RESUMO

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.

RESUMO

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.

RESUMO

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.

Assuntos

RESUMO

PIP: Scarcity of long-term funding has influenced Family Health International (FHI) to stop new animal studies on the safety of quinacrine pellets that are used in nonsurgical female sterilizations. These studies would have lasted 8 years and cost $8 million. FHI planned to examine quinacrine's potential toxicity, including life-time carcinogenicity in rodents. In the early 1980s, it sponsored toxicology studies but the US requirements for evaluating toxicity were different then. In 1994, a meeting of experts evaluated quinacrine research and FHI then decided to conduct short-term genetic toxicity tests on quinacrine. These tests proved that quinacrine causes genetic damage in vitro. FHI sent both the World Health Organization (WHO) and the US Agency for International Development (USAID) these results. FHI is presently conducting follow-up of two clinical studies in Chile (USAID-funded) and in Vietnam (Mellon Foundation-funded). A small cancer cluster promoted the follow-up study of 1492 women in Chile. One woman had developed the rare form of uterine cancer called uterine leiomyosarcoma. Data up to 1991 reveal that quinacrine did not increase the risk of cancer, but the sample size was too small to confirm quinacrine's safety relative to cancer. The Vietnamese government asked FHI to conduct a follow-up study that includes more than 2000 quinacrine acceptors and about 1500 controls. Ministry of Health providers had inserted the quinacrine pellets in the cases. Based on the findings of the original study, WHO recommended that Vietnamese officials suspend quinacrine sterilizations until more toxicologic evaluation of quinacrine could be performed.^ieng

Assuntos

RESUMO

PIP: Nonsurgical female sterilization, through use of quinacrine hydrochloride pellets inserted into the uterus, has the potential to make low cost permanent contraception accessible to the millions of women in developing countries who desire no more children but do not live close to surgical facilities or cannot spend time away from their families. Family Health International (FHI) has been studying this agent in clinical trials in Chile since 1976. The efficacy rate for 2 100-minute pellets is 95-98% at 12 months. The predominant side effects, temporary and minor, are amenorrhea of 1-3 months' duration, lower back pain, heavier menstrual bleeding, and headache. In 1990, however, FHI withdrew its Investigational New Drug application to explore the agent's toxicity, teratogenicity, and carcinogenicity. In 1989, 8 cases of cancer in 6 different anatomical sites were identified among the 572 Chilean women who had received quinacrine in clinical trials in the preceding decade. A retrospective study of 1492 Chilean women who were sterilized with quinacrine in 1977-89 revealed 17 cancer cases. Small sample sizes and the lack of cancer incidence data in Chile make it impossible to draw conclusions on the drug's carcinogenicity, but FHI will monitor this group for another 5 years. Early preclinical studies in pregnant rats and monkeys have indicated high rates of fetal death but no evidence of chromosomal damage; however, these studies must be repeated to meet new requirements, including the evaluation of bacterial gene mutation, mammalian cell gene maturation, and in vitro cytogenetics. Another research site has been Vietnam, where 31,781 quinacrine pellet sterilizations were performed in 1989-92 at the request of the government. FHI researchers are collecting data on health related outcomes as well as acceptor satisfaction, provider counseling, and service delivery among 1800 of these women and will complete its study in 1994. If the toxicology study yields favorable results, clinical trials will be repeated in the US.^ieng

Assuntos