Fibroids and Infertility - a Study of the Significance of Removal of Fibroids With Regard to Endometrial Receptivity (FIN)

Mechanisms of Reduced Fertility in Women With Uterine Leiomyomas

We aim to explore some of the molecular factors that reduce fertility for women with leiomyomas, taking into account leiomyoma location, size, number and vascularity. Tissue samples from the endometrium and leiomyomas will be obtained during the mid secretory phase before and 3-6 months after surgical excision for a comprehensive search for key molecular derangements.

Study Overview

• Status: Recruiting
• Conditions: Leiomyoma, Uterine
• Intervention / Treatment: Procedure: Transcervical resection of fibroids; Procedure: Myomectomy per laparoscopy or laparotomy

Detailed Description

Baseline medical information and standard questionnaire to record symptoms are collected from all participants and a gynaecological examination and a 2D and 3D vaginal ultrasonography including saline infusion sonography (SIS), if indicated, are performed. Blood samples for the biobank for extraction of germ line DNA and for identification of possible biomarkers are taken.

The women with submucosal leiomyomas will undergo hysteroscopic myomectomy and the women with intramural leiomyomas will undergo myomectomy per laparoscopy or laparotomy.

For the participants with intramural leiomyomas and the fertile/infertile controls, endometrial samples are taken with an endometrial suction curette in an outpatient setting at day 19-23 of the menstrual cycle. The endometrial sampling in the group of women with submucosal leiomyomas is being done during the hysteroscopic removal of the leiomyoma, also at day 19-23 of the menstrual cycle.

3-6 months after surgery, cycle day 19-23, endometrial samples will be taken from the women who have undergone myomectomy and ultrasound examination is being performed. The women with submucosal leiomyomas will undergo a second look hysteroscopy

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Thea F. Mikkelsen, MD; Phone Number: 004797612934; Email: themik@ous-hf.no
• Study Contact Backup: Name: Kirsten Hald, PhD; Phone Number: 004795224181; Email: UXKILD@ous-hf.no

Study Locations

• Norway
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Kirsten Hald, PhD; Phone Number: 004795224181; Email: UXKILD@ous-hf.no
    • Contact: Thea F Mikkelsen, MD; Phone Number: 004797612934; Email: themik@ous-hf.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patients referred to the Department of Gynaecology at Oslo University Hospital for treatment of submucosal or intramural leiomyomas.

Description

Inclusion Criteria:

• Age: 18 to 40 years
• Presence of leiomyoma(s)
• Regular menstrual cycle (28 +/- 7 days)
• Having had at least 2 normal menstrual cycles after ending the treatment if previously treated with GnRH analogue
• Signed informed consent

Exclusion Criteria:

• No treatment indication (no symptoms and/or no desire for fertility)
• Contraindication for surgery
• Known endometriosis
• Known PCOS
• Untreated hydrosalpinx
• Malignancy; gynaecological or other location
• Pre-malignant or malignant pap smear or endometrial biopsy
• Hormonal treatment including ulipristal acetat and levonorgestrel intrauterine device last three months before inclusion in the study
• Ongoing treatment with GnRH analogue
• Pregnancy last 3 months
• Ongoing lactation

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women with submucosal leiomyoma(s); Women with submucosal leimyomas undergoing hysteroscopical removal of the leiomyoma	Procedure: Transcervical resection of fibroids; Transcervical resection of fibroids
Women with intramural leiomyomas; Women with intramural leiomyomas undergoing myomectomy	Procedure: Myomectomy per laparoscopy or laparotomy; Myomectomy per laparoscopy or laparotomy
Infertility patients; Patients treated at the Department for Reproductive Medicine at the Oslo University hospital failing to conceive after 3 or more embryo transfers with good quality embryos.
Fertile women; Healthy, volunteering women with proved fertility with 1 or more deliveries and no history of infertility

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOXA 10 expression	Fold change of HOXA 10 Expression 3-6 months after myomectomy compared to pre-surgery Levels	3-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of other molecular markers	Fold change of other molecular markers than HOXA 10 of endometrial receptivity 3-6 months after myomectomy and compared to fertile/infertile controls	3-6 months
Endometrial vascular pattern	VI and FI of the endometrium and subendometrial myometrium of women with leimyomas 3-6 months after myomectomy and compared to fertile/infertile controls	3-6 months
Vascular characteristics of leiomyomas	Vascular characteristics of leiomyomas associated with endometrial changes	3-6 months
Leiomyoma size	Leiomyomas size in centimeters associated with endometrial changes	3-6 months
Leiomyoma location	Leiomyoma location associated with endometrial changes	3-6 months
Genomic characteristics	Genomic characteristics of leiomyomas associated with endometrial changes	3-6 months
Scar formation	Scar/fibrosis/adhesion formation after myomectomy; macroscopically and histologically	3-6 months
Pregnancy	Pregnancy and deliveries within 2 years after myomectomy.	2 years
HOXA10 in endometrium of women with leiomyomas compared to fertile/infertile controls	Difference in HOXA 10 expression in endometrium of women with leiomyomas compared to fertile/infertile controls	3-6 months
Expression of molecular markers adjacent to the leiomyoma versus remote from the leiomyoma	Difference in expression of molecular markers in endometrium adjacent to the leiomyoma compared to endometrium remote from the leiomyoma.	3-6 months
Partially resected leiomyomas	Alterations in molecular markers of endometrial receptivity after partially resected submucosal leiomyomas.	3-6 months
Submucosal leiomyomas versus intramural leiomyomas	Difference in expression of molecular markers in endometrium of women with submucosal leiomyomas compared with endometrium in women with intramural leiomyomas.	3-6 months
Biomarkers in blood	Biomarkers in blood related to leiomyomas and a possible correlation between certain biomarkers and reduced endometrial receptivity.	1 year

Collaborators and Investigators

• Sponsor: Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Anticipated): September 15, 2021
• Study Completion (Anticipated): September 15, 2024

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Infertility; Fibroid; Leiomyoma; Endometrial receptivity
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Myofibroma
• Other Study ID Numbers: 2017/9703

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No