title: Blockade of tubal patency following transcervical administration of polidocanol foam: initial studies in rhesus macaques.
abstract: OBJECTIVE
  To demonstrate the feasibility of polidocanol foam (PF) as a nonsurgical method of female permanent contraception using a nonhuman primate model.
  
  
  METHODS
  Four groups of adult female rhesus macaques underwent either transcervical treatment with 5% PF directly into the uterine cavity, treatment with inert (methylcellulose, MF) foam or no treatment followed by removal of the reproductive tract for histologic evaluation. Untreated animals were included in Group 1 (n=3). Group 2 animals (n=4) were treated once with MF. Group 3 (n=7) received a single, and Group 4 (n=5) received multiple monthly treatments with PF; in these 2 groups, baseline tubal patency was assessed either laparoscopically by chromopertubation (CP) or by hysterosalpingography.
  
  
  RESULTS
  Group 1 (untreated) and Group 2 (MF) animals had normal tubal histology. In contrast, Group 3 and 4 females treated with PF showed evidence of tubal damage. In Group 4, bilateral tubal blockade was noted on CP after two (n=2) or three (n=3) treatments. Histologic analysis confirmed complete tubal occlusion (loss of epithelium, fibrosis) in three of these animals, and one showed significant tubal damage localized to the intramural segment. Nontarget (cervix, vagina, endometrium, ovary) reproductive tissues were unaffected. While similar tubal changes were observed after a single treatment (Group 3), endometrial hemorrhage was also noted as an acute change.
  
  
  CONCLUSIONS
  PF is a promising candidate agent for nonsurgical permanent female contraception. The histologic features of PF occlusion are confined to the intramural portion of the tube.
  
  
  CONCLUSIONS
  This study in rhesus macaques supports further development of transcervical administration of PF as a nonsurgical approach to permanent contraception. A nonsurgical method could reduce risks and costs associated with surgical female sterilization and increase access to permanent contraception.
authors.affiliation: Department of Obstetrics & Gynecology, Oregon Health & Science University (OHSU), Portland, OR, USA; Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA. Electronic address: jensenje@ohsu.edu.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Jensen
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Hanna
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Micks
authors.affiliation: Department of Obstetrics & Gynecology, Oregon Health & Science University (OHSU), Portland, OR, USA; Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Edelman
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Holden
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: Ov D
authors.initials: OD
authors.lastname: Slayden
mesh_terms: D000818:Animals; D002406:Catheterization, Peripheral; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004717:Endometrium / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D005187:Fallopian Tubes / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D005355:Fibrosis; D007047:Hysterosalpingography; D010535:Laparoscopy; D008253:Macaca mulatta; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D012597:Sclerosing Solutions / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D013246:Sterilization, Tubal / Q000009:adverse effects*; D014463:Ultrasonography; D014592:Uterine Hemorrhage / Q000139:chemically induced / Q000473:pathology; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D015507:Drugs, Investigational; D012597:Sclerosing Solutions; D014622:Vaginal Creams, Foams, and Jellies; D000077423:Polidocanol; D011092:Polyethylene Glycols
keywords: Female; Nonhuman primate; Nonsurgical; Sterilization; Tubal occlusion