A Longitudinal Multilevel Analysis of the Effects of Contraceptive Failures on Unintended Pregnancies among Women in Urban Nigeria.

Unintended pregnancy is a global public health concern. However, the effect of contraceptive failure on unintended pregnancy remains unclear in Nigeria. We undertook a longitudinal analysis to examine the effect of contraceptive failure on unintended pregnancy among urban women in Nigeria. We used panel data from the Nigerian Urban Reproductive Health Initiative. The Measurement, Learning and Evaluation program conducted the surveys among a cohort of women aged 15-49 who were first interviewed at baseline in 2010/2011 and followed up at endline in 2014/2015. Analytic sample was 4140 women aged 15-49 who ever used contraceptives. We fitted three-level multilevel binary logistic regression models estimated with GLLAMM. The study established evidence that there is a significant effect of contraceptive failure on unintended pregnancy among urban women in Nigeria. The positive effect of between-person contraceptive failure indicates that respondents who experienced more contraceptive failure than the average in the sample had 5.26 times higher odds of unintended pregnancy (OR = 5.26; p-value < 0.001). Results also established a significant effect of within-person contraceptive failures among the respondents. Findings suggest there is evidence of a significant longitudinal effect of contraceptive failure on unintended pregnancy in urban Nigeria. Efforts to reduce unintended pregnancy must include interventions to address the problem of contraceptive failure among urban women in Nigeria.

A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

PURPOSE: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. METHODS: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. RESULTS: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. CONCLUSIONS: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

NOMAC-E2 shows a better contraceptive effectiveness than LNG combined oral contraceptives in women under 25: real-world PRO-E2 study.

Objective: To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COCLNG) users under 25 years.Methods: In this large, observational study, new users (first-ever users of an eligible COC or restarting with the same or a new eligible COC after a break of at least 2 months) of NOMAC-E2 and COCLNG were recruited in 12 countries in Europe, Australia, and Latin America and followed up via questionnaires for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 women-years). Crude (HRcrude) and adjusted hazard ratios (HRadj) were calculated. Mood and acne changes were defined as change of score from baseline. Weight change was defined as percent change of body weight.Results: Overall, 12,829 NOMAC-E2 users and 17,095 COCLNG users under 25 were followed-up. The risk of unintended pregnancy was statistically significantly lower in the NOMAC-E2 cohort; confirmed events: 30 NOMAC-E2 (PI 0.24; 95% CI, 0.16-0.35) vs 94 COCLNG (PI 0.51; 95% CI, 0.41-0.62). The HRcrude for unintended pregnancy comparing NOMAC-E2 to COCLNG was 0.47 (95% CI, 0.31-0.71) and the HRadj was 0.52 (95% CI, 0.34-0.78). No differential effect on acne, mood, and weight was observed between cohorts.Conclusions: NOMAC-E2 shows a significantly better contraceptive effectiveness in young women and has no differential effect on acne, mood, and weight compared to COCLNG.

A rise in births following contraceptive failure in France between 2010 and 2016: results from the French national perinatal surveys.

BACKGROUND: In France, while the prevalence of contraception is high, a significant proportion of pregnancies are unintended. Following the 2012 pill scare, the contraceptive method mix, which was mostly comprised of pills and intrauterine devices (IUD), has become more diversified. In this changing landscape, our objective was to describe trends in live births resulting from contraceptive failure and evaluate how patterns of contraceptive use have contributed to observed changes between 2010 and 2016. METHODS: We used data from the 2010 and the 2016 French National Perinatal surveys which included all births from all maternity units in France over a one-week period. Interviews collecting information about pre-conception contraceptive practices were conducted in the maternity ward post-delivery. Women were classified as having a contraceptive failure if they discontinued contraception because they were pregnant. Our study sample included adult women who had a live birth, had ever used contraception and did not undergo infertility treatment (n = 11,590 in 2010 and n = 9703 in 2016). We evaluated changes in contraceptive failure over time using multivariate Poisson regressions to adjust for sociodemographic characteristics and pre-pregnancy contraceptive methods. RESULTS: Pre-pregnancy contraception evolved between 2010 and 2016 with a 12.3% point-drop in pill use, and conversely, 4.6%- and 3.2%-point increases in IUD and condom use, respectively. Use of other barrier or natural methods doubled between 2010 and 2016 but remained marginal (1.4% in 2010 vs 3.6% in 2016). Between 2010 and 2016, the proportion of live births resulting from contraceptive failure rose from 7.8 to 10.0%, with higher risks among younger, parous and socially disadvantaged mothers. The risk ratio of contraceptive failure in 2016 compared to 2010 remained higher after sociodemographic adjustments (aRR = 1.34; 95% CI; 1.23-1.47) and after adjusting for pre-pregnancy contraceptive method mix (aRR = 1.35; 95% CI; 1.25-1.49). Increases in contraceptive failures were concentrated among pill and condom users. CONCLUSIONS: Recent shifts in contraceptive behaviors in France following the 2012 pill scare may be associated with a subsequent increase in births resulting from short acting contraceptives failures.

Determinants of induced abortion in Tehran, Iran: the role of contraceptive failure.

OBJECTIVES: Induced abortion is highly restricted in Iran and many married women with unintended pregnancies resort to clandestine procedures, resulting in adverse health outcomes. As there is a lack of reliable data on abortion in Iran, this study aimed to examine factors predisposing women to practise abortion, factors facilitating the use of abortion and factors determining women's 'need' to use abortion to control their number of children. METHODS: The study used data from the 2014 Tehran Survey of Fertility, conducted among 3012 married women aged 15-49 years. Bivariate and multivariate binary logistic regression analyses were used. RESULTS: About 6% of women reported that they had had an abortion. The proportion was higher among women who were in their later reproductive years, women who were employed, women who intended to continue their education, women who reported a low level of religiosity, women who had two children and women who wanted no/no more children. Multivariate analysis showed that abortion was twice as high among women who had conceived their most recent birth because of the failure of a modern contraceptive method, compared with women who had discontinued or did not use a contraceptive method. CONCLUSION: The high risk of abortion among women experiencing failure of a modern contraceptive method indicates an unmet need for family planning counselling and education rather than a shortage of contraceptive methods.

Real-world cost-effectiveness of etonogestrel implants compared to long-term and short term reversible contraceptive methods in France.

BACKGROUND: To estimate the cost-effectiveness (CE) of etonogestrel implants compared to other long-term and short-term reversible contraceptive methods available in France. RESEARCH DESIGN AND METHODS: A 6-year Markov model compared effectiveness between the implant and six other contraceptive methods in sexually active, not-pregnancy-seeking French females of reproductive age. Contraception efficacy, switch rates and outcomes were based on French current medical practice. Incremental CE ratios (ICERs) were calculated as incremental cost per unintended pregnancy (UP) avoided. Efficiency frontier was plotted to identify cost-effective methods. Uncertainty was explored through sensitivity analyses. RESULTS: The implant was on the efficiency frontier along with combined oral contraceptive pill (COC) and copper IUD. Implant avoids between 0.75% and 3.53% additional UP per person-year compared to copper IUD and second generation COC, respectively, with an ICER of €2,221 per UP avoided compared to copper IUD. For the 240,000 French women currently using the implant, up to 8,475 UPs and up to 1,992 abortions may be prevented annually. CONCLUSION: With more unintended pregnancies avoided and comparable costs to copper IUD, the implant is a cost-effective option among long-term and short-term reversible contraceptive methods.

Unintended pregnancy in users of nomegestrol acetate and 17ß-oestradiol (NOMAC-E2) compared with levonorgestrel-containing combined oral contraceptives: final results from the PRO-E2 study.

OBJECTIVE: To assess and compare the risk of unintended pregnancy in NOMAC-E2 users with levonorgestrel-containing COC (COCLNG) users in clinical practice. STUDY DESIGN: In this observational study, new users1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (contraceptive failures per 100 women-years [WY]), crude hazard ratios (HRcrude) and adjusted hazard ratios (HRadj). RESULTS: Overall, 44,559 and 46,754 users were recruited to the NOMAC-E2 and COCLNG user cohorts, respectively. There were 64 unintended pregnancies in NOMAC-E2 users (0.15 per 100 WY; 95% CI, 0.11-0.19) and 200 in COCLNG users (0.41 per 100 WY; 95% CI, 0.35-0.47). The unintended pregnancy risk was statistically significantly lower in the NOMAC-E2 cohort (p<.0001) compared to the COCLNG user cohort. The HRadj of NOMAC-E2 vs COCLNG was 0.45 (95% CI, 0.34-0.60; adjusted for age, body mass index, gravidity, COC user status, education level). CONCLUSIONS: NOMAC-E2 demonstrated superior contraceptive effectiveness compared to COCLNG, likely due to the comparatively short hormone-free interval and possibly reinforced by the long half-life of NOMAC.

Unintended pregnancies in Hamedan, Iran: Levels and determinants.

The recent limitation in the provision of publicly funded family planning services in Iran has concerned stakeholders in reproductive health about the incidence of unintended pregnancies. This study used data from Hamedan Survey of Fertility (HSF), conducted in April-June 2015 among a representative sample of 3,000 married women aged 15-49 years living in the city of Hamedan (Iran), to estimate levels of unintended pregnancies and examine factors related to pregnancy intentions for the most recent birth, using multinomial logistic regression analyses. Results showed that 23 percent of pregnant women reported their pregnancy as unintended (17 percent mistimed and 6 percent unwanted). Moreover, unintended pregnancies in the five years preceding the survey were the result of failures of withdrawal (35 percent) and of modern contraceptive use (33 percent), along with contraceptive discontinuation (23 percent) and non-use (9 percent). Multivariate results indicated that the risk of unintended pregnancy was lower among women reporting modern contraceptive failures and lower among those reporting contraceptive discontinuation and non-use, compared with women experiencing withdrawal failures. The high incidence of unintended pregnancies among women experiencing contraceptive failures and discontinuation imply their high unmet need for contraceptive knowledge and counseling rather than for access to contraceptive methods.

Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review.

OBJECTIVE: The purpose of this study was to determine whether interactions between non-rifamycin antibiotics and hormonal contraceptives result in decreased effectiveness or increased toxicity of either therapy. STUDY DESIGN: We searched MEDLINE, Embase, clinicaltrials.gov, and Cochrane libraries from database inception through June 2016. We included trials, cohort, case-control, and pharmacokinetic studies in any language that addressed pregnancy rates, pharmacodynamics, or pharmacokinetic outcomes when any hormonal contraceptive and non-rifamycin antibiotic were administered together vs apart. Of 7291 original records that were identified, 29 met criteria for inclusion. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently assessed study quality and risk of bias using the United States Preventive Services Task Force evidence grading system. Findings were tabulated by drug class. RESULTS: Study quality ranged from good to poor and addressed only oral contraceptive pills, emergency contraception pills, and the combined vaginal ring. Two studies demonstrated no difference in pregnancy rates in women who used oral contraceptives with and without non-rifamycin antibiotics. No differences in ovulation suppression or breakthrough bleeding were observed in any study that combined hormonal contraceptives with any antibiotic. No significant decreases in any progestin pharmacokinetic parameter occurred during co-administration with any antibiotic. Ethinyl estradiol area under the curve decreased when administered with dirithromycin, but no other drug. CONCLUSION: Evidence from clinical and pharmacokinetic outcomes studies does not support the existence of drug interactions between hormonal contraception and non-rifamycin antibiotics. Data are limited by low quantity and quality for some drug classes. Most women can expect no reduction in hormonal contraceptive effect with the concurrent use of non-rifamycin antibiotics.

Drug interactions between rifamycin antibiotics and hormonal contraception: a systematic review.

BACKGROUND: Rifamycin antibiotics are commonly used for treatment of tuberculosis, but may reduce the effectiveness of hormonal contraception (HC). OBJECTIVES: To determine whether interactions between rifamycins and HC result in decreased effectiveness or increased toxicity of either therapy. SEARCH STRATEGY: We searched MEDLINE, Embase, Cochrane and clinicaltrials.gov through May 2017. SELECTION CRITERIA: We included trials, cohort, and case-control studies addressing pregnancy rates, pharmacodynamics or pharmacokinetic (PK) outcomes when HC and rifamycins were administered together versus apart. Of 7291 original records identified, 11 met inclusion criteria after independent review by two authors. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted study details and assessed study quality using the United States Preventive Services Task Force grading system. Findings are reported descriptively. MAIN RESULTS: Studies only addressed combined oral contraceptives (COCs) and none reported pregnancy rates. Quality ranged from good to poor. Rifampin increased the frequency of ovulation in two of four studies, and reduced estrogen and/or progestin exposure in five studies. Rifabutin led to smaller PK changes than rifampin in two studies. In one study each, rifaximin and rifalazil did not alter hormone PK. CONCLUSIONS: No studies evaluated pregnancy risk or non-oral HCs. PK and ovulation outcomes support a clinically concerning drug interaction between COCs and rifampin, and to a lesser extent rifabutin. Data are limited for other rifamycins. TWEETABLE ABSTRACT: Rifampin and rifabutin reduce systemic exposure of oral contraceptives, but no studies have evaluated pregnancy risk.

Association between knowledge about levonorgestrel emergency contraception and the risk of ectopic pregnancy following levonorgestrel emergency contraception failure: a comparative survey.

OBJECTIVE: To study the association between knowledge about levonorgestrel emergency contraception (LNG-EC) and the risk of ectopic pregnancy (EP) following LNG-EC failure. METHODS: This study included 600 women who had visited the hospital with LNG-EC failure. Of these, 300 with EP and 300 with intrauterine pregnancy (IUP) were recruited to the EP group and IUP group respectively. The participants were interviewed face-to-face using a standardized questionnaire. MAIN OUTCOME MEASURES: Pearson's chi-square tests and t-test were used to compare the sociodemographic characteristics, reproductive and gynecological history, surgical history, previous contraceptive experience, and answers to 10 questions concerning the knowledge about LNG-EC. RESULTS: Those who gave incorrect answers to the question regarding the basic mechanism and specific method of levonorgestrel emergency contraceptive pills (LNG-ECPs) were at a higher risk of EP after LNG-EC failure. Women who did not strictly follow instructions or advice from healthcare professionals were more likely to subsequently experience EP (p < 10(-4) ). Women with LNG-EC failure reported friends/peers, TV, and Internet as the main sources of information. No difference was observed with regard to the sources of knowledge on LNG-EC (p = 0.07). CONCLUSIONS: The results illustrate the importance of strictly following the doctor's guidance or drug instructions when using LNG-ECPs. The media should be used to disseminate information about responsible EC, and pharmacy staff should receive regular educational training sessions in this regard. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Contraceptive failure with Copper T380A intrauterine device (IUD): A single tertiary center experience.

OBJECTIVE: The objective of this study was to assess the risk factors of pregnancy with Copper (Cu)T380A IUD and pregnancy outcomes. METHODS: A retrospective study evaluating the risk factors and pregnancy outcomes of 81 patients who conceived with CuT380A IUD in situ. RESULTS: Four ectopic pregnancies and 77 intrauterine pregnancies were detected. Twenty-six pregnancies (33.76%, 26/77) were terminated according to maternal desire. Twenty-five patients (32.46%, 25/77) whose IUDs were removed constituted the Removed IUD Group, and the remaining 26 patients constituted IUD Left in situ Group. Term pregnancy rates (76% vs. 20.8%, p=0.002) were significantly higher in the Removed IUD Group compared with the IUD Left in situ Group. Abortion rates (16% vs. 53.84%, p=0.008) were detected significantly higher in the IUD Left in situ Group. CONCLUSION: The main result of our study was that pregnancy with CuT380A in situ is a significant risk factor for adverse perinatal outcome. Adjusting the scheduled follow-ups for checking the IUD seems to be important in order to prevent accidental pregnancy.

European society of contraception statement on contraception in obese women.

The obesity 'epidemic' continues to increase, mostly but not only in developed countries. As overweight and obese women are at an increased risk for venous thromboembolism (VTE) at baseline and at a much higher risk during pregnancy, it is essential to help these women to plan pregnancies carefully and to use contraceptives with a positive ratio of benefits versus risks. The Expert Group on hormonal and molecular contraception of the European Society of Contraception convened to review the existing evidence and propose recommendations to the prescribers in line with most recent studies and with the Medical Eligibility Criteria of the World Health Organisation.

Contraceptive Risk Events among Family Planning Specialists: a Cross Sectional Study.

Background: Proponents of abortion restriction cite advancements in contraceptive technology as a reason against the need for abortion care today, most recently through oral arguments in the Supreme Court of the United States case, Dobbs v. Jackson Women's Health. However, consistent and correct use of contraception requires reproductive health literacy. Our objectives were to quantify contraceptive risk events and assess contraceptive history and preferences among a population well-equipped to evade contraceptive risks, family planning specialists following initiation of their medical training. "Risk events" are defined as reported episodes of contraceptive failure, emergency contraception use and/or unprotected or underprotected intercourse. Methods: This was a cross-sectional study among current members of a professional organization of family planning specialists. Inclusion criteria included: status as a current or retired clinician, consensual penile-vaginal intercourse since the start of medical training, and personal or partner capacity to become pregnant. Descriptive statistics were performed. This study was IRB exempt. Results: Among 229 respondents, 157 (69%) reported experiencing a contraceptive risk event since training. Twenty-nine (13%) respondents reported an occurrence within the last year. By category, 47% (108/229; 3 reported unknown) reported under- or unprotected intercourse, 35% (81/229) reported emergency contraception use, and 52% of participants (117/227; 2 unknown) reported known or suspected contraceptive failure. The mean number of contraceptive methods used was 3.7 (SD 1.7) out of the 13 methods listed. Almost all (97%) participants reported at least one method was not an acceptable option, with a mean of 5.6 (SD 2.7) of the 13 listed methods. Conclusions: The majority of family planning specialists have experienced contraceptive risk events during times of active pregnancy prevention since their medical training. Contraceptive method change is common and most respondents were limited in the number of methods that were personally acceptable to them. Dialogue idealizing the role of contraception in minimizing or eliminating abortion need is simplistic and inaccurately represents the lived realities of pregnancy-capable individuals and their partners, including among those with exceptional contraceptive literacy and access.

Prevalence of discontinuation of contraceptives due to failure among women aged 14 to 49 years in Uganda: a nation wide cross-sectional survey.

BACKGROUND: Sustained motivation is essential for effective use of contraceptive methods by women in low- and middle-income countries as many women are likely to abandon contraceptives, especially when they continually experience episodes of failure. We aimed to determine the prevalence of discontinuation of contraceptives due to failure and its associated factors among Ugandan women aged 14-49 years. METHODS: A cross sectional study was conducted using the UDHS 2016 data. Multi stage stratified sampling was used to select participants. All eligible women aged 15 to 49 years at the time of the survey were enrolled. Bivariable and Multivariable logistic regression analysis were used to determine the factors associated with contraceptive failure. All analysis were done using Stata version 13. Contraceptive failure (getting pregnant while on contraceptives) within five years preceding the survey was the dependent variable. RESULTS: A total of 9061 women were included in the study. The overall prevalence of contraceptive failure was 5.6% [n = 506, 95% CI: 5.1-6.1] and was higher (6.2%) among women aged 20-29 years or had completed secondary education (6.1%). Having informed choice on contraceptives [aOR = 0.59, 95% CI: 0.49 - 0.72] and older age [aOR = 0.46, 95% CI: 0.24-0.89] were associated with lower odds of contraceptive failure. CONCLUSION: The burden of contraceptive failure among women of reproductive age in Uganda is substantial and significantly varied by women's age, level of education, exposure to the internet, mass media, and informed choice. These findings highlight the need for improved counseling services and contraceptive quality to help women and couples use methods correctly and consistently.

Understanding contraceptive failure: an analysis of qualitative narratives.

Most American women wanting to avoid pregnancy use contraception, yet contraceptive failures are common. Guided by the Health Belief Model (HBM), we conducted a secondary qualitative analysis of interviews with women who described experiencing a contraceptive failure (n=69) to examine why and how this outcome occurs. We found three primary drivers of contraceptive failures (health literacy and beliefs, partners and relationships, and structural barriers), and we identified pathways through which these drivers led to contraceptive failures that resulted in pregnancy. These findings have implications for how individuals can be better supported to select their preferred contraception during clinical contraceptive discussions.

Pregnancy and pregnancy outcomes in a prospective cohort study: Final results from the Nexplanon Observational Risk Assessment Study (NORA).

OBJECTIVES: To monitor pregnancy occurrence and outcomes among Nexplanon users in the United States during standard clinical practice. STUDY DESIGN: The Nexplanon Observational Risk Assessment (NORA) study was a large prospective cohort study conducted in the United States (US). Study participants with a newly inserted Nexplanon implant were recruited by health care professionals (HCPs) who had completed the Nexplanon clinical training. Via a survey, study participants were followed up at 6-month intervals for 36 months and 6 months after implant removal. Reported unintended pregnancies were validated and classified as noninsertion, preinsertion, during-use, or postremoval. RESULTS: Four hundred and twenty-eight HCPs in 47 states recruited 7364 Nexplanon users. Pregnancies included one noninsertion, eight preinsertion, three during-use, and 14 postremoval pregnancies; of these 26 pregnancies, 22 resulted in the birth of a healthy child, two resulted in an induced abortion, one resulted in a spontaneous abortion, and one resulted in an ectopic pregnancy. Six pregnancies occurred during-use (n = 3) or within 7 days following implant removal (n = 3), yielding a Pearl Index of 0.04 (95% CI, 0.02-0.09). CONCLUSIONS: Nexplanon is an effective contraceptive in real-world users; the Pearl Index was 0.02 (95% CI, 0.00-0.06) for during-use pregnancies, and 0.04 when including pregnancies that occurred within 7 days following implant removal. IMPLICATIONS: This large real-world-use study indicates that Nexplanon is as effective as shown in the preapproval clinical trials.

Etonogestrel contraceptive implant failure in a woman taking rifampin: a case report.

BACKGROUND: The etonogestrel subdermal implant is the most efficacious hormonal contraceptive currently available and provides 99.7% effective contraception. However, similar to other hormonal contraception, its effectiveness is compromised with the use of cytochrome P450 inducing drugs resulting in an unplanned pregnancy. Despite this risk, little is known about the outcome of concomitant use of rifampin and contraceptive implants. CASE PRESENTATION: A 24-year-old woman was provided with an etonogestrel implant in September 2018. In July 2020, she was started with rifampin based anti-tuberculosis for tuberculosis of the lymph nodes. In December 2020, she presented to the family planning clinic of St. Paul's Hospital Millennium Medical college with a diagnosis of failed implant and second-trimester pregnancy at a gestational age of 19 weeks. The etonogestrel implant was removed and the patient was linked to antenatal care follow up. CONCLUSION: Concomitant use of hepatic cytochrome P450 enzyme-inducing medications with certain hormonal contraceptives may reduce effectiveness resulting in unintended pregnancy. Women should be given detailed counseling about the potential for drug interactions and a multidisciplinary approach with consultation or referral to reproductive health specialists is crucial for optimal management of women who are at increased risk of contraceptive failure and unintended pregnancy.

Comparison of contraceptive failures associated with CYP3A4-inducing drug-drug interactions by route of hormonal contraceptive in an adverse event reporting system.

OBJECTIVE: To estimate associations between contraceptive failures and concomitant CYP3A4-inducing medications by route of administration. STUDY DESIGN: Comparison of unintended pregnancy outcomes within U.S. Food and Drug Administration's Adverse Event Reporting System by couse of CYP3A4-inducing drugs and route of administration for levonorgestrel and etonogestrel/desogestrel. RESULTS: Among 14,504 levonorgestrel case reports, the reporting odds ratio (ROR) was increased for oral (ROR = 4.2 [3.0-5.7]), implants (ROR = 8.0 [5.8-11.0]), but not intrauterine (ROR = 0.9 [0.6-1.3]) levonorgestrel products. For 9348 etonogestrel/desogestrel case reports, oral and vaginal products were not associated with contraceptive failure. Etonogestrel containing implants (ROR = 4.9 [4.1-5.9]) were associated with increased contraceptive failure. CONCLUSION: Levonorgestrel containing combination oral products and implants containing levonorgestrel or etonogestrel were prone to CYP3A4-inducing drug-drug interactions that may increase contraceptive failures. IMPLICATIONS: The progestin components of hormonal contraceptives are susceptible to drug-drug interactions, but this susceptibility is influenced by route of administration. This study provides evidence from an Adverse Event Reporting System that CYP3A4-inducing medications increase the risk of unintended pregnancy for oral and implant contraceptives but not intrauterine or vaginal devices.