GLP-1 Receptor Agonists and Fertility: What Is Known So Far?

Abstract: GLP-1 receptor agonists (GLP-1RAs) have gained attention as a potential adjunct in preconception care for women with polycystic ovary syndrome (PCOS) and infertility. This narrative literature review (June 2025) searched PubMed, SciELO, and LILACS using the descriptors "weight loss medication," "GLP-1 receptor agonists," "liraglutide," "semaglutide," "fertility," "PCOS," and "reproductive outcomes," including studies published between 2014 and 2025, yielding 47 relevant articles. Overall, GLP-1RAs show consistent metabolic benefits and emerging evidence of improved reproductive outcomes in PCOS, with clinical trials reporting increased menstrual regularity, ovulation, and pregnancy rates-particularly when combined with metformin. Liraglutide (1.2-3.0 mg/day) and exenatide (10 µg twice daily) have been associated with improved follicular development and endometrial receptivity. Mechanistically, GLP-1 receptors are expressed in reproductive tissues, and these agents may exert anti-inflammatory, antifibrotic, and androgen-lowering effects; liraglutide has also been reported to restore granulosa-oocyte communication via suppression of CXCL10. In one randomized trial, pregnancy rates were higher with liraglutide plus metformin (69.2%) than with metformin alone (35.4%; p<0.05). Ovulation rates up to 86% have been described with exenatide plus metformin, exceeding those observed with monotherapy. Despite these signals of benefit, GLP-1RAs remain contraindicated during pregnancy due to limited human data and fetal risks observed in animal studies; semaglutide and tirzepatide require an 8-10 week washout period prior to conception, and tirzepatide may reduce oral contraceptive effectiveness because of delayed gastric emptying. In summary, GLP-1RAs are a promising strategy for preconception management in women with PCOS and obesity-related infertility, especially in combination with metformin, but they should be avoided during pregnancy and lactation, and individualized counseling is essential to align therapy with reproductive goals.


Definition of Infertility and Indications for Fertility Evaluation: Consensus Document

Phil C Boyle

NeoFertility Clinic, Suite 7, 1st Floor, Beacon Mall, Sandyford, Dublin 18, Ireland. Phil.Boyle@NeoFertility.ie.

Abstract:
Infertility is a clinical condition that is recognized by the symptom of an inability to conceive through sexual intercourse or to sustain a pregnancy, with that symptom indicating underlying male and/or female pathology.
METHODOLOGY
This definition of infertility was developed through a structured, consensus-informed process involving broad stakeholder engagement. Initially, multiple definitions currently used by various medical professional organizations were reviewed, and a definition document was drafted and submitted to the Board of Directors of the International Institute for Restorative Reproductive Medicine (IIRRM). All IIRRM members were invited to provide feedback on the draft. Approximately 2,500 individuals and 44 organizations from 92 countries were then invited to review the proposed document, representing clinical, scientific, patient, policy, and advocacy perspectives. Submitted comments were reviewed thematically, with suggested revisions evaluated for clarity, clinical relevance, inclusiveness, and consistency with contemporary restorative reproductive medicine. Following this review, 3 substantive changes, 18 minor changes, and 15 citation corrections were incorporated into the final draft which resulted in a revised definition intended to better reflect the medical, social, and practical realities of modern infertility evaluation and care. Final approval by the IIRRM Board of Directors was unanimous.

Journal of Restorative Reproductive Medicine


Modeling fertile window differences across the reproductive lifespan with quantitative urine hormone monitoring of the menstrual cycle

Maria Meyers

Western Health Center, Midfield, AL, USA

Abstract:
BACKGROUND: Reproductive hormones of the fertile window are often referenced to women in regular cycles, but this may not be representative of the hormonal profiles of women in different circumstances like polycystic ovarian syndrome, the postpartum period, and the perimenopause transition. This observational cohort study sought to identify the variability in the reproductive hormones in various clinical circumstances and to establish potential thresholds for each category based on hormone measurements with the Mira urinary hormone monitor.

RESULTS: A total of 57 women (ages 22-51) in various circumstances (regular cycles, polycystic ovarian syndrome, postpartum and perimenopause) tracked Mira urine hormone measurements (estrone-3-glucuronide, luteinizing hormone, pregnanediol glucuronide), contributing 444 cycles of data. Using additive mixed models, hormone values were stratified by the four different reproductive categories. The perimenopause and polycystic ovarian syndrome groups demonstrated relative hypoestrogenic states, while the perimenopause group showed low luteal pregnanediol glucuronide and the polycystic ovarian syndrome/polyendocrine metabolic ovarian syndrome (PCOS/PMOS) group showed high luteal pregnanediol glucuronide. The perimenopause group had significantly higher luteinizing hormone values throughout the whole cycle.

CONCLUSION: The fertile window hormone thresholds vary depending on a woman's specific reproductive category. Women in different circumstances should not necessarily use the same hormonal thresholds for the fertile window and ovulation. A larger dataset with ultrasound correlation to ovulation is required to delineate the fertile window with more precision. Hormone differences across the menstrual cycle could be used for targeted treatments in polycystic ovarian syndrome and perimenopause women.


Real World Fertility Evaluation & Care Prior to In Vitro Fertilization: Care Gaps That Could be Addressed by Restorative Reproductive Medicine: A Retrospective 5-Million Patient Claims Based Care-Gap Analysis

Craig Turczynski

RRM Diagnostics, Dallas, TX, USA; Duquesne University College of Osteopathic Medicine, Pittsburgh, PA, USA

Abstract:
Objective
To evaluate adherence to published American Society for Reproductive Medicine (ASRM) and American Urological Association (AUA) infertility evaluation and treatment recommendations among commercially insured infertility patients who subsequently underwent in vitro fertilization (IVF), and to assess whether observed care gaps support the need for a restorative reproductive medical framework.
Methods
A retrospective claims-based analysis was performed using MarketScan® Commercial Claims and Encounter Data between January 1, 2021, and December 31, 2024. Approximately five million commercially insured members were evaluated. Patients with infertility-related diagnoses who subsequently underwent IVF were identified. Claims were analyzed for evidence of selected diagnostic testing, medical treatment, or surgical interventions recommended by ASRM or AUA/ASRM guidance for specific infertility-related diagnoses before IVF initiation. Cumulative adherence rates were assessed up to nine months following initial infertility diagnosis and compared with the timing of initiating IVF.
Results
IVF initiation started early and consistently preceded completion of most recommended evaluations and treatments. By 3 months, the proportion of patients with IVF initiation ranged from 28% to 39% across different infertility-related diagnoses, while adherence to most recommended interventions remained low. Overall, by 9 months, IVF utilization had reached 70–85%, while many recommended evaluations and treatments remained below 40% adherence, with several interventions remaining below 15%. Observed care gaps (percentage of patients receiving IVF prior to other evaluation or treatment recommendations) ranged from approximately 13% to 78% for most recommended evaluations and treatments, with several measures demonstrating gaps over 50% of patients.
Discussion
These findings suggest substantial divergence between published infertility-care recommendations and observed practice patterns. From the perspective of restorative reproductive medicine (RRM), the gaps are clinically important because many recommended steps are directed toward identifying, correcting, restoring, or preserving reproductive function and anatomy before offering or initiating IVF treatment. Limitations to these data include lack of individualized patient medical data, preferences, or circumstances, and not capturing any treatment that was not reimbursed by commercial insurance (i.e., any cash payment for services). In addition, the recommendations assessed have variable levels of underlying evidence, and likely vary in the level of their acceptance among practicing clinicians.
Conclusions
Many commercially insured infertility patients progressed to IVF without documented evidence of diagnostic evaluation or therapeutic interventions recommended in ASRM and AUA/ASRM guidance. These findings raise important questions regarding the implementation of adequate evaluation before IVF and the extent to which patients receive meaningful opportunities for diagnosis-directed treatment of potentially reversible causes of infertility. The findings further suggest an important role for RRM as a quality-of-care framework focused on comprehensive evaluation, correction of underlying dysfunction, preservation of reproductive anatomy and physiology, and optimization of patient-centered fertility care, prior to considering IVF.


Diagnosis and treatment of luteal phase deficiency: a Committee Opinion

Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Reproductive Endocrinology and Infertility

Abstract: Luteal phase deficiency (LPD) is a clinical diagnosis associated with abnormal luteal phase length of ≤10 days. Potential etiologies of LPD include inadequate progesterone duration, inadequate progesterone levels, or endometrial progesterone resistance. Luteal phase deficiency has been described in association with medical conditions, but also in fertile, normally menstruating women. Although progesterone is important for the process of implantation and early embryonic development, LPD has not been proven to be an independent entity causing infertility or recurrent pregnancy loss. Controversy exists regarding the multiple proposed measures for diagnosing LPD, and assuming it can be diagnosed accurately, whether treatment improves outcomes. This document replaces the document of the same name, last published in 2021 (Fertil Steril 2021;115(6):1416-23).


Evidence That Semaglutide Represents an Important Tool for Treatment of Irregular Menses and Chronic Anovulation in Women with Polyendocrine Metabolic Ovarian Syndrome

Abstract: Background: Irregular menses and chronic anovulation are key components of Polyendocrine Metabolic Ovarian Syndrome (PMOS), but available treatments generally only mask the clinical problem, which presents itself again when the drugs are stopped. Because reduction of body weight in these patients is often associated with improvement of menstrual cycles, we evaluated the effects of treatment with semaglutide, a GLP-1 agonist that has emerged as an effective treatment for obesity. Methods: A total of 96 women with PMOS and body mass index (BMI) > 25 kg/m2 completed a six-month treatment protocol with semaglutide using an individualized dose-escalation regimen. Body weight, fasting glucose, insulin levels, insulin resistance (HOMA-IR), and ovulatory function were assessed before and after treatment. Results: After six months of treatment, mean body weight decreased significantly (-11.3 ± 5%, p < 0.01). Before treatment, 83% of PMOS patients presented with oligomenorrhea and anovulatory cycles. Following treatment, ovulatory cycles were observed in 52.5% of previously anovulatory women. The results were particularly good in overweight patients, with almost 95% of these PMOS patients achieving menstrual cycle normalization and ovulation, but also in patients with mild obesity. Results were less favorable in PMOS patients with moderate or severe obesity, but 25% of these patients achieved menstrual ovulatory cycle normalization when treated with semaglutide. Conclusions: This study represents an important therapeutic advancement, suggesting that women with PMOS and excessive body weight should be considered for treatment with GLP-1 receptor agonists before proceeding to therapies specifically aimed at inducing normal cycles and ovulation.


Effect of Myo-Inositol Supplementation in Polycystic Ovary Syndrome-Scoping Review

Abstract: Objectives: Polycystic ovary syndrome (PCOS) is a widespread and complex endocrine disorder affecting women of childbearing potential, characterized by reproductive dysfunction, hyperandrogenism, and metabolic disorders, including insulin resistance. Insulin resistance is a key pathogenetic factor contributing to ovarian dysfunction and reduced fertility. Myo-inositol (MI), a ubiquitous polyol, has earned a reputation as a promising dietary supplement due to its vital role in insulin signaling pathways. This scoping review aimed to map the available scientific literature on the effects of MI supplementation in women with PCOS, with particular emphasis on fertility and ovarian function, and to identify gaps in the current evidence base. Methods: This scoping review was conducted in accordance with the methodology developed by the Joanna Briggs Institute (JBI) and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. A literature search was conducted against six electronic databases: PubMed, Scopus, Web of Science, EBSCO (MEDLINE Complete), Cochrane Library and Google Scholar. Searches were conducted between 10 January and 20 February 2026. Eligibility sources included original articles (observational and randomized controlled trials), meta-analyses, systematic and narrative reviews, published in English with full text available, focusing on adult women with PCOS. Data extraction was performed independently by two reviewers using the Population-Concept-Context (PCC) framework. In accordance with the scope review methodology, no formal critical appraisal of study quality and no quantitative synthesis were performed. This is consistent with JBI methodology, which does not require critical appraisal for scoping reviews unless explicitly justified. Results: Of the 77 records initially identified, 13 studies were included in the review, and no duplicates were found. These potential benefits should be interpreted cautiously, as the available evidence is heterogeneous and varies across study designs. Potential benefits were also reported for hormonal and metabolic parameters, including reductions in hyperandrogenism and the improvement of insulin sensitivity. Some studies suggest benefits for oocyte and embryo quality, but results remain inconsistent. Conclusions: MI supplementation may support PCOS management, particularly in fertility-related outcomes. Its ability to improve ovulation, increase pregnancy rates, optimize ART outcomes, and mitigate the risk of OHSS highlights its clinical utility. However, the evidence remains heterogeneous, and some outcomes, particularly oocyte and embryo quality, remain inconclusive.


Stair-step versus traditional clomiphene citrate protocols in polycystic ovary syndrome: a systematic review and meta-analysis

Abstract: This review explores whether the clomiphene citrate stair-step protocol (SSP) for ovulation induction in patients with polycystic ovary syndrome (PCOS) outperforms the traditional protocol. The following databases were searched: PubMed, Cochrane Library, ClinicalTrials.gov, EMBASE and Google Scholar from inception to 15 June 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and with PROSPERO registration (CRD420251050294). Of 847 screened records, five randomized controlled trials were included (n = 520: SSP: n = 255; traditional protocol: n = 265). Analyses were conducted in Review Manager 5.4 using random-effects models. Risk ratios, mean differences and 95% confidence intervals were calculated. Heterogeneity was assessed with I², risk of bias with RoB2, certainty with GRADE and robustness with leave-one-out sensitivity analysis. The SSP increased ovulation rates compared with the traditional protocol (RR 1.28, 95% CI 1.10 to 1.49; five randomized controlled trials [RCTs], n = 520, I² = 0%). Clinical pregnancy also favoured SSP (RR 1.46, 95% CI 1.04 to 2.05; four RCTs, n = 460; I² = 0%), although this result was largely driven by one study. The SSP shortened treatment duration (mean difference -32.59 days, 95% CI -38.66 to -26.52 days; three RCTs, n = 320, I² = 83%). Endometrial thickness was similar (mean difference 0.32 mm, 95% CI -0.95 to 1.59 mm; four RCTs, n = 460, I² = 91%). SSP improves ovulation rate and shortens treatment without affecting endometrial thickness and may increase clinical pregnancy rates.


Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process

Abstract: 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.


Subfecundity, Infertility Treatment, and Child Neurodevelopment

Kahn LG, Hipwell AE, Stanford JB, Galai N, Zhao H, Alshawabkeh AN, Aschner JL, Barrett ES, Bertolla RP, Cajachagua Torres KN, Camargo CA Jr, Cordero JF, Croen LA, Deoni SC, Gogcu S, Herbstman JB, Karagas MR, LeWinn KZ, Lyall K, McEvoy CT, McKay K, O'Connor TG, Pilsner JR, Schantz SL, Schmidt RJ, Smith AK, Wilkening GN, Zhang E, Zhu Y, Ghassabian A; ECHO Cohort Consortium

Abstract: IMPORTANCE: Increasing numbers of children are conceived using infertility treatment; concerns remain about potential effects on child neurodevelopment. OBJECTIVE: To evaluate whether infertility treatment is associated with child neurodevelopment and whether such an association may be attributable to underlying subfecundity. DESIGN, SETTING, AND PARTICIPANTS: 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. EXPOSURE: 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. MAIN OUTCOMES AND MEASURES: 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). RESULTS: 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 problems: b = 0.47 [95% CI, 0.14-0.81]; SRS score: b = 1.08 [95% CI, 0.01-2.14]) and when restricted to natural conceptions (externalizing problems: b = 0.45 [95% CI, 0.07-0.83]; SRS score: 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]; natural conceptions: 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. CONCLUSIONS AND RELEVANCE: 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.


Potential increase of the U.S. total fertility rate resulting from restorative treatment of unresolved subfertility: a simulation study

Abstract: 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 including sensitivity analyses: 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.


Molecular mechanisms and multi-organ regulatory roles of anti-Müllerian hormone in female reproduction

Abstract: 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.


Recurrent pregnancy loss: a committee opinion

Practice Committee of the American Society for Reproductive Medicine

Abstract: Current strategies for the assessment and treatment of recurrent pregnancy loss are discussed. This replaces the previous document, titled, "Evaluation and treatment of recurrent pregnancy loss: a committee opinion," last published in 2012.


Intravaginal progesterone as a fertility-sparing treatment for symptomatic adenomyosis: preliminary results from a monocentric study

Francesco Plotti

Department of Obstetrics and Gynecology, University Campus Bio Medico, Rome, Italy. f.plotti@unicampus.it.

Roberto Angioli

Department of Obstetrics and Gynecology, University Campus Bio Medico, Rome, Italy. R.Angioli@unicampus.it.

Corrado Terranova

Department of Obstetrics and Gynecology, University Campus Bio Medico, Rome, Italy. C.Terranova@unicampus.it.

Abstract:
PURPOSE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.


Role of placental glucose metabolism in steroidogenesis in healthy pregnancies at term

Abstract:
BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: Placental release of estradiol and progesterone correlates with uteroplacental consumption of glucose that primarily occurs via non-glycolytic pathways in the third trimester placenta.


Tuboplasty

Tuboplasty

Textbook of Minimally Invasive Gynecologic Surgery


Restorative Reproductive Medicine Restricting Access to Care


Public Awareness, Perceptions, and Preferences in Fertility Treatment: Secondary Analysis of Two Public Surveys

Kathleen Copeland

International Institute for Restorative Reproductive Medicine

Abstract:
Objective: This study examined public attitudes toward restorative reproductive medicine (RRM) and in vitro fertilization (IVF) using secondary analysis and comparative reporting of two independent surveys conducted in the United States. It also explored preferences among individuals with fertility issues and the general population’s views on treatment options.

Method: A secondary analysis was conducted using data from two nationally representative online surveys, designed and administered by organizations independent of the researchers, whose samples demographically reflected the U.S. adult population. The surveys—conducted by J.L. Partners (N=1002) and McLaughlin & Associates (N=1000)—assessed familiarity, acceptance, and attitudes toward IVF and RRM. The J.L. Partners survey focused on IVF, including medical risks, creation and use of embryos, preimplantation genetic testing, arguments for government oversight of IVF, and overall attitudes toward IVF. The McLaughlin survey focused on comparative descriptions of IVF and RRM. Pearson’s Chi-Square tests of independence were used to assess differences in response distributions across demographic subgroups and between survey items of interest.

Findings: Overall, there was strong consistency of responses to items that were similar in the two surveys. Approximately 80% supported IVF initially, although both surveys found respondents to have limited knowledge about IVF procedures. In contrast, 33% supported RRM initially, with 43% having never heard of RRM. After learning more about the characteristics of RRM and IVF approaches, as presented within the surveys, preference shifted toward approaches consistent with RRM (e.g., 69% preference for an approach for natural fertilization in a woman’s body vs. 17% for fertilization in a lab). Respondents prioritized baby health (74%) over cost (13%) and time to conceive (6%). Many IVF patients were concerned about undiagnosed health issues and being rushed into IVF. Overall, 70% wanted treatments that addressed underlying causes; nearly half were unaware of any medical risks of IVF. Stated support for IVF declined by 10% overall after presentation of medical risks, questions about the creation and use of embryos and genetic testing, and arguments to support government oversight of IVF. Both surveys showed strong support for patient access to full information about treatments and treatment processes.

Conclusion: While IVF is widely accepted, these national survey data suggest preferences for fertility treatments that prioritize diagnosis and restoration of natural reproductive health, which is the focus of restorative reproductive medicine. Comprehensive assessment, restoration of healthy function, transparency regarding treatment processes, and sensitivity to ethical concerns in patient care reflect important public values. Greater awareness and public education, improved consent, more research, and ongoing surveys are needed to inform public health strategies and meet patient needs in fertility care.

Journal of Restorative Reproductive Medicine


Optimization of conception with intercourse for women with infertility

Abstract: 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.


The effectiveness and safety of restorative reproductive medicine (RRM) compared to assisted reproductive technology or medically unassisted conception: a systematic review

Abstract:
IMPORTANCE: 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.

OBJECTIVE: 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.

EVIDENCE REVIEW: 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.

FINDINGS: 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.

CONCLUSIONS AND RELEVANCE: 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.


YWHAZ loss is associated with endometrial dysfunction in proliferative-phase endometriosis

Steven L Young

University of North Carolina at Chapel Hill

Abstract: 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 across the menopausal transition and beyond: A narrative review

Abstract:
BACKGROUND: 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.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.


The Association Between History of Infertility and Dietary Practices: A Cross-Sectional Study Among Preconception Females

Wendy Kuohung

Boston University Chobanian and Avedisian School of Medicine

Lauren A Wise

Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia

Abstract:
Objective: To evaluate the extent to which a history of infertility is associated with adherence to specific diets among reproductive-aged females.

Design: Cross-sectional analysis

Subjects: 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.

Exposure: Infertility history, defined as: 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).

Main Outcome Measure: 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).

Results: 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, and all other diets: <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: 0.19-0.98), and Weight Watchers® (PR=0.55; 95% CI: 0.34-0.91) 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).

Limitations: The cross-sectional design cannot establish temporality or causality. Data on dietary patterns and infertility history were self-reported, which can introduce misclassification. Generalizability may be limited because participants were pregnancy planners not using fertility treatments; participants were also more likely to be non-Hispanic White and of higher socioeconomic status than the general population.

Conclusion: The ketogenic diet was more prevalent among females with an infertility history, while vegetarian, Paleo, and Weight Watchers® diets were less prevalent. These associations mirror the results of studies evaluating the reverse relationship, suggesting that some patients with infertility seek information for behavioral modifications via evidence-based medicine.


Fertility awareness methods and waiting conduct in idiopathic infertility: a prospective observational study

F Parazzini

Mario Negri Institute for Pharmacological Research

Giuseppe Grande

Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Padova, Italy.

Abstract: INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.


Beyond IVF: What People Really Want from Fertility Care

Abstract: 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 appetite of any pathway: 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. Sample: 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.


Vasectomy Reversal Provides Symptomatic Relief in Patients With Postvasectomy Pain Syndrome: A Systematic Review

Chi-Chen Hong

Roswell Park Comprehensive Cancer Center

Abstract:
INTRODUCTION: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.


Hormonal Profile and Anthropometric Indices As Determinants of Metabolic Risk in Polycystic Ovary Syndrome: A Prospective Observational Study

Abstract: 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.


Gestational progesterone restores menstrual cycle in PCOS patients via enhancing ovary estrogen production

Xiqian Zhang

Guangdong Province Women and Children Hospital

Abstract: 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.


Fertility preservation in patients with medical indications: a committee opinion

Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org

Abstract: 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 therapy or gonadectomy: a committee opinion," last published in 2019.


Endometriosis phenotypes and staging in relation to lipid biomarkers: Findings from the ENDO Cohort Study

Hediyeh Baradaran

UNIVERSITY UTAH, Salt Lake City, Utah, United States

Leslie V Farland

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; Department of Obstetrics and Gynecology, College of Medicine -...

Abstract:
Background: 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. MATERIALS AND METHODS: 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.

Results: 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 revealed stronger patterns: 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.

Conclusions: 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.

Journal of gynecology obstetrics and human reproduction


Neonatal characteristics of children conceived with in vitro fertilization or intrauterine insemination compared with sibling births from unassisted conceptions

Matthew R Reeder

Office of Cooperative Reproductive Health, Department of Family and Preventive Medicine, University of Utah School of Medicine , Salt Lake City, UT, USA

Abstract:
Objective: To examine birth outcomes between children conceived with in vitro fertilization (IVF) or intrauterine insemination (IUI) and sibling births from unassisted conceptions.

Design: Retrospective sibling cohort.

Subjects: 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).

Exposure: In vitro fertilization, with or without intracytoplasmic sperm injection, or IUI.

Main outcome measures: Preterm birth, low birth weight, small for gestational age, large for gestational age (LGA), and major congenital anomalies.

Results: 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.

Conclusion: 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.


Endometriosis Surgery: Debates About Restorative Reproductive Medicine

Leigh Ann Humphries

National Confidential Enquiry into Patient Outcome and Death

Abstract: 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.


The influence of the menstrual cycle on muscle injuries - a systematic review and meta-analysis

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: 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. Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-36763-0.


The False Promise of Restorative Reproductive Medicine-Restricting Access to Care in the Name of "Natural" Medicine

Amanda Kallen

Division of Reproductive Endocrinology and Infertility, University of Vermont Larner College of Medicine , Burlington, VT,

Abstract: 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.


Incident endometriosis diagnosis and anti-müllerian hormone (AMH): how surgical staging and typology relate to serum AMH levels

Rachael B. Hemmert

Division of Public Health, Department of Family and Preventive Medicine, University of Utah Health, Salt Lake, UT, USA.

Madeline Paulsen

Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT, USA.

Michelle Valenti

Department of Epidemiology and Biostatistics, The University of Arizona, Tucson, AZ; Department of Community, Environment and Policy, The University of Arizona, Tucson, AZ. Electronic address: mval...

Abstract:
Background: 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.

Objective: 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.

Study Design: 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.

Results: 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; deep: -34.3%; 95% confidence interval, -56.2 to -1.4; superficial: -24.8%; 95% confidence interval, -43.9 to -0.8).

Conclusion: 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.

American journal of obstetrics and gynecology


Influence of Tubal Patency on Endometriosis Recurrence: A Retrospective Matched  Case-control Study

Sofie Neutens

Department of Obstetrics and Gynaecology, AZ Delta Hospital, Roeselare, Belgium (Dr. Neutens).

Carla Tomassetti

Leuven Institute for Fertility and Embryology

Barbara Van Elst

Centre Hospitalier Interrégional Edith Cavell

Abstract:
STUDY OBJECTIVE: To study whether bilateral nonpatency of fallopian tubes is correlated with a lower recurrence rate of endometriosis. DESIGN: Retrospective 2:1 matched case-control study. SETTING: University hospital with a tertiary referral center for fertility and endometriosis surgery in Leuven, Belgium.

PATIENTS: 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).

INTERVENTIONS: Comparison between patients with bilateral nonpatent or absent fallopian tubes and matched controls with at least 1 patent fallopian tube. MEASUREMENTS AND

MAIN RESULTS: Primary outcome was the recurrence rate, which was analyzed on 4 levels: 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).

CONCLUSION: 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.

Journal of Minimally Invasive Gynecology


Alpha-Lipoic Acid and Leucine as Adjunct Therapy for Persistent First-Trimester Subchorionic Hematomas in Assisted Reproductive Technology Pregnancies

Abstract: 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.


Disordered eating behaviors during adolescence and risk of endometriosis: a prospective cohort study

Leslie V Farland

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; Department of Obstetrics and Gynecology, College of Medicine -...

Audrey J Gaskins

Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia. Electronic address: Audrey.jane.gaskins@emory.edu.

Sarah Thornburgh

Abstract:
Objective: 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. Design: Prospective, longitudinal cohort (1996-2021).

Subjects: Female participants (n = 11,773) from the Growing Up Today Study.

Exposure: Frequency of binge eating, laxative use, and self-induced vomiting over the past year was self-reported on repeated questionnaires during follow-up.

Main outcome measures: 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).

Results: 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.

Conclusion: 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.


Association between the Modified Cardiometabolic Index and Endometriosis in an American Cohort: Insights from a Cross-sectional Analysis

Yue Cao

Affiliated Hospital of Southwest Medical University

Journal of visualized experiments : JoVE


"Reply of the authors: ""Response to ""The illusion of reproductive choice: how restorative reproductive medicine violates informed consent for infertility treatment"""""

Eve C. Feinberg

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois.


Identification of predictors of the ovarian response to clomiphene citrate in infertile women with polycystic ovary syndrome: A post-hoc analysis of a randomized controlled trial

Haonan Yu

Tianjin Medical University General Hospital

Abstract:
BACKGROUND: Clomiphene citrate (CC) is the first-line medication for inducing ovulation in women with polycystic ovary syndrome (PCOS). However, approximately 20% of patients with PCOS are resistant to CC. This study aims to identify reliable baseline predictors of CC resistance in infertile women with PCOS.

METHODS: A post-hoc analysis of a large, multicenter randomized controlled trial (PCOSAct trial) conducted in China. The current analysis comprised the 471 participants who were randomized to the active CC arm and completed the requisite follow-up. To identify potential candidate variables, we employed multivariable logistic and LASSO regression analyses. Within the framework of a multivariable logistic regression model, we also estimated the independent associations between the identified candidate variables and resistance to CC. Additionally, we plotted the Receiver Operating Characteristic (ROC) curve and utilized the DeLong method to compare the statistical differences in the area under the curve (AUC). Finally, we constructed a restricted cubic spline (RCS) logistic regression model to illustrate the dose-response relationship between continuous predictor variables and CC resistance.

RESULTS: CC resistance was identified in 32 (6.8%) participants. Body Mass Index (BMI), Total Testosterone (TT), and Anti-Müllerian Hormone (AMH) were useful predictors of ovarian response to CC. The "T+BMI" dual-factor model demonstrated high discriminative power (AUC = 0.801) and was statistically comparable to the three-factor model including AMH (AUC = 0.818; P = 0.347). TT was the strongest individual predictor (OR = 2.73 per 1-unit), while BMI was the most significant modifiable risk factor (OR = 2.49 per 1-SD).

CONCLUSIONS: A simplified "T + BMI" assessment provides comparable prognostic utility without the need for AMH testing. For patients at high risk of CC resistance, we recommend upfront use of aromatase inhibitors or low-dose gonadotropins. This strategy avoids ineffective treatment cycles and enables personalized ovulation induction.

TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov under the identification number NCT01573858 on July 6, 2012.


Signal Detection and Pharmacovigilance Analysis of Tamoxifen, Clomiphene, and Letrozole in Polycystic Ovarian Syndrome: A FAERS Database Study

Duojia Zhang

First Affiliated Hospital of Heilongjiang University of Chinese Medicine

Jiong Zhou

Second Affiliated Hospital of Zhejiang University

Abstract:
BACKGROUND: Tamoxifen, clomiphene, and letrozole are primary pharmacological options for inducing ovulation in polycystic ovary syndrome (PCOS). Given the high clinical prevalence of PCOS, a comprehensive characterization of the adverse drug event (ADE) profiles associated with these treatments is essential.

METHODS: We performed disproportionality analyses using FAERS data to detect ADE signals at the Preferred Term (PT) and System Organ Class (SOC) levels via four established algorithms (ROR, PRR, BCPNN, and EBGM). A drug-ADE network was constructed to visualize these associations.

RESULTS: Of 21,730 identified PCOS-related reports, letrozole predominated (n=17,185), followed by tamoxifen (n=4465) and clomiphene (n=80). Most cases involved women aged 18-65 years (weight: 50-100 kg), primarily from the United States. Letrozole-related reports increased steadily, peaking at 2323 cases in 2021, while tamoxifen and clomiphene counts remained comparatively low. At the PT level, fatigue was a common signal for both tamoxifen and letrozole. Notably, malignant tumor progression, fatigue, and arthralgia emerged as shared signals across all three agents. At the SOC level, ADEs for tamoxifen and letrozole were frequently categorized under neoplasms; letrozole was specifically linked to hematological disorders (e.g, neutropenia). In contrast, clomiphene exhibited stronger associations with psychiatric and gastrointestinal events.

CONCLUSION: Distinct safety signals characterize these three primary PCOS treatments. These pharmacological variations underscore the necessity of personalized medicine; treatment selection must be tailored to the patient's specific risk profile, with targeted clinical monitoring for relevant ADEs to optimize therapeutic outcomes.


Clinical, metabolomic, and proteomic profiles associated with reproductive outcomes in unexplained recurrent pregnancy loss

Zhenghong Zhu

Guangdong Province Women and Children Hospital

Abstract:
OBJECTIVE: To identify preconception clinical and multi-omics factors associated with conception and early pregnancy loss in women with unexplained recurrent pregnancy loss (URPL).

METHODS: In this prospective cohort study, 149 women with URPL selected from 420 outpatients based on guideline-recommended criteria were enrolled between November 2024 and May 2025 and followed-up for 12 months. Preconception fasting plasma was analyzed for clinical biomarkers, untargeted metabolomics, and data-independent acquisition proteomics. Outcomes included conception, ongoing pregnancy beyond 12 weeks and early pregnancy loss before 12 weeks. Multivariable logistic regression was used to evaluate the associations of clinical and multi-omics factors with reproductive outcomes, adjusting for maternal age, body mass index, number of prior losses, and use of assisted reproductive technology.

RESULTS: Of 149 women, 99 conceived (66.4%) during the follow-up. By 12 weeks of gestation, 67 (67.7%) had ongoing pregnancies and 32 (32.3%) experienced early pregnancy loss. Higher testosterone was associated with lower probability of conception (adjusted odds ratio [aOR] 0.50, 95% confidence interval [CI] 0.28-0.89, p = 0.019). Women who conceived showed higher levels of progesterone-related metabolites, including 17-hydroxyprogesterone (fold change, FC = 3.89), pregnanediol 3-O-glucuronide (FC = 2.37), and pregnanetriol 3α-O-β-D-glucuronide (FC = 2.39). Among women who conceived, higher prolactin was associated with higher odds of early pregnancy loss (aOR 1.09, 95% CI 1.01-1.18, p = 0.036), and anti-phosphatidylserine/prothrombin showed a borderline association (aOR 1.07, 95% CI 1.00-1.14, p = 0.052). Early pregnancy loss was characterized by lower bile acid-related metabolites and higher caffeine and methylxanthine metabolites. Proteomic analysis showed enrichment of bile acid biosynthetic process. After adjustment, higher 7α,12α-dihydroxy-3-oxocholest-4-en-27-oic acid was associated with lower odds of early pregnancy loss (aOR 0.64, 95% CI 0.44-0.95, p = 0.025).

CONCLUSIONS: Higher testosterone was associated with lower odds of conception. Among women who conceived, early pregnancy loss was associated with higher prolactin, borderline higher anti-PS/PT, lower bile acid-related metabolites, and higher caffeine-related metabolites, with 7α,12α-dihydroxy-3-oxocholest-4-en-27-oic acid identified as an exploratory metabolomic candidate. These findings suggest that potential androgen-related biology, prolactin, non-criteria antiphospholipid antibodies, and bile acid metabolism may be associated with reproductive outcomes in URPL, warranting validation in independent cohorts.


PMOS international consensus renaming

PMOS international consensus renaming


Regulatory T cells in human pregnancy: mechanisms, dysregulation, and therapeutic perspectives

Abstract: 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.


Multidimensional factors increase menstrual distress in patients with endometriosis

European journal of obstetrics, gynecology, and reproductive biology


Clinician registry and recognition framework

International Institute for Restorative Reproductive Medicine


Human Endometriotic Lesion-Derived Small Extracellular Vesicles Impair Macrophage Function in the Peritoneal Microenvironment


"Uterine closure after cesarean delivery: surgical technique, biological rationale, and clinical implications."

Roberto Romero

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Emmanuel Bujold

Department of Obstetrics and Gynecology, Faculty of Medicine Université Laval, Quebec City, Quebec, Canada; Reproductive, Maternal and Child Health Research Axe, Centre Hospitalier Universitaire de...

Abstract: 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 important than a fast repair: 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.

American Journal of Obstetrics and Gynecology


Protocol for PRP Use at Surgery: SOP for Fertility PRP Injection in Gynecologic Surgery

Abstract: A standard operating procedure (SOP) for platelet-rich plasma (PRP) injection into the ovaries, cervix, and uterus during gynecologic surgery. Covers patient selection and contraindications, PRP preparation using 80-120 mL venous blood with dual-spin centrifugation, and injection techniques for ovarian intraovarian injection (4 cc per ovary with calcium activation), uterine/endometrial infusion, and cervical injection. Indications include diminished ovarian reserve, thin/refractory endometrium, Asherman syndrome, poor ovarian response, implantation failure, low cervical mucus, and chronic endometritis.


RRM postgraduate education pathways: certificate, diploma, fellowship, and board certification program framework


Fertility awareness among Chinese university students: scale development and cross-sectional study

Abstract:
BACKGROUND: Global fertility rates are declining. In China, the total fertility rate dropped sharply from 5.59 in 1971 to 1.15 in 2021. Chinese university students often lack adequate fertility awareness, yet no validated instrument exists to assess this construct in this population, despite its recognized importance for informed reproductive decision-making.

METHODS: The Fertility Awareness Scale for University Students (FASUS) was developed through literature search, semi-structured interviews, and two rounds of Delphi expert consultation. Psychometric properties were tested using exploratory and confirmatory factor analysis, Cronbach's α, split-half reliability, and test-retest reliability. A cross-sectional survey of 750 students examined fertility awareness levels and influencing factors via univariate analysis and multiple linear regression.

RESULTS: The final FASUS Scale consisted of 22 items across three dimensions: fertility-related knowledge, reproductive health attitudes, and reproductive health skills, with a cumulative variance contribution rate of 67.952%. The scale demonstrated strong reliability (Cronbach's α = 0.97, split-half reliability = 0.885, test-retest reliability = 0.981). A survey of 750 students revealed an average fertility awareness score of 78.01 ± 16.44, indicating a low to moderate level. Key influencing factors included gender, ethnicity, education level, only-child status, and prior fertility knowledge education.

CONCLUSION: This study utilized a self-developed scale to assess fertility awareness among Chinese university students. The results showed that the fertility awareness level of Chinese university students was generally low. We suggest that health care institutions implement targeted intervention measures to improve reproductive health outcomes.


Balancing metabolic optimization and reproductive safety in Polycystic Ovary Syndrome: a Bayesian-informed framework for GLP-1 receptor agonists

Le Fang

Women's Hospital, School of Medicine, Zhejiang University

Hui He

Heilongjiang University of Chinese Medicine

Abstract:
BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) address key metabolic drivers of Polycystic Ovary Syndrome (PCOS), yet their integration into fertility management remains challenging because reproductive efficacy is variably reported, preconception washout is required, and standardized clinical pathways are lacking.

MAIN BODY: We present a structured, fertility-centered, hypothesis-generating narrative synthesis of the metabolic-reproductive-pregnancy continuum in PCOS, integrating evidence from randomized trials, observational studies, reviews, and clinical guidance. Heterogeneous findings are organized by intervention/comparator, follow-up window, and key effect modifiers, including baseline obesity/insulin-resistance phenotype, concomitant metformin, and lifestyle co-interventions. The clinical framework is derived from this narrative synthesis rather than from quantitative reproductive meta-analysis. As a methodological proof-of-concept only, we additionally performed a Bayesian network meta-analysis restricted to body-weight change within a prespecified 12-16-weeks window in the largest connected treatment network. Because ovulation, clinical pregnancy, time to pregnancy, and live birth were inconsistently defined and sparsely reported across trials, no confirmatory quantitative synthesis or treatment ranking was undertaken for these reproductive outcomes. We therefore distinguish evidence domains explicitly, with relatively robust support for short-term metabolic benefit but substantially greater uncertainty for reproductive translation and periconception safety.

CONCLUSION: The narrative evidence supports positioning GLP-1RAs as time-limited, preconception metabolic-optimization tools, not as confirmed fertility-enhancing therapies per se. Their use in PCOS fertility care should be individualized through shared decision-making, with explicit discussion of the difference between established metabolic benefit and hypothesis-generating reproductive benefit, together with drug-specific washout planning and strategies to minimize post-discontinuation rebound. Future trials should standardize reproductive endpoints and systematically capture periconception exposure to enable confirmatory synthesis and individualized benefit-risk estimation.


Information and misinformation on assisted human reproduction techniques in Europe: a normative analysis of the information provided on the websites of medically assisted reproduction clinics

Abstract: BACKGROUND: As part of the European Be better informed about Fertility project (B2-InF), we carried out a normative analysis of the information provided online by assisted reproduction clinics to the European public. This analysis aimed to determine the degree to which this information complies with regulations of medically assisted reproduction (MAR) and commercial information, and the main ethical implications related to the duty of information. METHODS: Information was gathered from the websites of 33 clinics across 8 European countries (Albania, Belgium, Spain, Italy, Kosovo, Northern Macedonia, Slovenia, Switzerland). Nearly 2000 pages of information were reviewed and checked for compliance with relevant frameworks of national and international law. RESULTS: The assessment revealed significant inconsistencies in how clinics present information online, with particular concerns regarding transparency about success rates, associated risks, add-on techniques and the legal and ethical issues that may arise during the use of these techniques. CONCLUSIONS: The results of our analysis indicate an urgent need for enhanced regulatory oversight and standardized information requirements for assisted reproduction clinics across Europe. These findings suggest the necessity for harmonized legal frameworks that mandate comprehensive disclosure standards and establish effective enforcement mechanisms to ensure transparent and accurate information provision to potential patients.


Global, regional, and national burden of breast cancer among females, 1990-2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023


The Role of Nutrition on the Pathogenesis of Endometriosis

Andrzej Woźniak

Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland.

Dominika Osińska

The Independent Public Hospital No. 4 in Lublin, Jaczewskiego 8, 20-954 Lublin, Poland


Lipid metabolism drives dietary effects on T cell ferroptosis and immunity

Wang N, Chen Z, Yao Y, Sun C, Wei W, Sun L, Zhang H, Li F, Butcher D, Sun SR, Gong J, Jiang YC, Qi Y, Huang J, Nettelfield S, Liu R, Zheng X, Li C, Fu Y, Geng H, Zhao L, Sun H, Yang Y, Ge Y, Pazhouhandeh M, Barlow CK, Jeppe KJ, Yunis J, Zhu C, Wei Y, Liang X, Bridle K, Frazer DM, Tey SK, Li Y, Yang Z, Shu M, Liu Z, Crawford D, Yu D


Reply of the authors: "Response to "The illusion of reproductive choice: how restorative reproductive medicine violates reproductive autonomy and informed consent"" by Frank-Herrmann et al

Eve C. Feinberg

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois.