Follicle Activation by Inhibition of the Hippo Pathway

Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02792569
• Other study ID #: H-15011975
• Status: Completed
• Phase: N/A
• Start date: April 2016
• Est. completion date: January 2019

Study information

• Verified date: January 2020
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• Infertility

Intervention

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.

Locations

Country	Name	City	State
Denmark	The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Anders Nyboe Andersen

Country where clinical trial is conducted

Denmark, 

References & Publications (3)

Hsueh AJ, Kawamura K, Cheng Y, Fauser BC. Intraovarian control of early folliculogenesis. Endocr Rev. 2015 Feb;36(1):1-24. doi: 10.1210/er.2014-1020. Epub 2014 Sep 9. Review. — View Citation

Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho CH, Kawamura N, Tamura M, Hashimoto S, Sugishita Y, Morimoto Y, Hosoi Y, Yoshioka N, Ishizuka B, Hsueh AJ. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17474-9. doi: 10.1073/pnas.1312830110. Epub 2013 Sep 30. — View Citation

Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, Morimoto Y, Kawamura K. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015 Mar;30(3):608-15. doi: 10.1093/humrep/deu353. Epub 2015 Jan 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AFC count	Number of antral follicles (AFC) at the biopsy side versus that of the contralateral side	Up to 10 month after auto-transplantation
Other	AMH changes	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
Other	Pregnancy	Numbers of pregnancies (spontaneously/assisted)	Through study completion, an average of 1 year
Primary	Number of follicles > 12 mm	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	Side of ovulation	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