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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Biopsy at Right side | Experimental | Biopsy of ovarian cortical tissue (50% right side) |
|
| Biopsy at Left side | Experimental | Biopsy of ovarian cortical tissue (50% left side) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biopsy of ovarian cortical tissue | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| AFC count | Number of antral follicles (AFC) at the biopsy side versus that of the contralateral side | Up to 10 month after auto-transplantation |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anders N Andersen, Professor | Rigshospitalet, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital | Copenhagen | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24082083 | Background | 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. | |
| 25202833 |
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| ID | Term |
|---|---|
| D007246 | Infertility |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
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| Up up to 10 month after auto-transplantation |
| Pregnancy | Numbers of pregnancies (spontaneously/assisted) | Through study completion, an average of 1 year |
| 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. |
| 25567618 | Background | 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. |
| 31593582 | Derived | Lunding SA, Pors SE, Kristensen SG, Landersoe SK, Jeppesen JV, Flachs EM, Pinborg A, Macklon KT, Pedersen AT, Andersen CY, Andersen AN. Biopsying, fragmentation and autotransplantation of fresh ovarian cortical tissue in infertile women with diminished ovarian reserve. Hum Reprod. 2019 Oct 2;34(10):1924-1936. doi: 10.1093/humrep/dez152. |