Introduction Access to accurate, non-invasive diagnostics remains a critical unmet need in women’s health. Menstrual effluence, containing endometrial tissue, immune cells, and microbial communities, represents a clinically relevant specimen for genomic and molecular pathology applications, yet has historically been underutilized due to concerns about sample integrity and variability.

Methods We developed and validated a standardized, at-home tampon-based collection system designed to preserve nucleic acids at ambient temperature for clinical-grade analyses. 1,067 tampon samples from 328 participants underwent, exome sequencing, RNA sequencing, and metatranscriptomic profiling to assess specimen transcript integrity, diagnostic fidelity, and microbial composition over time.

Results RNA extracted from menstrual effluence maintained stability for up to 14 days without refrigeration, achieving sufficient yield and quality for sequencing in >97% of samples. Variant detection via exome sequencing demonstrated 100% concordance among overlapping single nucleotide variants between menstrual fluid and matched venous blood, confirming clinical equivalency for genetic testing. Transcriptomic analyses revealed cycle-dependent variation in key reproductive and immune markers, while metatranscriptomic profiling identified shifts in microbial communities consistent with known reproductive tract dysbiosis.

Conclusions Standardized at-home collection of menstrual effluence provides a clinically actionable platform that supports remote specimen acquisition without compromising molecular assay fidelity, offering a scalable solution to improve access to carrier screening, reproductive health assessment, and infectious disease monitoring in clinical practice.

Ridhi Tariyal, Stephen Gire, Xitong Li, and Claire Toth are or were employed by NextGen Jane, Inc. which manufactures the tampon collection kit. The other authors did not report any potential conflicts of interest.

The analyses in this paper were partly funded through an SBIR Fast Track grant with the National Institute of Child Health and Disease 5R44HD103159

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