Human fertility control by transvaginal application of quinacrine on the fallopian tube.

The development of a technic for noniurgical steri l ization having acceptable clinical effectiveness and a minimum of undesirable side effects is one of the principal &jectiVeS of physicians who are concerned shout the demographic problems of the world. As noted by Corfman,l who recently reviewed the relevant historic aspects, transvaginal sterilization technics have been studied for more than 1 century. Froriep2 in 1849 applied silver nitrate to the cornual areas of the tubal ostia. Kocks4 in 1878 attempted to effect tubal occlusion by transuterine electrocoagulation of the ame areas. Nonspecific caustic agents such s,s phenol and solutions of iodine have been instilled into the endometrial cavity in attempts to produce tubal obstruction.5y 8 In two recent communicationss* lo we described our experiences in humans using an intrauterine instillation of a 29% solution of formaldehyde in ethanol. Our preliminary observations with this nonspecific type of caustic material suggest that they should be dissolved in ethanol before their instillation. Their combination with ethanol enhances, and possibly hastens, the coagulation_ of the endometrial proteins, thus reducing to a minimum the quantity of caustic material which may escape through the fallopian tube into the peritoneal cavity. Retention of the caustic material within the tubal lumina is thereby extended over a longer period of time, permitting * Samuel L. Siegler Lecture, presented at the 26th Annual Meeting of The American Fertility Society, March 18-21, 1970, in Washington, D. C. This work was supported in part by Grant M69.67 from The Population Council, New York, N. Y. progressive diffusion into the tubal epithelium and into the subepithelial tissues. In our previous studies we found that at least six successive monthly instillations with the formaldehyde-ethanol solution were necessary in order to effect tubal occlusion. According to the Life Table method of analysis, we calculated that the cumulative rate of pregnancy/100 women after 30 months followup in women who had been shown to have tubal occlusion was 8.7. During the period of instillations it was 8.4. There was a dropout rate of 26.0 and a total continuation rate of 45.010 (see Table 1). It is logical to assume that these same rates might prevail for other nonspecific caustic agents used in a similar manner. I The most important side effects observed in patients receiving instillations .of this type of caustic material were hypomenorrhea and amenorrhea. This indicates that the functional capacity of the endometrium is either partially or completely suppressed as a result of the instillations. Our observations also clearly indicated that this “local” functional effect was only temporary, and was invariably followed by complete restoration to normalcy. As seen in Fig. 1 the histology of the deep layers of the endometrium in these patients was normal and in subsequent biopsies showed no consistent changes.g On the other hand, histologic studies of the fallopian tubes showed rather marked fibrosis of the intramural zone (see Fig. 2). These preliminary studies prompted us