Attempts to Improve Human Ovarian Tissue Grafting with Small Intestinal Submucosa

Yossi Taieb 1,2 Benjamin Fisch 1,2 Rinat Gabbay-Benziv 1,2 Avi Ben-Haroush 1,2 Raoul Orvieto 2,3 Ronit Abir 1,2
1Infertility and IVF Unit, Beilinson Women Hospital, Rabin Medical Center
2Sackler Faculty of Medicine, Tel Aviv University
3Infertility and IVF Unit, Department of Obstetrics and Gynecolog, The Chaim Sheba Medical Center

Introduction

Slow ovarian graft neovascularization leads to follicular loss.Host treatment with melatonin with graftincubation withhyaluronan-rich biological glue+vascular endothelial growth factor A + vitamin E (host and graft treatment) improved human ovarian implantation. Small intestinal submucosa (SIS) enhanced wound healing and tissue remodeling also of ovaries.

Aim

To evaluate if SIS grafted with human ovaries can further improve the effects of host and graft treatment.

Material & Methods

Tissue was obtained from 6 girls/women. Slow frozen-thawed human ovarian samples were transplanted into immunodeficient mice divided into groups with various combinations of tissue sutured on swine SIS (Cook Biotechnology) with/without host and graft treatment. Graft survival was assessed by follicle counts, apoptosis assay, immunohistochemical studies of Ki67 [follicular proliferation] and ofplatelet endothelial cell adhesion molecule (PECAM) [neovascularization]expression.

Results

Only tissue grafted after host and graft treatment with/without SIS retained their original size. Apoptosis was low in all grafted groups as well as in the ungrafted controls. There was a slight increase in apoptosis in grafted groups without host and graft treatment (irrelevant of SIS addition). PECAM staining was identified in all grafts. Very few follicles were detected in the grafted tissues. All these follicles were in samples after host and graft treatment with/without SIS. Granulosa cell Ki67 staining was identified in all morphologically normal follicles.

Conclusions

Host and graft treatment promoted the best results after grafting. SIS supplementation did not have an additional benefit for implantation. Further studies to improve post-transplantation follicular survival are warranted.









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