Life-table Pregnancy Rates Research Articles

Contraceptive efficacy should primarily be measured using life table pregnancy rates

Contraceptive efficacy should primarily be measured using life table pregnancy rates

Pooled efficacy results of estetrol/drospirenone combined oral contraception phase 3 trials

ObjectiveTo evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen. Study designWe pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors. ResultsAnalyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m2. The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%–1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94–2.57) and 1.43 (0.78–2.40), respectively; in new starters and switchers of 1.88 (1.09–3.00) and 1.24 (0.68–2.08), respectively; and by BMI <25 kg/m2, 25 to 29.9 kg/m2, and ≥30 kg/m2 of 1.14 (0.64–1.88), 2.19 (1.05–4.03), and 2.27 (0.83–4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56–8.38]), Black race (HR 4.61[1.97–10.80]), age 16 to 25 years (HR 2.37[1.09–5.15]) and compliance <99% of expected pills (HR 4.21[2.04–8.66]) with conception. ConclusionE4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable. Implications StatementPooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non–modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure.

Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use

Extending hormonal intrauterine system duration will allow users to have less need for procedures to provide long-term contraception. This study aimed to evaluate the efficacy and safety of the levonorgestrel 52 mg intrauterine system during years 7 and 8 of use. A total of 1751 nulliparous and multiparous participants aged 16 to 45 years enrolled in a phase 3, multicenter trial to evaluate the efficacy and safety of the use of the Liletta levonorgestrel 52 mg intrauterine system for up to 10 years. Participants aged 36 to 45 years at enrollment underwent safety evaluation only. After the first year, we evaluated participants every 6 months for intrauterine system location confirmation and urine pregnancy testing at each visit. We assessed the Pearl Indices in years 7 and 8 and the life-table analysis for cumulative pregnancy rates through 8 years of use. For the primary efficacy analyses, all participants aged 16 to 35 years at enrollment were included through year 6; years 7 and 8 included only users aged ≤39 years at the start of each use year. Safety outcomes were assessed in all participants regardless of duration of use. We assessed amenorrhea rates, defined as no bleeding or spotting in the 90 days before the end of the year. After intrauterine system placement, we followed 1568 participants aged 16 to 35 years and 146 participants aged 36 to 45 years. The 16- to 35-year-old participants included 986 (57.5%) nulliparous and 433 (25.3%) obese users. Overall, 569 participants started year 7, 478 completed year 7 (380 aged ≤39 years at beginning of year) and 343 completed year 8 (257 aged ≤39 years at beginning of year); 77 completed 10 years of use. Eleven pregnancies occurred over 8 years, 7 (64%) of which were ectopic. Two pregnancies occurred in year 7 (Pearl Index, 0.49; 95% confidence interval, 0.06-1.78), 1 in a participant with implantation 4 days after a desired removal; no pregnancies occurred in year 8. The cumulative life-table pregnancy rate in the primary efficacy population through year 8 was 1.32 (95% confidence interval, 0.69-2.51); without the postremoval pregnancy, the rate was 1.09 (95% confidence interval, 0.56-2.13). Two perforations (0.1%) occurred, none noted after year 1. Expulsion occurred in 71 (4.1%) participants overall, with 3 in year 7 and 2 in year 8. Pelvic infection was diagnosed in 16 (0.9%) participants during intrauterine system use, 1 each in years 7 and 8. Only 44 (2.6%) participants overall discontinued because of bleeding complaints (4 total in years 7 and 8) with rates per year of 0.1% to 0.5% for years 3 to 8. Amenorrhea rates were 39% at both years 7 and8. The levonorgestrel 52 mg intrauterine system is highly effective over 8 years of use and has an excellent extended safety profile. This report details the longest period of efficacy and safety data for continuous use of a levonorgestrel 52 mg intrauterine system for contraception.

Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results

ObjectiveTo assess efficacy, cycle control, and safety of an oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg. Study designWomen aged 16 to 50 years with a body mass index ≤35 kg/m2 enrolled in this multicenter, open-label, 13-cycle, phase 3 trial evaluating E4/DRSP in a 24-active/4-placebo regimen. Follow-up was scheduled at Cycles 2, 4, 7, and 10 and within 3 weeks of completing Cycle 13. Participants used daily diaries to record pill use and vaginal bleeding. We evaluated efficacy outcomes in women 16 to 35 years and bleeding patterns and safety (adverse events [AEs]) in all participants. We assessed overall and method-failure pregnancy rates using the Pearl index (PI) and life-table analysis. Scheduled bleeding included spotting or bleeding starting during the 4-day placebo period or first 3 days of the next cycle. ResultsWe enrolled 1864 women of whom 1674 were 16 to 35 years. Women 16 to 35 years had a PI of 2.65 (95% CI 1.73–3.88), method-failure PI of 1.43 (95% CI 0.7–2.39) and 13-cycle life-table pregnancy rate of 2.1%. Scheduled bleeding occurred in 82.9% to 87.0% of women per cycle; median duration was 4.5 days. Unscheduled bleeding decreased from 30.3% in Cycle 1 to 21.3% to 22.1% during Cycles 2 to 4 and remained stable (15.5% to 19.2%) thereafter. The most frequently reported AEs were headache (5.0%) and metrorrhagia (4.6%). One-hundred thirty-two (7.1%) women discontinued the study early for an AE, most commonly for metrorrhagia (0.9%) and menorrhagia (0.8%). No thromboembolic events occurred. ConclusionE4/DRSP is an effective oral contraceptive with a predictable bleeding pattern for most women and low AE rates. Implications statementA new oral contraceptive with a novel estrogen, estetrol, combined with drospirenone has efficacy and safety within the range of other available oral contraceptives. Large phase 4 studies will be needed to confirm if this combination is associated with an improved adverse event profile or lower thrombosis risk.

Six-year contraceptive efficacy and continued safety of a levonorgestrel 52 mg intrauterine system

ObjectiveTo assess 6-year contraceptive efficacy and safety of a levonorgestrel 52 mg intrauterine system (IUS). Study DesignWe assessed pregnancy rates through 72 months in women aged 16–35 years at enrollment and safety in all participants (aged 16–45 years, n = 1751) in an ongoing 10-year phase-3 trial. ResultsOver six years, nine pregnancies occurred (none in year 6) for a life-table pregnancy rate of 0.87 (95% CI 0.44–1.70). Adverse event rates remain low through 6 or more years of use. Two expulsions occurred in year 6. ConclusionThis levonorgestrel 52 mg IUS is a highly effective and safe contraceptive over 6 years of use. ImplicationsThe levonorgestrel 52 mg IUS shows high 6-year contraceptive efficacy and a low rate of adverse events through 6 or more years of use.

The Levonorgestrel 52 mg Intrauterine System Is Effective and Safe for Six Years [13M

INTRODUCTION: Liletta®, a levonorgestrel (LNG) 52mg contraceptive intrauterine system (IUS), is under investigation in an ongoing multicenter trial for up to ten years of use. Here we evaluate six-year efficacy and safety data. METHODS: We enrolled women aged 16-45 years with participants aged 36-45 years undergoing safety evaluation only in this IRB-approved trial. After IUS placement, we followed 1,568 women aged 16-35 years and 146 women aged 36-45 years, assessing pregnancy rates through six years and safety outcomes in all women regardless of duration of use. RESULTS: The 16–35 year-old subjects included 986 (57.5%) nulliparous and 433 (25.3%) obese women. To date, more than 375 women have completed 6 years of use; more than 125 have completed 8 years. Nine pregnancies occurred over 6 years including two in year 1, four in year 2, one each in years 3-5, and none in year 6. Six (67%) pregnancies were ectopic. The cumulative life-table pregnancy rate through year 6 was .87 (95% CI .44-1.70). Two perforations following IUS placement were diagnosed within the first year and none since. Expulsion occurred in 68 (4.0%) participants, most (50 [73.5%]) during the first year with 2 per year in years 6 and 7. Pelvic infection was diagnosed in 15 (.9%) women, most (11 [73.3%]) occurring after 6 or more months of use. Only 40 (2.3%) women discontinued due to bleeding complaints, primarily (n=30 [75.0%]) in the first 2 years. CONCLUSION: The LNG 52 mg IUS is highly effective over six years of use and has an excellent extended safety profile.

Five-Year Efficacy and Safety of the Liletta® Levonorgestrel Intrauterine System [13F

INTRODUCTION: Liletta is a levonorgestrel 52 mg contraceptive intrauterine system (IUS) currently approved for contraception for up to four years based on an ongoing multicenter trial currently planned to continue for up to eight years of use. We evaluated the five-year efficacy and safety data for Liletta. METHODS: Women aged 16-45 years were enrolled; those women aged 36-45 years received the IUS for safety evaluation only. We followed 1,568 women aged 16-35 years and 146 women aged 36-45 years after successful IUS placement. We assessed five-year pregnancy rates and safety outcomes. RESULTS: The 16-35 year old subjects included 1,011 (57.7%) nulliparous and 438 (25.1%) obese women. Among these women, nine pregnancies occurred including four in nulliparous women and one in an obese woman. One pregnancy occurred following perforation and one following expulsion. Six (67%) pregnancies were ectopic. The Pearl Index in the first year was .15 (95% CI .02-.55). Cumulative life-table pregnancy rates through years three and five were .59 (95% CI .28-1.25) and .92 (95% CI .46-1.82), respectively. Perforation following IUS placement occurred in two (0.1%) women; both were diagnosed within the first year. Expulsion occurred in 63 (3.7%) participants, most (50 [80.6%]) during the first year of use. Pelvic infection was diagnosed in 11 (.6%) women. Only 39 (2.3%) women discontinued due to bleeding complaints, primarily (n=29 [74.3%]) in the first year. CONCLUSION: Liletta is highly effective and has an excellent safety profile over five years of use; most expulsions and discontinuation for bleeding occur during the first year of use.

Four-Year Efficacy and Safety of the Liletta® Levonorgestrel Intrauterine System [11A

INTRODUCTION: Liletta is a levonorgestrel 52 mg contraceptive intrauterine system (IUS) currently approved for contraception for up to three years based on an ongoing multicenter trial evaluating the product for up to seven years of use. We evaluated four-year efficacy and safety data for Liletta. METHODS: Women aged 16-45 years were enrolled and followed in the clinical trial. Women aged 36-45 years received the IUS for safety evaluation only. We assessed four-year pregnancy rates (by Pearl Index and life-table analysis) and safety outcomes. RESULTS: Successful IUS placement occurred in 1,568 (98%) women aged 16-35 years and 146 (97%) women aged 36-45 years, including 1,011 (57.7%) nulliparous and 438 (25.1%) obese women. Among women 16-35 years at enrollment, eight pregnancies occurred including one following perforation and one following expulsion. Six (75%) pregnancies were ectopic. The eight pregnancies included three nulliparous women and one obese woman. The Pearl Index in the first year was .15 (95% CI .02-.55). Cumulative life-table pregnancy rates through years two, three and four were .49 (95% CI .22-1.09), .60 (95% CI .28-1.26) and .78 (95% CI .37, 1.60). Perforation following IUS placement occurred in two (0.1%) women; both were diagnosed within the first year. Expulsion was reported in 63 (3.7%) participants, most (50 [80.6%]) during the first year of use. Pelvic infection was diagnosed in 12 (.7%) women. Only 38 (2.2%) women discontinued due to bleeding complaints. CONCLUSION: Liletta is highly effective and safe over four years of use in nulliparous and parous women as well as non-obese and obese women.

Lactational amenorrhoea method for family planning.

It is estimated that about 40% of pregnancies in the world are unintended and that the major part of these are unwanted. There are several reasons no or ineffective contraception is used to prevent these pregnancies, including difficulty in obtaining contraceptives. The lactational amenorrhoea method (LAM) is a contraceptive method where the mother is informed and supported in how to use breastfeeding for contraception. LAM is available and accessible to many women. To assess the effectiveness of LAM, as defined in the 1988 Bellagio Consensus statement, as a contraceptive method in fully breastfeeding women, who remain amenorrheic, using pregnancy and menstruation life tables. We searched MEDLINE, EMBASE, POPLINE, and LILACS to 10 October 2014; reference lists of studies; review articles; books related to LAM; published abstracts from breastfeeding, reproductive health conferences; e-mails with study coordinators. Out of 459 potentially relevant studies, 159 investigated the risk of pregnancy during LAM or lactational amenorrhoea. Our inclusion criteria were as follows: prospective study; cases (intervention group) and, if available, controls, had to be sexually active; pregnancy had to be confirmed by physical examination or a pregnancy test. Our endpoints were life table menstruation rates and life table pregnancy rates. We included 15 studies reporting on 11 intervention groups and three control groups. We identified one additional uncontrolled study in the 2007 update and one additional controlled study in this 2015 update. Two review authors independently extracted data, resolving disagreements through discussion. We analysed the studies using narrative methods because of their heterogeneity. For the primary outcome, pregnancy, two controlled studies of LAM users reported life table pregnancy rates at six months of 0.45% and 2.45%, one controlled study reported 5% pregnancies in the absence of life table rates per month, and eight uncontrolled studies of LAM users reported pregnancy rates of 0% to 7.5%. Life table pregnancy rates for fully breastfeeding women who were amenorrheic but not using any contraceptive method were 0.88% in one study and 0.9% to 1.2% (95% confidence interval 0.0 to 2.4) in a second study, depending on the definition of menstruation used. The life table menstruation rate at six months in all studies varied between 11.1% and 39.4%. We found no clear differences in life table pregnancy rates between women using LAM and being supported in doing so, and fully breastfeeding amenorrheic women not using any method. As the length of lactation amenorrhoea in women using LAM differed greatly between the populations studied, and was population specific, it is uncertain whether LAM extends lactational amenorrhoea.

Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system

ObjectiveTo assess 3-year data on the efficacy and safety of a new 52-mg levonorgestrel intrauterine contraceptive (LNG20) designed for up to 7 years use. Study DesignNulliparous and parous women aged 16–45 years at enrollment with regular menstrual cycles and requesting contraception were enrolled in an open-label, partially randomized trial to evaluate LNG20. The primary outcome was pregnancy rate for women aged 16–35 years calculated as the Pearl Index. Women aged 36–45 years received LNG20 for safety evaluation only. All participants had in-person or phone follow-up approximately every 3 months during the study. ResultsA total of 1600 women aged 16–35 years and 151 women aged 36–45 years agreed to LNG20 placement, including 1011 (57.7%) nulliparous and 438 (25.1%) obese women. Successful placement occurred in 1714 (97.9%) women. Six pregnancies occurred, four of which were ectopic. The Pearl Index for LNG20 was 0.15 (95% CI 0.02–0.55) through Year 1, 0.26 (95% CI 0.10–0.57) through Year 2, and 0.22 (95% CI 0.08–0.49) through Year 3. The cumulative life-table pregnancy rate was 0.55 (95% CI 0.24–1.23) through 3 years. Expulsion was reported in 62 (3.5%) participants, most (50 [80.6%]) during the first year of use. Of women who discontinued LNG20 and desired pregnancy, 86.8% conceived spontaneously within 12 months. Pelvic infection was diagnosed in 10 (0.6%) women. Only 26 (1.5%) LNG20 users discontinued due to bleeding complaints. ConclusionThe LNG20 intrauterine system is highly effective and safe over 3 years of use in nulliparous and parous women. Implications statementA new 52-mg levonorgestrel-releasing intrauterine system is effective and safe for nulliparous and parous women for at least 3 years.

Phase 3 Study of Desogestrel and Ethinyl Estradiol Combined Oral Contraceptive for Pregnancy Prevention

INTRODUCTION: Substituting low-dose ethinyl estradiol for the typical hormone-free interval in combined oral contraceptives may enhance ovarian suppression and improve tolerability. This phase 3 study evaluated the efficacy and safety of a 28-day combined oral contraceptive regimen including 21 days of desogestrel and ethinyl estradiol followed by 7 days of ethinyl estradiol. METHODS: This was a multicenter, open-label, phase 3, single-arm study that enrolled sexually active women 18–40 years old at risk for pregnancy. Women received up to 1 year, or 13 consecutive 28-day cycles, of 150 micrograms desogestrel and 20 micrograms ethinyl estradiol for 21 days and 10 micrograms ethinyl estradiol alone for 7 days. Patients kept diaries to record compliance, bleeding or spotting, and other contraceptive use. Efficacy was measured using the Pearl Index and life table approach. Safety and tolerability were assessed through reported adverse events. RESULTS: A total of 2,858 women were enrolled and 1,680 completed the study. Forty-six pregnancies in 2,401 women aged 18–35 years occurred after combined oral contraception initiation and up to 7 days after the last desogestrel and ethinyl estradiol or ethinyl estradiol-only tablet was taken. When cycles in which another birth control method was used were excluded, the Pearl Index was 2.68 (95% confidence interval [CI] 1.96–3.57). The life table pregnancy rate was 2.47% (95% CI 1.85%–3.29%) for all users aged 18–35 years. When only cycles during which women considered compliant were included, the Pearl Index was 2.00 (95% CI 1.39–2.80). Adverse events were similar to those seen with other oral contraceptives. CONCLUSIONS: This 28-day desogestrel and ethinyl estradiol combined oral contraceptive, including 7 days of low-dose ethinyl estradiol, was efficacious and well tolerated for pregnancy prevention.

Efficacy and safety of an ascending-dose, extended-regimen levonorgestrel/ethinyl estradiol combined oral contraceptive

ObjectiveTo evaluate the efficacy and safety of an ascending-dose, extended-regimen (ADER) combined oral contraceptive consisting of levonorgestrel (LNG) 150 mcg/ethinyl estradiol (EE) 20 mcg for 42 days, LNG 150 mcg/EE 25 mcg for 21 days, LNG 150 mcg/EE 30 mcg for 21 days and EE 10 mcg for 7 days. Study DesignThis was a multicenter, open-label, phase 3, single-arm study. Sexually active women aged 18–40 years were enrolled and received ADER for up to 1 year (4 consecutive 91-day cycles). Participants kept diaries to record adherence, bleeding/spotting and other contraceptive use. Efficacy was measured using the Pearl Index and the life-table method; safety and tolerability were assessed through reported adverse events (AEs). ResultsA total of 3701 women were enrolled and 2144 completed the study. The Pearl Index was 3.19 [95% confidence interval (CI), 2.49–4.03], based on 70 pregnancies that occurred after ADER initiation and ≤7 days after the last LNG/EE or EE-only pill in women aged 18–35 years, excluding cycles in which another contraceptive method was used. Life-table pregnancy rate was 2.82% (95% CI, 2.23%–3.57%) for all users aged 18–35 years. Unscheduled bleeding/spotting decreased with increasing EE doses within each cycle and decreased after cycle 1. No unexpected AEs or changes in laboratory parameters were reported. ConclusionThis study demonstrated that ADER effectively prevented pregnancy with a favorable safety and tolerability profile.

A Bridge for postpartum women to Standard Days Method®: II. Efficacy study

BackgroundIn a companion article, we described the development of a new fertility-awareness-based Bridge for postpartum women starting with their first postpartum menses and until they are eligible to use the Standard Days Method®. This article presents the results of an efficacy trial to test the Bridge. Study DesignThis was a prospective, nonrandomized, multicenter study following 157 women for up to 9 months. Participants were aged 18–39 years, had menstruated at least once since their baby was born, and wished to avoid or delay pregnancy using a fertility-awareness-based approach. Acceptability and correct use were examined. Life table pregnancy rates were calculated to assess method effectiveness. ResultsThe typical-use failure rate is 11.2 for 6 months of Bridge use. ConclusionThe Bridge can offer significant protection from pregnancy for postpartum women who prefer using a fertility-awareness-based approach to avoiding pregnancy but are not yet eligible to use the Standard Days Method. Counseling should emphasize the importance of following the Bridge guidelines for it to be effective.

The efficacy and safety of a low-dose, 91-day, extended-regimen oral contraceptive with continuous ethinyl estradiol

Background This clinical trial was conducted to demonstrate the efficacy and safety of a 91-day extended-regimen, low-dose combination oral contraceptive (OC) consisting of 84 days of ethinyl estradiol (EE) 20 mcg/levonorgestrel (LNG) 100 mcg, followed by 7 days of 10 mcg EE in place of placebo. Study Design A multicenter open-label, single-treatment, Phase 3 study evaluated women aged 18 through 40 years over a treatment period of up to 1 year (four 91-day extended cycles). All subjects completed daily paper diaries to monitor compliance, bleeding and additional forms of contraception used during the course of the study. Results A total of 1249 subjects completed the study. The Pearl Index was 2.74 (95% confidence interval, 1.92–3.78), based on 36 pregnancies that occurred after the onset of treatment and within 14 days after the last combination tablet in women aged 18–35 years. Among compliant-use subjects 18–35 years old, the Pearl Index was 1.73 based on 22 on-treatment pregnancies. The life table pregnancy rate for subjects 18–35 years of age was 2.39%. Cycle control and adverse events reported with this regimen were similar to those reported with other low-dose OCs. Conclusions This study demonstrated effective prevention of pregnancy with a 20-mcg EE, 91-day extended-regimen OC. In addition, the regimen was well tolerated and incidence of adverse events were consistent with what has been reported with other low-dose OCs.

Safety, efficacy and patient acceptability of the contraceptive and non-contraceptive uses of the LNG-IUS.

Intrauterine devices (IUDs) provide highly effective, long-term, safe, reversible contraception, and are the most widely used reversible contraceptive method worldwide. The levonorgestrel-releasing intrauterine system (LNG-IUS) is a T-shaped IUD with a steroid reservoir containing 52 mg of levonorgestrel that is released at an initial rate of 20 μg daily. It is highly effective, with a typical-use first year pregnancy rate of 0.1% - similar to surgical tubal occlusion. It is approved for 5 years of contraceptive use, and there is evidence that it can be effective for up to 7 years of continuous use. After removal, there is rapid return to fertility, with 1-year life-table pregnancy rates of 89 per 100 for women less than 30 years of age. Most users experience a dramatic reduction in menstrual bleeding, and about 15% to 20% of women become amenorrheic 1 year after insertion. The device's strong local effects on the endometrium benefit women with various benign gynecological conditions such as menorrhagia, dysmenorrhea, leiomyomata, adenomyosis, and endometriosis. There is also evidence to support its role in endometrial protection during postmenopausal estrogen replacement therapy, and in the treatment of endometrial hyperplasia.

Efficacy of the new TwoDay Method of family planning

To test the efficacy of the TwoDay Method, a new fertility awareness-based method of family planning that provides women with simple instructions to identify the days each cycle when they are most likely to become pregnant. Users avoid unprotected intercourse on days when cervical secretions are present on that day or on the day before, to prevent pregnancy. Prospective, nonrandomized, multicenter study. Five culturally diverse sites in Guatemala, Peru, and the Philippines. Four hundred fifty women, aged 18-39 years, wishing to use a fertility awareness-based method to prevent or delay pregnancy. Study participants were followed for up to 13 cycles of method use. Life table pregnancy rate. The first-year pregnancy rate was 3.5 (pregnancies per 100 women/years) with correct use of the method (pregnancies and cycles with no intercourse on identified fertile days), 6.3 with use of a backup method on the fertile days, and 13.7 including all cycles and all pregnancies in the analysis. The TwoDay Method offers a valuable addition to the services that reproductive health and other programs can offer. Its efficacy compares well with that of other coitus-dependent family-planning methods; it is easy to teach, learn, and use; and it can address the need of women for simple, accurate instructions for identifying their fertile days.

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.

Lactational amenorrhea for family planning.

50 % of pregnancies are unwanted. For several reasons including difficulty in obtaining contraceptives, no or ineffective contraception is used to prevent these unwanted pregnancies. The Lactational Amenorrhoea Method(LAM) however is a contraceptive method available and accessible for many women. To assess in fully breastfeeding women, staying amenorrheic, the efficacy of the Lactational Amenorrhoea Method as a contraceptive method. The efficacy of LAM, as defined in 1988 in Bellagio, was compared with alternative definitions of LAM; the outcomes were measured using pregnancy and menstruation life tables. MEDLINE searches from 1966 until 2002 and EMBASE from 1988 until 2002; reference lists of studies and review articles; books related to LAM; published abstracts from breastfeeding, reproductive health, contraceptive conferences; and e-mail communication with coordinators of such studies. From 454 potentially relevant studies 154 investigated the risk of pregnancy during LAM or lactational amenorrhea. Two reviewers applied the following inclusion criteria: prospective study, cases and -if available- controls had to be sexually active, pregnancy had to be confirmed by physical examination or a pregnancy test. Life table menstruation rates and life table pregnancy rates were taken as endpoints. Thirteen publications, reporting on 9 intervention groups and 2 control groups, met the inclusion criteria and were included in this systematic review. Their quality was assessed. Two reviewers independently extracted data, disagreements were resolved through discussion. Because of the heterogeneity of the included studies, the studies were analyzed using narrative methods. For the outcome two controlled studies of LAM users reported life table pregnancy rates at 6 months of 0.45 and 2.45 percent and 5 uncontrolled studies of LAM users reported 0-7.5 percent. Life table pregnancy rates of women fully breastfeeding and amenorrheic but not using any contraceptive method were 0.88 in one study and 0.9-1.2 percent (95% CI 0. 0-2.4 ) in a second study, depending on the definition of menstruation used. The life table menstruation rate at 6 months in all studies varied between 11.1-39.4 percent. No clear difference in life table pregnancy rates was found between women using LAM and supported in doing so, and fully breastfeeding, amenorroic women not using any method. Because the length of lactation amenorrhoea of women using LAM is too different between populations studied, and population specific, it is uncertain whether LAM extends lactational amenorrhoea.

Vasectomy effectiveness in Nepal: a retrospective study

The main purpose of this retrospective, cross-sectional study was to evaluate the effectiveness of vasectomy in an ongoing public sector program in Nepal. We evaluated semen samples from men who had previously had a vasectomy, and asked about the occurrence of pregnancies in the men’s partners. In addition, the surgeons who performed the vasectomies completed a questionnaire about their techniques. A two-stage stratified sampling procedure was used to select 1263 men from among over 30,000 men, who had previously undergone a no-scalpel vasectomy, mostly by ligation and excision, in 32 districts between July 1996 and June 1999. Semen samples were preserved and analyzed at a central laboratory. A US andrology laboratory validated the lab results. Twenty-three men (2.3%, 95% confidence interval [CI] 1.1–3.6) had ≥500,000 sperm/mL in their semen. Fifteen of those men reported pregnancies conceived after their vasectomy. In addition, six men with azoospermia reported pregnancies for which conception occurred within 3 months after vasectomy. Eleven men with azoospermia reported pregnancies for which conception occurred more than 3 months after vasectomy. Reported pregnancy was more likely in younger partners. The life table pregnancy rates for all men interviewed were 0.7 (95% CI 0.2–1.1), 1.7 (95% CI 1.4–2.1) and 4.2% (95% CI 3.2–5.2) at 3, 12 and 36 months, respectively. In low-resource, programmatic settings, vasectomy failure rates may be higher than commonly cited rates, especially in younger populations. Additional research is needed to determine if other occlusion techniques could reduce failure rates. Counseling on vasectomy should always convey the possibility of failure and partner pregnancy.

Breastfeeding patterns and return to fertility in Australian women.

The purpose of this study was to understand the relationship between infant feeding patterns and the return of fertility during lactation. Mother-infant pairs were followed up prospectively from the first week postpartum until the return of two normal menstrual bleeds (as judged by the woman) or pregnancy This study was conducted in the Sydney and Melbourne areas of Australia, and was part of a seven-country research project. Six hundred and twenty-four Australian mother-infant pairs participated in the study Follow-up interviews occurred in the mothers' homes every two weeks. Mothers completed a daily diary record chart of vaginal bleeding and infant feeding, and completed a detailed diary card of the time and duration of breastfeeds and the frequency and nature of all other feedings once every two weeks. MAIN OUTCOME MEASURES The main outcomes of the study were measured as the median duration of lactational amenorrhoea and lifetable pregnancy rate during lactational amenorrhoea. The median duration of amenorrhoea in the Australian breastfeeding women who participated in the study was over 8.5 months. Breastfeeding was shown to be an effective method of fertility control in that no non-contracepting, sexually active, amenorrhoeic, breastfeeding woman became pregnant in the first six months after delivery. Regular supplements commenced on average at five months and the Australian women rarely introduced noncaloric (water), caloric (juices), or milk-based supplements before this time. This confirmed the Bellagio Consensus and the effectiveness of the Lactational Amenorrhoea Method.