Fibrin-based Matrix Spurs Hope for Artificial Ovary Transplantation

By Tiffany Parnell
Tuesday, May 1, 2018

A Belgian research team has developed a fibrin matrix that closely resembles human ovarian tissue. The promising result, published in the Journal of Assisted Reproduction and Genetics, brings physicians closer to making artificial ovary transplantation an option for fertility preservation following cancer treatment.

As many as 10 percent of all cancer patients receive their diagnoses prior to age 40, according to a Journal of Women’s Health articleDepending on the type and duration of therapy required to treat the cancer, these men and women may struggle with infertility after treatment.

Ovarian transplantation is an investigational method of preserving fertility that requires harvesting one ovary or a section of ovarian tissue prior to cancer treatment, freezing the tissue and reimplanting it following remission. The technique may benefit women who are not candidates for oocyte or embryo cryopreservation and for prepubescent girls, who, according to the American Cancer Society, have no other options for fertility preservation because their eggs have not matured.

Despite the promise of this technique, concerns about cancer recurrence limit the number of young girls and women who can benefit. For example, ovarian transplantation is not appropriate for young women with blood-borne cancers or cancers that may metastasize to the ovaries, such as Ewing sarcoma and neuroblastoma. Transplanting egg-producing follicles independently from ovarian tissue may resolve concerns about cancer recurrence.

“The fully isolated follicles are surrounded by a basement membrane, which excludes any possible contamination with blood cells and/or any other kind of malignant cells,” says Maria Costanza Chiti, PhD, postdoctoral fellow at the Université Catholique de Louvain, Institute of Experimental and Clinical Research, Pôle de Recherche en Gynécologie.

“[Hematologists] might have in mind that we cannot freeze ovarian tissue for leukemia patients. The message is, ‘Yes, we should freeze ovarian tissue’ because the research is evolving, and we will very soon find a solution for these leukemia patients to use that tissue.”
— Marie-Madeleine Dolmans, MD, PhD, Research Director, Gynecology Research Laboratory, Université Catholique de Louvain, Institute of Experimental and Clinical Research, Brussels, Belgium

The Artificial Ovary Prototype

To transplant follicles independently, researchers must encapsulate the follicles within a bioscaffold. Previous research indicates the clotting protein fibrin is a useful material for this bioscaffold.

“Fibrin itself is the safest material and provides an excellent matrix for follicle implantation,” says Ariella Shikanov, PhD, an Assistant Professor of Biomedical Engineering at the University of Michigan, who was not involved in the study but performs similar research.

To identify the correct fibrinogen-thrombin concentration for the bioscaffold, the Belgian researchers analyzed human ovarian tissue and then created fibrin matrices using four concentrations of fibrinogen-thrombin. They found that a concentration of 50 percent fibrinogen and 50 percent thrombin produced the most natural ovary prototype, closely mimicking human tissue in rigidity and porosity.

Subsequently, the team encapsulated human follicles within the matrix and grafted the matrix into mice. They plan to perform a similar study in a larger mammal before conducting clinical trials in humans.

“We really hope that in a few years we can have the first ovary prototype for clinical trials,” Chiti says.