Endometriosis diagnostics may be approaching a meaningful inflection point as molecular assays, advanced imaging and updated clinical guidelines begin to chip away at the historic reliance on laparoscopic surgery. The shift is being driven by saliva-based microRNA tests such as Ziwig Endotest, blood-based multi-omic assays such as HerAnova Lifesciences’ HerResolve, and investigational molecular imaging agents such as 99mTc-maraciclatide, all targeting one of women’s health’s most stubborn diagnostic gaps. The World Health Organization estimates that endometriosis affects about 10 percent, or 190 million, reproductive-age women worldwide, while average time to diagnosis remains between four and 12 years in many settings. The commercial and clinical question is no longer whether endometriosis needs better diagnostics; it is whether these emerging tools can move from impressive validation signals into routine, reimbursed, guideline-supported care.
Why is endometriosis diagnosis still so delayed despite ultrasound, MRI and laparoscopy?
Endometriosis remains difficult to diagnose because symptoms are broad, variable and often overlap with other causes of chronic pelvic pain, dysmenorrhoea, bowel symptoms, bladder symptoms and infertility. The World Health Organization has noted that symptoms can be difficult for health workers to recognise and that many patients may not know their symptoms point to endometriosis. That creates a clinical funnel problem before technology even enters the room: patients may cycle through primary care, gastroenterology, urology, fertility care and pain management before gynaecological referral is prioritised.
The historic reliance on laparoscopy created another bottleneck. Laparoscopy can visualise lesions and allow tissue sampling, but it is invasive, resource-intensive and not equally accessible across health systems. Imaging has improved materially, especially for ovarian endometriomas and deep endometriosis, but superficial peritoneal disease remains harder to detect. That is where the next diagnostic race is forming, because the patient most likely to be missed by standard imaging is also the patient most likely to remain trapped in years of symptoms without diagnostic certainty.
Guidelines are now catching up to this clinical reality. The European Society of Human Reproduction and Embryology’s 2022 guideline reframed the diagnostic process by moving away from a rigid view of laparoscopy and histology as the only diagnostic anchor, while the World Health Organization states that clinical diagnosis can be made on symptoms and imaging and that surgery is not necessarily required before treatment begins. The 2024 update to National Institute for Health and Care Excellence guidance still advises clinicians to consider laparoscopy even when ultrasound or MRI is normal, which keeps surgery in the pathway but also acknowledges that imaging-negative disease remains clinically important.
How saliva-based microRNA testing is moving endometriosis diagnostics beyond symptom suspicion
Ziwig Endotest has become one of the most visible examples of a non-invasive endometriosis diagnostic moving toward broader clinical use. Ziwig describes the test as an in vitro diagnostic device for professional use that analyses salivary microRNA through next-generation sequencing and artificial intelligence modelling to identify profiles associated with endometriosis. The company says the device carries CE certification through a notified body, giving it a regulatory foothold in Europe and selected international markets.
The most important development for Ziwig Endotest is the publication of external validation data. NEJM Evidence published a prospective, multicentre external validation study in 2025 that reported accurate performance for a saliva-based microRNA signature in the diagnosis of endometriosis. Ziwig has also stated that the assay evaluates 109 salivary microRNAs using next-generation sequencing and artificial intelligence, although payer, clinician and regulator confidence will depend less on the elegance of the model and more on reproducibility across populations, disease subtypes and real-world referral settings.
The commercial appeal is obvious. A saliva test could be simpler to collect, easier to distribute through specialist clinics and potentially more acceptable to patients than surgical confirmation. However, the adoption hurdle is not just analytical validity. For clinicians, the test must answer a practical question: does a positive or negative result change the next step in care, referral, fertility planning or surgical decision-making? For payers, the question is harder still: does earlier testing reduce downstream costs from repeated visits, delayed treatment, avoidable imaging or unnecessary laparoscopy? Until those health-economic data mature, saliva-based testing may initially sit as a triage or adjunctive tool rather than a wholesale replacement for specialist assessment.
Why blood-based multi-omic assays could become a rival route into earlier endometriosis detection
HerAnova Lifesciences’ HerResolve represents a different non-invasive strategy by combining molecular and clinical variables in a blood-based assay. Public reports on the peer-reviewed validation study indicate that the assay was evaluated in 298 reproductive-age women with suspected endometriosis across 11 clinical sites in the United States, Europe and Hong Kong. PubMed’s indexed summary of the 2026 publication states that, compared with transvaginal ultrasound and/or magnetic resonance imaging, the blood-based assay identified 61.5 percent of histologically confirmed endometriosis cases that imaging had missed.
That detail matters because it targets the most commercially valuable gap in the pathway: patients with persistent symptoms but inconclusive imaging. A blood test does not need to outperform expert ultrasound in obvious endometrioma cases to be useful. It needs to improve decision-making in the ambiguous middle, where clinicians are weighing empirical hormonal therapy, fertility planning, pain management, referral to an endometriosis centre or diagnostic surgery.
Reported performance metrics for HerResolve include an 80 percent sensitivity and around 97 percent specificity in the validation cohort, with one public summary describing an area under the curve of 0.944. Those figures are promising, but they should be read with diagnostic discipline. A test with high specificity may be useful in confirming risk and accelerating referral, while sensitivity limitations mean a negative result cannot automatically rule out disease in a symptomatic patient. In practical terms, the assay may become more valuable as a clinical decision support tool than as a one-stop answer, especially in patients whose imaging does not explain pain severity or infertility history.
The multi-omic structure also reflects where diagnostics is heading. Single biomarkers have struggled in endometriosis because the disease is heterogeneous across lesion type, inflammatory biology, menstrual cycle phase, hormonal exposure and anatomical location. Combining microRNA, protein, hormonal and clinical variables may improve signal capture, but it also raises implementation questions around algorithm transparency, population calibration, laboratory reproducibility and regulatory classification.
Could molecular imaging solve the superficial peritoneal endometriosis problem?
The most intriguing recent imaging signal comes from 99mTc-maraciclatide, an investigational SPECT-CT imaging agent being studied for endometriosis detection. University of Oxford researchers reported that the Phase 2 DETECT study evaluated 19 individuals with suspected or confirmed pelvic or thoracic endometriosis who underwent preoperative SPECT-CT imaging after intravenous administration of 99mTc-maraciclatide. The agent binds to αvβ3 integrins, which are upregulated during angiogenesis, a biological process relevant to endometriotic lesions.
The early clinical signal is small but notable. Public study summaries reported concordance between imaging findings and surgical presence or absence of endometriosis in 16 of 19 cases, with endometriosis imaged in 14 of 17 surgically positive participants and no false positives in the study. The technology’s potential significance lies in its ability to visualise lesion biology rather than relying only on anatomical distortion, which could make it relevant for superficial peritoneal endometriosis, one of the hardest forms to identify with standard scans.
The caveat is scale. A 19-participant Phase 2 study is not enough to reset diagnosis. It is, however, enough to justify larger trials if the imaging signal remains clean. If future studies confirm performance across scanners, operators, lesion types and disease severity, molecular imaging could become more than a diagnostic tool. It could support patient selection in clinical trials, lesion monitoring, treatment response assessment and drug-development endpoints. That would make it strategically important not only for gynaecology but also for companies attempting to build therapeutics in a disease where trial enrolment and objective disease measurement are persistent challenges.
How updated guidelines are creating room for non-invasive endometriosis diagnostics
The diagnostic shift is not happening because one test has suddenly solved endometriosis. It is happening because the clinical pathway itself is becoming less binary. The older paradigm treated laparoscopy as the final gatekeeper. The emerging paradigm is more layered: symptom history, validated questionnaires, expert ultrasound, magnetic resonance imaging, empirical treatment, biomarker testing, molecular imaging and surgery may all have roles depending on patient presentation and care goals.
The World Health Organization now explicitly recognises that new diagnostic approaches include symptom checklists, blood tests, saliva tests and menstrual blood-based self-tests, while also emphasising that access to early diagnosis remains limited in many settings. That framing is important because it positions diagnostics not just as laboratory innovation but as an access problem. A technically strong test that remains confined to private fertility clinics will not solve the global endometriosis burden. A moderately priced test integrated into referral pathways might.
For regulators and payers, the threshold will be clinical utility. Diagnostic developers must show that testing leads to earlier referral, better treatment selection, fewer unnecessary procedures, improved fertility decision-making or measurable quality-of-life gains. Accuracy claims alone are unlikely to be enough, especially in health systems already under pressure from imaging backlogs, specialist shortages and surgical waitlists. The winner in this market may not be the assay with the flashiest sensitivity and specificity headline, but the platform that proves it can change care at the lowest operational friction.
What the competitive landscape says about the next phase of women’s health diagnostics
The endometriosis diagnostics market is becoming a test case for women’s health innovation more broadly. For years, the field has suffered from under-recognition, fragmented care pathways and limited commercial incentives. Now, the convergence of molecular biology, artificial intelligence, imaging and guideline reform is creating a more investable category.
Ziwig Endotest has the advantage of visibility, CE certification and published saliva-based validation. DotLab’s EMPOWER study shows that United States developers are pursuing prospective multicentre evidence for microRNA-based diagnostic testing, with the trial designed to enrol 750 women aged 18 to 49 undergoing laparoscopy, laparotomy or other pelvic procedures. HerAnova Lifesciences brings a blood-based multi-omic approach with early commercial deployment in reproductive medicine settings. Serac Healthcare’s 99mTc-maraciclatide adds a radiopharmaceutical imaging angle that could be especially relevant for lesion localisation and clinical trial infrastructure.
That diversity is good for the field, but it also complicates adoption. A saliva test, blood test and SPECT-CT scan do not answer identical clinical questions. Saliva and blood assays may be better suited for earlier risk stratification and referral triage. Advanced imaging may be better suited for lesion mapping, surgical planning and research endpoints. The likely future is not a single diagnostic winner but a tiered pathway in which non-invasive tools reduce uncertainty before surgery is considered.
The bigger story is that endometriosis is moving from a diagnosis-of-exclusion model toward a measurable disease biology model. That transition could unlock not only diagnostics but drug development, payer engagement and real-world evidence generation. The long diagnostic delay has been bad medicine, bad economics and bad market design. Non-invasive diagnostics will not fix all three overnight, but the sector is finally building tools that can be judged on measurable clinical value rather than patient persistence alone.
What non-invasive endometriosis diagnostics mean for clinicians, diagnostics developers and payers
- Non-invasive endometriosis diagnostics are gaining momentum because clinical guidelines and public health agencies increasingly recognise that surgery is not always required before treatment begins.
- Ziwig Endotest is one of the most advanced saliva-based approaches, using salivary microRNA, next-generation sequencing and artificial intelligence to support professional diagnosis.
- HerAnova Lifesciences’ HerResolve shows how blood-based multi-omic assays may help identify histologically confirmed cases that standard ultrasound or magnetic resonance imaging can miss.
- DotLab’s EMPOWER study reflects the importance of prospective, multicentre evidence in a field where biomarker enthusiasm has historically outpaced clinical utility.
- 99mTc-maraciclatide could become strategically important if larger studies confirm its ability to detect superficial peritoneal endometriosis and support lesion monitoring.
- The biggest near-term market opportunity is not replacing laparoscopy outright, but improving triage for symptomatic patients with normal or inconclusive imaging.
- Payers will likely demand evidence that testing reduces diagnostic delay, unnecessary procedures, repeat consultations or downstream fertility and pain-management costs.
- Diagnostic developers must avoid overclaiming, because negative biomarker results are unlikely to safely rule out endometriosis in all symptomatic patients.
- The future diagnostic pathway will likely combine symptom assessment, expert imaging, molecular testing and selective surgery rather than depend on one technology.
- Women’s health diagnostics is becoming a more investable category because endometriosis offers a large unmet need, measurable patient burden and clear system-level inefficiency.
