Efficacy and histological changes following collagen plug closure of fetoscopic access ports in the Rhesus monkey

Abstract

FETOSCOPIC ACCESS PORTS IN THE RHESUS MONKEY JAN DEPREST, WOUT FEITZ, LIESBETH LEWI, ELINE POLIARD, ROLAND DEVLIEGER, ALEX HANSSEN, PAUL VAN DEN BERG, KU Leuven, Centre for Surgical Technologies, Leuven, Belgium, University Medical Center Nijmegen, Urology, Nijmagen, Netherlands, Katholieke Universiteit Nijmegen, Dierenlaboratorium, Nijmegen, Netherlands, University Medical Center Nijmegen, Obstetrics and Gynecology, Nijmegen, Netherlands OBJECTIVE: In rabbits we demonstrated that collagen-plugs (Gratacos, AJOG 2000) prevent consequences of iatrogenic PPROM. We evaluated efficacy, fetal side effects and histological changes following collagen plug closure of fetoscopic cannulation in a non-human primates. STUDY DESIGN: 10 Rhesus monkeys (Macaca mulatta) underwent @88-105 d a standardized fetoscopy and partial amnioexchange using two 3mm cannulas. Port sites were randomly assigned to closure with collagen plug (n Z 6) or left for spontaneous closure (normal; n Z 4). At 140 d cesarean section (CS) was performed to evaluate membrane integrity and harvest port sites.Outcome measures were amniotic fluid index (AFI) before and 1 week after fetoscopy and at CS, PPROM, membrane appearance and fetal side effects. Microscopy included morphology and immunohistochemistry (Ki-67 for proliferation, cytokeratin as epithelial marker and CD68 for macrophages). RESULTS: None miscarried, showed amniorrhexis or amniotic bands and all fetuses survived. In 9/12 (75%) plugged sites the membranes were clinically sealed; 5 with apparent intact membranes and 4 with visible plug in the defect. The 3 others had a membrane defect without visible plug. In controls, 3/8 ports sealed (37%), while in 5 a persistent defect was present (P Z .09). AFI dropped from 6.2 (3.0–12.2) to 3.0 (0-7.2) at CS in all (P .004) without difference between groups. One plugged subject had membrane separation and oligohydramnios. In the 4 with plug in the defect, membranes were on histology not restored. The plug was invaded with cytokeratin-negative cells and macrophages. At the interface there were more macrofages, small blood vessels and increased proliferative activity around the site. CONCLUSION: Collagen plugs sealed in 75% vs 37% in controls. Small numbers and low incidence of iPPROM may explain absence of significant differences. There were no fetal side effects. Despite clinically and functionally effective sealing there was no true membrane restoration and decrease in AFI. Healing response consists of fibroblast invasion, mild inflammation and angiogenesis. S100 SMFM Abstracts