Contraceptive delivery in the developing world.

A strong demand for family planning exists in most developing countries and family size is falling rapidly in many of them. Effective family planning programmes offer a world-wide range of choices (including voluntary sterilisation and abortion) through a variety of distribution channels. Universal access to voluntary family planning can be achieved easily and cheaply by the turn of the century, but only if conservative medical policies are overcome and funding is greatly expanded. The international community faces a genuine choice: if it responds to current opportunities the global population will stabilize at approximately 10 billion or fewer; if it fails, population may grow to 14 billion or more. The difference between these two projections (approximately equal to the present world population of 5.4 billion) may well determine the future of the planet.

PIP: 48% of couples in the developing world use some form of contraception. The global fertility rate has fallen from a total fertility rate (TFR) of 6.1 million in the 1960s to 4.2 million in 1991. Education and employment opportunities for women, income, and urbanization are all positively correlated with smaller families. Effective, low-dose, combined oral contraceptives (OCs) are used by over 60 million women worldwide. The injectable contraceptive, Depo-Provera, is competitive in price with OCs. The new generation of implantable contraceptives, as represented by Norplant, will not gain widespread use until competition drives the price down and the present 6-rod device is simplified or biodegradable implants are developed. Modern IUDs are increasingly acceptable, but only when the woman and her partner are not exposed to the risk of sexually transmitted diseases. Voluntary surgical contraception (VSC) is the commonest single method of fertility regulation in the UK and the US. OC distribution in parts of Francophone Africa has been made contingent on tests that cost the equivalent of approximately 3 months' per capita income. In one Anglophone country, women are subjected to an unnecessary 45-minute physical examination before receiving OCs. Many family planning (FP) programs are still constrained by a close linkage to primary health care services. In Kenya, contraceptive prevalence was held at a low level because administrators had the mistaken notion that African women did not want to plan their families. International agencies should allocate funds using cost per couple year of protection. Much of the bilateral program of governments and the United Nations Population Fund is not very cost effective. The FP component has actually fallen from 2% of all foreign aid in the 1970s to less than 1% in the early 1990s, although the total cost of FP services will need to double by the year 2000.

Political constraints on contraceptive development in the United States.

PIP: In the US there is a great need for new contraceptives because the current available choices are too limited. Many groups of women, teenagers, women over 40 and lactating mothers have even greater need because of their special requirement. There are 6 million annual pregnancies in the US, 50% of them are unintended. This is the highest percentage of unintended pregnancies in the developed world with Canada having only 39%, the UK 32%, and the Netherlands 17%. 46% of women can expect to have at least 1 unintended pregnancy in their lifetime. Almost half of these unintended pregnancies end in abortion. Of those seeking abortion, 26% are under 20 and 81% are under 30. 69% are white and 82% are single. 49% of these women reported not using contraception when they conceived. Even when a woman uses contraceptives she is still exposed to the risk of contraceptive failure. These failure rates vary from 5-30% for the pill to spermicides. Over a 10-year period the rate climbs to 25-50% for the pill or the IUD. In the US, contraceptives are the most expensive with the pill selling for 60 times what is costs for similar formulations in other countries. Norplant and IUDs, the most reliable reversible methods cost hundreds of dollars and thus make them unavailable for teenagers and poor women who need them most. The primary benefit of increased contraceptive prevalence (CP) is a reduction in the number of unwanted pregnancies and thus abortions. The CP rate for married women of reproductive age in the us is 66%, compared to 73% in Canada, 83% in the UK, 78% in Sweden, and 72% in the Netherlands. The reason new methods are not being developed are multiple: fear of product liability litigation; fear of poor product sales due to public fear; regulation and market pressures that simply do not make them profitable. It can take 12 years and $200 million to develop a new drug and US patents only last 17 years. Thus in order to make a profit the company must have a high rate of sales. Changes in the approval process and financial incentives similar to those for orphan drugs could bring new methods to market.^ieng

IUDs and PID: a comparative trial of strings versus stringless devices.

An international multicentered clinical trial was designed to determine the possible role of intrauterine device (IUD) marker strings in the etiology of pelvic inflammatory disease (PID). A total of 1265 women were admitted and randomly allocated to receive either a standard TCu200 IUD or a TCu200 IUD without marker strings. These patients were followed-up through 12 months postinsertion. No statistically significant differences were found between the two groups of IUD users with respect to the incidence of PID or other types of infection or inflammation. The 12-month life table termination rates and overall continuation rates were also similar for users of the respective devices, with the exception of removal rates for bleeding/pain, which were significantly higher in the strings group than in the stringless group. However, the number of bleeding/pain complaints ever reported during the study were not statistically different in the two study groups. The study results indicate that the IUD string does not play an important role in the etiology of PID associated with the use of IUDs.

The future of hormonal contraception.

PIP: Well over 100,000,000 women have used the combined oral contraceptive (OC) pill. As a result of the population explosion in the 1970s and 1980s, there will be almost one third more women in fertile age in the year 2000 than in 1991. In the developing world outside China, the total number of contraceptive users could double in roughly 10 years. China, the total number of contraceptive users could double in roughly 10 years. The pill has a low failure rate, but one study in Egypt found that 90% of women made errors in moving from one packet to the next. Similarly, a 60% error rate was found among users in Colombia. The vaginal ring delivers combined progestogen and estrogen through a silastic wall. The device can be left in place for 21 days out of 28, and such delivery would virtually eliminate the low risk of hepatocellular carcinoma among OC users. A vaginal progestogen ring is being tested. Over 700,000 women have used Norplant, the subdermal implant method with an effectiveness rate of 99%. Depo-provera and norethindrone enanthate injections last 2 to 3 months. The Progestasert IUD, containing 38 mg progesterone released at a rate of 65 mcg per day, is effective. Progesterone-releasing IUDs lasting from 3 to 5 years could complement subdermal implants. Ethinyl estradiol (205 mg) and diethylstilbestrol (25-50 mg) have both been used as postcoital agents taken within 36 hours for 5 consecutive days after unprotected intercourse. In more than 3000 cases there were 17 pregnancies (.05%). These regimens are replaced by giving combined oral contraceptive tables (e.g., .25 mg d-norgestrel and 50 mg ethinyl estradiol), taken 2 at a time and repeated 12 hours later, within 72 hours of unprotected intercourse. Epidemiological studies have confirmed that the use of the combined oral contraceptive for 3 to 5 years halves a woman's risk of ovarian or endometrial cancer, and the protection persists for 10 to 18 years after cessation of use.^ieng

Accidental burn deaths to Egyptian women of reproductive age.

Among women of reproductive age in Menoufia, Egypt, deaths from burns constitute a major public health problem. Burns account for 9 per cent of the deaths occurring to women aged 15-49, and were the third cause of death (after disease of the circulatory system and complications of pregnancy and childbirth). Nearly two-thirds of the burns were caused by kerosene cooking stoves. The data were obtained from a population-based survey of all deaths to women of reproductive age. There were 1691 deaths from all causes during the 3 years of the study, 152 of these were due to burns. Information on the cause of death was gathered from interviews with surviving family members; interviews were reviewed by physicians and a cause of death established. Although hospital-based studies provide valuable information for the management of burn injuries presenting for treatment, establishing rates of injury, comparing the incidence in one population group relative to another, or comparing the incidence of burns relative to other forms of injury requires a population-based study.

An evaluation of the TCu 380Ag and the Multiload Cu375.

The TCu 380Ag (Outokumpu Oy, Pori, Finland) and the Multiload Cu375 (Multilan, Organon, Oss, The Netherlands) were evaluated in 1477 women in a multicenter clinical trial. The intrauterine devices showed similar, low-event rates. Cumulative life-table pregnancy rates were less than 1.0, and continuation rates were approximately 90 per 100 women at 1 year after insertion. The risk of subsequent hospitalization or pelvic infection was low.

PIP: This study evaluated the effectiveness, safety, and acceptability of the TCu 380Ag and the Multiload Cu375 IUDs in a multicenter international trial involving 1499 acceptors. The 2 devices were randomly assigned to women who entered the trial at 5 centers in Yugoslavis, Panama, Costa Rica, and Egypt between September 1980 and June 1982. The median age of the 737 women in the TCu 380Ag group was 26.7 years, with an average parity of 1.8; the median age of the 740 women in the Multiload Cu375 group was 27.5 years, with an average parity of 1.9. At insertion, 6.8% of women in the TCu 380Ag group and 6.2% of those in the Multiload Cu375 group complained of mild pain, 1.1% of women in both groups reported moderate pain, and there were no reports of severe pain. 1-year bleeding and pain removal rates were 3.8; removal rates for other medical reasons were less than 1.0/100 women. Significantly more women in the TCu 380Ag group reported intermenstrual pelvic pain, but this difference was confined to women under 30 years of age. The continuation rate at 1 year was 90.9% for the TCu 380Ag group and 88.7% for the Multiload Cu375 group. These rates are considerably higher than those reported for other IUDs. Of the 7 pregnancies reported in the 1st year after insertion, 2 occurred in the Tcu 380Ag group and 5 occurred in the Multiload Cu375 group. The results from this trial suggest that both the TCu 380Ag and Multiload Cu375 IUDs provide a highly effective, safe, and acceptable method of contraception. For women who wish to achieve contraceptive effectiveness for long periods, the TCu 380Ag may be the IUD of choice. It remains effective for 10-15 years, while the Multiload Cu375 has a life span of only 3-5 years.

Studies on membrane-active vaginal spermicides.

PIP: Spermicides have long been used for vaginal contraception. Quinine was the prototype membrane-active drug used as a vaginal spermicide. Subsequently, propranolol, in both racemic and D-isomeric forms, has been shown to be a powerful inhibitor of sperm motility. The transmembrane migration ratio method was used to quantify the effects of various drugs with membrane stabilizing activity such as propranolol on sperm motility in vitro. Preliminary data from a clinical trial suggests that propranolol tablets used as a vaginal spermicide produce a pregnancy rate of between 3-4/100 women-years in a fertile population. Propranolol is extensively absorbed from the vagina since systolic blood pressure fell below baseline values and plasma concentrations were higher after vaginal administration than after oral administration. Pulse rates also declined. The clinical implications of these studies are discussed.^ieng

Postpartum insertion of modified intrauterine devices.

The immediate postpartum insertion of standard intrauterine devices (IUDs) and those specially modified for postpartum use was evaluated in a multicenter clinical trial. The immediate postpartum insertion of IUDs was not associated with any increased risk of perforation or infection, although expulsion rates were higher than with interval insertions. The expulsion rate varied widely between centers using similar devices, suggesting that training in insertion is essential. Postpartum IUD insertions can be a practical contraceptive option for patients and providers of medical services.

PIP: The postpartum insertion of IUDs, especially in the case of institutional deliveries, has a number of advantages, including ease of insertion, availability of skilled personnel, appropriate facilities, and convenience for the mother. Immediate postpartum insertion of IUDs is not associated with increased risk of perforation or pelvic inflammatory disease (PID), although expulsion rates are higher than with interval insertions. In studies by Family Health International (FHI), expulsion rates varied widely between centers using similar devices. Expulsion rates ranged from 6-37/100 women at 6 months after insertion. This finding suggests that insertion may be as important a factor in influencing expulsion as the configuration of the device. FHI has developed modified IUDs with added suture material to project into the endometrium and reduce expulsion. After insertion the suture projections become soft and pliable and biodegrade completely within 6 weeks. Standard IUDs used for modification were the TCu and Lippes Loop. Adequate training and supervision of delivery room staff in insertion of IUDs is necessary. Midwives can betrained to insert the IUD after parturition through demonstrations and followup monitoring. Timing of IUD insertion is very important; FHI data show a significantly higher (p0.05) expulsion rate associated with insertions performed within the period of 10 minutes to 36 hours as compared to the immediate postpartum period (within 10 minutes). The use of postpartum IUDs raises questions of how much overlap there will be with the natural suppression of ovulation, especially in breastfeeding women, and whether the altered physiology of the reproductive tract interacts with the method. The inability to predict for individual women when ovulation will return, particularly among those who are breastfeeding, combined with inconvenience and sometimes impossibility of returning to a medical facility for insertion make the compromise of immediate postpartum insertion demographically effective and reasonable in many circumstances.

Where next with long-acting steroids?

PIP: A new generation of steroidal contraceptives is undergoing clinical trials or has reached the stage of national drug authority approval. In November 1983, Norplant contraceptive implants were approved for marketing in Finland as a longacting contraceptive. Norplant continues to be evaluated in large-scale clinical trials in a number of developing and developed countries. A continuous low dose of levonorgestrel is released into the woman's blood from 6 small silastic capsules implanted under the skin of the arm. A variation using 2 implants is under study. The implant systemmay be used for up to 5 years. The mechanism of action of levonorgestrel has 3 components: inhibition of ovulation in about 1/2 of cycles, suppression of the endometrium, and alteration of the cervical mucus to make it less permeable to sperm. The annual pregnancy rate is about .5/100 women. Fertility returns rapidly after removal, and the implant system has a good safety profile. The most frequent side effects in the 1st months of use are apparently menstrual irregularity or spotting, but total blood loss may be decreased. The steroid does not influence blood pressure and hasno unfavorable effect on blood lipids. The Population Council, developer of Norplant, is expected to seek US Food and Drug Administration approval on the basis of specific clinical experience. A vaginal ring consisting of a 3-layer ring of silastic containing levonorgestrel and estradiol has also been developed by the Population Council. The 2 hormones are released into the vagina at a constant rate and absorbed into the woman's blood, resulting in inhibition of ovulation. The rings imitate the action of combined oral contraceptives but do not require daily administration. The World Health Organization is also developing a vaginal ring which contains only a progestogen and is worn without a 1-week break in use. A new sustained-release formulation of norethindrone (NET) is entering expanded clinical trials in the US and developing countries. The system consists of biodegradable polymeric microspheres containing NET which are injected intramuscularly as a suspension. Depending on the size of the microspheres the product can provide 30,90, or 180 day contraceptive protect ive with a single dose. The availability of the 3 formulations each with different durations of action will serve the contraceptive needs of varied populations. Most longacting steroidal contraceptives give rise to menstrual irregularities, but they have the convenience of long action and the physiological advantage of low doses delivered directly to the systemic circulation. Use by millions of women for 1-2 decades will be required before they are completely understood.^ieng

Propranolol as a novel, effective spermicide: preliminary findings.

The efficacy and tolerability of 80 mg propranolol tablets as a vaginal contraceptive were studied in 198 fertile women for 11 months. The calculated one year life table pregnancy rate was 3.4/100 women and the Pearl index was 3.9/100 women years. No major adverse effects were encountered. The findings suggested that propranolol is an effective vaginal contraceptive whose failure rate compares favourably with that of other methods of contraception. Further study of propranolol and similar compounds is warranted.

Wider opportunities for IUD insertion.

PIP: The timing of IUD insertion has important implications for those who insert the devices as well as the users. In 1978 the US Food and Drug Administration recommended insertion during menstruation but acknowledged that it is also "necessary and proper" to insert IUDs at other times in the cycle. A 1977 study found that 30% of European and North American obstetricians limited insertion to the time of menstruation. Nearly half those in Africa and the Middle East and 13% of those in Asia followed this practice. Consequently, many women are required to make more than 1 visit to a clinic, meaning inconvenience for both the user and provider and some unintended pregnancies. In developing countries women may depend on mobile clinics or infrequent visits by trained personnel and many seek help without an appointment. 1 reason for insertion at or just after menstruation is to ensure that the woman is not pregnant when the IUD is inserted. 2 recent articles attempt to assess the best time for IUD insertion with regard to IUD performance. White et al. found that women whose Copper T IUDs were inserted on days 1-5 of the menstrual cycle had a lower continuation rate in the 1st few months than did those whose IUDs were inserted at a later time in the cycle. Edelman et al. found that Copper T and Copper 7 IUDs could be inserted at any time during the menstrual cycle without any increased risk of subsequent pregnancy, removal for medical reasons or expulsion during the 1st 12 months after insertion. Pooled International Fertility Research Program (IFRP) data indicate that there is no consistent pattern with regard to the time in the cycle that the IUD is inserted and its later performance. In no case is there a distinct advantage for the 1st 5 days of the menstrual cycle. It is much simpler to offer a woman an IUD when she is first seen, provided she is reasonably sure she is not pregnant. New practices are evolving in relation to recently pregnant women. The postabortal use of IUDs has been extensively researched and is a useful option, using a variety of currently available devices. In regard to the postpartum use of IUDs, some programs have reported a high expulsion rate. Provided proper insertion technique is used, IUDs can be inserted immediately postpartum with a high degree of retention. Another use for copper containing IUDs is insertion within 5 days of unprotected sexual intercourse. In sum, women can be provided with IUDs upon request at any time during the menstrual cycle.^ieng

Abortion.

PIP: Human beings seem to make private and irrevocable decisions regarding fertility control. There is little that physicians or lawyers can do to change these decisions. The relationship between induced abortion and contraceptive practice has long been documented. When fertility begins to decline in a country, there is often a rise in both induced abortion (either legal or illegal) and contraceptive practice. As time passes, contraception becomes more important as a fertility control method and induced abortion declines in importance. This transition has occurred in the history of Western countries and in contemporary developing nations. The transition appears to take place more rapidly in nations where abortion is recognized and legal. Subgroups within a society may lag behind the pace of the national transition. Any attempts to reimpose restrictions on abortion will not serve to reduce the actual numbers of abortions which take place, but may actually lead to greater numbers of abortions.^ieng

Reproductive mortality.

PIP: The concept of reproductive mortality and the assumptions used for calculating this phenomenon are the topics of this letter. The author revised a previously published statistical study of reproductive mortality, which was based on 11 assumptions including contraceptive risks, prevalence of use, and relation between risks in ever users and current users, by including the factor of duration of contraceptive use. The following statistics were obtained from the previous and the present study, respectively, for women aged 25-34 and aged 35-44, respectively: 1950 (8.7 and 8.7), 1960 (5.5 and 5.5), 1970 (2.8 and 2.9), and 1975 (2.4 and 2.5); 1950 (6.2 and 6.2), 1960 (2.9 and 2.9), 1970 (3.7 and 2.5), and 1975 (5.0 and 2.8). As expected, adjustments to the reproductive mortality rates for the differing proportions of long-term pill users resulted in a reduction in the rates for the 35-44 year old group. It is argued that were there are so many assumptions in data calculation, ranges rather than single estimates are in order. In addition, it should be remembered that estimates are country specific and probably group specific.^ieng

Seasonality of birth in India.

PIP: The article compares seasonal variation in conception in Baroda and Manipal, both at sea level on the west coast of India. The maximum seasonal difference in mean monthly temperature is 3.5 degrees C in Manipal, and 11.3 degrees C in Baroda. Both are industrialized towns, Manipal serving the surrounding taluk of Udupi. Clinical records were obtained from local hospitals; it must be remembered that birth registration in India is compulsory. The number of births in each month were aggregated for the period under review and adjusted to standard month of 30 days, from which an annual mean was calculated. A similar procedure was used to find mean annual temperature. A few relationships are apparent: 1) conception correlates inversely with temperature at both places, 2) abortions and stillbirths are higher in the hottest weather at both places, 3) in Baroda, but not in Udupi, the maximum prematurity rate occurs 5 months after the hottest weather. The links between weather and variations in human reproduction are not clear. Although patterns are not consistent, the conception rate appears to be low at times of maximum temperature. A number of biological and social factors, such as a rise in testicular temperature, can lead to oligospermia. Maternal body temperature can affect the life of spermatozoa, and climate influences the frequency of coitus. Implications from these variations must be taken into consideration in designing new family planning services.^ieng

Acceptability of an oral contraceptive that reduces the frequency of menstruation: the tri-cycle pill regimen.

The frequency of menstruation was reduced to once every three months in 196 women by the continuous administration of the oral contraceptive pill, Minilyn, for 84 days (tri-cycle regimen). No pregnancies occurred. One hundred and sixty-one women (82%) welcomed the reduction in the number of periods with the associated freedom from menstrual and premenstrual symptoms, and many found the tri-cycle regimen easier to follow. Weight gain of more than 2 kg, irregular cycle control, especially in the first three months, breast tenderness, and headaches were the main side effects. Menstrual loss was unchanged or reduced in all but seven women. The doctors and nurses on the clinic staff were less enthusiastic about this regimen than the volunteers themselves.