Female Sterilization Using Pharmacologically Active Agents

Attempts to utilize pharmacologically active agents to close the fallopian tubes date back at least to 1849 when Froriep reported passing a cannula transcervically to the uterine tubal ostia and cauterizing the tubal lumen with a nitric acid-coated probe.14 Salgado reported in 194 1 that Brazilian midwives lavaged the uterine cavity with a mixture of tincture of iodine and carbolic acid as a contraceptive measure. 3g The procedure was designed to be temporary but in fact produced severe endometrial scarring and tubal closure that resulted in permanent sterility. The publication of Salgado’s paper prompted the midwives to abandon this technique. 4o Dieckmann and Harrod reported in 1954 that they had used sodium morrhuate as an adjunct to tubal ligation in over 200 patients in the preceding eight years. g They reported no failures. Pitkin, however, reported a 4% failure rate using a similar procedure in which sodium morrhuate was introduced into an isolated tubal segment to produce tubal sclerosis.27 Aside from these sporadic reports there was no systematic effort to develop chemically-induced tubal blockage until the 1960s. At that time, a number of groups began to explore a variety of methods for producing tubal closure, including electrocoagulation, cryotherapy, intratubal devices, and the instillation of a variety of active chemical agents. These efforts have been considered extensively in a series of monographs and individual review articles~10,13,1S,25,35,36,41,42 The active agents which have been studied for their tube-closing properties contain representatives from most major classes of toxic chemical compounds; the list includes silver nitrate, zinc chloride, formaldehyde, formalin-ethanol, paraformaldehyde, ethanol, copper sulfate, sodium lauryl sulfate, phenol, cadmium, iodoacetate, thio-TEPA, talc suspensions, podophyllin, colchicine, granuloma-producing agents, quinacrine, gelatin-resorcinol-formalin (GRF), and cyanoacrylates. Silicone rubber has also been used as a tube-occluding agent and, although its properties are principally mechanical rather than sclerotic, it will be included in this review because the delivery problems are similar to those associated with the delivery of toxic chemicals. It became clear from the initial experiments in a variety of laboratory animals that, with the possible exception of quinacrine, prolonged tubal exposure to the chemical was necessary to produce a high rate of tubal occlusion. Although strong oxidizing or reducing agents could produce extensive necrosis