Follicle Activation by Inhibition of the Hippo Pathway

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.

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