Research
Minjeur M et al., 2026·Journal of Restorative Reproductive Medicine
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.
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.
Research
Parnell T et al., 2026·Journal of Restorative Reproductive Medicine
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.
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.
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.
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.
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.
Research
Teede HJ et al., 2026·Lancet (London, England)
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.
Research
Kahn LG et al., 2026·JAMA Network Open
Increasing numbers of children are conceived using infertility treatment; concerns remain about potential effects on child neurodevelopment. To evaluate whether infertility treatment is associated with child neurodevelopment and whether such an association may be attributable to underlying subfecundity. DESIGN, SETTING, This cohort study was conducted among mother-child dyads in the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) Cohort, with infants conceived between 1998 and 2022. Associations of subfecundity and infertility treatment with neurodevelopmental outcomes were assessed among children ages 2 to 10 years. Data were analyzed from May 14, 2025, to March 31, 2026. Subfecundity was defined as prior consultation for, treatment of, or diagnosis of infertility for either partner; at least 2 prior miscarriages; or ever having had unprotected heterosexual intercourse for 12 months without conceiving. Infertility treatment was categorized as in vitro fertilization (IVF) or non-IVF treatment. Harmonized caregiver responses to the Strengths and Difficulties Questionnaire and the Child Behavior Checklist yielded continuous raw scores for externalizing and internalizing problems. The total raw Social Responsiveness Scale (SRS) score quantified autism-like symptoms. Caregivers reported physician diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Among 15 382 mother-infant dyads, there were 14 191 unique maternal participants (mean [SD] age at delivery, 30.9 [5.33] years; 8780 parous participants [57.1%]). ASD and ADHD were diagnosed in 876 offspring (7.6%) and 819 offspring (7.1%), respectively. In generalized linear models, subfecundity was associated with higher externalizing problem and SRS scores among all pregnancies (externalizing b = 0.47 [95% CI, 0.14-0.81]; b = 1.08 [95% CI, 0.01-2.14]) and when restricted to natural conceptions (externalizing b = 0.45 [95% CI, 0.07-0.83]; b = 1.12 [95% CI, -0.09 to 2.34]). Offspring of parents with subfecundity had higher odds of ASD (overall: odds ratio [OR], 1.27 [95% CI, 1.03-1.57]; OR, 1.31 [95% CI, 1.04-1.64]). Children conceived via non-IVF treatment had higher odds of ADHD compared with those conceived via natural conception with subfecundity (OR, 1.77 [95% CI, 1.16-2.68]) or without subfecundity (OR, 1.54 [95% CI, 1.05-2.25]). There were no significant associations for IVF treatment. In this large US cohort study, subfecundity was associated with elevated scores for caregiver-reported symptoms of behavioral problems and higher odds of ASD diagnosis, independent of infertility treatment. Non-IVF treatment was associated with ADHD, warranting further research into specific indications for treatment that may increase risk of offspring neurodevelopmental problems.
Research
Stanford JB et al., 2026·Frontiers in Reproductive Health
Background The total fertility rate (TFR) in most developed countries has been declining for decades. In the United States (U.S.), the total fertility rate has remained below replacement level since 2007. Subfertility affects at least 15% of women or couples over their reproductive lifespan and contributes to reduced TFR. Restorative reproductive medicine (RRM) is a medically based approach to subfertility care that can be delivered in primary care settings to increase live birth rates. Objective To estimate the theoretical impact of use of RRM among subfertile couples in the United States. Methods We conducted a simulation study. Model inputs included the number of women of reproductive age in the United States by 5-year age groups; current age-specific and total fertility rates; the proportion of women in each age group with subfertility; estimated spontaneous live birth rates among women with subfertility; and age-specific crude live birth rates with RRM treatment. We evaluated fifteen scenarios two different varying assumptions for spontaneous conception (25% vs. 50%), two levels of RRM utilization among subfertile women (20% vs. 50%), three different estimates of the number of subfertile women who would be potentially eligible for RRM treatment, and 4 different levels of effectiveness (live birth) from RRM treatment. Results The baseline TFR in the United States was 1.77 during 2015-2019, and 13.5% of women ages 20-44 were estimated to have subfertility. In a conservative scenario (50% spontaneous births; 20% RRM utilization; married women trying to conceive for at least 12 months, 20.7% RRM live births), the TFR increased to 1.79, representing a 1.0% relative increase (absolute +0.02). In an optimistic scenario (25% spontaneous births; 50% RRM utilization; all subfertile women), the TFR increased to 2.02, a 14.5% relative increase (absolute +0.26), approaching replacement-level fertility. Conclusion Simulation results suggest that expanding access to RRM within primary care settings could meaningfully increase the U.S. TFR, by reducing unresolved subfertility. Realizing this potential would require policy and health system changes to address workforce capacity, insurance coverage, and equitable access. These findings underscore the potential contribution of non-IVF fertility care pathways in addressing population-level fertility decline.
Research
Li J et al., 2026·Communications Biology
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.