Pcwhf.co.uk

T h e n e w e ng l a n d j o u r na l o f m e dic i n e Brooke Winner, M.D., Jeffrey F. Peipert, M.D., Ph.D., Qiuhong Zhao, M.S., Christina Buckel, M.S.W., Tessa Madden, M.D., M.P.H., Jenifer E. Allsworth, Ph.D., BACKGROUND
From the Department of Obstetrics and The rate of unintended pregnancy in the United States is much higher than in Gynecology, Washington University other developed nations. Approximately half of unintended pregnancies are due to School of Medicine, St. Louis. Address reprint requests to Dr. Peipert at the De- contraceptive failure, largely owing to inconsistent or incorrect use.
partment of Obstetrics and Gynecology, Division of Clinical Research, Washing- ton University School of Medicine in St. Louis, 4533 Clayton Ave., Campus Box We designed a large prospective cohort study to promote the use of long-acting 8219, St. Louis, MO 63110, or at reversible contraceptive methods as a means of reducing unintended pregnancies in our region. Participants were provided with reversible contraception of their choice at no cost. We compared the rate of failure of long-acting reversible contraception Copyright 2012 Massachusetts Medical Society. (intrauterine devices [IUDs] and implants) with other commonly prescribed contra- ceptive methods (oral contraceptive pills, transdermal patch, contraceptive vaginal ring, and depot medroxyprogesterone acetate [DMPA] injection) in the overall co- hort and in groups stratified according to age (less than 21 years of age vs. 21 years RESULTS
Among the 7486 participants included in this analysis, we identified 334 unin-
tended pregnancies. The contraceptive failure rate among participants using pills, patch, or ring was 4.55 per 100 participant-years, as compared with 0.27 among participants using long-acting reversible contraception (hazard ratio after adjust- ment for age, educational level, and history with respect to unintended pregnancy, 21.8; 95% confidence interval, 13.7 to 34.9). Among participants who used pills, patch, or ring, those who were less than 21 years of age had a risk of unintended pregnancy that was almost twice as high as the risk among older participants. Rates of unintended pregnancy were similarly low among participants using DMPA injection and those using an IUD or implant, regardless of age.
CONCLUSIONS
The effectiveness of long-acting reversible contraception is superior to that of con-
traceptive pills, patch, or ring and is not altered in adolescents and young women. (Funded by the Susan Thompson Buffet Foundation.) n engl j med 366;21 nejm.org may 24, 2012 mately 3 million pregnancies per year — STUDY ENROLLMENT
50% of all pregnancies — are unintended, and The Contraceptive CHOICE Project is a prospec- this rate is significantly higher than that in other tive cohort study with the primary goal of pro- developed countries.1 Unintended pregnancy in moting the use of long-acting reversible contra- the United States results in 1.2 million abortions ceptive methods as a means of reducing per year,2 has negative effects on women’s health unintended pregnancies.13 From August 2007 and education and the health of newborns, and through September 2011, we enrolled 9256 par- imposes a considerable personal burden as well ticipants at risk for unintended pregnancy. All as a financial burden on families and society.3 participants chose a contraceptive method and Approximately half of unintended pregnancies received it at no cost. Study participants were a result from contraceptive failure, usually owing convenience sample of women and adolescents in to incorrect or inconsistent use of contraception, the St. Louis region, recruited by means of refer- rals from medical providers, newspaper reports, The most commonly used contraceptive study flyers, and word of mouth.
method in the United States is the oral contra- The study protocol was approved by the local ceptive pill.7 Because the pill requires daily com- institutional review board before recruitment was pliance, failure rates calculated on the basis of initiated. All participants provided written in- “perfect use” differ from real-world failure rates formed consent.
calculated on the basis of typical use. Annual Eligible participants were 14 to 45 years of age, failure rates with typical use of oral contracep- were not currently using a contraceptive method tive pills are estimated at 9% for the general or were willing to switch to a new reversible con- population, 13% for teenagers, and 30% or traceptive, had no desire for pregnancy for at least higher for some high-risk subgroups.4,8 Prior the next 12 months, were sexually active or were estimates of the failure rates with typical oral- planning to become sexually active with a male contraceptive use have relied on retrospective partner during the next 6 months, resided in the survey data, primarily from the National Survey St. Louis region, and spoke English or Spanish. Persons were excluded if they had undergone a Long-acting reversible contraceptive methods, hysterectomy or sterilization procedure.
including intrauterine devices (IUDs) and sub- dermal implants, are not user-dependent and STUDY DESIGN
have very low failure rates (less than 1%), which Before enrollment in the study, all potential par- rival those with sterilization.9 Despite their ticipants were read a standardized script regard- proven safety in women and adolescents of all ing long-acting reversible contraceptive methods ages,10,11 IUDs are used by only 5.5% of women that stated that the two IUDs and the subdermal who use contraception in the United States.7 implant were the most effective methods of con- Other developed countries, such as the United traception (see the Supplementary Appendix, avail- Kingdom and France, where IUDs are used more able with the full text of this article at NEJM.org). frequently, have rates of unintended pregnancy If they were eligible for enrollment, participants that are lower than those in the United States.12 received contraceptive counseling regarding all Prospective data on contraceptive failure from reversible contraceptive methods, including their a large number of women in the United States effectiveness, side effects, risks, and benefits. Each are limited. We analyzed data from a cohort of participant was then provided with a reversible participants at risk for unintended pregnancy, contraceptive method of her choice at no cost for who received contraceptive counseling and free 3 years (first 5090 participants) or 2 years (re- contraception, to compare the rate of failure of mainder of cohort). Participants were permitted long-acting reversible contraception (IUDs and to discontinue or switch methods as many times implants) with the failure rates for other com- as desired during the follow-up period. A com- monly prescribed contraceptive methods (pills, prehensive baseline interview was performed, and transdermal patch, vaginal ring, and depot me- participants were screened for sexually transmit- droxyprogesterone acetate [DMPA] injection).
n engl j med 366;21 nejm.org may 24, 2012 T h e n e w e ng l a n d j o u r na l o f m e dic i n e Participants were followed prospectively, with asked to come in for urine pregnancy testing. A telephone interviews at 3 and 6 months and ev- pregnancy log was used to record all pregnancies. ery 6 months thereafter for the duration of fol- Participants who had a pregnancy were asked if it low-up. Participants received a $10 gift card for was intended and what contraceptive method (if every completed follow-up interview. In the base- any) they were using at the time of conception. line and follow-up interviews, we collected com- The conception date was estimated from the date prehensive information on demographic charac- of the last menstrual period or from the gesta- tional-age assessment on ultrasonography. Con- This analysis includes the first 7486 partici- traceptive-method failure was defined as con- pants who used an IUD, implant, DMPA injection, ception that occurred during a period when the pills, patch, or ring during the study. Periods of contraceptive method was used. If the participant condom use or other contraceptive method use stated that she had stopped using the method, (e.g., diaphragm or natural family planning) were this was listed as “no method” and was not con- excluded from the analysis of contraceptive fail- sidered a contraceptive-method failure. We ex- ure. At each survey, participants were asked about cluded conception that occurred after a partici- missed menses and possible pregnancy. Any par- pant stopped using a method owing to a desire to ticipant who thought she might be pregnant was conceive (intended pregnancy).
Table 1. Characteristics of Study Participants, According to Contraceptive Method Chosen at Baseline.*
Characteristic
(N = 1527)
(N = 5781)
Educational level — no./total no. (%)‡ Receiving public assistance — no. (%)¶ Trouble paying basic expenses — no. (%)∥ n engl j med 366;21 nejm.org may 24, 2012 Table 1. (Continued.)
Characteristic
(N = 1527)
(N = 5781)
Previous unintended pregnancies — no./ * Plus–minus values are means (±SD). P<0.001 for comparisons of the three groups. The total number of participants does not equal 7486 because 2 participants chose natural family planning as their contraceptive method at baseline but then went on to choose another method later in the study. Percentages may not necessarily add up to 100 be- cause of rounding. DMPA denotes depot medroxyprogesterone acetate; LARC long-acting reversible contraception (intrauterine device or implant); PPR pill, patch, or ring; and STI sexually transmitted infection.
† Race was self-reported. Data were missing for 8 participants in the PPR group and 31 in the LARC group.
‡ Data on educational level were missing for 1 participant in the DMPA group and 3 in the LARC group.
§ Data on monthly income were missing for 60 participants in the PPR group, 1 in the DMPA group, and 74 in the ¶ “Receiving public assistance” was defined as self-reported current receipt of food stamps; vouchers from the supple- mentary nutritional program for women, infants, and children (WIC); welfare; or unemployment benefits.
∥ “Trouble paying basic expenses” was defined as self-reported difficulty in paying for transportation, housing, health or ** Data on health insurance were missing for 20 participants in the PPR group and 33 in the LARC group.
†† Data on previous unintended pregnancies were missing for 5 participants in the PPR group and 11 in the LARC group.
‡‡ Data are based on a self-reported history of chlamydia infection, gonorrhea, syphilis, trichomoniasis, genital herpes, human papillomavirus infection, or human immunodeficiency virus infection.
Information about periods of contraceptive was used). However, if the participant was un- use, including start and stop dates, was collected aware that the device had fallen out, the preg- from three sources: scheduled telephone inter- nancy was attributed to IUD failure.
views; pharmacy data obtained from the partner At each follow-up interview, we asked partici- pharmacy where participants obtained pills, pants if they were still using the same contra- patch, or ring; and the participant contraceptive- ceptive method, if they had stopped using it, and method log, which documented in our research their start and stop dates. For participants who records when the participant initiated or discon- did not answer these questions, we reviewed tinued use of a method or switched to another their contraceptive-method log and pharmacy- method (i.e., insertion or removal of an IUD or refill records to confirm their status. If the data implant; receipt of an initial pill supply, patch, from the log, follow-up interview, and pharmacy or ring; and DMPA injection). A participant was records were conflicting, we used the data source considered to have used DMPA for the 3-month with the most detailed information. If multiple interval after a record of an injection. In the case contraceptive methods were used simultaneously of expulsion of an IUD, if the participant knew (e.g., pills and condoms), the most effective meth- the device had fallen out and she became preg- od was assigned.9 Data from participants who nant, the unintended pregnancy was attributed were lost to follow-up were censored at the time to “no method” (unless an alternative method of their last completed interview.
n engl j med 366;21 nejm.org may 24, 2012 T h e n e w e ng l a n d j o u r na l o f m e dic i n e STUDY OUTCOMES
variables and a chi-square test was performed for The primary outcome of the study was contracep- categorical data.
tive failure. We also evaluated pregnancy rates by We measured distinct segments of contracep- age group as a secondary outcome. Our hypothe- tive-method use that represented the months each ses were, first, that participants using pills, patch, participant used the method. We calculated par- or ring would have higher rates of contraceptive ticipant-years of use for each method by captur- failure than those using long-acting methods ing all segments of use. Thus, participants who and, second, that the rate of failure with the pills, switched methods contributed distinct segments patch, or ring would be higher among younger to multiple methods. Cox proportional-hazard women and adolescents (<21 years of age) than models were used to estimate the hazard ratios for unintended pregnancy with different methods. We used clustering of variance–covariance estima- STATISTICAL ANALYSIS
tion methods to account for the effect of correla- Statistical analyses were performed with the use tion among different periods of contraceptive use of Stata software, version 11 (StataCorp). The sig- and multiple pregnancies for the same participant. nificance level (alpha) was set at 0.05. To describe Effect modification was assessed by including an the demographic characteristics of the study par- interaction term between the method and the co- ticipants, we used means, standard deviations, variate of interest in the model. The final multi- frequencies, and percentages. For the compari- variate model included adjustment for confounders son among users of different contraceptive meth- and other variables with the potential to influence ods, Student’s t-test was used for continuous the outcome.
Table 2. Baseline Characteristics of Participants with No Pregnancy and Those with an Unintended Pregnancy
during the Study Period.*
Unintended
No Pregnancy
Pregnancy
Characteristic
(N = 7152)
Educational level — no./total no. (%)‡ Trouble paying basic expenses — no. (%) n engl j med 366;21 nejm.org may 24, 2012 Table 2. (Continued.)
Unintended
No Pregnancy
Pregnancy
Characteristic
(N = 7152)
Previous unintended pregnancies — no./ * Plus–minus values are means (±SD). Percentages may not add up to 100 because of rounding.
† Data on race were missing for 39 participants in the no-pregnancy group.
‡ Data on educational level were missing for 4 participants in the no-pregnancy group.
§ Data on monthly income were missing for 127 participants in the no-pregnancy group and 8 in the unintended- ¶ Data on health insurance were missing for 50 participants in the no-pregnancy group and 3 in the unintended- ∥ Data on previous unintended pregnancies were missing for 15 participants in the no-pregnancy group and 1 in the mitted infection. Participants who chose DMPA injections were more likely to be black, to be less CHARACTERISTICS OF THE PARTICIPANTS
educated, to have a lower socioeconomic status, to From August 2007 through May 2011, a total of have no health insurance, and to have a history 8445 participants enrolled in the study, and 7486 of a sexually transmitted infection. Participants met the eligibility criteria for this analysis. We who chose an IUD or implant were more likely to identified 334 unintended pregnancies; of these, be older, to have public health insurance, and to 156 were attributed to IUD, implant, DMPA injec- have higher parity.
tion, pill, patch, or ring failure. Table 1 summa- Table 2 shows the baseline characteristics of rizes the demographic and reproductive charac- participants who had no pregnancy and those who teristics of the participants, according to the had an unintended pregnancy during the study method of contraception chosen at baseline. Par- period. Participants who had an unintended preg- ticipants who chose pills, patch, or ring at enroll- nancy were younger, less educated, more likely to ment, as compared with those who chose other be black, and more likely to rely on public assis- contraceptive methods, were more likely to be tance or to report difficulty paying for basic ex- nulliparous, more likely to have private health penses. They were also more likely to have a insurance, and less likely to have had a previous history of unintended pregnancy, abortion, or unintended pregnancy, abortion, or sexually trans- sexually transmitted infection.
n engl j med 366;21 nejm.org may 24, 2012 T h e n e w e ng l a n d j o u r na l o f m e dic i n e To determine whether participants less than 21 years of age who used pills, patch, or ring had a higher rate of unintended pregnancy than older women using these methods, we stratified our sample according to age. Participants less than 21 years of age who were using pills, patch, or ring had almost twice the risk of unintended pregnancy Contraceptive
as older women (hazard ratio after adjustment for educational level and history with respect to unin- tended pregnancy, 1.9; 95% CI, 1.2 to 2.8) (Fig. 2). The rate of contraceptive failure did not differ sig- Participants
nificantly according to age group among partici- pants who used DMPA injections or among those who used long-acting reversible contraception, but Figure 1. Cumulative Percentage of Participants Who Had a Contraceptive
numbers for these analyses were smaller and the Failure at 1, 2, or 3 Years, According to Contraceptive Method.
power to detect differences was low.
Bars depict the cumulative percentage of participants who had a contra-ceptive failure with long-acting reversible contraception (LARC), depot medroxyprogesterone acetate (DMPA), or pill, patch, or ring (PPR) at 1, 2, or 3 years. Participants using PPR had significantly more unintended preg- We found that participants using oral contracep- nancies than those using LARC (P<0.001) or DMPA (P<0.001).
tive pills, a transdermal patch, or a vaginal ring had a risk of contraceptive failure that was 20 times CONTRACEPTIVE FAILURE RATES
as high as the risk among those using long-acting Figure 1 shows the cumulative percentage of reversible contraception. The failure rate among participants with a contraceptive failure at 1, 2, participants who used pills, patch, or ring was or 3 years, according to the contraceptive method. 4.55 per 100 participant-years, as compared with At all three time points, participants using pills, 0.22 for those who used DMPA and 0.27 for those patch, or ring had higher rates of unintended preg- who used an IUD or implant. Participants less than nancy than those using long-acting reversible con- 21 years of age who used pills, patch, or ring had traception. Failure rates in the group of participants almost twice the risk of unintended pregnancy as who used the pills, patch, or ring were 4.8%, 7.8%, older women using the same methods.
and 9.4% in years 1, 2, and 3, respectively; the cor- Our findings on contraceptive-method effec- responding rates in the group using IUDs or im- tiveness are supported by previous studies. The plants were 0.3%, 0.6%, and 0.9% (P<0.001). The National Survey of Family Growth estimates that failure rates among participants who used DMPA 9% of women using oral contraceptive pills will injections were similar to those among participants have an unintended pregnancy within the first who used IUDs or implants (0.1%, 0.7%, and 0.7% year, as compared with only 0.001%, 0.14%, and for years 1, 2, and 3, respectively; P = 0.96).
0.7% of women who use the subdermal implant, Table 3 shows the risks of contraceptive failure levonorgestrel IUD, or copper IUD, respectively.8 associated with the chosen contraceptive meth- However, these data were derived from retrospec- ods and other characteristics of the participants. tive surveys that asked women to recall their con- The failure rate for the pills, patch, or ring was traceptive use and pregnancies over the past (on 4.55 per 100 participant-years, as compared with average) 3.75 years.4,8 The failure rate for DMPA 0.22 for DMPA injections and 0.27 for IUDs or injections in our study is lower than other re- implants (P<0.001 for both comparisons). The ported rates because we categorized a pregnancy risk of unintended pregnancy among participants as a contraceptive failure only in users who had using pills, patch, or ring was markedly higher returned for injections; thus, these rates repre- than that among participants who used long- sent “perfect use” rather than typical use, given acting reversible contraception (hazard ratio after that more than 40% of women who use DMPA adjustment for age, educational level, and number will discontinue use in the first year.10 of previous unintended pregnancies, 21.8; 95% Half of all pregnancies in the United States confidence interval [CI], 13.7 to 34.9).
are unintended, and half of those result from con- n engl j med 366;21 nejm.org may 24, 2012 Table 3. Hazard Ratio for Unintended Pregnancy, According to Contraceptive Method and Selected Characteristic.
Unintended
Pregnancy
Total Participant-
Variable
(N = 156)*
Incidence
Hazard Ratio (95% CI)†
* The remaining 178 of the 334 unintended pregnancies were attributed to failure of condoms, withdrawal, or any form of contraception that was not included in this analysis. Only periods of index contraceptive-method use (pills, patch, ring, DMPA injection, implant, or intrauter- ine device) and associated pregnancies were included in this analysis.
† Hazard ratios were adjusted for age, educational level, and number of previous unintended pregnancies.
traceptive failure.1,4 Among women using revers- College of Obstetricians and Gynecologists.15 ible contraception, 70% use pills or condoms,7 and Modern IUDs do not carry an increased risk of one in every eight users of reversible methods will pelvic inflammatory disease after the first 20 days have a contraceptive failure in the first year.4 We following insertion.16 Women who are at average have previously shown in the same cohort that risk for sexually transmitted infections are good participants using long-acting reversible methods candidates for IUDs, as long as they do not have of contraception have higher continuation rates cervicitis at the time of insertion.15 IUDs and im- (>80%) at 12 months than participants using plants are also associated with acceptable adverse- other reversible methods (range, 49 to 57%).10 If event rates among adolescents and nulliparous more women used the highly effective, long- women; satisfaction rates among adolescents and acting reversible methods, we would expect a young women using the levonorgestrel IUD or decrease in the number of unintended pregnan- the implant are similar to the rates among older cies, because there would be more women con- women.10,11,17 Implants also have very few contra- indications. Unpredictable bleeding is the most There are few contraindications to long-acting common side effect and the most frequent rea- reversible contraception; almost all women are son for discontinuation.18 eligible for an IUD or implant. The U.S. Medical In our age-stratified analysis, participants less Eligibility Criteria for Contraceptive Use provides than 21 years of age who used pills, patch, or guidelines from the Centers for Disease Control ring had a significantly increased risk of contra- and Prevention that are endorsed by the American ceptive failure, as compared with older women; in n engl j med 366;21 nejm.org may 24, 2012 T h e n e w e ng l a n d j o u r na l o f m e dic i n e sessment of contraceptive use (including objective pharmacy data), and a low rate of loss to follow-up. There are few prospective reports in the medical literature that assess the effectiveness of contra- ceptive methods in large, diverse U.S. populations. One limitation of our study is the nonrandom- ized design, resulting in potential confounding Pregnancy
of the association between contraceptive method and outcomes by characteristics associated with the choice of contraception. However, women Unintended
Probability
who chose long-acting methods tended to be less educated and to have higher rates of previ- ous pregnancies and abortions — features ex- pected to be associated with higher (not lower) rates of unintended pregnancy. In addition, study participants were a selected group (at high risk Figure 2. Probability of Not Having an Unintended Pregnancy, According to
for unintended pregnancy and willing to begin Contraceptive Method and Age.
using a new method). Insofar as women may be Survival curves show the probability of not having an unintended pregnan- more likely to consistently use a method they cy, stratified according to age group. LARC methods were the most effec- have chosen than one they have been assigned, tive, and failure rates did not vary according to age (P = 0.49). PPR methods were less effective, and failure rates in participants younger than 21 years the compliance rates may be higher, and failure old were twice as great as in women 21 years of age or older (P = 0.02).
rates lower, than would be expected in a ran- domized trial. Another potential limitation of our study is generalizability. Participants were at high risk for unintended pregnancy and had to be will- contrast, younger and older participants who ing to switch to a new contraceptive method, used an IUD, implant, or DMPA had similarly low which may have resulted in overestimation of con- risks of pregnancy. Other study data have also in- traceptive failure rates, as compared with rates in dicated that the risk of contraceptive failure with the general U.S. population. However, contracep- pills is more than twice as high among teenagers tion was provided at no cost, which may have im- as it is among women older than 30 years of age.4 proved adherence and led to an underestimation of The increased risk of contraceptive failure among failure rates, counterbalancing this potential bias.
adolescents, as compared with women, may reflect In conclusion, we found that long-acting revers- lower adherence to a daily pill regimen. In a sam- ible methods of contraception (IUDs or implants) ple of girls who were 14 to 17 years of age and were more effective in preventing unintended preg- who were seeking primary care, 25% of those who nancy than contraceptive pills, patch, or ring and used oral contraceptive pills reported that they worked well regardless of age.
missed taking two or more pills per cycle.19 These data underscore the potential benefits of offering Supported by the Susan Thompson Buffet Foundation.
Dr. Peipert reports receiving compensation for consultation and adolescents long-acting reversible contraception expert testimony for the defense regarding the association of (which does not require daily, weekly, or monthly thromboembolic disorders and the contraceptive vaginal ring, re- compliance) to reduce unintended pregnancies in ceiving lecture fees from Omnia Education and lecture fees to his institution from Merck as an etonogestrel-implant trainer, and re- ceiving royalties from Lippincott; and Dr. Madden, receiving lec- The strengths of our study include the prospec- ture fees from Bayer HealthCare Pharmaceuticals. No other poten- tive design of the Contraceptive CHOICE Project, tial conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with a large sample, multiple sources of data for as- the full text of this article at NEJM.org.
REFERENCES
1. Finer LB, Zolna MR. Unintended Henshaw SK. Estimated pregnancy rates being of children and families. Washing-
pregnancy in the United States: incidence for the United States, 1990-2005: an up- ton, DC: National Academy Press, 1995.
and disparities, 2006. Contraception 2011; date. Natl Vital Stat Rep 2009;58(4):1-14.
4. Kost K, Singh S, Vaughan B, Trussell J,
3. Brown S, Eisenberg L. The best inten-
2. Ventura SJ, Abma JC, Mosher WD, tions: unintended pregnancy and the well-
failure from the 2002 National Survey of n engl j med 366;21 nejm.org may 24, 2012 Family Growth. Contraception 2008;77: 10. Peipert JF, Zhao Q, Allsworth JE, et al. 15. U.S. medical eligibility criteria for
Continuation and satisfaction of revers- contraceptive use, 2010. MMWR Recomm 5. Finer LB, Henshaw SK. Disparities in ible contraception. Obstet Gynecol 2011; Rep 2010;59(RR-4):1-86.
rates of unintended pregnancy in the 117:1105-13.
16. Farley TM, Rosenberg MJ, Rowe PJ,
United States, 1994 and 2001. Perspect 11. ACOG Committee opinion no. 392, Chen JH, Meirik O. Intrauterine devices
December 2007: intrauterine device and and pelvic inflammatory disease: an in- 6. Frost JJ, Darroch JE, Remez L. Im-
adolescents. Obstet Gynecol 2007;110: ternational perspective. Lancet 1992;339: proving contraceptive use in the United 1493-5.
States. Issues Brief (Alan Guttmacher 12. Bajos N, Leridon H, Goulard H, Ous- 17. Davis AJ. Intrauterine devices in ado-
try P, Job-Spira N. Contraception: from lescents. Curr Opin Pediatr 2011;23:557- 7. Mosher WD, Jones J. Use of contra-
accessibility to efficiency. Hum Reprod 65.
ception in the United States: 1982-2008. 2003;18:994-9.
18. Mansour D, Korver T, Marintcheva-
13. Secura GM, Allsworth JE, Madden T, Petrova M, Fraser IS. The effects of Impla-
8. Fu H, Darroch JE, Haas T, Ranjit N. Mullersman JL, Peipert JF. The Contracep-
non on menstrual bleeding patterns. Eur J Contraceptive failure rates: new estimates tive CHOICE Project: reducing barriers Contracept Reprod Health Care 2008;13 from the 1995 National Survey of Family to long-acting reversible contraception. Suppl 1:13-28.
Growth. Fam Plann Perspect 1999;31:56- Am J Obstet Gynecol 2010;203(2):115.e1- 19. Woods JL, Shew ML, Tu W, Ofner S,
Ott MA, Fortenberry JD. Patterns of oral 9. Trussell J. Contraceptive efficacy. In: 14. Cleland K, Peipert JF, Westhoff C, contraceptive pill-taking and condom use
Hatcher RA, Nelson TJ, Guest F, Kowal D, Spear S, Trussell J. Family planning as among adolescent contraceptive pill us- eds. Contraceptive technology. 19th ed. a cost-saving preventive health service. ers. J Adolesc Health 2006;39:381-7.
New York: Ardent Media, 2007:747-826.
Copyright 2012 Massachusetts Medical Society. n engl j med 366;21 nejm.org may 24, 2012

Source: http://pcwhf.co.uk/images/Effectiveness%20of%20Long-Acting%20Reversible.pdf