Follicle Activation by Inhibition of the Hippo Pathway

January 29, 2020 updated by: Anders Nyboe Andersen

Auto-transplantation of Fragmented Ovarian Cortical Tissue in Infertile Patients With Premature Ovarian Oocyte Depletion - a Study to Promote Follicular Activation and Subsequent Fertility

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 39 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Biopsy at Right side
Biopsy of ovarian cortical tissue (50% right side)
Procedure: Biopsy of ovarian cortical tissue
Biopsies will be taken from either right or left side. The cortical tissue will be isolated and fragmented in 1x1 mm2 pieces, followed by auto-transplantation to a peritoneal pocket.
Experimental: Biopsy at Left side
Biopsy of ovarian cortical tissue (50% left side)
Procedure: Biopsy of ovarian cortical tissue
Biopsies will be taken from either right or left side. The cortical tissue will be isolated and fragmented in 1x1 mm2 pieces, followed by auto-transplantation to a peritoneal pocket.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of follicles > 12 mm
Time Frame: 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
Up to 6 month after the auto-transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Side of ovulation
Time Frame: 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
Up to 6 months after auto-transplantation

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
AFC count
Time Frame: Up to 10 month after auto-transplantation
Number of antral follicles (AFC) at the biopsy side versus that of the contralateral side
Up to 10 month after auto-transplantation
AMH changes
Time Frame: Up up to 10 month after auto-transplantation
Changes (increase - decrease) in serum AMH over time, using the highly sensitive new AMH Assay (Elecsys Assay; Roche), which has been implemented as a routine analysis at The Department of Clinical Biochemistry Rigshospitalet in June 1st 2015
Up up to 10 month after auto-transplantation
Pregnancy
Time Frame: Through study completion, an average of 1 year
Numbers of pregnancies (spontaneously/assisted)
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Anders Nyboe Andersen

Investigators

  • Principal Investigator: Anders N Andersen, Professor, Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2016

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

January 1, 2019

Study Registration Dates

First Submitted

May 23, 2016

First Submitted That Met QC Criteria

June 6, 2016

First Posted (Estimate)

June 7, 2016

Study Record Updates

Last Update Posted (Actual)

January 30, 2020

Last Update Submitted That Met QC Criteria

January 29, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-15011975

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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