Follicle Activation by Inhibition of the Hippo Pathway

Not Applicable

Completed

• Conditions: Infertility
• Interventions: Procedure: Biopsy of ovarian cortical tissue

• Registration Number: NCT02792569
• Lead Sponsor: Anders Nyboe Andersen

Brief Summary

The aim of this project is to activate recruitment and growth of resting primordial follicles in the ovaries of women with diminished ovarian reserve, in attempt to increase the chance to become pregnant, either naturally or after assisted reproduction.

Detailed Description

For this study investigators will carefully select 20 women with low AMH and imminent POI.

They will be randomized to have cortical ovarian biopsies taken from either the left or right ovary. The biopsies will be fragmented in 1x1 mm2 pieces and immediately auto-transplanted in a peritoneal pocket under the right ovary.

The contralateral untouched ovary will act as the control, making each woman their own control.

Follow up: each week in 2,5 months the women will be assessed by transvaginal ultrasound and hormonal status. After 2,5-6 months the women will receive a FSH stimulation cycle (rFSH 300 IU or Corifollitropin) followed by standard IVF/ICSI,

Hypothesis: the ovaries contain a pool of resting primordial follicles. By fragmentation of cortical ovarian tissue, manipulation of the local environment in the tissue will inhibit the Hippo Pathway and hereby active recruitment and growth of primordial follicles.

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2016-05-23
• Study First Submitted QC: 2016-06-06
• Study First Posted: 2016-06-07
• Primary Completion: 2018-12
• Study Completion: 2019-01
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-29
• Last Update Posted: 2020-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

• Infertility with indication for IVF/ICSI
• Imminent POI, still cycling
• Age 25 - 39 years
• Two ovaries
• Serum AMH measurements < 5 pmol/l (two independent measurements)
• Antral follicle count (AFC) (sum of both ovaries < 5)

Exclusion Criteria

• Ovarian pathology (endometriosis, cysts)
• Known chromosomal abnormality
• Known autoimmune disease (except TPO-antibodies)
• Patients who have contraindication for laparoscopy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Biopsy at Right side	Biopsy of ovarian cortical tissue	Biopsy of ovarian cortical tissue (50% right side)
Biopsy at Left side	Biopsy of ovarian cortical tissue	Biopsy of ovarian cortical tissue (50% left side)

Primary Outcome Measures

Name	Time	Method
Number of follicles > 12 mm	Up to 6 month after the auto-transplantation	Number of follicles \> 12 mm in response to controlled ovarian stimulation with corifollitropin from the biopsied ovary versus the contralateral untreated ovary

Secondary Outcome Measures

Name	Time	Method
Side of ovulation	Up to 6 months after auto-transplantation	Frequency of ovulations occurring at the "biopsy side" versus the contralateral side in the subsequent 4- 6 months

Trial Locations

Locations (1)

The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital; 🇩🇰 Copenhagen, Denmark