Next-Generation Endometriosis Diagnostics Through Comprehensive Multi-Dimensional Analysis

NCT06572852 | Recruiting

• 1 other identifier: PNRR-MCNT2-2023-12378346
• Study Type: observational
• Target: 530
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a multicentric, observational, case-control, non-profit with additional procedures. It aims to deepen the understanding of the chronic gynecological conditions of endometriosis and adenomyosis, which significantly impact women's reproductive health. Its purpose is to improve early diagnosis and personalized treatment of these conditions using a multi-omic approach, that integrates genetic, epigenetic, imaging, and endometrial receptivity data. The goal is also to refine image-based predictions through recent advancements in artificial intelligence and to study uterine extracellular vesicles to assess fertility non-invasively. The study targets patients with endometriosis and/or adenomyosis and involves women seeking fertility treatments at assisted reproduction centers, who will serve as a control population. The study comprises both prospective and retrospective components. The prospective recruitment involves the collection of blood and uterine fluid samples, while the retrospective element utilizes pre-existing biobank samples for comprehensive genetic and epigenetic analysis.

Conditions

Endometriosis; Adenomyosis

Keywords

Case-control; Retrospective; Prospective; Genetic; Endometriosis; Adenomyosis; Machine learning; Epigenetic

Outcome Measures

Primary Outcomes (2)

• Identification of epigenetic profile

  To identify specific CpG sites that exhibit differential methylation levels between endometriosis cases and controls. These methylation profiles, polygenic risk scores (PRS), and clinical questionnaire data will be used to classify cases and controls through machine learning analysis.

  2 years

• Identification of genetic profile

  In addition to the differential methylation analysis, 'high-resolution SNP genotyping' will be employed. This genotyping will adjust the methylation analysis and aid in deriving polygenic risk scores.

  2 years

Secondary Outcomes (1)

• Development and validation of a diagnostic model

  2 years

Other Outcomes (1)

• Characterization of uterine fluid extracellular vesicles (UF-EVs)

  2 years

Study Arms (5)

Cases with both endometriosis and adenomyosis

100 women diagnosed with both endometriosis and adenomyosis (cases). These participants are part of couples seeking fertility treatment at Assisted Reproduction Centers. The diagnosis of both endometriosis and adenomyosis will be made through ultrasound imaging at the IVF centers. The recruitment involves the collection of blood for genetic and epigenetic analysis, and acquiring ultrasound images for machine learning analysis.

Other: No intervention

Cases with only endometriosis

15 women diagnosed exclusively with endometriosis (cases): This subgroup consists of women who have been diagnosed with endometriosis but show no ultrasound evidence of adenomyosis. The recruitment involves the collection of blood for genetic and epigenetic analysis, acquiring ultrasound images for machine learning analysis, and collecting uterine fluid samples to study gene expression profiles through uterine fluid extracellular vesicles (UF-EVs).

Other: No intervention

Cases with only adenomyosis

15 women diagnosed exclusively with adenomyosis (cases): This subgroup includes women diagnosed solely with adenomyosis, without any ultrasonographic signs of endometriosis. The recruitment involves the collection of blood for genetic and epigenetic analysis, acquiring ultrasound images for machine learning analysis, and collecting uterine fluid samples to study gene expression profiles through uterine fluid extracellular vesicles (UF-EVs).

Other: No intervention

Controls

400 women from couples seeking fertility treatment at infertility clinics (controls): These participants, who will be part of couples attempting to conceive, will be actively seeking treatment for infertility or other gynecological symptoms. Crucially, these individuals will have undergone ultrasound screenings that have excluded the presence of endometriosis or adenomyosis. The recruitment involves the collection of blood for genetic and epigenetic analysis, and acquiring ultrasound images for machine learning analysis.

Other: No intervention

Cases of endometriosis with pre-existing genotyping data

This group will consist of 300 DNA biobanked samples from women diagnosed with endometriosis. These samples come with pre-existing genotyping data, which will be integrated into the study to provide a robust genetic baseline for comparative analyses.

Other: No intervention

Interventions

No intervention OTHER

No intervention

Cases of endometriosis with pre-existing genotyping data; Cases with both endometriosis and adenomyosis; Cases with only adenomyosis; Cases with only endometriosis; Controls

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study will involve a total of 530 participants selected from two Assisted Reproduction Centers. The participant population includes: * Group A: 100 women diagnosed with both endometriosis and adenomyosis (cases). * Group B: 15 women diagnosed exclusively with endometriosis (cases). * Group C: 15 women diagnosed exclusively with adenomyosis (cases). * 400 women from couples seeking fertility treatment at infertility clinics (controls). Additionally, Group D will consist of 300 DNA biobank samples from women diagnosed with endometriosis.

You may qualify if:

• Participants eligible for cases with endometriosis and adenomyosis, must meet the following criteria:
• Able to give informed consent for participation in the study.
• European descent.
• Confirmed diagnosis of both endometriosis and adenomyosis through ultrasound screening.
• Listed for assisted reproductive treatment, specifically within their first or second IVF cycle.
• Participants eligible for cases with only endometriosis must meet the following criteria:
• Able to give informed consent for participation in the study.
• European descent.
• Confirmed diagnosis of endometriosis with no ultrasound evidence of adenomyosis.
• Enrolled in an assisted reproductive treatment cycle involving embryo thawing.
• Participants eligible for cases with only adenomyosis must meet the following criteria:
• Able to give informed consent for participation in the study.
• European descent.
• Confirmed diagnosis of adenomyosis with no ultrasound evidence of endometriosis.
• Enrolled in an assisted reproductive treatment cycle involving embryo thawing.

You may not qualify if:

• Patients unable or unwilling to sign the informed consent
• Individuals who exhibit the presence of sactosalpinx or other uterine pathologies such as fibroids, polyps, or irregular endometrial thickening will be excluded from participation in this study.

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• AUO Renato Dulbecco: collaborator

Study Sites (2)

Azienda Ospedaliero Universitaria Renato Dulbecco di Catanzaro

Catanzaro, Catanzaro, 88100, Italy

ACTIVE NOT RECRUITING

IRCCS San Raffaele Hospital

Milan, Milano, 20132, Italy

RECRUITING

Related Publications (2)

• Giacomini E, Scotti GM, Vanni VS, Lazarevic D, Makieva S, Privitera L, Signorelli S, Cantone L, Bollati V, Murdica V, Tonon G, Papaleo E, Candiani M, Vigano P. Global transcriptomic changes occur in uterine fluid-derived extracellular vesicles during the endometrial window for embryo implantation. Hum Reprod. 2021 Jul 19;36(8):2249-2274. doi: 10.1093/humrep/deab123.

  PMID: 34190319 BACKGROUND

• Vercellini P, Vigano P, Bandini V, Buggio L, Berlanda N, Somigliana E. Association of endometriosis and adenomyosis with pregnancy and infertility. Fertil Steril. 2023 May;119(5):727-740. doi: 10.1016/j.fertnstert.2023.03.018. Epub 2023 Mar 21.

  PMID: 36948440 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

The biological samples collected for the study include blood and uterine fluid.

MeSH Terms

Conditions

Endometriosis; Adenomyosis

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Diseases

Study Officials

• MASSIMO CANDIANI

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

LUCA PAGLIARDINI

CONTACT

0226434834; pagliardini.luca@hsr.it

ENRICO PAPALEO

CONTACT

0226434310; papaleo.enrico@hsr.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 27, 2024
• Study Start: November 7, 2024
• Primary Completion: February 28, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)