale, randomized controlled trials. Emerging evidence supports the integration of curcumin into multimodal treatment strategies, particularly in oncology and chronic inflammatory conditions. In light of the need to improve treatment efficacy and enhance patients' quality of life, the exploration of novel adjuvant therapeutic strategies is highly warranted. Recent studies have demonstrated the beneficial effects of curcumin and its novel analogues across a range of gynecologic diseases, while advances in formulation technologies have led to improved pharmacokinetic profiles and therapeutic outcomes. Nevertheless, further robust clinical investigations are required to optimize curcumin formulations, enhance bioavailability, and establish evidence-based guidelines for its integration into gynecologic care. This review synthesizes current evidence and highlights the underlying molecular mechanisms responsible for the observed effects, aiming to support the rational development of curcumin-based strategies in gynecology.
Regulatory T cells (Tregs) play a central role in maintaining immune tolerance and supporting maternal-fetal homeostasis throughout human pregnancy. Clinical and experimental evidence demonstrates that dysregulation of peripheral and decidual Tregs manifested as quantitative deficits, impaired suppressive function or lineage instability increased the risk of various pathological pregnancies, such as recurrent implantation failure (RIF), recurrent spontaneous abortion (RSA), pre-eclampsia (PE) and preterm birth (PTB). Recently, novel therapeutic strategies targeting Tregs have emerged in oncology, transplantation, and autoimmune diseases. However, their application in pathological pregnancy remains in its infancy. This review outlines the spatiotemporal dynamics of peripheral and decidual Tregs throughout gestation, elucidating their roles in maintaining maternal-fetal homeostasis and their dysregulation in pathological pregnancies. We also critically evaluated the therapeutic strategies targeting Tregs and Tregs-associated signaling pathways, including hormonal support, traditional intravenous immunoglobulin, as well as emerging interventions such as immunometabolic reprogramming and engineered cellular therapies like chimeric antigen receptor Tregs. This review may provide insights for understanding the roles of Tregs in physiological and pathological pregnancy, as well as provide new idea in the immunotherapy of pathological pregnancy.
EndometriosisMenstrual Distress and PainPsychological FactorsDysmenorrhea and Endometriosis
Zafman KB et al., 2026·International journal of behavioral medicine
The objective of this study was to determine if Edinburgh Postnatal Depression Scale (EPDS) scores at delivery discharge are predictive of EPDS scores at 2-6 weeks postpartum. This was a retrospective cohort study of all patients who delivered at an urban academic medical center from 6/2021 to 6/2022. Universal EPDS screening was implemented for all patients prior to discharge; a score of ≥ 9 was considered at risk for postpartum depression. Patients were re-screened at 2-6 weeks postpartum. The primary outcome was mean EPDS score at 2-6 weeks postpartum. One thousand six hundred three patients were included; 219 (13.7%) scored ≥ 9 at delivery discharge and 37 (2.3%) endorsed self-harm at delivery discharge. Mean EPDS score at the postpartum visit was significantly higher for patients who had an elevated EPDS at delivery discharge compared to those with a low-risk score (7.9 vs. 2.7, p < 0.001). Of patients who had an EPDS ≥ 9 at delivery discharge, 42.0% (92/219) continued to score ≥ 9 postpartum. Most patients who scored < 9 at delivery discharge continued to score low at 2-6 weeks postpartum (1270/1384, negative predictive value 91.8%). A small proportion of patients who had a low score at delivery discharge scored ≥ 9 at the postpartum visit (114/1384, 8.2%). EPDS screening at delivery discharge is feasible and identifies patients at risk of postpartum depression. Interventions should target patients with an elevated EPDS score at delivery discharge, as many patients will continue to score high at their postpartum visit. Rescreening at the postpartum visit remains important, as there are patients who will not be captured immediately postpartum.
GBD 2021 AEMT Collaborators, 2026·The Korean journal of internal medicine
This study aims to evaluate the global burden of adverse effects of medical treatment (AEMT) using data from the Global Burden of Disease Study (GBD) 2021. Data were extracted from the GBD 2021, covering 204 countries/territories from 1990 to 2021. AEMT was defined using ICD-9 and ICD-10 codes, encompassing complications from medical procedures, treatments, or healthcare exposures. Estimates were categorized into fatal and non-fatal outcomes and stratified by age, sex, year, and covariates, including the Socio-demographic Index (SDI). Mortality-incidence ratios (MIRs), defined as the ratio of mortality calculated by dividing the number of deaths by the total incident cases, were analyzed. In 2021, the global age-standardized prevalence, incidence, disability-adjusted life years (DALYs), and mortality rates of AEMT were 11.48 (95% uncertainty interval [UI], 8.86-14.13), 150.44 (131.19-171.81), 64.19 (51.06-73.11), and 1.53 (1.29-1.68) per 100,000 population, respectively. DALY rates were highest in the early neonatal group (4,789.47 per 100,000 population [95% UI, 3,682.00-5,963.30]), while mortality rates followed a U-shaped pattern across age groups. In 2021, MIRs were highest the early neonatal group (0.58 [95% UI, 0.55-0.58]) and the 95+ age group (0.05 [0.04-0.06]). This pattern was consistent across all SDI quintiles, with higher MIRs observed in lower SDI quintiles. The significantly higher prevalence and incidence rates of AEMT among the older population in high SDI quintiles, compared to lower SDI quintiles, could be attributed to the healthcare overutilization, highlighting the need for policy adjustments.
General OB/GYNUterine Closure TechniqueHysterotomy RepairCesarean Scar Complications
Bujold E et al., 2026·American Journal of Obstetrics and Gynecology
Normal uterine function depends on cyclical regeneration and the capacity to sustain pregnancy. A cesarean incision represents an injury to this remarkable organ. Although the uterus possesses exceptional healing potential, cesarean delivery increases the risk of secondary infertility, pelvic pain, uterine rupture, and abnormal placentation in subsequent pregnancies. The two most important determinants of successful hysterotomy healing after cesarean delivery are the location of the incision and the surgical technique used for closure. The anatomic site of entry-whether the corpus, lower uterine segment, or cervix-defines the tissue composition, vascularity, and contractility at the wound margins, which in turn influence how the scar remodels and withstands subsequent pregnancies. Surgical technique is also important. A robust body of experimental and clinical evidence demonstrates that restoring anatomic integrity by reapproximating uterine layers while excluding the endometrium produces stronger scars and reduces late complications. The rationale for excluding the endometrium is to prevent displacement of endometrial tissue into the myometrium and to avoid mucosal tearing against a foreign body (i.e. suture material), both of which predispose to defective healing. When the endometrium is incorporated, healing is often impaired, leading to niches or isthmoceles, adenomyosis, and endometriosis at the scar site. Over time, these defects have been recognized as contributors to abnormal bleeding, pelvic pain, infertility, uterine rupture, and placenta accreta spectrum disorders. Despite this evidence, single-layer closures that incorporate endometrium became widely adopted because of their speed and simplicity, while their long-term sequels were initially underappreciated. This has prompted renewed scrutiny of closure techniques, including comparisons of single-layer vs double-layer closure, locking vs nonlocking sutures, type of sutures, and the direction of suture. Collectively, the data show that optimal closure respects uterine anatomy, restores the natural alignment of tissues, and achieves hemostasis without compromising perfusion or strangulating tissues. Building on these principles, we herein describe a refined 3-layer closure. The first layer approximates decidua and junctional myometrium while excluding surface endometrium to prevent tissue entrapment and bacterial contamination. The second layer restores anatomic wall integrity by reapproximating the bulk of the myometrium, thereby reinforcing strength and distributing tension across the scar. The third layer reapproximates superficial myometrium and serosa, smoothing the uterine surface and reducing adhesions. This technique is not simply a return to traditional double-layer methods or an extension of single-layer practice, but rather a refinement that integrates lessons from visceral surgery and contemporary obstetric data. Its rationale is to restore anatomy, secure hemostasis without ischemia, and preserve long-term uterine function. While short-term safety appears comparable across closure methods, evidence increasingly indicates that long-term reproductive outcomes depend on how closure respects tissue biology. We argue that appropriate repair is more meticulous restoration of uterine anatomy should take precedence over operative speed. The enduring success of a hysterotomy repair depends on the surgical technique employed, as it directly affects women's future reproductive health.
Sebire E et al., 2026·The Lancet regional health. Europe
Down's syndrome (DS) is the most common chromosomal congenital condition diagnosed in pregnancy. Antenatal screening for DS is available in Scotland, and in September 2020, non-invasive prenatal testing (NIPT) was added to the screening pathway. This study aimed to examine trends in total birth (TB) and live birth (LB) prevalence of DS (2000-2021) in Scotland and associations with maternal and infant socio-demographic factors. A retrospective, observational, population-based study using the Scottish Linked Congenital Conditions Dataset (SLiCCD). Poisson and generalised Poisson regression analyses were used to model TB and LB prevalences of DS. Associations with year, maternal age, Scottish Index of Multiple Deprivation, health board of residence, and infant sex (live births only) were assessed. Prevalence rate ratios (PRR), 95% confidence intervals (CIs) and p values were reported. There were 2098 singleton pregnancies and 1135 live births with DS (2000-2021), with a TB prevalence of 17.4 (95% CI 16.7, 18.2) per 10,000 TBs, and LB prevalence of 9.5 (95% CI 8.9, 10.0) per 10,000 LBs. There was evidence of a non-linear time trend in TB prevalence, increasing between 2013 and 2015 [PRR: 1.13 (95% CI 1.07, 1.19); p < 0.001] and decreasing between 2016 and 2021 [PRR: 0.95 (95% CI 0.92, 0.98); p = 0.002]. No time trend was observed for LB prevalence. Maternal age and health board of residence were associated with TB and LB prevalence of DS. Our population-based insights into TB and LB prevalence of DS in Scotland are important in establishing baseline trends to investigate the impact of NIPT. This enables up-to-date counselling for those undergoing DS screening, and appropriate planning of healthcare services. ES received Medical Research Scotland PhD Studentship funding (grant no. PHD-50200-2020).
Spermatogenesis relies on the intricate interactions between testicular somatic cells and germ cells. While follicle-stimulating hormone (FSH) and testosterone (T) are considered pivotal regulatory factors in this process, the mechanisms by which these hormones regulate the spermatogonial stem cell (SSC) microenvironment via Sertoli cells during testicular development in roosters remain unclear. Here, we examined how FSH and T regulate Sertoli-cell proliferation and the expression of glial cell-derived neurotrophic factor (GDNF) during rooster testicular development. We observed that at 4 weeks of age, the seminiferous tubules of roosters were fully developed, accompanied by the migration of spermatocytes into the lumen. At this stage, both serum and testicular levels of FSH and T were elevated in parallel. In highly purified Sertoli cells cultures, FSH treatment (25-100 ng/mL) significantly promoted proliferation and cell-cycle progression, and induced GDNF protein expression in a time- and dose-dependent manner, with the strongest response observed at 75 ng/mL. Although T did not significantly affect Sertoli cell proliferation, it markedly upregulated GDNF protein expression via the androgen receptor (AR) signaling pathway. Specifically, T (0.1-0.4 ng/mL) increased GDNF without altering proliferation, and this effect was blunted by pharmacological AR blockade (enzalutamide), indicating AR dependence. Furthermore, combined treatment with FSH and T demonstrated a synergistic effect, amplifying the expression of GDNF protein. In vivo experiments revealed that subcutaneous FSH administration increased Sertoli-cell proliferative activity (PCNA) and testicular growth, whereas testosterone administration enhanced testicular GDNF expression. Notably, combined FSH+T treatment produced the highest testicular GDNF level among groups, consistent with a synergistic effect in vivo. These findings suggest that FSH drives the expansion of Sertoli cell numbers by promoting their proliferation and cell cycle progression, while testosterone enhances the functional maturation of Sertoli cells through the regulation of GDNF expression. The synergistic actions of these two hormones together optimize the spermatogenic microenvironment, providing novel insights into the hormonal regulation of male reproduction.