Nonsurgical Method Of Female Sterilization Research Articles

FHI's decision to halt development of quinacrine: why and how

Quinacrine has been studied as a method of nonsurgical female sterilization for over 25 years but does not have FDA approval for this indication. It has been the subject of controversy, and FHI's work on quinacrine is closely followed by researchers and stakeholders. For 10 years, FHI has been working toward development of an FDA-approved quinacrine product for nonsurgical sterilization.

Transcervical polidocanol as a nonsurgical method of female sterilization: A pilot study

We have studied the effects of transcervically administered polidocanol on uterine and fallopian tube morphology in Wistar rats and Rhesus monkeys. Polidocanol is a synthetic, long-chain fatty acid that is widely used as a sclerosing agent in Europe. The goal of the study was to determine whether polidocanol would safely cause tubal occlusion in an animal model. Twenty female Wistar rats and three female Rhesus monkeys underwent transcervical injection of polidocanol or physiological saline. The animals were followed for 30 days and then a lower laparotomy was performed, with excision of the entire upper reproductive tract. Specimens were subsequently examined for macroscopic and microscopic changes. Only cyclic changes were observed in the control animals of both species. Fifteen macroscopic and 37 microscopic changes were observed in the uterine horns of the 10 rats treated with polidocanol. There was no observed effect in the monkey fallopian tube. These results suggest that species differences that exist between rodents and primates may influence the effects of transcervical polidocanol. Experiments using a primate model are needed as proof of concept prior to human studies of candidate agents for transcervical tubal sterilization.

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.

Non-surgical female sterilization with quinacrine: an update

The intrauterine installation of quinacrine represents a simple, inexpensive, effective, and seemingly safe method of non-surgical female sterilization. Existing clinical data on its use are very encouraging: Results of a large study conducted in Vietnam with an overall sample of over 30,000 women showed high effectiveness; in addition, when a retrospective study was conducted in these women, cumulative 5-year pregnancy rates were estimated to be 13% in women younger than 35 years and 6.8% in the women older than 35. Overall, failure rates with quinacrine have been estimated, at 10 years, to be between 1.9 and 4 times higher than those obtainable with conventional surgical procedures of tubal interruption. Unfortunately, existing toxicology for topical use of quinacrine pellets is incomplete. This prompted an expert group convened by WHO, to comment, in 1994, that the toxicology of locally applied quinacrine is inadequate. To counter this statement the proponents of the method argue that it is unfair to apply the stringent pre-clinical requirements that are mandatory in the industrialized world, to methods utilized in countries plagued by both high fertility and high maternal mortality. This controversy will soon be resolved since conventional toxicological evaluation is now underway. In conclusion, the future of quinacrine for non-surgical female sterilization will depend on the results of long-term animal studies, as well as the retrospective human studies now being carried out.

Nonsurgical female sterilization: comparison of intrauterine application of quinacrine alone or in combination with ibuprofen

This study compares the results of nonsurgical female sterilization with quinacrine hydrochloride pellets alone or in combination with ibuprofen. From February 12 1988 to September 9 1992 150 women (group 1) aged 35 years or older underwent intrauterine application of quinacrine hydrochloride. 7 pellets of 36 mg were administered using a modified copper T IUD inserted during the early proliferative phase of two consecutive menstrual cycles. From September 11 1992 to May 14 1998 the same protocol was used in 222 women (group 2) of similar age except that 3 pellets each containing 18.5 mg of ibuprofen were added. After intrauterine application of the drugs the women lay supine with the pelvis elevated for 2 hours and were advised to use additional contraception (condom plus 5% nonoxynol-9 vaginal cream) between the first and second applications and for 2 months after the second application. The cumulative pregnancy rate after these methods of sterilization was calculated using the life table method. Overall results indicate that the 2-year and 5-year cumulative pregnancy rate signify the failure of ibuprofen to show any beneficial effects on the efficacy of quinacrine sterilization. Moreover age is a key determinant of the pregnancy rate after quinacrine sterilization. From the findings nonsurgical female sterilization such as intrauterine application of quinacrine pellets is generally less successful than surgical methods in prevention of pregnancy. Therefore attempts to improve its effectiveness should be considered.

Meeting the contraceptive and AIDS prevention needs of people living on a dollar a day.

The new millennium sees the largest cohort of young people in history entering its fertile years. Many of these people are too poor to pay the full cost of modern contraception, but the money available for subsidizing their needs is exceedingly limited. The AIDS pandemic is placing additional, unprecedented demand on already overstretched resources. Existing methods of contraception that are well established and off-patent can be produced in bulk at low cost, and will remain the backbone of future programmes. The use of misoprostol as an abortifacient is likely to spread rapidly. New methods must take into account the limitations of the health infrastructure in developing countries and the imperative of low cost. Given the constraints of money, skills and facilities, it is essential to set realistic priorities for future contraceptive research and development. It is suggested that the greatest needs are for a woman-controlled method of preventing HIV transmission and for a non-surgical method of female sterilization.

Putting an ear to the ground: where now with Quinacrine?

Quinacrine has been one focus of the search for a safe and effective method of nonsurgical female sterilization. Questions about its safety and efficacy as well as about ethics policy rights and the prioritization of resources have been raised by womens health advocates and agencies concerned with public health. Nevertheless interest in the method by researchers and donors has continued. Yet global experience shows that the users of contraceptive technologies possess perspectives necessary to successful and ethical research and introduction of any new method into general service. Without an inclusive process for discussing and resolving the many questions that continue to surround quinacrine the method is likely to face an embattled future and its pursuit may jeopardize other important efforts to make quality family planning and sterilization services available. (authors)

Quinacrine sterilization: experience among women at high risk for surgery.

A non-surgical method of female sterilization is needed because many women are at high risk of complications with standard surgical methods, especially in developing countries. Also, some women who desire sterilization refuse it for fear of surgery. To meet these special needs, we initiated a trial of quinacrine sterilization (QS), a non-surgical method involving transcervical insertion of 252 mg quinacrine as pellets by a modified IUD inserter. Diclofenac (50 mg) was inserted with the quinacrine pellets. This insertion was repeated a month later and a 150-mg injection of depo medroxyprogesterone was administered at the time of the first insertion. One hundred and thirty-four women of reproductive age entered the trial. Of these, 92 were considered to be at high risk for surgery, 27 had refused surgery, and 15 had had failed surgical sterilization. Mean follow-up was 3.46 years. No pregnancies or serious complications were experienced. The main side-effect was menstrual irregularity, due probably to the depo medroxyprogesterone injection. QS is a suitable option for women at high risk of surgical complications.

Four-year clinical evaluation of quinacrine pellets for non-surgical female sterilization.

The aim of this study was to evaluate the efficacy, safety and acceptability of two monthly transcervical applications of quinacrine 252 mg and ibuprofen 55.5 mg as pellets for non-surgical female sterilization. From August 1992 through October 1996, a prospective clinical study was conducted on 200 normal women seeking surgical sterilization voluntarily in the Family Planning Clinic of the Department of Obstetrics and Gynecology, Regency Hospital, Wonosobo, Central Java, Indonesia. Quinacrine 252 mg and ibuprofen 55.5 mg were inserted transcervically, as pellets, using a Copper T IUD insertor in the proliferative phase of two consecutive menstrual cycles. The women were followed up 6, 12, 24 and 48 months after insertion. There were no major complications during the insertion procedures, and side-effects which occurred during the use of the methods were transient. Cumulative life-table continuation rate per 100 women at four years was 0.91+/-0.02 (SE). The pregnancy failure rate was 0.04 or 4.3%. The results of this study indicate that intrauterine insertion of quinacrine pellets is a safe, acceptable and effective method of non-surgical female sterilization.

Quinacrine pellet nonsurgical female sterilization in Wonosobo, Indonesia

Objective: To evaluate the efficacy, safety, and acceptability of two monthly transcervical applications of quinacrine, 252 mg, and ibuprofen, 55.5 mg, as pellets for sterilization. Design: Prospective clinical study. Setting: Family planning clinic of a referral hospital. Patient(s): Two hundred normal women who requested sterilization and volunteered for this method. Intervention(s): Each woman received quinacrine, 252 mg, and ibuprofen, 55.5 mg, transcervically as pellets in the proliferative phase of two consecutive menstrual cycles from August 1992 to October 1993. Main Outcome Measure(s): Life-table pregnancy failure rates and incidence of complications and side effects. Result(s): The pregnancy failure rate was 2.0 per 100 women at 24 months. There were no serious complications, and side effects were transient. Conclusion(s): Intrauterine insertion of quinacrine pellets is a safe and acceptably effective method of nonsurgical female sterilization.

Quinacrine Pellet Method of Nonsurgical Female Sterilization in Iran: Preliminary Report on a Clinical Trial

An evaluation of 160 women from Tehran Iran who underwent female sterilization with quinacrine pellets in a private-practice setting indicates that this nonsurgical technique is safe and effective. 52% of acceptors were 26-35 years old; 76% had 4 or more living children. Informed consent for sterilization was obtained from both acceptors and their husbands. Two monthly doses consisting of 252 mg of quinacrine plus 50 mg of an antiprostaglandin were administered to the last 98 patients; the initial group received 3 quinacrine doses at 1-month intervals. Women returned to the facility for follow-up 1 2 and 15 days after each insertion; 1 2 3 and 6 months after the last insertion; and then annually for 3 years. By the end of the 3-year study 2 women had become pregnant (1 who received 2 doses and another who received 3 doses) for a gross pregnancy rate of 1.2%; neither pregnancy was ectopic. Although half the women experienced side effects such as lower abdominal pain (18 women) local itching (16 women) and fever for 5 or more days (14 women) these effects were restricted to the first 2 months after the procedure and easily remedied. The cost of this technique was one-tenth that of surgical sterilization. A major obstacle to more widespread use of this method in Iran is lack of knowledge within the medical community. Several study participants reported that their physicians had erroneously informed them that pellets are incapable of producing sterilization.

Experimental Nonsurgical Female Sterilization: Transcervical Implantation of Microspindles in Fallopian Tubes

A nonsurgical method of female sterilization was investigated in rabbits. A self-expanding microspindle (length 9-18 mm, diameter 1.5-2.0 mm) made from tubular metal mesh was implanted in a single fallopian tube of 12 rabbits via catheterization of a single uterus. The contralateral fallopian tube and uterus served as controls. Each rabbit was scheduled to undergo three cycles of breeding. Before delivery, absence of pregnancy on the side with the microspindle was verified with hysterography. Eight rabbits completed three cycles of breeding and pregnancy. Two rabbits had one pregnancy. Two rabbits did not conceive. Spindles were placed correctly in 11 rabbits. Successful contraception was achieved in nine rabbits, who had 25 gestations on the nonspindle side and no gestation on the spindle side. One rabbit, which received the shortest spindle, was bilaterally pregnant, indicating a failure of contraception on the spindle side. No spindles dislocated. Histologic study showed all spindles firmly embedded in the tubal wall without signs of inflammation. Microspindles of a certain minimum length have potential as a transcervically implantable, permanent intratubal contraceptive device.

Sterilization Without Surgery

This article summarizes the results of the International Workshop on Nonsurgical Methods for Female Tubal Occlusion a 3-day workshop held in Chicago in June 1982 by the Program for Applied Research in Fertility Regulation. Researchers reported on experiments with various chemical sterilants--phenol based compounds quinacrine and methoxylcyanoacrylate (MCA)--and with silicone rubber delivered by a variety of techniques. However the goal of developing a safe 95% effective method of nonsurgical female sterilization that can be performed under local anesthesia on an outpatient basis by nonphysicians preferably after only a brief training period remains elusive; either failure rates have exceeded 5% the methods safety cannot be assured the procedure is too complex or the method requires too many administrations. A technique utilizing a thick paste containing carbolic acid (phenol) which is applied to the epithelial tissue lining the fallopian tubes is described based on the treatment of 2000 women between 1972 and 1976 by Chinese physicians. Side effects include heavy perspiration; dizziness during or immediately after the procedure; nausea; some loss of appetite and vaginal discharge for up to 10 days after the procedure. Uterine perforation in 3 women and 33 cases of pelvic inflammatory disease are reported. Quinacrine used to close the tubes is reported on by Chilean and Indian physicians; its use in a pellet that slowly releases the drug into the tubes and as a liquid is described. Almost 95% effectiveness has been achieved with a quinacrine bearing IUD especially the No Gravid IUD. MCA acts by destroying the tubal epithelium as it solidifies; scar tissue replaces it as it biodegrades. Tested in New York City side effects include abdominal pain for up to 1 month; fevers; and pelvic inflammatory disease (1%). Several methods for plugging the fallopian tubes are also described which use silicone rubber. Clinical trials in the U.S. had an 82% success rate when both tubes were occluded. This method necessitates using a hysteroscope an expensive delicate fiberoptic device that requires careful handling maintenance and a significant amount of training for personnel. It may soon be approved for use in the U.S. but is seen as having limited potential in the developing world. Further research will be directed to progesterone therapy quinacrine related drugs and MCA used with muscle relaxants. (summary in FRE)

Nonsurgical Female Sterilization

The development of a safe, effective nonsurgical method of female sterilization that can be performed by paramedical personnel remains a high priority. The method should have a blind delivery system and require only one application. Methyl cyanoacrylate and quinacrine hydrochloride are the two most promising chemical agents. Quinacrine has evolved from instillations of a solution to the development of pellets to the use of an IUD vector. By using an IUD vector to deliver the quinacrine, tubal occlusion can be achieved with a reduction in total dosage and with one insertion instead of the three necessary with the solution and pellet methods.

Quinacrine hydrochloride pellets: preliminary data on a nonsurgical method of female sterilization.

The efficacy of transcervical insertions of quinacrine hydrochloride pellets to produce tubal occlusion has been evaluated in a study of 139 women in Santiago, Chile. At one year, the pregnancy rate was 3.1%, an acceptable rate for a nonsurgical method of female sterilization.