Follicle Activation by Inhibition of the Hippo Pathway
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Other Outcome Measures
- AFC count [Up to 10 month after auto-transplantation]
Number of antral follicles (AFC) at the biopsy side versus that of the contralateral side
- AMH changes [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
- Pregnancy [Through study completion, an average of 1 year]
Numbers of pregnancies (spontaneously/assisted)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Infertility with indication for IVF/ICSI
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Imminent POI, still cycling
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Age 25 - 39 years
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Two ovaries
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Serum AMH measurements < 5 pmol/l (two independent measurements)
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Antral follicle count (AFC) (sum of both ovaries < 5)
Exclusion Criteria:
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Ovarian pathology (endometriosis, cysts)
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Known chromosomal abnormality
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Known autoimmune disease (except TPO-antibodies)
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Patients who have contraindication for laparoscopy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital | Copenhagen | Denmark | 2100 |
Sponsors and Collaborators
- Anders Nyboe Andersen
Investigators
- Principal Investigator: Anders N Andersen, Professor, Rigshospitalet, Denmark
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- H-15011975