Modifiable life style factors and risk for incident endometriosis

Definition of Infertility and Indications for Fertility Evaluation: Consensus Document

Minjeur M et al., 2026 · Journal of Restorative Reproductive Medicine · Free to read

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.

Subfecundity, Infertility Treatment, and Child Neurodevelopment

Kahn LG et al., 2026 · JAMA Network Open · Free full text on PubMed Central

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 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. 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

Stanford JB et al., 2026 · Frontiers in Reproductive Health · Free full text on PubMed Central

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.

Restorative Reproductive Medicine Restricting Access to Care

Minjeur M et al., 2026 · JAMA

A metaanalysis on alcohol consumption and risk of endometriosis

Parazzini F et al., 2013 · American journal of obstetrics and gynecology

To offer a general figure of the available data on the relation between alcohol intake and risk of endometriosis, we conducted a systematic review and a metaanalysis of studies published up to May 2012. We carried out a literature search of all case-control and cohort studies published as original articles in English up to May 2012. Only those papers that were published as full-length articles were considered. Pooled estimates of the relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated using fixed or, when significant heterogeneity among estimates emerged, random effects models. A total of 15 studies were identified for the review. The summary estimate was 1.24 (95% CI, 1.12-1.36) for any alcohol intake vs no alcohol intake. Considering the results of the analyses of infrequent, moderate/regular, and heavy alcohol intake vs no alcohol intake, the summary RR estimates were, respectively, 1.14 (95% CI, 0.86-1.52), 1.23 (95% CI, 1.08-1.40), and 1.19 (95% CI, 0.99-1.43). Three studies reported separate results for current and former drinkers, and the summary RR were 1.42 (95% CI, 1.14-1.76) and 1.09 (95% CI, 0.83-1.43), respectively. The present metaanalysis provides evidence for an association between alcohol consumption and endometriosis risk. Further studies are needed to clarify whether alcohol consumption may exacerbate an existing disease or could be related to the severity of the disease.

In utero exposures and endometriosis: the Endometriosis, Natural History, Disease, Outcome (ENDO) Study

Wolff EF et al., 2013 · Fertility and sterility

To assess in utero exposures and the odds of an endometriosis diagnosis. Matched cohort design. Fourteen participating clinical centers in geographically defined areas in Utah and California. PATIENT(S): Operative cohort comprised 473 women undergoing laparoscopy/laparotomy, and an age- and residence-matched population cohort comprising 127 women undergoing pelvic magnetic resonance imaging (MRI), 2007-2009. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Women completed standardized interviews before surgery or MRI regarding in utero exposures: mothers' lifestyle during the index pregnancy, and the index woman's gestation and birth size. Endometriosis was defined as visually confirmed disease in the operative cohort, and MRI visualized disease in the population cohort. The odds of an endometriosis diagnosis and corresponding 95% confidence intervals (CI) were estimated for each exposure by cohort using logistic regression and adjusting for current smoking, age at menarche, body mass index, and study site. RESULT(S): Endometriosis was diagnosed in 41% and 11% of women in the operative and population cohorts, respectively. In the primary analysis, adjust odds ratios (AORs) were elevated for maternal vitamin usage (1.27; 95% CI, 0.85-1.91), maternal cigarette smoking (1.16; 95% CI = 0.61-2.24), and low birth weight (1.1; 95% CI, 0.92-1.32). Reduced odds were observed for maternal usage of caffeine (0.99; 95% CI, 0.64-1.54), alcohol (0.82; 95% CI, 0.35-1.94), paternal cigarette smoking (0.72; 95% CI, 0.43-1.19), and preterm delivery (0.98; 95% CI, 0.47-2.03). Sensitivity analyses mostly upheld the primary results except for a decreased AOR for preterm birth (0.41; 95% CI, 0.18-0.94) when restricting to visualized and histologically confirmed endometriosis in the operative cohort. CONCLUSION(S): In utero exposures were not statistically significantly associated with the odds of an endometriosis diagnosis in either cohort.

Fruit and vegetable consumption and risk of endometriosis

Harris HR et al., 2018 · Human reproduction (Oxford, England) · Free full text on PubMed Central

Is there an association between intake of fruits and vegetables and risk of laparoscopically confirmed endometriosis? Higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis. Two case-control studies have examined the associations between fruit and vegetable intake and endometriosis risk with contrasting results. Diets rich in fruits and vegetables include higher levels of pro-vitamin A nutrients (alpha-carotene, beta-carotene, beta-cryptoxanthin) and women with endometriosis have been reported to have lower intake of vitamin A than women without endometriosis. STUDY DESIGN SIZE, A prospective cohort study using data collected from 70 835 premenopausal women from 1991 to 2013 as part of the Nurses' Health Study II cohort. PARTICIPANTS/MATERIALS, SETTING, Diet was assessed with a validated food frequency questionnaire (FFQ) every 4 years. Cases were restricted to laparoscopically confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% CI. MAIN During 840 012 person-years of follow-up, 2609 incident cases of laparoscopically confirmed endometriosis were reported (incidence rate = 311 per 100 000 person-years). We observed a non-linear inverse association between higher fruit consumption and risk of laparoscopically confirmed endometriosis (Psignificance of the curve = 0.005). This inverse association was particularly evident for citrus fruits. Women consuming ≥1 servings of citrus fruits/day had a 22% lower endometriosis risk (95% CI = 0.69-0.89; Ptrend = 0.004) compared to those consuming <1 serving/week. No association was observed between total vegetable intake and endometriosis risk. However, women consuming ≥1 servings/day cruciferous vegetables had a 13% higher risk of endometriosis (95% CI = 0.95-1.34; Ptrend = 0.03) compared to those consuming <1 serving/week. Of the nutrients examined, only beta-cryptoxanthin intake was significantly associated with lower endometriosis risk (RR fifth quintile = 0.88; 95% CI = 0.78-1.00; Ptrend = 0.02). LIMITATIONS Some error in the self-reporting of dietary intake is expected, however, use of a validated FFQ and examining diet prospectively across multiple time points, make it unlikely that this non-differential misclassification strongly influenced the results. Our findings suggest that a higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis, and beta-cryptoxanthin in these foods may partially explain this association. In contrast to what we hypothesized, consumption of some vegetables increased endometriosis risk which may indicate a role of gastrointestinal symptoms in both the presentation and exacerbation of endometriosis-related pain; however, it is not clear what components of these foods might underlie the observed associations. Future studies examining dietary patterns that consider different combinations of food intake may help clarify these associations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by research grants HD4854, HD52473 and HD57210 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and grant P30 DK046200 from the National Institute of Diabetes and Digestive and Kidney Diseases. The Nurses' Health Study II is supported by the Public Health Service grant UM1 CA176726 from the National Cancer Institute, National Institutes of Health. HRH is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). No competing interests. n/a.

Endometriosis, dysmenorrhoea and diet

Hansen SO et al., 2013 · Eur J Obstet Gynecol Reprod Biol

To review the literature on the effects of diet on endometriosis and dysmenorrhoea. A systematic search for trials investigating a relationship between diet and endometriosis/dysmenorrhoea was undertaken, and 23 studies were included in this review. Data on the relationship between diet and endometriosis were limited to 12 trials, three of which were animal studies, resulting in a total of 74,708 women. One large study (n=70,709) found a relatively strong association between endometriosis and trans-fatty acid consumption, and a lower risk of endometriosis with increased consumption of long-chain omega-3 fatty acids. The latter finding was also supported by smaller studies. No further dietary recommendations for reducing the risk of endometriosis were possible, and results for intake of vegetable, fibre and fruit were equivocal. The relationship between diet and dysmenorrhoea was investigated in 11 trials with different designs, including a total of 1433 women. Intake of fish oil seemed to reduce dysmenorrhoea. The literature on endometriosis and dysmenorrhoea in relation to diet is sparse, yielding equivocal results on specific elements. Overall, however, the literature suggests that specific types of dietary fats are associated with endometriosis and/or dysmenorrhoea, thereby indicating that there may be modifiable risk factors. Further research is recommended on both subjects.