Vietnam conducted the largest quinacrine sterilization (QS) field trial starting in January 1989.  The first cases were performed in Namha Province as a clinical trial with side effects and hysterosalpingo- gram endpoints.  The field trial, with pregnancy failures, major complications and ectopic pregnancy as endpoints, spread rapidly over 24 provinces.  By October 1992, 31,781 cases had been performed and followed by 1307 clinicians.  Most procedures were carried out in commune health centers where follow-up was completed by our doctors who visited these centers by bicycle.

The initial procedural technique involved inserting the manually loaded device to the fundus, withdrawing it ½ cm and then advancing the plunger to deposit all pellets at the fundus.  The field trial progressed very rapidly which did not permit training in this insertion technique for all clinicians.  Some used the Copper T insertion technique resulting in a column of pellets from the fundus to the lower uterine segment.  At the time of trial analysis we were unable to differentiate between these two insertion techniques.

The results of this field trial were very satisfactory.  There were no deaths and only 8 serious complications.  Side effects as reported in one province (Table 1) were transient and readily treated.  Pregnancy failures for 2 insertion cases were 2.63 per 100 women at 1 year but approximately twice this rate for 1 insertion cases. Ectopic pregnancy incidence in Namha Province was 0.89 per 1000 woman-years of use, which is comparable to surgical sterilization experience in the USA (Table 2).

We were puzzled by the variation in efficacy of inserting clinicians (Figure 1).  Experience had little effect after 10 insertions among 32 clinicians in Namha Province who reported pregnancy failures.  But 56 clinicians experienced no pregnancy failures.  We suspected, but could not prove, that variation in failures among clinicians could be due to variation in insertion technique.  Assistant doctors and midwives had lower crude pregnancy rates than senior doctors, 3% vs. 4.5%, respectively.

The field trial continued to December 1993 when over 50,000 cases had been completed.  It was suddenly brought to a halt by the newly appointed Minister of Health when a message from WHO suggested that quinacrine might be carcinogenic.

The quinacrine sterilization (QS) method was developed by Dr. Jaime Zipper of Santiago, Chile.  The large number of septic abortions in hospitals of Chile among high parity women had convinced him of the need for a simple, permanent method of fertility control.  Several agents were tried by transcervical applications in rats.  He chose quinacrine for the first clinical trial in 1970, as it had been successfully used to control human neoplastic effusions by intrapleural administration. The first trials were a quinacrine slurry similar to the one for intrapleural application, using a syringe and canula for transcervical administration.  But pregnancy failures were high and a 2% incidence of cortical excitation was noted.  To avoid rapid intravascular absorption, a quinacrine pellet was formed for transcervical administration with a modified Copper T IUD inserter, starting in 1977.  

This change gave higher efficacy and eliminated the cortical excitation side effect.  Trials expanded in Sótero del Rio Hospital under Dr. Zipper’s direction and he was joined by trials of colleagues in Regional Hospital of Valdivia and San José Hospital in Santiago. This report summarizes experience of 2592 cases in these 3 hospitals from 1977 through 1998.  The protocols followed are noted in Table 1.  Efficacy and ectopic pregnancy rates are shown in Table 2.  Complaints and complications can be seen in Table 3.

As Chile has the longest experience with QS, long-term follow-up was initiated of 1492 women receiving QS between 1977 and 1989.  During 13,444 person-years of follow-up, 25 invasive cancers were identified in comparison to the expected number using the Cali, Colombia cancer registry that would be 21.9 for an observed/expected ratio of 1.14, 95% CI=0.74- 1.68, a statistically nonsignificant difference.  While this does not rule out quinacrine as a weak carcinogen, this is unlikely due to this drug’s widespread human use without reports of carcinogenicity.

The Chilean experience with QS includes over 30 years of basic and clinical research.  Although our experience shows a generally higher pregnancy failure rate than for surgical sterilization, we consider it acceptable in view of the lower risk of serious complications and the moderate cost of QS.  Our 10-year rate is equivalent to that of bipolar laparoscopic sterilization for younger women, a widely accepted procedure.  Ectopic pregnancy risks of QS in our experience are fewer than reported for surgical sterilization.  And what is also important, well informed women prefer QS over surgical sterilization.  We continue our interest in further development of QS, but we consider the protocols reported here as safe for routine use.

*EP:  Ectopic pregnancies
**WY: Woman-years

NB:  One or more events can be reported by each patient
There was one uterine perforation
* < 3 months
** pelvic inflammatory disease
*** probably in incubation at insertion