Polidocanol induced tubal occlusion in nonhuman primates: immunohistochemical detection of collagen I-V

Abstract

ObjectiveIntrauterine administration of polidocanol foam (PF) can create fallopian tube occlusion in nonhuman primates. The objective of this study was to determine if PF-induced tubal obstructions contain collagen in the extracellular matrix.Study designWe compared tissue samples of the intramural fallopian tube obtained from previous studies evaluating the effects of intrauterine infusion of 5% PF 2–12 weeks after treatment. Serial sections of the intramural portion of the fallopian tube obtained from representative treated (rhesus macaques, n=7; baboon, n=11) and untreated control (macaque, n=3; baboon, n=5) animals were stained with hematoxylin and eosin to identify tubal occlusion and by immunohistochemistry for collagens Col-I, Col-III and Col-IV. Descriptive results are summarized.ResultsControl animals exhibited histologically normal fallopian tubal epithelium with no staining for Col-1, light staining for Col-III and Col-V in the lamina propria and Col-IV distributed evenly in the extracellular matrix of the lamina propria. Treatment with PF resulted in acute tissue damage confined to the intramural tube; no epithelial damage or occlusion occurred in the tubal isthmus or ampulla. Blockade of the intramural tube demonstrated fibrosis with the epithelium replaced with extracellular matrix that stained strongly for Col-I, Col-III, Col-IV and Col-V. Col-II was undetectable.ConclusionTubal blockage induced by PF resulted in loss of normal epithelium and accumulation of collagens Col-I, Col-III, Col-IV and Col-V at the site of obstruction. The presence of dense collagen staining supports the hypothesis that PF infusion creates lasting tubal obstructions.ImplicationsThis study demonstrates that PF-induced tubal occlusion results in deposition of collagens suggesting the potential for a more lasting blockade. The structural nature of this occlusion supports the development of intrauterine administration of PF as a nonsurgical method of permanent contraception.

Tubal patency during the menstrual cycle and during treatment with hormonal contraceptives: a pilot study in women

“…Our long-term goal is to develop a low-cost, non-surgical approach to female permanent contraception. We have shown that a single treatment with 5% polidocanol foam results in a permanent collagen occlusion of the intramural Fallopian tube in non-human primates ( 7 , 8 ) and female baboons successfully treated do not become pregnant ( 9 ). However, not all females treated with polidocanol foam develop bilateral occlusion after a single treatment as is the case with quinacrine sterilization ( 3 ).…”

Update on Permanent Contraception for Women

“…Polidocanol (hydroxyl-polyethocydodecane) is a synthetic long-chain fatty acid alcohol approved by the U.S. FDA for the treatment of varicose veins [56]. This agent, when administered transcervically in baboons, caused scarring that obliterated the lumen of the oviduct, resulting in pregnancy prevention [57,58,59]. This approach has not entered human clinical trials.…”