title: Contraceptive efficacy and safety studies of a novel microemulsion-based lipophilic vaginal spermicide.
abstract: OBJECTIVE
  To investigate the in vivo contraceptive potency and safety of a novel microemulsion-based lipophilic vaginal spermicide.
  
  
  METHODS
  In vitro and in vivo spermicidal activity and safety of a submicron-particle-size, lipophilic gel-microemulsion (GM-4).
  
  
  METHODS
  Center for Advanced Preclinical Sciences at the Parker Hughes Institute.
  
  
  METHODS
  Nine male volunteer sperm donors.
  
  
  METHODS
  Motile human sperm in semen and medium were exposed to eight GM-4 components or GM-4 formulation. Forty-eight ovulated NZW rabbits in subgroups of 16 with or without intravaginal administration of GM-4 or nonoxynol-9 gel (N-9; Gynol II) were artificially inseminated and allowed to complete pregnancy. Eleven rabbits were exposed to daily intravaginal application of GM-4 with and without N-9 for 10 consecutive days. Ten of 20 B(6)C(3)F(1) mice were given repetitive intravaginal application of GM-4 for 5 days/week over 13 consecutive weeks.
  
  
  METHODS
  The motility of human sperm treated with GM-4 components and GM-4. Term pregnancy in rabbits and histopathological grading of rabbit vaginal tissue for irritation. Evaluation of mice for survival, growth, hematologic parameters, blood-chemistry profiles, absolute and relative organ weights, and histopathology.
  
  
  RESULTS
  The individual components of GM-4 lacked spermicidal activity in human semen, whereas the GM-4 formulation containing all the eight pharmacological excipients exhibited potent spermicidal activity with rapid kinetics. GM-4 showed remarkable contraceptive activity in the rigorous rabbit model. None of the 16 (0%) rabbits given GM-4 intravaginally before artificial insemination became pregnant. By contrast, 15 of 16 (93.7%) control rabbits and 5 of 16 (31.2%) Gynol II-treated rabbits became pregnant and delivered newborns. Thus, GM-4 was a significantly more effective contraceptive than a commercially available N-9 gel [100% vs. 68.7% protection; P< 0.05, Fisher's exact test]. Unlike the rabbits treated with N-9, none of the rabbits that were given GM-4 intravaginally for 10 consecutive days developed epithelial ulceration, edema, leukocyte influx, or vascular congestion characteristic of inflammation. Furthermore, repeated intravaginal application of GM-4 for up to 13 weeks in mice had no adverse effects on survival, growth, metabolism, or organ function.
  
  
  CONCLUSIONS
  We conclude that the novel spermicidal GM-4 formulation is safe and significantly more effective than N-9 in preventing conception.
authors.affiliation: Department of Reproductive Biology, Parker Hughes Institute, St. Paul, Minnesota 55113, USA. odcruz@ih.org
authors.forename: O J
authors.initials: OJ
authors.lastname: D'Cruz
authors.forename: S H
authors.initials: SH
authors.lastname: Yiv
authors.forename: B
authors.initials: B
authors.lastname: Waurzyniak
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002624:Chemistry, Clinical; D002627:Chemistry, Physical; D004655:Emulsions; D005260:Female; D005782:Gels; D066298:In Vitro Techniques; D007509:Irritants; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D011247:Pregnancy; D011817:Rabbits; D013081:Sperm Motility / Q000187:drug effects; D013089:Spermatocidal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D004655:Emulsions; D005782:Gels; D007509:Irritants; D013089:Spermatocidal Agents