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.
Highlights
There remains an unmet need for effective contraception worldwide
We recently demonstrated that transcervical intrauterine infusion with polidocanol foam (PF) can create tubal occlusion in nonhuman primates [9,10]
We examined tissue samples obtained from adult cycling female rhesus macaques housed at the Oregon National Primate Research Center (ONPRC) and baboons housed at the Southwest National Primate Research Center (SNPRC) used in these prior experiments. (All studies were reviewed and approved by the ONPRC and SNPRC Institutional Animal Care and Use Committees, in accord with the National Institutes of Health Guidelines for Care and Use of Laboratory Animals.) Necropsies and tissue collection were carried out on by veterinary pathologists at the ONPRC and by the pathology services unit at SNPRC after euthanasia by the attending veterinarian
Summary
There remains an unmet need for effective contraception worldwide. In developing countries, greater than 24% of married women wanting contraception lack modern methods. A recent review of data from the 2011–2013 National Survey of Family Growth revealed that, in the United States, 44.2% of women aged 35–44 years choose permanent female contraception compared to 7.6% choosing long-acting reversible methods. Even in younger women aged 25–34 years, 21.7% choose permanent female contraception compared to 16.5% who choose long-acting reversible methods [3]. Development of inexpensive nonsurgical methods of permanent contraception would greatly improve family planning for many women in low-resource settings. One approach to nonsurgical permanent contraception is the intrauterine administration of chemical agents that cause fallopian tube sclerosis and occlusion. The most studied chemical agent used to create tubal sclerosis was quinacrine hydrochloride [5,6] Development of this approach was stopped due to concerns over the potential toxicity of quinacrine [7]. The goal of this study was to characterize, by immunohistochemistry, collagen deposition in the intramural zone of the nonhuman primate oviduct after PF therapy
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