Infertility
Conditions
Keywords
IVA, Hippo Pathway, Follicle activation, Low Responder, POI, Poor Ovarian Reserve, Poor Ovarian Response, Salvador/Warts/Hippo pathway
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.
Interventions
PROCEDUREBiopsy 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.
Sponsors
Anders Nyboe Andersen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 39 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
Denmark
Outcome results
None listed