Quinacrine sterilization: a retrospective.

OBJECTIVE: To trace development of quinacrine sterilization (QS). METHODS: Review of published reports. RESULTS: The high prevalence of septic abortion among high parity women in Santiago, Chile, motivated Zipper to find a safe, inexpensive method of non-surgical female sterilization. Various cytotoxic drugs were tried in rats. Because quinacrine was already accepted for intrapleural injection it was chosen for the first clinical trial. A slurry consisting of quinacrine and xylocaine was instilled into the uterine cavity with a transcervical syringe. Reasonable efficacy was noted and a limited scar of the intramural tube demonstrated. However, a side effect of cortical excitation and reports of 3 deaths ended this approach. Zipper and Wheeler hypothesized that the difficulty was due to rapid absorption of quinacrine under pressure and designed a pellet form that dissolves slowly and could be delivered transcervically using a modified IUD inserter. A standard protocol of 252 mg in seven 36 mg pellets placed at the uterine fundus on two occasions a month apart has now been widely used with considerable evidence for safety and efficacy. Indeed, protection is greater than 98% at 2 years of use. CONCLUSION: QS is ready for widespread use, especially where surgical sterilization is not safely available or when women are poor candidates for surgery or have such a fear of surgery that they will not seek surgical sterilization.

25 years of quinacrine sterilization experience in Chile: review of 2,592 cases.

OBJECTIVES: To assess short-term side effects, long-term risks and efficacy of quinacrine sterilization (QS) in Chile. METHODS: Review experience of 2,592 cases sterilized with 2 or 3 transcervical insertions of 252 mg quinacrine as pellets since 1977; review the Chilean pre-clinical experience and epidemiological studies on cervical, endometrial and other cancers. RESULTS: Among 2,592 women who underwent QS, the total number of pregnancies was 119 (4.6%); 59 (49.5%) were carried to term with no birth defects related to QS. Nine cases were ectopic pregnancies. The ectopic pregnancy risk per 1,000 woman-years was 0.41, similar to that for surgical sterilization. The cumulative life-table pregnancy rates per 100 women at 10 years varied from 5.2 to 6.9. Mild and transient side effects were reported in 13.5% of quinacrine intrauterine insertions and pelvic inflammatory disease was diagnosed in 4 cases (0.15%). Long-term follow-up of quinacrine-sterilized patients shows no increased risk of cervical, endometrial or other cancer. CONCLUSIONS: QS efficacy at 10 years is comparable to widely accepted tubal clip and single point bipolar electrocoagulation laparoscopic procedures. QS has a low risk of serious, immediate side effects. No long-term risks have been identified after 25 years of use.

25 years of quinacrine sterilization experience in Chile: review of 2,592 cases.

OBJECTIVES: To assess short-term side effects, long-term risks and efficacy of quinacrine sterilization (QS) in Chile. METHODS: Review experience of 2,592 cases sterilized with 2 or 3 transcervical insertions of 252 mg quinacrine as pellets since 1977; review the Chilean pre-clinical experience and epidemiological studies on cervical, endometrial and other cancers. RESULTS: Among 2,592 women who underwent QS, the total number of pregnancies was 119 (4.6%); 59 (49.5%) were carried to term with no birth defects related to QS. Nine cases were ectopic pregnancies. The ectopic pregnancy risk per 1,000 woman-years was 0.41, similar to that for surgical sterilization. The cumulative life-table pregnancy rates per 100 women at 10 years varied from 5.2 to 6.9. Mild and transient side effects were reported in 13.5% of quinacrine intrauterine insertions and pelvic inflammatory disease was diagnosed in 4 cases (0.15%). Long-term follow-up of quinacrine-sterilized patients shows no increased risk of cervical, endometrial or other cancer. CONCLUSIONS: QS efficacy at 10 years is comparable to widely accepted tubal clip and single point bipolar electrocoagulation laparoscopic procedures. QS has a low risk of serious, immediate side effects. No long-term risks have been identified after 25 years of use.

Quinacrine sterilization: a retrospective.

OBJECTIVE: To trace development of quinacrine sterilization (QS). METHODS: Review of published reports. RESULTS: The high prevalence of septic abortion among high parity women in Santiago, Chile, motivated Zipper to find a safe, inexpensive method of non-surgical female sterilization. Various cytotoxic drugs were tried in rats. Because quinacrine was already accepted for intrapleural injection it was chosen for the first clinical trial. A slurry consisting of quinacrine and xylocaine was instilled into the uterine cavity with a transcervical syringe. Reasonable efficacy was noted and a limited scar of the intramural tube demonstrated. However, a side effect of cortical excitation and reports of 3 deaths ended this approach. Zipper and Wheeler hypothesized that the difficulty was due to rapid absorption of quinacrine under pressure and designed a pellet form that dissolves slowly and could be delivered transcervically using a modified IUD inserter. A standard protocol of 252 mg in seven 36 mg pellets placed at the uterine fundus on two occasions a month apart has now been widely used with considerable evidence for safety and efficacy. Indeed, protection is greater than 98% at 2 years of use. CONCLUSION: QS is ready for widespread use, especially where surgical sterilization is not safely available or when women are poor candidates for surgery or have such a fear of surgery that they will not seek surgical sterilization.

Pregnancy rates among Chilean women who had non-surgical sterilization with quinacrine pellets between 1977 and 1989.

We describe cumulative pregnancy probabilities among women who underwent quinacrine pellet sterilization in Chile between 1977 and 1989 (N = 1492). We interviewed the women or relatives in 1991-93 and 1994-96, and reviewed hospital records. Mean follow-up was 9.6 years (median 9 years). We recorded 120 pregnancies, including 40 that went to term or near-term. There were nine adverse outcomes in eight infants: one fetal death at 18 weeks gestation; three infants born prematurely; one stillbirth (placental infarct); and four infants with birth defects. There was no clustering of any particular kind of birth defect. For two insertions, the 10-year cumulative pregnancy probability was 8.9 (95% confidence interval 3. 7, 14.1). For 3 insertions, the 10-year rate was 7.0 (4.4, 9.5). For women who were under 35 years at insertion, the 10-year rate was 10. 7 (7.4, 14.1). For women who were 35 or older at insertion, the 10-year rate was 3.1 (0.6, 5.7). The pregnancy rate varied little for 2 vs. three insertions, but the rate did vary significantly by age, with women who received quinacrine at 35 years or older 0.3 (0. 2, 0.5) times as likely to become pregnant as younger women. The 10-year cumulative ectopic pregnancy probabilities for women with two and three insertions of quinacrine were 0.9 (<0.1, 2.6) and 0.5 (<0.1, 1.2), respectively. Pregnancy rates after quinacrine insertion are higher than after surgical sterilization, but ectopic pregnancy rates appear similar.

Cancer risk among women sterilized with transcervical quinacrine in Chile: an update through 1996.

OBJECTIVE: To determine whether further follow-up of a cohort of Chilean women would demonstrate an increased risk of invasive cancer associated with quinacrine sterilization. DESIGN: Cohort study. Cancer cases were evaluated using cohort analyses. SETTING: Santiago and Valdivia, Chile. SUBJECT(S): Fourteen hundred ninety-two women who received transcervical quinacrine pellets for contraceptive sterilization between 1977 and 1989. METHOD(S): Interviews and reviews of medical records. MAIN OUTCOME MEASURE(S): Age- and site-specific incidence of invasive cancers. RESULT(S): During 13,444 person-years of follow-up, 25 invasive cancers were identified, including 8 new cases. This compares with 21.9 expected cancers, based on age-specific rates from the Cali, Colombia, cancer registry. Eight cases of cervical cancer were observed, compared with the 6.3 expected. Since the initial study's confirmation of a single case of leiomyosarcoma, no other noncervical uterine cancers have been diagnosed. The number of observed person-years gives an expectation of 0.62 noncervical uterine cancers. One case of ovarian cancer was diagnosed, compared with the 0.99 expected. CONCLUSION(S): Rates of cancer among women exposed to intrauterine quinacrine are not significantly different from population-based rates.

Opposing effects of quinacrine and chloroquine on the development of TA3 transplanted tumors in mice.

Both quinacrine and chloroquine had been used as antimalarial agents. Furthermore, antineoplastic and antiviral effects have been described for quinacrine, while chloroquine has been described to induce viral replication and promote tumor growth. To search for differences in the growing rate of transplanted tumors, chloroquine or quinacrine were administered orally to AJ mice from 30 days previous to the inoculation of TA3 transplantable tumor cells, treatment being continued up to the end of the experiment. A control group, transplanted with tumor cells received tap drinking water. Marked differences between the three groups were found. Quinacrine had antitumoral effect, while chloroquine promoted a faster tumoral growth than controls. (p < 0.01). Results suggest caution in the use of chloroquine, because it might have a similar promoting effect on human neoplasia.

Opposing effects of quinacrine and chloroquine on the development of TA3 transplanted tumors in mice

Both quinacrine and chloroquine had been used as antimalarial agents. Furthermore, antineoplastic and antiviral effects have been described for quinacrine, while chloroquine has been described to induce viral replication and promote tumor growth. To search for differences in the growing rate of transplanted tumors, chloroquine or quinacrine were administered orally to AJ mice from 30 days previous to the inoculation of TA3 transplantable tumor cells, treatment being continued up to the end of the experiment. A control group, transplanted with tumor cells received tap drinking water. Marked differences between the three groups were found. Quinacrine had antitumoral effect, while chloroquine promoted a faster tumoral growth than controls. (p < 0.01). Results suggest caution in the use of chloroquine, because it might have a similar promoting effect on human neoplasia

[Standardized rates of incidence and prevalence of cervical preclinical pathology in 1,061 women sterilized with intrauterine quinacrine]. / Tasas estandarizadas de incidencia y prevalencia de patologia cervical preclínica en 1061 mujeres esterilizadas con quinacrina intrauterina.

The use of intrauterine quinacrine, as a esterilization method in women during the period of fertility age, demonstrated no relation whatsoever with increase in cervical cancer comparative with the rest of the population. This study was done in 1061 patients.

[Non-surgical female sterilization using quinacrine: efficacy of two insertions of quinacrine pellets]. / Stérilisation féminine, non chirurgicale avec l'emploi de quinacrine: efficacité de deux insertions de pellets de quinacrine.

In a group of 159 women at Santiago du Chili, fertility control by means of chemical occlusion of the utero-tubular junction was assessed. Two transcervical intra-uterine insertions of 216 mg of quinacrine, carried out at an interval of one month and associated with 50 mg of intra-uterine diclofenac and 150 mg of intra-muscular diclofenac resulted in a pregnancy rate after 12 months of 2.1 per 100 women and a Pearl index of 1.63 at 27 months after the sterilization process. The complications and adverse events appear to be similar to those which occur during insertion of an IUD and were minor and transient, disappearing within a few hours or at most 2 days after the procedure.

PIP: A group of 147 women participated in a study of outpatient tubal occlusion with quinacrine pellets at a hospital in Santiago, Chile. Six pellets, each containing 36 mg of quinacrine, were inserted transcervically into the uterus by means of a plastic tube in a procedure resembling IUD insertion. The women also received 50 mg of intrauterine diclofenac and 150 mg of intramuscular diclofenac. The initial procedure was carried out within the first postmenstrual cycle week, and was repeated at the same cycle phase on month later. No procedures were done within 42 postpartum days. The study women were 34.9 years old an average and had an average of 4.9 living children. Of the 159 patients who completed the two scheduled insertions, 140 were followed for 27 months and the other 19 were lost to follow-up. Three women became pregnant within two years. The Pearl index was 1.63 for 2198 woman-months. The percentages of pregnancies were 0.62 for the first year and 1.25 for the second year. None of the pregnancies was ectopic. One pregnancy was terminated by a medical abortion, and the patient was surgically sterilized. No abnormality was observed during laparotomy. The other two pregnancies terminated in normal delivery of healthy infants. Twenty women had adverse reactions during the 24 months of observation, but most were minor. No hospitalization or additional surgical procedures were required. Three women had post-insertion metrorrhagia, which lasted a maximum of two days.

Evaluation of Copper I IUD's.

The development of the Copper 1 IUD (Cu 1) was an attempt to decrease the incidence of unpleasant side effects (primarily pain and bleeding) associated with IUD use, by reducing the size of the vector carrying the copper. The Cu 1 consists of a straight stem with crossarms in an "X" configuration, designed to anchor the IUD in place. The device was tested in 98 interval women in the Hospital Barros Luco in Santiago, Chile who were asked to return at 1, 3, 6, and 12 months post-insertion for follow-up examinations. There was only 1 removal for bleeding and pain; however, both pregnancy and expulsion rates were high at 9.0 and 16.0 respectively after 12 months. The crossarms did not keep the device in place as expected. The high pregnancy rate may have been due to the reduced size of the IUD and to increased displacement/expulsion. Future efforts to decrease IUD size will be dependent on designing an IUD which will be less easily expelled or displaced.

IUD insertions by midwives: five years' experience in Santiago, Chile.

This report includes data on insertions of Lippes Loop D, Copper-7, and Copper-T intrauterine devices (IUDs) performed by certified nurse-midwives and physicians with comparable levels of training and experience in inserting IUDs. Net 1-year pregnancy, expulsion, and removal rates were used to compare the experiences of the 2 groups. There were no significant differences between the groups in most of the event rates or in the overall method discontinuation rates. The authors conclude that, with adequate training and experience, nurse-midwives can provide this family planning service with no additional risk to patients.