RH FC1: Auto-transplantation of fragmented ovarian cortical tissue in infertile patients with low ovarian reserve – a study to promote follicular activation and fertility

This study is performed at Rigshospitalet Fertility Clinic in collaboration with Laboratory of Reproductive Medicine and Department of Gynecology.

Background
Women experience a natural decline in their pool of eggs throughout childhood, puberty and adulthood. However, around 1 % of women show an accelerated depletion of eggs, which in extreme cases result in premature ovarian insufficiency (POI) before the age of 40 years.

Women with a diminished ovarian reserve and imminent POI often experience infertility and constitute the most difficult group of infertile patients to successfully treat. One clinical problem in this group of patients is to obtain multiple follicular developments with ovarian stimulation despite the fact that the ovary still contains some resting follicles. Even extreme doses of FSH (Follicle Stimulating Hormone) only result in a very limited number of follicles and retrieved oocytes.

The so-called “Hippo signalling” serves to maintain optimal size across organs and species. When these are disrupted growth is initiated, and one theory is that the primordial follicles constitute clusters where each follicle inhibits its closest neighbour follicles. Therefore, growth is more likely to involve follicles lying in the periphery. Also, the ovarian cortex releases inhibitory factors, as growing secondary follicles typically are located closer to the medulla. Such data support that any change/disturbance of the anatomical structure of the tissue may stimulate growth of primordial follicles. It seems possible to promote follicular growth following simple physical fragmentation of murine ovarian tissue and auto-transplantation. This has resulted in an increased weight of the grafts, and a shift towards more mature stages of follicles.

Aim of the study
The aim is to test in vivo the hypothesis that fragmentation and auto-transplantation of ovarian cortical biopsies, in infertile women with diminished ovarian function, may disrupt the normal inhibitory signals on initiation of follicle growth and thus increase the number of developing follicles, resulting in an increase in the number of oocytes available for either natural conception and/or for IVF.

Results
20 patients are randomized to have biopsies taken from either the left or the right ovary. Three of the biopsies will be cut into small fragments on site in the operating theatre and the fragments will be relocated under the peritoneal serosa lying next to the biopsied ovary.

Currently we have included all patients and the biopsies were taken without complications. The procedure will be published in the official high-ranking journal of American Society of Reproductive Medicine Fertility and Sterility soon. Data is being processed and analyzed at this moment. A noticeable and surprisingly positive result is, that 50% of the women are pregnant or have given birth.

A description of the method including a video of the transplantation can be found here as well as in the publication below.

Publication: Lunding S et al. Autotransplantation of fragmented ovarian cortical tissue: a laparoscopic demonstration. Fertility and Sterility. 2018; 11(6):1181-83.

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