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MON-201 Female Subfertility and Long-Term Cardiovascular Risk
Abstract
Disclosure: E. Armeni: None. C. Polymeropoulou: None. N. Mili: None. E. Siliogka: None. A. Augoulea: None. I. Lambrinoudaki: None.
Objective: Infertility and cardiovascular disease (CVD) are widespread health concerns that share common risk factors, such as oxidative stress, endothelial dysfunction, and chronic inflammation. Although research has suggested a potential link between female infertility and an increased risk of CVD, findings remain inconclusive. This systematic review (SR) and meta-analysis (MA) aim to investigate whether women with infertility have a greater likelihood of developing cardiovascular conditions later in life. Methods: This SR and MA of 21 studies followed PRISMA guidelines and was registered in PROSPERO (CRD42023420300). The Newcastle-Ottawa Scale assessed study quality. Statistical analyses included odds ratios (OR) and hazard ratios (HR) using Mantel-Haenszel and inverse variance methods. Heterogeneity was evaluated via I². We performed sensitivity analyses to assess the impact of the participant's age at recruitment, the duration of follow-up (FU, cut-off 10 years for short vs extended), and exposure to assisted reproduction techniques (ART) on the observed associations. Results: We compared 178,828 women with a history of infertility with 3,398,781 controls and found a higher prevalent and incident risk of future CVD (HR = 1.14, 95% CI: 1.12–1.16; I² = 89%), CHD (HR = 1.17, 95% CI: 1.12–1.23; I² = 0%) and cerebrovascular events (HR=1.16; 95% CI: 1.11–1.21; I² = 73%). Compared to controls, studies evaluating infertile women aged < 40 years showed a higher risk of CVD (HR=1.20; 95% CI: 1.17-1.23; I2=81%; I² = 81%), whereas those studies evaluating infertile women aged 40 years or more showed a comparable risk for CVD (HR=1.04; 95% CI: 1.00-1.07; I² = 29%). Studies with shorter observation periods (FU < 10 years) reported higher incident risk for all cardiovascular events compared to the pooled risk retrieved from studies with extended FU (> 10 years). We found that women exposed to ART vs controls (392,266 and 33,630,919, respectively) had a higher incident risk for CVD (HR = 1.18; 95% CI: 1.11–1.25; I² = 97%), although ART exposure did not significantly increase the risk of CHD, cerebrovascular events, or heart failure.Discussion: This study reveals an elevated risk of CVD, encompassing CHD and cerebrovascular events, among women with a history of infertility. The risk is higher for women experiencing infertility early on during their reproductive life. ART exposure was linked to a higher risk of CVD; however, the true impact of ART remains unclear due to substantial variability across studies, likely influenced by differing methodologies and ART protocols.
Presentation: Monday, July 14, 2025
Journal Article
Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial
Women with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth.
In this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (-6.6 ± 5.4% versus -0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful.
A preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity.
ClinicalTrials.gov NCT02432209.
Journal Article
Barren women : religion and medicine in the medieval Middle East
\"Barren Women is the first scholarly book to explore the ramifications of being infertile in the medieval Arab-Islamic world. Through an examination of legal texts, medical treatises, and works of religious preaching, Sara Verskin illuminates how attitudes toward mixed-gender interactions; legal theories pertaining to marriage, divorce, and inheritance; and scientific theories of reproduction contoured the intellectual and social landscape infertile women had to navigate. In so doing, she highlights underappreciated vulnerabilities and opportunities for women's autonomy within the system of Islamic family law, and explores the diverse marketplace of medical ideas in the medieval world and the perceived connection between women's health practices and religious heterodoxy. Featuring copious translations of primary sources and minimal theoretical jargon, Barren Women provides a multidimensional perspective on the experience of infertility, while also enhancing our understanding of institutions and modes of thought which played significant roles in shaping women?s lives more broadly. This monograph has been awarded the annual BRAIS ? De Gruyter Prize in the Study of Islam and the Muslim World.\"-- Back cover.
Book
Male infertility due to testicular disorders
Abstract
Context
Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date.
Evidence Acquisition
The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail.
Evidence Synthesis/Results
Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trials data is currently lacking.
Conclusions
Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in “idiopathic” male infertility and long-term follow-up studies of babies conceived through ART.
Journal Article