Factors and outcomes associated with the induction of labour in Latin America.

OBJECTIVE: To describe the prevalence of labour induction, together with its risk factors and outcomes in Latin America. DESIGN: Analysis of the 2005 WHO global survey database. SETTING: Eight selected Latin American countries. POPULATION: All women who gave birth during the study period in 120 participating institutions. METHODS: Bivariate and multivariate analyses. MAIN OUTCOME MEASURES: Indications for labour induction per country, success rate per method, risk factors for induction, and maternal and perinatal outcomes. RESULTS: Of the 97,095 deliveries included in the survey, 11,077 (11.4%) were induced, with 74.2% occurring in public institutions, 20.9% in social security hospitals and 4.9% in private institutions. Induction rates ranged from 5.1% in Peru to 20.1% in Cuba. The main indications were premature rupture of membranes (25.3%) and elective induction (28.9%). The success rate of vaginal delivery was very similar for oxytocin (69.9%) and misoprostol (74.8%), with an overall success rate of 70.4%. Induced labour was more common in women over 35 years of age. Maternal complications included higher rates of perineal laceration, need for uterotonic agents, hysterectomy, ICU admission, hospital stay>7 days and increased need for anaesthetic/analgesic procedures. Some adverse perinatal outcomes were also higher: low 5-minute Apgar score, very low birthweight, admission to neonatal ICU and delayed initiation of breastfeeding. CONCLUSIONS: In Latin America, labour was induced in slightly more than 10% of deliveries; success rates were high irrespective of the method used. Induced labour is, however, associated with poorer maternal and perinatal outcomes than spontaneous labour.

The medical profession and the defense and promotion of sexual and reproductive rights.

The values of the medical profession and other healthcare providers allow assessment of the relationship between physicians, healthcare teams, patients, and healthcare networks regarding the defense and promotion of sexual and reproductive health and rights. This paper questions the traditional model of the relationship between healthcare professionals and patients, based on the classic paternalistic role of the physician. It describes the tools available to the medical profession and healthcare teams for the promotion of sexual and reproductive rights, and proposes specific actions that would lead to improvements for women and communities.

Expanding access to emergency contraception.

Emergency contraception (EC) is safe and has the potential to prevent unwanted pregnancies. However, use remains low in most settings, due to a range of barriers to access. This paper reviews key issues related to EC and describes recommendations reached during the Women's Health Alliance pre-Congress workshop, held in advance of the FIGO 2006 World Congress. The working group concluded that national societies of obstetrics and gynecology can play an important role in increasing access to this unique contraceptive method.

Misoprostol for the termination of pregnancy up to 12 completed weeks of pregnancy.

The aim was to review the current knowledge about the use of misoprostol alone for abortion induction during the first 12 weeks of pregnancy. Publications reporting experiences with misoprostol alone for pregnancy termination within the first 12 weeks of pregnancy were included in the analysis. Vaginal administration of 800 microg repeated up to three times at 6, 12 or 24 h intervals has an 85% to 90% effectiveness, defined as complete abortion, in most studies. Oral administration is less effective, but sublingual administration at 3-hour interval has the same effectiveness, with more frequent side effects. The oral and sublingual routes appear to be better accepted than vaginal administration. Most studies are limited to the first 9 weeks of pregnancy. The experience on pregnancy termination between 10 and 12 weeks is not yet sufficient for a recommendation.

Misoprostol for induction of labor with a live fetus.

Induction of labor is common in clinical practice. Many different medical and mechanical methods have been used, but the current gold standard is vaginal dinoprostone. Misoprostol has been used for the induction of labor since 1987. In early studies with large misoprostol doses (e.g. 200 microg) there were high rates of uterine hyperstimulation. Cochrane meta-analysis, however, shows that when used in low doses it is as effective as vaginal dinoprostone and with no excess of hyperstimulation. 25 microg vaginal misoprostol 4-hourly, 50 microg oral misoprostol 4-hourly or 20 microg oral misoprostol solution 2-hourly are all safe and effective regimens. Reports of uterine rupture in women with previous cesarean sections mean that it remains contraindicated in this group.

A risk reduction strategy to prevent maternal deaths associated with unsafe abortion.

INTRODUCTION: Worldwide, 13% of maternal deaths are caused by complications of spontaneous or induced abortion, 29% in Uruguay and nearly half (48%) in the Pereira Rossell Hospital. PURPOSE: This paper describes a risk reduction strategy for unsafe abortions in Montevideo, Uruguay, where over one-fourth of maternal deaths are caused by unsafe abortion. METHODS: Although abortion is not legal in Uruguay, women desiring abortions can be counseled before and immediately after to reduce the risk of injury. Women contemplating abortion were invited to attend a "before-abortion" and an "after-abortion" visit at a reproductive health polyclinic. At the "before-abortion" visit, gestational age, condition of the fetus and pathologies were diagnosed and the risks associated with the use of different abortion methods (based on the best available scientific evidence) were described. The "after-abortion" visit allowed for checking for possible complications and offering contraception. RESULTS: From March 2004 through June 2005, 675 women attended the "before-abortion" and 495 the "after-abortion" visit, the number increasing over time. Some women (3.5%) decided not to abort, others were either not pregnant, the fetus/embryo was dead or the woman had a condition that permitted legal termination of pregnancy in the hospital (7.5%). Most women, however, aborted. All women used vaginal misoprostol in the doses recommended in the medical literature. There were no serious complications (one mild infection and two hemorrhages not requiring transfusion). CONCLUSION: The strategy is effective in reducing unsafe abortions and their health consequences.

Blood levels of levonorgestrel in women following vaginal placement of contraceptive pills.

PIP: 6 healthy women aged 25-38 years, attending a family planning clinic in the Dominican Republic, participated in an experiment to determine blood levels of levonorgestrel (1Ng) resulting from daily vaginal placement of contraceptive pills containing .5 mg dl-norgestrel and .05 mg ethinyl estradiol and to evaluate the effect on ovulation. Subjects were observed for 3 cycles. Blood samples were taken on days 14, 18, 23 and 27 following the 1st day of menses on a pretreatment cycle. In 1 cycle the pill was taken daily for 21 days by the oral route, and in another it was placed in the vagina on the same schedule. Blood samples were taken frequently during the 1st 24 hours and subsequently on days 5, 8, 12, 15, 18, and 21 of experimental cycles. Plasma levels of 1Ng reached a peak of 3-4 ng/ml 1-4 hours after oral administation of dl-norgestrel and fell slowly thereafter to a level slightly over 1 ng at 24 hours after ingestion. Plasma concentrations of 1Ng rose at a slower rate and reached a lower peak value after vaginal placement. After 4 hours the 2 curves were approximately parallel. The mean 1Ng plasma concentration 24 hours after vaginal insertion was less than 1/2 the value after oral administration. The differences in plasma levels were statistically significant for each of the times studied. Differences were most pronounced in the 1st 2 weeks. In each pretreatment cycle, progesterone levels reached a peak above 4 ng/ml, indicating ovulation. All but 1 treatment cycle by either route had progesterone values suggesting anovulation; the exception was a vaginal administration cycle. 4 of the 6 women maintained low estradiol levels, mostly between 20-40 pg/ml, during treatment cycles by either route. The lower plasma levels of 1Ng after vaginal insertion of pills may reflect inefficient absorption of steroids within the vagina, or a difference in metabolic degradation when the drug is administered parenterally via the vaginal blood supply. It was still possible to suppress ovulation in 5 of the 6 vaginal cycles without attempting to adjust the dose.^ieng

Prospective study of the pituitary-ovarian function after tubal sterilization by the Pomeroy or Uchida techniques.

Surgical sterilization has become one of the most widely used methods of fertility regulation in the world. A common concern is the not yet clarified possible disturbance of the ovarian function resulting from the surgical procedure. A prospective study was carried out to contribute toward answering this question. Twenty subjects were enrolled in a longitudinal study of ovarian endocrine function before, and 2 and 6 months after, tubal ligation. The Pomeroy technique, which may compromise ovarian circulation, and the Uchida technique, which is free of this risk, were used randomly. Eight women who underwent to the Pomeroy technique and 9 who underwent the Uchida technique completed the protocol. Luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone were measured daily from days 10 through 18 of the cycle and every other day until the onset of the next menses. No change in any of the hormones studied was observed, with the exception of a significant increase in progesterone 2 months after tubal ligation by the Uchida technique.

Effect of preovulatory insertion of Norplant implants over luteinizing hormone secretion and follicular development.

OBJECTIVE: To determine whether the process of ovulation could be interrupted by the insertion of Norplant implants (Leiras Pharmaceuticals, Turku, Finland) in the advanced preovulatory phase. DESIGN: Prospective study. SETTING: The Department of Biomedical Research at the Family Planning Clinic of PROFAMILIA, Santo Domingo, Dominican Republic. PATIENTS: Healthy women of reproductive age, requesting Norplant implants contraception. Thirteen of 15 women volunteers who were admitted completed the study. INTERVENTIONS: Norplant implants were inserted when the dominant follicle reached a mean diameter of 16 mm, based on serial vaginal ultrasounds (US) beginning on day 10 of the cycle. Blood samples for determination of E2, P, LH, and levonorgestrel, were taken and vaginal US performed at 0, 4, 24, 48, and 72 hours after insertion. If follicle rupture had not occurred at 72 hours after insertion, blood sampling and US were done three times per week during 2 additional weeks. RESULTS: Follicle rupture occurred in 11 of 13 subjects within 72 hours after insertion, with the exception of 1 subject in whom rupture occurred between 72 and 192 hours. Two women already had an LH peak at the time of insertion. In 9 of the remaining 11 women, a shortlasting, blunted LH surge was observed at 4 hours postinsertion. In the remaining two women, who had the lowest E2 levels, ovulation was inhibited, and a persistent follicle developed without luteinization. CONCLUSIONS: The insertion of Norplant implants in the advanced follicular phase will not inhibit ovulation if sufficient E2 priming has occurred. On the contrary, the exogenous progestin may rapidly foster ovulation shortly after.

PIP: 15 healthy women of reproductive age requesting Norplant were admitted into this prospective study conducted to determine whether the ovulation process can be interrupted by the insertion of Norplant implants during the advanced preovulatory phase. The implants were inserted when the dominant follicle reached a mean diameter of 16 mm, based upon serial vaginal ultrasounds (US) beginning day 10 into the cycle. Blood samples to determine levels of E(2), P, LH, and levonorgestrel were taken and vaginal US performed at 0, 4, 24, 48, and 72 hours after insertion. If follicle rupture had not occurred by 72 hours after insertion, blood sampling and US were done three times per week for two additional weeks. Follicle rupture occurred in 11 of the 13 subjects who completed the study within 72 hours after insertion, except for one subject who experienced rupture at 72-192 hours. Overall, it was determined that the insertion of Norplant implants during the advanced follicular phase will not inhibit ovulation if sufficient E(2) priming has occurred. The exogenous progestin, however, may rapidly foster ovulation shortly thereafter.

Norplant implants: the mechanism of contraceptive action.

OBJECTIVE: To determine if fertilization occurs unnoticed among Norplant users who are ovulatory. DESIGN: Serial blood samples were obtained during 1 month from sexually active Norplant users experiencing regular menstrual bleeding patterns and a control group of noncontracepting women trying to conceive. The sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG). SETTING: All samples were obtained from women receiving contraceptive service and health care at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. Assays for hCG were performed at the Department of Biomedical Sciences, University of Tampere, Finland. PATIENTS, PARTICIPANTS: A total of 32 women using Norplant implants were enrolled in the treatment group, and 20 women of proven fertility who were attempting to conceive served as a control group. INTERVENTIONS: Duration of Norplant use was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th year, 3 in the 5th year, and 1 in the 7th year. MAIN OUTCOME MEASURE: The determination of pregnancy was based on the presence of hCG in the luteal phase, using a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days after ovulation. RESULTS: Nine pregnancies were detected. All were in the control group trying to conceive. Six of these advanced to clinical pregnancies, and three did not proceed beyond the next expected menses. None of the Norplant users had evidence of hCG production, whether the observed cycles were anovulatory or ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1 in 50 and 1 in 150,000. The null hypothesis that Norplant users conceive at a natural rate can be rejected at the 0.05 level. CONCLUSION: Interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants.

PIP: This study sought to determine if fertilization can occur unnoticed among Norplant users who are ovulatory. Serial blood samples were obtained during a 1-month period from women receiving contraceptive service and healthcare at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. These women were all sexually active Norplant users who experienced regular menstrual bleeding patterns, and their sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG) at the Department of Biomedical Sciences at the University of Tampere, Finland. There was also a control group of 20 noncontracepting women included who were trying to conceive. Duration of Norplant was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th, 3 in the 5th year, and 1 in the 7th year. Pregnancy determination was based on the presence of hCG in the luteal phase by use of a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days postovulation. 9 pregnancies were detected, all in the control group who were trying to conceive. 6 of these advanced to clinical pregnancies and 3 terminated spontaneously at the next menstrual period. None of the Norplant users evidenced and hCG production, whether or not the observed cycles were ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1/50 and 1/150,00. The null hypotheses that Norplant users conceive at a natural rate can be rejected at the 0.05 level. Thus, interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants.

Ovulatory dysfunction during continuous administration of low-dose levonorgestrel by subdermal implants.

OBJECTIVE: To study the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. DESIGN: Observational, prospective, case-controlled comparative study. SETTING: The Family Planning Clinic of PROFAMILIA, in Santo Domingo, Dominican Republic. PATIENTS, PARTICIPANTS: Thirty one regularly cycling Norplant users and 12 nonhormonal contraceptors who volunteered to participate. INTERVENTIONS: Norplant contraceptive implants were inserted in 31 subjects between 13 and 77 months before this study. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for one menstrual cycle. RESULTS: Almost half of the cycles among Norplant users were anovulatory; all the rest (55%) had some form of dysfunction: diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from normal controls. CONCLUSIONS: Anovulation is clearly one of the main mechanisms of action of Norplant, but even in presumptive ovulatory cycles, the dysfunctions described possibly contribute to the high contraceptive effectiveness of Norplant.

PIP: The study sought to examine the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. This observational, prospective, case-controlled, comparative study occurred at the Family Planning Clinic of PROFAMILIA in Santo Domingo, Dominican Republic. 31 subjects agreed to receive Norplant contraceptive implants between 13-77 months prior to this study and there were 12 nonhormonal contraceptors who also volunteered to participate. Follicle stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for 1 menstrual cycle, and almost 1/2 of the cycles of norplant acceptors were anovulatory: the remainder (55%) had some form of dysfunction such as diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from controls. Anovulation is clearly 1 of the main mechanisms of Norplant action, but even in presumptive ovulatory cycles, the dysfunctions described could have contributed to the high contraceptive effectiveness of Norplant.

The menstrual cycle in women using an intrauterine device.

The duration and hormonal characteristics of the menstrual cycles of women using Copper T intrauterine devices (IUDs) were studied. Daily load samples were obtained during both the pre- and postovulatory phases of 30 IUD-associated cycles and the hormone values were compared with those of 15 normally menstruating women not using contraception. The ovulation rate and peak levels of 17 beta-estradiol and luteinizing hormone (LH) were not significantly different between the two groups. The average number of days from the 1st day of menstrual bleeding to the LH peak (the proliferative phase) was longer in the IUD users. The number of days from the LH peak to the onset of menstrual bleeding (the luteal phase) was shorter in the IUD users. Because of the compensating nature of these statistically significant differences, the total cycle length appeared to be unchanged. At the time of menstruation, the plasma levels of both progesterone and 17 beta-estradiol were significantly higher among IUD users. It is concluded that the presence of an IUD does not influence ovarian function, but that ovarian steroid production and endometrial events become asynchronous.

PIP: The duration and hormonal characteristics of the menstrual cycles of women using the Copper T IUD were studied. Daily blood samples were obtained during the pre- and postovulatory phases of 30 IUD-associated cycles and the hormone values were compared with those of 15 normally menstruating women not using contraception. The ovulation rate and peak levels of 17 beta-estradiol and (LH) luteinizing hormone were not significantly different between the 2 groups. The average number of days from the 1st day of menstrual bleeding to the LH peak (proliferative phase) was longer in IUD users. The number of days from the LH peak to onset of the menstrual bleeding (luteal phase) was shorter in the IUD users. Because of the compensating nature of these statistically significant differences, the total cycle length appeared to be unchanged. At the time of menstruation, the plasma levels of both progesterone and 17 beta-estradiol were significantly higher among IUD users. It is concluded that the presence of an IUD does not influence ovarian function, but the ovarian steroid production and endometrial events do become asynchronous.

Timing of onset of contraceptive effectiveness in Depo-Provera users: Part I. Changes in cervical mucus.

OBJECTIVE: To evaluate the changes in cervical mucus within the first hours or days after depot medroxyprogesterone acetate (MPA) injection so as to estimate the time at which cervical mucus becomes hostile enough to prevent pregnancy. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinic. PATIENT(S): Thirty women who were between days 8 and 13 of their menstrual cycle and who had requested Depo-Provera were enrolled in the study. INTERVENTION(S): Cervical mucus and blood samples were obtained; transvaginal ultrasonography was performed. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, ovarian follicular size, and serum levels of progesterone and estradiol. RESULT(S): From 6 to 24 hours after injection, there was a sharp decline in the cervical mucus score for most of the subjects. All subjects exhibited poor mucus on day 3 after injection, and by day 7, all subjects had zero scores, with the exception of two outliers on each day. Sperm penetration, as measured by the vanguard sperm distance, was already poor (< 1 cm) in 7 of the 30 subjects at the time of injection and was reduced progressively up to 24 hours after injection, when only four subjects had a sperm penetration of > 1 cm. A rapid decline in the estimated number of sperm was observed at 12 hours and more so at 24 hours in the majority of subjects. CONCLUSION(S): The data presented in this report confirmed that depot MPA causes profound changes in cervical mucus after injection. Although very little change was seen at 6 hours, alterations were observed subsequently, with 90% of the subjects showing a poor cervical mucus score 24 hours after administration of the progestin. No reliable clinical marker is available to identify in which women depot MPA might exert its effect on cervical mucus within 3 days. Thus, we believe that at present, women should be informed of this uncertainty and should use a backup method of contraception for 7 days when the first injection of depot MPA is provided after the seventh day of the menstrual cycle.

PIP: More accurate knowledge of the time of onset of cervical mucus changes after Depo-Provera injection would enable family planning providers to counsel new acceptors to use a backup method only for the amount of time it is really needed. To obtain such data, 30 women from a family planning clinic in Campinas, Brazil, who requested Depo-Provera in 1995-96 were recruited. At baseline, 11 women had a poor cervical mucus score (0-4), 12 had a fair score (3-8), and 7 scored in the good range (9-12). Between 6 and 24 hours after injection, a sharp decline occurred in the cervical mucus score in all but 3 patients (each of whom had a "good" score at baseline). On day 3, 29 women had "poor" mucus and the remaining woman had a cervical mucus score in the fair range. By day 7, 29 women had zero mucus scores; the score in the last woman was 1. 24 hours after injection, sperm penetration (measured by vanguard sperm distance) had decreased to under 1 cm in all but 4 women. At day 3, 1 of the 2 women with good penetration at 24 hours maintained a vanguard sperm distance of 2.5 cm and an estimated sperm count of 15,363. By day 7, sperm penetration was zero in all but 1 woman (0.5 cm). These findings confirm that depot medroxyprogesterone acetate causes profound changes in cervical mucus after injection. The lack of a more complete hostility to sperm penetration at day 3 was unexpected, however. Given the nonavailability of a reliable clinical marker to verify a contraceptive effect at 3 days, it seems prudent to advise new Depo-Provera acceptors to use a backup method for the first 7 days.

Pituitary-ovarian function after tubal ligation.

Pituitary-ovarian function was evaluated by measurement of daily serum levels of luteinizing hormone (LH), 17 beta-estradiol, and progesterone in women with a previous history of tubal ligation. Normally menstruating women served as controls. The duration of the proliferative and luteal phase was similar for both groups. The midluteal progesterone level averages did not differ between the two groups. Preovulatory LH and 17 beta-estradiol peaks were significantly lower in the tubal ligation group; average midluteal LH and 17 beta-estradiol levels were also lower. These results reveal that pituitary-ovarian function can be altered following surgical sterilization.

PIP: Menstrual disorders have been reported following tubal surgery. This study investigates luteinizing hormone (LH), 17beta-estradiol, and progesterone levels in 30 women (age range, 24-38 years; average age, 32 years), who had had elective tubal ligation for fertility control. Elective surgical sterilization was performed between 1 month and 8 years previously. The controls consisted of 15 normally menstruating women (aged 20-32 years; average age, 24), seeking to become pregnant who had not used either oral contraceptives or IUDs for at least 1 month before the study. Daily blood samples were collected starting from day 10 of the menstrual cycle until the onset of the next menstruation. Case selection and specimen collections were done in Santo Domingo, Dominican Republic. Hormone determinations by radioimmunoassays were done on a double-blind basis at the Population Council in New York. Progesterone and 17-b estradiol were determined by radioimmunoassay according to the method of Thorneycroft and Stone, while human luteinizing hormone (hLH) was measured by the double antibody technique of Vaitukaitis et.al. Average duration of the proliferative and luteal phase were 14.4 + or - 3.0 and 13.3 + or - 2.9 days, respectively, for the control group and 13.5 and 2.4 and 14.2 + or - 1.7 days for the women with tubal ligation. The total length of the cycle, 27.7 days, is the same for both groups. The midluteal progesterone level averages did not differ between the 2 groups, although when the controls were compared with tubal ligated women 30 years of age or younger, the difference was significant. Preovulatory LH and 17beta-estradiol peaks were significantly lower in the tubal ligation group, as were the average midluteal LH and 17beta-estradiol levels. These results suggest that surgical sterilization can result in subtle changes in ovarian function, even though ovulation itself is not affected. Bleeding irregularities following tubal ligation may in part be due to the fact that different surgical procedures may have different effects on ovarian blood supply. Further research should be done to compare specific effects of different sterilization procedures on ovarian function.

Timing of onset of contraceptive effectiveness in Depo-Provera users. II. Effects on ovarian function.

OBJECTIVE: To determine the timing of onset of contraceptive effectiveness after the first injection of 150 mg of depot medroxyprogesterone acetate (DMPA) administered between days 8 and 13 of the menstrual cycle. DESIGN: Descriptive, prospective study. SETTING: A tertiary university referral center. PATIENT(S): Thirty healthy women between 18 and 40 years of age. INTERVENTION: Volunteers were injected with DMPA between days 8 and 13 (5 women on each day) of the menstrual cycle. MAIN OUTCOME MEASURE(S): Ovarian function determined by serum levels of E2 and progesterone and follicular development evaluated by vaginal ultrasound. RESULT(S): In nine (30%) of 30 women studied, DMPA did not prevent ovulation. All ovulations occurred in women receiving DMPA between days 10 and 13 of the cycle. No woman who received injections on day 8 or 9 ovulated. Ovulation suppression was more effective in women with low ovarian activity. All ovulation occurred within 3 days after the injection. CONCLUSION: A back-up contraceptive method, used after the 7th day of the menstrual cycle, is recommended for up to 7 days after the first injection of DMPA.

PIP: To ensure ovulation does not occur, it is recommended that Depo-Provera injections be administered within the first 7 days of the menstrual cycle. In some settings, this requirement acts as a barrier to women's free access to injectable contraception. Thus, the present study investigated the timing of onset of contraceptive effectiveness when the first injection of depot medroxyprogesterone acetate is administered between days 8-13 of the menstrual cycle. 30 women 18-40 years of age attending a university referral center in Campinas, Brazil, in 1995-96, were enrolled. Ovulation, detected through serum progesterone and estradiol assays and confirmed by follicle rupture at vaginal ultrasound, occurred in 9 cases (30%). No ovulations occurred when injection was administered on day 8 (n = 5) or day 9 (n = 5) of the menstrual cycle; only 1 of the 5 women treated on day 10 ovulated. On the other hand, 4 of the 10 women treated on days 11 and 12 and 4 of the 5 injected on day 13 showed evidence of ovulation. All ovulation occurred within 3 days after injection. Ovulation occurred only among women who had serum estradiol levels of 100 pg/ml and above and a leading follicle diameter greater than 13 mm at the time of injection. Ovulation suppression was more effective in women with low ovarian activity. A back-up contraceptive method used for 4 days after Depo-Provera injection should provide sufficient protection when the method is administered after day 7 of the menstrual cycle. However, given the uncertainty of the assumption of short viability of the human oocyte, it is safer to recommend 1 week's use of a back-up method or abstinence.

Absence of chorionic gonadotropin in sera of women who use intrauterine devices.

A controlled study was undertaken to determine whether unnoticed pregnancies routinely occur in users of the intrauterine contraceptive device (IUD). Starting on day 10 of the menstrual cycle and continuing through the onset of menstruation or until the diagnosis of pregnancy, we collected daily blood samples from three groups of normally menstruating young women. The study groups were (A) IUD users (n = 30), (B) women with tubal ligation (n = 30), and (C) women trying to become pregnant (n = 15). The sequential serum samples were analyzed by radioimmunoassay for progesterone (P), human luteinizing hormone (hLH), and human chorionic gonadotropin (hCG). No positive hCG assays in luteal phase blood sera of IUD users were observed. The only positive hCG determinations of IUD users coincided with the preovulatory surge of hLH. Two subjects who became pregnant, as judged by progressive increases in hCG and P levels in the luteal phase, belonged to the group planning pregnancy. The finding of two pregnancies in 15 months of exposure is consistent with the assumption of natural fertility. The probability of no pregnancies in 30 months at risk, as observed among the IUD users, is between 1 in 200 and 1 in 100,000, depending on the assumption made for natural fertility. The study demonstrates that IUD users do not retain their natural fertility, and that IUDs do not exert their antifertility effect as abortifacient agents. If a confirmed pregnancy is detected in an IUD user, it may be assumed to represent an isolated case of contraceptive failure.

PIP: A controlled study was undertaken to determine whether unnoticed pregnancies routinely occur in users of the IUD. Beginning on day 10 of the menstrual cycle and continuing through the onset of menstruation or until the diagnosis of pregnancy, the authors collected daily blood samples from 3 groups of normally menstruating young women. The study groups were: a) IUD users (n=30); b) women with tubal ligation (n=30); and c) women trying to become pregnant (n=15). The sequential serum samples were analyzed by radioimmunoassay for progesterone (P), human luteinizing hormone (hLH), and human chorionic gonadotropin (hCG). No positive hCG assays in luteal phase blood sera of IUD users were observed. The only positive hCG determinations of IUD users coincided with the preovulatory surge of hLH. 2 subjects who become pregnant as judged by progressive increases in hCG and P levels in the luteal phase belonged to the group planning pregnancy. The finding of 2 pregnancies in 15 months of exposure is consistent with the assumption of natural fertility. The probability of no pregnancies in 30 months at risk, as observed among the IUD users, is between 1 in 200 and 1 in 100,000, depending on the assumption made for natural fertility. The study demonstrates that IUD users do not retain their natural fertility, and that IUDs do not exert their antifertility effect as abortifacient agents. If a confirmed pregnancy is detected in an IUD user, it may be assumed to represent an isolated case of contraceptive failure.

Progestin-only contraceptive rings.

Several progestin-only long acting contraceptives are currently available in the form of implants or injectables. Vaginal rings are another contraceptive option in the final stages of development. These steroid-containing polymer rings are placed in the vagina, providing relatively constant drug release, thus allowing for lower effective doses. Vaginal rings have the advantage of being user-controlled and non-provider dependent, and their use is non-coital related. The first clinical study with medroxyprogesterone acetate vaginal rings was published in 1970. Since then numerous clinical trials testing different steroids and doses have followed. A large Phase III multicenter clinical trial with a levonorgestrel ring, releasing 20 microg/day, was coordinated and sponsored by WHO. The cumulative one-year pregnancy rate was 4. 5%. The principal reasons for discontinuation were menstrual disturbances (17.2%), followed by frequent expulsion of the ring (7. 1%), and vaginal symptoms (6.0%). The finding of erythematous lesions in the vagina in some women has led to the development of a more flexible device. Collaboration with industry should facilitate the manufacture of a redesigned levonorgestrel ring with a higher release rate. The Population Council is also developing a vaginal ring containing Nestorone for 6 months of continuous use. Ovulation inhibition was achieved in over 97% of the segments studied, with rings releasing either 50, 75, or 100 microg/day. No pregnancies occurred in women using the low-dose ring, while one pregnancy each occurred in the intermediate- and high-dose ring groups for a 6-month cumulative pregnancy rate of 0.0, 1.9, and 2.1%. Bleeding irregularities were common. Nestorone is orally inactive; therefore this ring is also excellent for use in lactating women.

Risk-benefit effects of implantable contraceptives in women.

Contraceptive implant technology has been used by millions of women throughout the world. The three marketed implant systems today are levonorgestrel-releasing implants: Norplant and Jadelle, and a single etonogestrel-releasing implant, Implanon. The main benefits common to these delivery systems are their safety, high effectiveness, ease of use, long duration of action (3 - 5 years) and reversibility. Bleeding disturbances are the main adverse events associated with implantable contraceptives. Other minor risks relate to the insertion and removal procedures, which require adequately trained providers as well as aseptic techniques. Furthermore, since initiation and discontinuation of use is provider-dependent and not controlled by the user, there may be a risk of coercion of use on the one hand or, on the other hand, difficulty in access to initiating use, if trained providers are not readily available. Although no single contraceptive method is perfect or appealing to all, contraceptive implants are safe and fulfil a very important need among fertility regulation methods.

Long acting contraceptive implants. An analysis of menstrual bleeding patterns.

The menstrual patterns of women using subdermal implants of levonorgestrel and norgestrienone included in a double-blind clinical trial was evaluated by the method developed by the International Committee on Contraception Research. Women using Copper T200 randomly selected in the same clinics were used as controls. Both implant regimens were associated with a high frequency of reduced bleeding and norgestrel patients had also a high proportion of increased and irregular bleeding. Termination of use was associated to increased bleeding but not so much to reduced bleeding.

Evaluation of the clinical performance of a levonorgestrel-releasing IUD, up to seven years of use, in Campinas, Brazil.

The clinical performance of a levonorgestrel IUD, releasing 20 mcg/day, used by 293 women at the Family Planning Clinic of the State University of Campinas, was evaluated up to the end of the seventh year of use. No pregnancies occurred in 899 women-years of observation. The cumulative removal rate for amenorrhea or severe hypomenorrhea was 15.7 per 100 women at seven years. The expulsion rate was within ranges observed with copper IUDs in the same clinic. The continuation rate was 49.5% at three years and 23.7 at seven years. The cumulative loss to follow-up rate was 13.7% at seven years. The effectiveness, good continuation rate, and reduction of the amount of blood loss make this device appropriate to be offered to Brazilian women, as an additional contraceptive option.