Saliva test for the diagnosis of endometriosis: a major breakthrough for women’s health

“A better detection of the disease”: this is one of the main focuses of the French national strategy to fight endometriosis, wich implementation was announced on January 11, 2022 by Emmanuel Macron.

Most women suffering from endometriosis are going through a long period of medical wandering (8 years on average), during which they undergo numerous appointments, tests and examinations before a diagnosis is made, most often requiring a surgery.

A global innovation can now allow them to avoid this obstacle course. A French team of endometriosis experts and artificial intelligence engineers has developed a diagnostic test based on the sequencing of microRNAs present in saliva.

This simple, non-invasive salivary test, called Ziwig Endotest®, has been validated by the largest clinical trial ever conducted in this field. It allows the early detection of all forms of endometriosis, even the most complex, with a reliability close to 100%.

It should revolutionize the diagnosis and management of the disease, and constitute in the near future a major breakthrough for women’s health.

Our scientific publications

Our work has been published in several scientific journals:

November 2022

Saliva microRNA signature to diagnose endometriosis: A cost-effectiveness evaluation of the Endotest®

Ferrier C., Bendifallah S., Suisse S., Dabi Y., Touboul C., Puchar A., Zarca K. and Durand Zaleski I.

Objective: To evaluate a saliva diagnostic test (Endotest®) for endometriosis compared with the conventional algorithm. Design: A cost-effectiveness analysis with a decision-tree model based on literature data. Setting: France. Population: Women with chronic pelvic pain.

October 2022

Endometriosis-associated infertility diagnosis based on saliva microRNA signatures

Dabi Y., Suisse S., Puchar A., Delbos L., Poilblanc M., Descamps P., Haury J., Golfier F., Jornea L., Bouteiller D., Touboul C., Daraï E. and Bendifallah S.

Research question: Can a saliva-based miRNA signature for endometriosis-associated infertility be designed and validated by analysing the human miRNome? Design: The prospective ENDOmiARN study (NCT04728152) included 200 saliva samples obtained between January 2021 and June 2021 from women with pelvic pain suggestive of endometriosis.

July 2022

A Bioinformatics Approach to MicroRNA‐Sequencing Analysis Based on Human Saliva Samples of Patients with Endometriosis

Bendifallah S., Dabi Y., Suisse S., Delbos L., Poilblanc M., Descamps P., Golfier F., Jornea L., Bouteiller D., Touboul C., Puchar A. and Daraï E.

Endometriosis, defined by the presence of endometrium-like tissue outside the uterus, affects 2–10% of the female population, i.e., around 190 million women, worldwide. The aim of the prospective ENDO-miRNA study was to develop a bioinformatics approach for microRNA- sequencing analysis of 200 saliva samples for miRNAome expression and to test its diagnostic accuracy for endometriosis.

May 2022

Endometriosis Associated-miRNome Analysis of Blood Samples: A Prospective Study

Bendifallah S., Dabi Y., Suisse S., Delbos L., Poilblanc M., Descamps P., Golfier F., Jornea L., Bouteiller D., Touboul C., Puchar A. and Daraï E.

The aim of our study was to describe the bioinformatics approach to analyze miRNome with Next Generation Sequencing (NGS) of 200 plasma samples from patients with and without endometriosis. Patients were prospectively included in the ENDO-miRNA study that selected patients with pelvic pain suggestive of endometriosis.

March 2022

MicroRNome analysis generates a blood-based signature for endometriosis

Bendifallah S., Suisse S., Dabi Y., et al.

Endometriosis, characterized by endometrial-like tissue outside the uterus, is thought to affect 2–10% of women of reproductive age: representing about 190 million women worldwide. Numerous studies have evaluated the diagnostic value of blood biomarkers but with disappointing results. Thus, the gold standard for diagnosing endometriosis remains laparoscopy. We performed a prospective trial, the ENDO-miRNA study, using both Artificial Intelligence (AI) and Machine Learning (ML),…

January 2022

Salivary MicroRNA Signature for Diagnosis of Endometriosis

Bendifallah S., Suisse S., Puchar A., et al.

Background: Endometriosis diagnosis constitutes a considerable economic burden for the healthcare system with diagnostic tools often inconclusive with insufficient accuracy. We sought to analyze the human miRNAome to define a saliva-based diagnostic miRNA signature for endometriosis.

January 2022

Clues for Improving the Pathophysiology Knowledge for Endometriosis Using Serum Micro-RNA Expression

Dabi Y., Suisse S., Jornea L., et al.

The pathophysiology of endometriosis remains poorly understood. The aim of the present study was to investigate functions and pathways associated with the various miRNAs differentially expressed in patients with endometriosis. Plasma samples of the 200 patients from the prospective “ENDO-miRNA”; study were analyzed and all known human miRNAs were sequenced.

January 2022

Machine learning algorithms as new screening approach for patients with endometriosis

Bendifallah S., Suisse S., Puchar A., et al.

Endometriosis—a systemic and chronic condition occurring in women of childbearing age—is a highly enigmatic disease with unresolved questions. While multiple biomarkers, genomic analysis, questionnaires, and imaging techniques have been advocated as screening and triage tests for endometriosis to replace diagnostic laparoscopy, none have been implemented routinely in clinical practice.

Pain and infertility at the forefront

Endometriosis affects 10% of women of childbearing age in France, being 1.5 to 2.5 million women. It potentially concerns all menstruating women and can appear as early as adolescence.

This disease is characterized by the presence of endometrium (mucous membranes lining the inside of the uterus) outside the uterine cavity, in various organs: ovaries, vagina, rectum, bladder, intestines, lungs… At the time of menstruation, these endometrial fragments found in abnormal locations cannot be removed (3).

The disease can also be completely asymptomatic. In this case, it is usually discovered by chance during a consultation motivated by difficulties to conceive a child. UA significant proportion of patients with endometriosis also suffer from infertility.

Three forms of endometriosis are classically described: superficial or peritoneal endometriosis, ovarian endometriosis and deep endometriosis. There is no systematic correlation between the symptoms and the severity of the disease (3).

Worsening of symptoms over time

In about one third of cases (especially in superficial forms), endometriosis can stagnate or even regress, either with treatment or on a spontaneous way. But more often, the symptoms, including pain, get worse over time.

The persistence of pain favors the phenomenon of hypersensitivity: the pain perception level decreases, resulting in the evolution of the pain towards chronicity. .

This chronic pain can appear at any stage of endometriosis and persist even after the lesions of endometriosis are no longer visible (4,5).

Hypersensitivity is favored by the remanence of pain over time and in turn reinforces the evolution of the pain towards chronicity.

Treatments targeting the pain of symptoms

Today, there is no treatment that can cure endometriosis. Beyond the analgesic treatment adapted to each patient, hormonal treatments, which are based on the use of estrogen-progestin contraceptives or continuous progestins, aim to block the occurrence of periods. This background treatment prevents recurrence and the development of new lesions. These treatments can also call upon, in second intention, drugs (Gn-RH agonists, anti-androgens) which put the patient in a state of transitory menopause. These treatments may lead to hot flashes, mood disordes, weight gain…, but an add-back therapy (pill given at the same time) most often avoids these side effects (6).

Surgical treatment is considered when medical treatments are insufficient to relieve the pain. Its goal is to remove endometriosis lesions and correct anatomical abnormalities caused by the disease, including adhesions that reduce organ mobility. The procedure is most often performed by laparoscopy (6).

A major impact on personal and social life

Endometriosis is the cause of a significant deterioration in quality of life.. The pain is responsible for sleep disorders which induce chronic fatigue and psychological disorders (irritability, depression…), causing deterioration in family and social relationships. This in turn leads to a deterioration in family and social relationships. Sexuality is altered, often with major repercussions on the couple. Infertility and uncertainties related to the MAP process also have an important impact (3).

Average annual cost of endometriosis is € 9579 per woman, with an average of 33 days of sick leave per year. The overall societal cost of the disease is estimated at 10.6 billion euros in France (7,8).

The need of a non-invasive diagnostic test

The laparoscopy is now considered as the reference examination for the diagnosis of endometriosis (10). It is nevertheless an invasive procedure that must be performed under general anesthesia and may, like any surgical procedure, be accompanied by intra- or post-operative complications.

The development of a non-invasive diagnostic test for endometriosis has therefore been a major medical need for many years. More than a hundred potential biomarkers (angiogenesis factors, growth factors, hormonal, immune and inflammatory markers, etc.) have been evaluated over the past decades (10).

Among these biomarkers, a new class of molecules discovered in 2000, microRNAs, has emerged as a promising option, supported by a growing number of evidence from studies on cancer and degenerative disorders (11,12).

A global innovation based on 2 breakthrough technologies

High-throughput sequencing and artificial intelligence

Ziwig, in partnership with expert endometriosis physicians, uses two cutting-edge technologies:

High-throughput sequencing or massively parallel sequencing, or next-generation sequencing (NGS), which allows the simultaneous acquisition of data on millions of DNA or RNA fragments.

Artificial intelligence (associated with machine learning), which allows the analysis of the very large volume of data generated by high-throughput sequencing.

A revolution in the care of endometriosis

Beyond diagnosis, it is the entire management of endometriosis that should be improved by the arrival of Ziwig’s Endotest®.

Allowing the slowing down or even stopping of the worsening of pain (by reducing the risk of hypersensitivity) and other symptoms, optimizing the care of infertility and limiting the deterioration in the quality of life of patients.

Ziwig Endotest® makes diagnostic laparoscopy obsolete and should help avoid unnecessary surgery, especially for patients with symptoms similar to endometriosis but who do not have the disease.

Ziwig Endotest® is CE marked. Its provision to patients is currently the subject of consultation with the French health authorities, with a view to its inclusion in the care pathway and its possible reimbursement by the health insurance system.

Ziwig Endotest® saliva test should reduce the average time to diagnosis from 8 years to a few days.

It should, in the long term, allow a significant reduction in the medico-social cost of the disease and contribute to health democracy by allowing all patients, including those living in medical deserts, to benefit from a reliable, early and non-invasive diagnosis.


Our ambition to make progress in endometriosis research and treatment in order to change the way of understanding this disabling disease which affects so many women all over the world, would never have succeeded without all the women and men who have believed in our project.

They fought alongside us to make this innovation possible and to win this cause.  On behalf of all those who will benefit from our innovative approach, we say thank you!


Bibliographic references:

  1. Zondervan  KT et al. Nat Rev Dis Primers 2018;4(1):9 ;

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  6. Haute Autorité de Santé. Prise en charge de l’endométriose. Fiche de synthèse. Décembre 2017. ;

  7. Kanj O. Evaluation économique de la prise en charge de l’endométriose. ;

  8. Fourquet J et al. Fertil Steril 2010; 93(7): 2424–2428. ;

  9. Kiesel L et al. Climacteric 2019;22(3):296-302.

  10. Nisenblat V et al. Cochrane Database Syst Rev 2016;2016 (5):CD012179. ;

  11. Baulande S et al Medsci 2014; 30 : 289-296 ;

  12. Agrawal S et al.Int J Mol Sci 2018;19(2):599

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