Association of Ultrasound Features of the Myometrium Suggestive of Adenomyosis and Clinical Symptoms

Association of Ultrasound Features of the Myometrium Suggestive of Adenomyosis and Clinical Symptoms (MUSA 3)

The goal of this study/research is to assess the relationship between ultrasound features of the myometrium suggestive of adenomyosis and clinical symptoms of adenomyosis and to establish a reporting system for adenomyosis assessing disease severity. Consecutive pre- and perimenopausal symptomatic and asymptomicasymptomatic women with an uterus presenting for gynaecological ultrasound exams will be asked to participate in the study. Routine gynecologicalgynaecological ultrasound exams will be performed and study participants will fill out a questionnaire on their symptoms (if any) and bleeding pattern. There will be one visit and no interventions.

In adenomyosis endometrial tissue is embedded in the myometrium of the uterus. It is considered a relevant benign, underreported disease of the uterus and is a frequent cause of dysmenorrhea, bleeding disorders and abdominal pain and subfertility. The reference standard for diagnosis is histology, but the majority of women will have hormonal medical treatment, are in the reproductive age and will not undergo surgery (i.e. hysterectomy). Today ultrasound has become the first line imaging method for diagnosis.

The proportion of women that show ultrasound features of adenomyosis without symptoms is unknown but a third of young, nulliparous women without other associated disease will show signs of adenomyosis.

The MUSA consensus describes ultrasound features suggestive of adenomyosis: asymmetrical thickening of the myometrium, cysts within the myometrium, echogenic subendometrial lines and buds, hyperechoic islands, fan shaped shadowing and an irregular or interrupted junctional zone. More recently the MUSA criteria have been specified further and now distinguish between direct features, that are typical for adenomyosis and indirect features that result from ectopic endometrium in the myometrium.

This is a cross sectional exploratory non-interventional observational multicenter study with one visit and no interventions with assessment of participant demographics, standardized assessment of bleeding, standardized assessment of pain, standardized ultrasound exam.

The primary objective of the study is to assess the relationship between MUSA-defined ultrasound features of the myometrium suggestive of adenomyosis and the severity of clinical symptoms, specifically pain (NRS) and abnormal uterine bleeding (PBAC).

Secondary objectives are:

• to identify which individual ultrasound features best explain variation in symptom severity scores.
• to estimate the prevalence of ultrasound features in different subgroups of women, including symptomatic and asymptomatic participants.
• to develop an exploratory ultrasound-based grading system for adenomyosis that integrates MUSA features with clinical symptom severity.

The participants are consecutively enrolled at the sites when they present for a scheduled gynecologic ultrasound exam, fit the inclusion criteria, and do not have any positive exclusion criteria.

The files or referrals of the participants will be screened for eligibility at the participating site's department. Participants will be included if they have signed the consent for the study (ideally prior to the ultrasound exam, but recruitment after the routine exam is also possible). Since the ultrasound data is assessed within routine care the additional exam time for the participants should be almost unchanged. The filling out of the questionnaire for assessment of pain and bleeding will take some extra time (10-15min). The clinical and ultrasound data will be entered into the electronic patient file immediately by the examiner and the transfer into the data miner will occur within one month of the ultrasound exam by the examining physician or a member of the study team.

The investigators plan to include 1000 participants from at least seven centres in Europe and Switzerland. Out of that the investigators plan to include 400 from Switzerland. The study duration is estimated to be three years.

Inclusion Criteria:

• Women of pre- and perimenopausal age presenting for gynaecologic ultrasound exam giving voluntary informed written consent.
• Symptomatic and asymptomatic women
• Patients with hormonal contraceptives and Hormone Replacement Therapy (HRT) can be included, but information will be noted.

Exclusion Criteria:

• Missing written consent (study consent)
• Any serious underlying medical, psychiatric or psychological condition, which may interfere with the patient's capacity of discernment.
• Postmenopausal women
• Pregnancy
• History of pelvic urogynaecologic surgery (TVT, mesh surgery, etc.)
• Malignancy or premalignancy of uterus/cervix
• Prior myomectomy for FIGO 3-6 fibroids
• Patients with coagulation disorders under current anticoagulation medication
• Prior history of diagnosed intraabdominal adhesions (surgery)
• Prior diagnosis of pelvic congestion syndrome
• Psychiatric disease precluding a reliable estimation of pain
• Prior surgery or treatment for deep infiltrating endometriosis
• Acute other symptoms:
• Urinary symptoms (dysuria, urgency, grade III stress incontinence)
• Acute of chronic pelvic infection (cervicitis, endometritis, salpingitis, frozen pelvis)
• Ovarian lesions
• Sonographic signs of deep infiltrating endometriosis (DIE)
• Intracavitary pathology (Fibroid 0-2, polyp, adhesions)
• Retained products of conception
• >3 small fibroids below 2 cm in largest diameter FIGO 3-8 (i.e. the presence of three fibroids below 2cm is NOT considered an exclusion criterion)
• Presence of any fibroid >2cm.