Gire Stephen, Li Xitong, Toth Claire, Doshi Meet, Gupta Sachin Kumar, Parker Scott, Boles Debbie, Tariyal Ridhi
NextGen Jane, Inc. Oakland, California.
Elucidata, San Francisco, California.
medRxiv. 2025 Jun 2:2025.05.21.25327630. doi: 10.1101/2025.05.21.25327630.
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.
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, RNA sequencing and metatranscriptomic profiling to assess specimen transcript integrity, diagnostic fidelity, and microbial composition over time. 12 patients were exome sequenced using matched menstrual effluence and whole blood to assess assay concordance between sample types.
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.
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.
获得准确的非侵入性诊断方法仍然是女性健康领域一项尚未满足的关键需求。月经流出物包含子宫内膜组织、免疫细胞和微生物群落，是基因组学和分子病理学应用中具有临床相关性的标本，但由于对样本完整性和变异性的担忧，其在历史上一直未得到充分利用。
我们开发并验证了一种基于家用卫生棉条的标准化采集系统，该系统旨在在常温下保存核酸以进行临床级分析。对来自328名参与者的1067份卫生棉条样本进行了RNA测序和宏转录组分析，以评估标本转录本的完整性、诊断准确性以及随时间变化的微生物组成。使用匹配的月经流出物和全血对12名患者进行外显子组测序，以评估不同样本类型之间检测结果的一致性。
从月经流出物中提取的RNA在无需冷藏的情况下可保持稳定长达14天，超过97%的样本获得了足以用于测序的产量和质量。通过外显子组测序进行的变异检测显示，月经液和匹配的静脉血之间重叠的单核苷酸变异的一致性为100%，证实了基因检测的临床等效性。转录组分析揭示了关键生殖和免疫标志物的周期依赖性变化；而宏转录组分析则确定了与已知生殖道生态失调一致的微生物群落变化。
标准化的在家采集月经流出物提供了一个具有临床可操作性的平台，该平台支持远程获取标本而不影响分子检测的准确性，为改善临床实践中携带者筛查、生殖健康评估和传染病监测的可及性提供了一种可扩展的解决方案。
