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.

Is the multinational, surveillance PRO-E2 study informative for all countries? The Italian data on VTE and contraceptive effectiveness.

PURPOSE: To evaluate whether the thromboembolic risk and contraceptive effectiveness of NOMAC-E2 observed in the PRO-E2 study can be extended to each participating country, as lifestyle, cardiovascular risk factors and prescribing habits may differ geographically. This analysis was performed on the PRO-E2 Italian subpopulation, where smoking habit and women over 35 years were more prevalent compared with the overall study population. MATERIALS AND METHODS: Data from NOMAC-E2 or levonorgestrel-containing COCs (COCLNG) new users were descriptively analysed. Incidence rates of thrombosis (events/10,000 women-years [WY]) and the Pearl Index (pregnancies/100 WY) were calculated. RESULTS: Overall, 11,179 NOMAC-E2 and 8,504 COCLNG users were followed up to 2 years (34,869 WY). The NOMAC-E2 cohort included more women over 35 vs. COCLNG (37.7% vs. 31.8%; p = 0.001). A comparable low risk of combined deep venous thrombosis of lower extremities (DVT) and pulmonary embolism (PE) was observed in NOMAC-E2 (1.7/10,000 WY; 95% CI: 0.21-6.2) and COCLNG users (6.6/10,000 WY; 95% CI: 2.4-14.4). Similar results were obtained by considering all thromboembolic events (VTE). Unintended pregnancies did not differ between NOMAC-E2 (0.12/100 WY; 95% CI: 0.06-0.21) and COCLNG (0.15/100 WY; 95% CI: 0.08-0.26) cohorts. CONCLUSION: Despite the higher age and tobacco use, findings from the Italian subpopulation were broadly consistent with overall PRO-E2 results, confirming a similar low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 and COCLNG. SHORT CONDENSATION: This subgroup analysis of the PRO-E2 study provides comprehensive epidemiological data on the use of combined oral contraceptives in a large Italian cohort, with a higher prevalence of women over 35 years and smokers. The study confirms the low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 pill.

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.

Exploring rise of pregnancy in Bangladesh resulting from contraceptive failure.

The objective of this study was to determine how changes in pre-pregnancy contraceptive methods used between 2011 and 2017/18 contributed to the changes in pregnancy resulting from contraceptive methods failure in Bangladesh. We used 2011 and 2017/18 Bangladesh Demographic and Health Survey data. Pre-pregnancy contraceptive methods failure was our outcome of interest, which was determined using women's response about whether they became pregnant while using contraceptives before the most recent pregnancy. The year of the survey was the main explanatory variable. Descriptive statistics were used to describe the characteristics of the respondents. The difference in contraceptive methods failure across the socio-demographic characteristics was assessed by Chi-squared test. Multilevel poison regressions were used to determine the changes in the prevalence ratio of contraceptive methods failure across the survey years. Contraceptive methods failure rate increased between the surveys, from 22.8% in 2011 to 27.3% in 2017/18. Also, male condom use increased by 2.8%, while withdrawal/periodic abstinence and/or other methods decreased by 2.9%. The failure rates in these two categories of contraceptive methods increased substantially by 4.0% and 9.0%, respectively. Compared to the 2011 survey, the prevalence ratio (PR) of contraceptive methods failure was 20% (PR 1.2, 95% CI 1.1-1.3) high in the 2017/18 survey. This PR declined 13% (PR 1.1, 95% CI 1.04-1.2) once the model was adjusted for women's and their partner's characteristics along with the last contraceptives used. This study provides evidence of increasing rates of pregnancy due to contraceptive failure in Bangladesh. Given that this type of pregnancy is known to cause adverse pregnancy outcomes, including abortion, pregnancy complications, maternal and early child morbidity and mortality, policy and programs are needed to reduce its prevalence. Effective coordination between the contraception providers at the healthcare facilities and the households and a proactive role of family planning workers to make couples aware of the effective use of contraceptives are recommended.

A Semimechanistic Pharmacokinetic Model for Depot Medroxyprogesterone Acetate and Drug-Drug Interactions With Antiretroviral and Antituberculosis Treatment.

Depot medroxyprogesterone acetate is an injectable hormonal contraceptive, widely used by women of childbearing potential living with HIV and/or tuberculosis. As medroxyprogesterone acetate is a cytochrome P450 (CYP3A4) substrate, drug-drug interactions (DDIs) with antiretroviral or antituberculosis treatment may lead to subtherapeutic medroxyprogesterone acetate concentrations (< 0.1 ng/mL), resulting in contraception failure, when depot medroxyprogesterone is dosed at 12-week intervals. A pooled population pharmacokinetic analysis with 744 plasma medroxyprogesterone acetate concentrations from 138 women treated with depot medroxyprogesterone and antiretroviral/antituberculosis treatment across three clinical trials was performed. Monte Carlo simulations were performed to predict the percentage of participants with subtherapeutic medroxyprogesterone acetate concentrations and to derive alternative dosing strategies. Medroxyprogesterone acetate clearance increased by 24.7% with efavirenz coadministration. Efavirenz plus antituberculosis treatment (rifampicin + isoniazid) increased clearance by 52.4%. Conversely, lopinavir/ritonavir and nelfinavir decreased clearance (28.7% and 15.8%, respectively), but lopinavir/ritonavir also accelerated medroxyprogesterone acetate's appearance into the systemic circulation, thus shortening the terminal half-life. A higher risk of subtherapeutic medroxyprogesterone acetate concentrations at Week 12 was predicted on a typical 60-kg woman on efavirenz (4.99%) and efavirenz with antituberculosis treatment (6.08%) when compared with medroxyprogesterone acetate alone (2.91%). This risk increased in women with higher body weight. Simulations show that re-dosing every 8 to 10 weeks circumvents the risk of subtherapeutic medroxyprogesterone acetate exposure associated with these DDIs. Dosing depot medroxyprogesterone every 8 to 10 weeks should eliminate the risk of subtherapeutic medroxyprogesterone acetate exposure caused by coadministered efavirenz and/or antituberculosis treatment, thus reducing the risk of contraceptive failure.

Emerging approaches to male contraception.

Despite significant interests in contraception by men, effective methods of male contraception are limited to vasectomy and condoms. Recently, there have been several promising advances in male contraceptive research. This review will update readers on recent research in both hormonal and nonhormonal approaches to male contraception. Hormonal approaches to male contraception have been stymied by adverse effects, formulations requiring injections or implants, a 5% to10% nonresponse rate, as well as poor understanding of user acceptability. In the last several years, research has focused on novel, orally bioavailable androgens such as dimethandrolone undecanoate and 11ß-methyl-19-nor-testosterone. Additionally, combinations of a topical testosterone gel combined with a gel containing segesterone acetate, a potent progestin, have shown promise in clinical trials recently. Simultaneously, significant preclinical progress has been made in several approaches to nonhormonal male contraceptives, including compounds that inhibit sperm motility such as eppin, compounds that inhibit retinoic acid binding or biosynthesis, and reversible approaches to obstruction of the vas deferens. It is imperative for these areas of research to continue making strides so that there is a gamut of contraceptive options for couples to choose from. Some of these approaches will hopefully reach clinical utility soon, greatly improving contraceptive choice for couples.

Vasectomy and vasectomy reversal: a comprehensive approach to the evolving spectrum of care.

Male reproduction and male contraception form an important spectrum within men's health. In this issue's Views and Reviews, four author groups detail important new developments in vasectomy clinical practice guidelines, emerging and investigational techniques in the fields of hormonal and nonhormonal male contraception, useful paradigms for patient care when deciding between sperm extraction with in vitro fertilization and vasectomy reversal, and finally, a state-of-the-art overview of recent developments in vasectomy reversal microsurgery. These articles will provide readers with a contemporary understanding of the rapidly evolving spectrum of male reproductive and contraceptive health care.

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.

Efficacy as safety: Dominant cultural assumptions and the assessment of contraceptive risk.

To reduce rates of unintended pregnancy, medical and public health associations endorse a contraceptive counseling model that ranks birth control methods by failure rate. This tiered model outlines all forms of birth control but recommends long-acting reversible contraceptives (LARC) to eliminate user error and increase continuation. Our critical discourse analysis of gynecology textbooks and medical recommendations examines how gendered and neoliberal ideas influence risk assessments underlying the tiered contraceptive counseling model. Specifically, we explore how embodied, lifestyle, and medical risks are constructed to prioritize contraceptive failure over adverse side effects and reproductive autonomy. We find that the tiered model's focus on contraceptive failure is justified by a discourse that speciously conflates distinct characteristics of pharmaceuticals: efficacy (ability to produce intended effect) and safety (lack of unintended adverse outcomes). Efficacy discourse, which filters all logic through the lens of intended effect, magnifies lifestyle and embodied risks over medical risks by constructing two biased risk assessments. The first risk assessment defines ovulation, menstruation, and pregnancy as hazardous (i.e., embodied risk); the second insinuates that cisgender women who do not engage in contraceptive self-management are burdensome to society (i.e., lifestyle risk). Combined, these assessments downplay side effects (i.e., medical risks), suggesting that LARC and other pharma-contraceptives are worth the risk to protect cisgender women from their fertile bodies and to guard society against unintended pregnancy. Through this process, ranking birth control methods by failure rates rather than by side effects or reproductive autonomy becomes logical as efficacy is equated with safety for cisgender women and society. Our analysis reveals how technoscientific solutions are promoted to address social problems, and how informed contraceptive choice is diminished when pharma-contraceptives are framed as the most logical option without cogent descriptions of their associated risks.

Evaluation of the frequency of coitus interruptus and the effect of contraception counselling on this frequency.

In this prospective study, the aim was to determine the frequency and effectiveness of the coitus interruptus method, to compare the demographic characteristics of women using modern contraception methods and those using the coitus interruptus method and to demonstrate how effective contraceptive counselling is in choosing a contraception method. The researchers collected data from 1000 sexually active women in their reproductive period at the gynaecological clinic of a university hospital in Turkey. The researchers used an introductory information contraceptive counselling form, which they prepared for the data collection tool. The rate of the coitus interruptus method use among the interviewed women was 42.8%. There was a statistically significant difference between the coitus interruptus group and the group using modern contraceptive methods regarding mean age, educational status, smoking, awareness of last menstrual period, number of pads used during the menstrual period, and information sources. Following effective contraception counselling, the rate of switching to a modern and proven contraceptive method was found to be 73.8%.Impact statementWhat is already known on this subject? Although the traditional method of coitus interruptus has been used for many years, its incidence is not clearly known. What we know about the subject is based on ancient research. All the studies on the subject are very old and need to be updated.What do the results of this study add? With the help of the data obtained from this study, it is understood that withdrawal method is still widely used today, it is still not known that it is not a modern contraceptive method and the rate of transition to modern methods with effective contraception counselling is very high.What are the implications of these findings for clinical practice and/or further research? In the outpatient clinic conditions, even a very short period of time for contraception counselling will be very beneficial for women and will contribute to family planning and prevent unwanted pregnancies.

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.

Misrepresentation of contraceptive effectiveness rates for fertility awareness methods of family planning.

AIM: Simplified contraceptive method-efficacy and/or typical-use effectiveness rates are commonly used for direct comparison of the various contraceptive methods. Use of such effectiveness rates in this manner is, however, problematic in relation to the fertility awareness methods (FAMs). The aim of this review is to critically examine current international representation of contraceptive effectiveness for the various FAMs in clinical use. This review also details important issues when appraising and interpreting studies on FAMs used for avoiding pregnancy. METHODS: Current international literature regarding contraceptive effectiveness of FAMs was surveyed and appraised. This included World Health Organization and Centers for Disease Control (USA) resources, key clinical studies and recent systematic reviews. Chinese literature was also searched, since these data have not been reported in the English literature. RESULTS: Reliance on certain historical studies has led to the misrepresentation of contraceptive effectiveness of FAMs by perpetuation of inaccurate figures in clinical guidelines, the international literature and the public domain. Interpretation of published study results for FAMs is difficult due to variability in study methodology and other clinical trial quality issues. Recent systematic analyses have noted the considerable issues with study designs and limitations. Several non-English published studies using the Billings Ovulation Method have demonstrated that a broader review of the literature is required to better capture the data potentially available. CONCLUSION: A deeper understanding by clinicians and the public of the applicability of contraceptive effectiveness rates of the various FAMs is needed, instead of reliance on the inaccurate conglomerate figures that are widely presented.

Contraceptive Effectiveness of an FDA-Cleared Birth Control App: Results from the Natural Cycles U.S. Cohort.

Background: Digital fertility awareness-based methods of birth control are an attractive alternative to hormonal or invasive birth control for modern women. They are also popular among women who may be planning a pregnancy over the coming years and wish to learn about their individual menstrual cycle. The aim of this study was to assess the effectiveness of the Natural Cycles app at preventing pregnancy for a cohort of women from the United States and to describe the key demographics of current users of the app in such a cohort. Materials and Methods: This prospective real-world cohort study included users who purchased an annual subscription to prevent pregnancy. Demographics were assessed through answers to in-app questionnaires. Birth control effectiveness estimates for the entire cohort were calculated using 1-year pearl index (PI) and 13-cycle cumulative pregnancy probability (Kaplan-Meier life table analysis). Results: The study included 5879 women who contributed an average of 10.5 months of data for a total of 5125 woman-years of exposure. The average user was 30 years old with a body mass index of 24 and reported being in a stable relationship. With typical use, the app had a 13-cycle cumulative pregnancy probability of 7.2% and a 1-year typical use PI of 6.2. When the app was used under perfect use, the PI was 2.0. Conclusions: The data presented in this study give insights into the cohort of women using this app in the United States, and provide country-specific effectiveness estimates. The contraceptive effectiveness of the app was in line with previously published figures from Natural Cycles (PI of seven for typical use and two for perfect use).

Pearl Index study with levonorgestrel-releasing intravaginal rings: using pharmacokinetic results to investigate treatment compliance as a potential contributor for contraceptive failure.

STUDY QUESTION: What is the reason for insufficient contraceptive efficacy of levonorgestrel (LNG) delivered by intravaginal ring (IVR) releasing comparable amounts of LNG as approved progestogen-only pills (POPs)? SUMMARY ANSWER: The pharmacokinetic (PK) evaluation in a subpopulation indicated that the steady-state concentration of plasma LNG was markedly lower in the participants in the USA compared to those in Japan suggesting non-compliance in the US participants which may explain a clearly higher Pearl Index (PI) in USA (8.2, unadjusted PI) compared to Japan (1.4, unadjusted PI). WHAT IS KNOWN ALREADY: Contraceptive efficacy of LNG in POPs has been demonstrated following different routes of administration (e.g. orally, implants, intrauterine systems), and the PK is well-characterized including a target exposure needed for contraception. Exposure above this target concentration was reached in Phase 1 studies using IVR delivering 40 µg LNG per day. STUDY DESIGN, SIZE, DURATION: The primary objective of this multicenter, open-label, single-arm study conducted in the USA and in Japan was to assess the contraceptive efficacy of an LNG-containing IVR during a planned treatment period of 1 year in healthy women 18-35 years of age. The study was planned to be conducted in 1600 participants (1300 in the USA, 300 in Japan). The study was prematurely terminated after approximately one-third of the planned exposure was reached due to a high number of pregnancies (28) in the US study population. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 1471 participants were treated (1166 participants in the USA and 305 participants in Japan). The PI as a measure of contraceptive efficacy was calculated from the frequency of unintended pregnancies during treatment. LNG exposure in the systemic circulation was assessed during treatment in 136 participants (PK subgroups: 106 in the USA and 30 in Japan). MAIN RESULTS AND THE ROLE OF CHANCE: The PK evaluation in the PK subgroups indicated that the steady-state concentration of plasma LNG after 6 months was markedly lower in the participants in the USA (geometric mean 91.2 ng/l) compared to those in Japan (263.8 ng/l). This PK finding cannot be explained by the regional differences in body weight observed between the PK subgroups, thus suggesting non-compliance in the US participants. In 15.7% of the samples collected in the USA and 3.5% samples in Japan, the LNG concentration at steady state was below the lower limit of quantification (10 ng/l), which is not expected with the required continuous use of the IVR documented in most of the eDiaries. LIMITATIONS, REASONS FOR CAUTION: The planned duration of treatment was 12 months, but due to the premature termination of the study none of the participants completed the 12-month treatment. All data collected until the study termination were considered, but it is to be noted that the amount of missing data limits the conclusions that can be drawn from the data. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study triggered the termination of the project, because the objective to show sufficient contraceptive efficacy of the LNG IVR was not met. The choice of a user-dependent contraceptive method with an LNG dose that is not inhibiting ovulation is not advisable for women who may have compliance issues. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Bayer AG and all authors are employees of Bayer AG. TRIAL REGISTRATION NUMBER: NCT02403401.