Examining the co-occurrence of endometriosis and polycystic ovarian syndrome

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

The Association Between Endometriosis Treatments and Depression and/or Anxiety in a Population-Based Pathologically Confirmed Cohort of People with Endometriosis

Goodwin E et al., 2023 · Women's health reports (New Rochelle, N.Y.) · Free full text on PubMed Central

Endometriosis patients have a high rate of co-occurring anxiety and depression. There is currently no literature investigating how this may affect endometriosis treatment and outcomes. This study examines the prevalence of depression and anxiety in a pathologically confirmed population-based endometriosis cohort and examines how endometriosis treatments and outcomes differ by the presence of co-occurring depression and/or anxiety. This retrospective cohort study using population-based administrative data sets included pathologically confirmed endometriosis patients identified from the complete pathology records of Vancouver Coastal Health Authority (British Columbia, Canada) between 2000 and 2008. These data were linked with population-based health data for follow-up to 2017. Bivariate analyses assessed differences between patients with depression and/or anxiety and those without. Odds ratios (ORs) were calculated to assess the odds of binary postsurgical outcomes. Our final cohort consisted of 3815 patients. There were 603 patients (15.8%) with depression and/or anxiety. They were more likely to visit a physician for pelvic pain, more likely to take some hormonal medications, and more likely to fill prescription-level analgesics, including opioids both before and after surgery. They also had a significantly higher risk of reoperation for their endometriosis than people without co-occurring depression and/or anxiety (OR 1.32, 95% confidence interval [CI]: 1.07-1.61). Endometriosis patients with co-occurring depression and/or anxiety used more health services for pain, including prescription-level analgesics, and were more likely to have an endometriosis reoperation. We recommend that future study should aim to better understand the direction of this association between depression and/or anxiety and increased health services use.

The prevalence of polycystic ovaries in healthy women

Koivunen R et al., 1999 · Acta Obstet Gynecol Scand

To study the prevalence of polycystic ovaries (PCO) in women of reproductive age. A total of 189 healthy volunteers aged 20-45 years were examined. The subjects were divided into two groups according to age: < or =35 and > or =36 years. Transvaginal ultrasonography was performed and blood samples were collected on cycle day 1-6. The prevalence of PCO in the entire study population was 14.2% (27/189). In the age group of < or =35 years the prevalence was 21.6% (19/88) and in the age group of > or =36 years 7.8% (8/101). Compared to women with normal ovaries, those with PCO had significantly higher serum testosterone (T) concentrations. Women with PCO tended to have lower serum FSH concentrations and higher LH/FSH ratios than controls. Women with PCO had significantly more irregular cycles (44% vs. 19%, p=0.001) and problems in conceiving (25.9% vs. 9.2%, p=0.01) than women with normal ovaries. The findings demonstrate that the prevalence of PCO in healthy women varies with age, being more common among women aged < or =35 years than in those aged > or =36 years. Although the hormonal parameters and clinical findings among women with PCO mimicked those of PCOS, it remains unclear if these women will later develop full-blown syndrome.

Chapter 43: Polycystic Ovarian Disease

Hilgers TW, 2004 · The Medical and Surgical Practice of NaProTECHNOLOGY

Polyendocrine metabolic ovarian syndrome (PMOS), formerly polycystic ovary syndrome (PCOS), is far more prevalent than its classic presentation suggests, affecting roughly six percent of reproductive-age women and carrying systemic consequences well beyond fertility disruption. This chapter from the foundational NaProTECHNOLOGY textbook maps the hormonal architecture of the condition, its ovulatory defect patterns, its frequent co-occurrence with endometriosis, and the restorative surgical and cycle-tracking approaches developed at the Pope Paul VI Institute.

Changes in the prevalence of polycystic ovary syndrome in China over the past decade

Yang R et al., 2022 · Lancet Reg Health West Pac · Free full text on PubMed Central

Polycystic ovary syndrome (PCOS) has become a major international public health concern. However, because of controversy about the diagnostic criteria and patient selection, estimates of its absolute prevalence and change with time vary greatly. We conducted two consecutive nationwide epidemiological surveys of the prevalence of PCOS in representative samples of reproductive-aged women in China in 2010 and 2020. Face-to-face interviews were performed by trained interviewers in each survey. All participants completed a questionnaire and underwent a physical examination, blood sampling, and transvaginal pelvic ultrasound. We assessed hyperandrogenism (H), chronic anovulation (O), and polycystic ovaries (P) to classify the presence of PCOS using the Rotterdam criteria. The prevalence of PCOS among reproductive-aged women was estimated after consideration of differential probabilities of selection and population distribution. We conducted a logistic regression analysis by using the probability of PCOS as a function of the survey year to acquire the trend information across the years. Findings: 28,739 respondents completed the survey, including 15,924 in the previously published 2010 survey and 12,815 in the new 2020 survey. In 2020, 826 participants could be diagnosed as having PCOS, with a weighted prevalence of 7.8% (95%CI: 7.0%, 9.0%) among women aged 20-49 years, leading to an estimate of 24.0 million women of reproductive age affected by this condition in China as a whole. The estimated prevalence in 2020 was higher than that of a decade ago despite identical research methods suggesting a two-thirds increase over the study period. Women with PCOS in 2020 also appeared to have a more severe phenotype overall than those of a decade ago, possibly reflecting a significantly higher prevalence of obesity, hyperandrogenism, and infertility. Interpretation: The prevalence of PCOS in Chinese women has increased significantly over the past 10 years. PCOS is a significant public health problem in women of reproductive age in China and national policy and guidelines should be re-examined in the light of the current data. National Key R&D Program of China and the National Natural Science Foundation of China.