FERTIMPACT is a prospective clinical study based on the hypothesis that exposure to micro- and nanoplastics (MNPs) is associated with impaired reproductive function. The study will quantify MNPs in human reproductive biospecimens (semen, follicular fluid, endometrial samples, stool and serum) and evaluate their association with clinically relevant fertility parameters, including semen, follicular fluid, and endometrial samples quality, and assisted reproductive technology (ART) outcomes. By integrating biomonitoring with standardized clinical assessment, the study aims to provide robust evidence on exposure-effect relationships in real-world populations undergoing infertility evaluation. This will contribute to improved understanding of environmental determinants of reproductive health and support future risk assessment strategies.

Although the presence of MNPs in the human body, including reproductive fluids and placental tissue, has recently been documented, their health implications remain poorly understood, particularly in the context of the function of the human reproductive system. FERTIMPACT is the first project to systematically investigate the links between MNP exposure and reproductive toxicity by leveraging Machine Learning (ML) and multi-omics, while also exploring transgenerational effects, enabling real-time risk prediction and tracking through an integrated AI-driven platform, and developing evidence-based countermeasures and policy tools for exposure reduction. The project introduces several innovative and ground-breaking elements, derived from several diagnostic needs, including an integrated methodological approach that combines state-of-the-art label-free spectroscopic imaging techniques, thermo-analytical tools, advanced particle characterization methods and multiparametric graphene-based biosensing at the point of care for comprehensive exposure assessment in the human body and environment; a novel conceptual framework linking environmental contamination to reproductive dysfunction via shared molecular mechanisms such as oxidative stress, endocrine disruption, and genotoxicity; an AI-powered Environmental Health Intelligence Platform capable of integrating environmental and health data to dynamically assess exposure-health relationships and generate real-time risk maps; and a transdisciplinary approach bridging lab-based science with public health action through environmental monitoring, clinical research, AI, and regulatory science. Crucially, FERTIMPACT emphasizes co-development of policy recommendations and mitigation strategies with stakeholders to ensure meaningful real-world impact and uptake. Preliminary patent and publication searches indicate no prior integrated platform that combines real-world biomonitoring, mechanistic analysis, and predictive modeling of MNPs reproductive risks at this scale. Recent publication form the scientific foundation, but FERTIMPACT will extend these findings into actionable health interventions.

Link from scientific questions to answer by the FERTIMPACT clinical study: reliable detection of MNPs in human reproductive fluids. Scientific question 1#: How to develop and validate standard, contamination-controlled SOPs for semen, serum, stool, endometrial samples and follicular fluid and create interoperable protocols across EU labs? Is it possible to develop a graphene-based multiparametric biosensing platform for the rapid detection of MNPs and measure its impact on humans? FERTIMPACT answer: Reliable detection of MNPs in human reproductive fluids. Development and validation of standardized, contamination-controlled SOPs for semen, serum, stool, endometrial samples and follicular fluid. Creation of interoperable protocols across EU labs. Deployment of a graphene-based multiparametric biosensing platform for the rapid detection of MNPs and its impact on humans at the point of care. Scientific question 2#: How to harmonize of analytical methods across centres? How to make a label-free spectroscopic characterization methods and introduce it into a comprehensive, validated workflow? How to make a linking MNPs presence to clinical reproductive outcomes. FERTIMPACT answer: First prospective, human biomonitoring cohort systematically connecting MNPs burden to semen quality, ovarian reserve, and hormonal parameters. Scientific question 3#: How to elucidate mechanistic understanding of MNP-induced reproductive toxicity? FERTIMPACT answer: Application of omics to uncover molecular pathways (oxidative stress, endocrine disruption, genotoxicity) and identify biomarkers. Scientific question 4#: How to integrate a heterogeneous datasets (environmental, clinical, lab)? FERTIMPACT answer: Deployment of an AI-powered Environmental Health Intelligence Platform, enabling dynamic risk modelling, prediction, and early warning capabilities. Scientific question 5#: How to make a tool to predict and prevent MNPs related health risks? FERTIMPACT answer: Development of real-time risk maps, exceedance forecasts, anomaly detection, and citizen-facing alerts, ensuring actionable early warning for health authorities and the public. Scientific question 6#: How to translate scientific findings into policy and public health strategy? FERTIMPACT answer: Stakeholder co-creation of countermeasures, validated behavioural and regulatory interventions, and evidence-based recommendations for EU environmental and reproductive health policies.

Although the present study is non-interventional, it is based on a biologically plausible hypothesis supported by emerging experimental and translational evidence. Micro- and nanoplastics (MNPs) have been shown to induce oxidative stress, leading to the generation of reactive oxygen species and disruption of cellular homeostasis, which may impair gamete quality and reproductive function. In addition, MNPs can act as carriers of endocrine-disrupting chemicals, potentially interfering with hormonal regulation critical for reproductive processes. Experimental studies have also demonstrated genotoxic effects, including DNA damage and chromosomal instability, which may affect fertility and early embryonic development. These mechanisms provide a strong biological rationale for investigating the association between MNP exposure and reproductive outcomes in human populations. However, clinical evidence in humans remains limited, particularly in well-defined reproductive cohorts, justifying the need for the proposed prospective clinical study.

Inclusion Criteria:

• Men: 18-55 years and women: 18-45 years (premenopausal).
• Residence: ≥ 2 years in the participating region.
• Ability to give informed consent and complete questionnaires (diet, lifestyle, occupational exposure).
• Willingness to provide required samples: semen, serum, stool for men and for women serum, stool, follicular fluid and endometrial sample.
• Availability for study visits and compliance with pre-analytical rules: Abstinence 2-7 days before semen collection and timed sampling in women (e.g., follicular phase or per protocol).
• For patient cohort: diagnosed reproductive disorder per site SOPs (e.g., male factor infertility, endometriosis, diminished ovarian reserve).
• For control cohort: no known infertility diagnosis; trying to conceive or healthy volunteers.
• Necessary for all participants will be possess the ability to understand the information contained in the "informed consent" document.

Exclusion Criteria:

• Pregnancy or lactation.
• Acute febrile illness or active urogenital/reproductive tract infection in the last 4 weeks.
• Systemic therapies likely to confound biomarkers within prespecified windows: chemotherapy/radiotherapy (past 12 months), high-dose corticosteroids/immunosuppressants (past 3 months), hormonal stimulation outside scheduled ART cycles per protocol.
• Substance abuse (investigator judgment) impeding consent/compliance.

Adults of reproductive age