OBJECTIVES: To provide updated and more detailed pooled IUD expulsion rates and expulsion risk estimates among women with postpartum IUD placement by timing of insertion, delivery type, and IUD type to inform current IUD insertion practices in the United States. DATA SOURCES: We searched PubMed, Cochrane Library, and ClinicalTrials.gov through June 2019. STUDY ELIGIBILITY CRITERIA: We included all studies, of any study design, that examined postpartum placement of Copper T380A (copper) or Levonorgestrel (LNG)-containing IUDs that reported counts of expulsion. STUDY APPRAISAL AND SYNTHESIS METHODS: We evaluated IUD expulsion among women receiving postpartum IUDs in the 'immediate' (within 10 minutes), 'early inpatient' (greater than 10 minutes to less than 72 hours), 'early outpatient' (72 hours to less than 4 weeks) and interval (4 weeks or greater) time periods after delivery. We assessed study quality using the U.S. Preventive Services Task Force evidence grading system. We calculated pooled absolute rates of partial and complete IUD expulsion separately and estimated adjusted relative risks by the timing of postpartum placement, delivery type and IUD type using log-binomial multivariable regression. RESULTS: We identified 48 level I to II-3 studies of poor to good quality that reported a total of 7,661 IUD placements. Complete IUD expulsion rates varied by timing of placement: 10.2% (range 0.0-26.7) for immediate, 13.2% (3.5-46.7) for early inpatient, 0% for early outpatient, and 1.8% (0.0-4.8) for interval placements. Complete IUD expulsion rates also varied by delivery type: 14.8% (range 4.8-43.1) for vaginal and 3.8% (0.0-21.1) for cesarean deliveries. Among immediate postpartum vaginal placements, the expulsion rate for LNG-IUDs was 27.4% (18.8-45.2) and 12.4% (4.8-43.1) for copper IUDs. Compared with interval placement, immediate and early postpartum placements (inpatient and outpatient combined) were associated with greater risk of complete expulsions (adjusted RR (aRR), 8.33; 95% CI, 4.32-16.08 and aRR, 5.27; 95% CI, 2.56-10.85, respectively). Among immediate postpartum placements, risk of expulsion was greater for placement after vaginal compared with cesarean deliveries (aRR, 4.57; 95% CI, 3.49-5.99). Among immediate placements at the time of vaginal delivery, LNG-IUDs were associated with a greater risk of expulsion compared with copper IUDs (aRR, 1.90; 95% CI, 1.36-2.65). CONCLUSION: While IUD expulsion rates vary by timing of placement, type, and mode of delivery, IUD insertion can take place at any time. Understanding the risk of IUD expulsion at each time period will enable women to make an informed choice about when to initiate an IUD in the postpartum period based on her own goals and preferences.

In response to the Zika virus outbreak in Puerto Rico (2015-2016), the Zika Contraception Access Network (Z-CAN) was established to provide same-day access to the full range of reversible contraception at no cost to women. Formative research was conducted to inform the development of a communication campaign about Z-CAN. Ten focus groups with women and men, aged 18 to 49 years, in Puerto Rico were conducted to collect data on contraception awareness, use, and decision making during the Zika outbreak, as well as culturally appropriate messaging and outreach strategies. Thematic analysis was conducted using the constant comparative method. Data showed that there was community awareness regarding Zika in Puerto Rico. However, it was not a motivating factor in contraception decision making; instead, economic factors were the major drivers. Most participants preferred to receive information on contraception, potential side effects, and where to access contraceptive services via Internet-based channels and health care providers. Based on these findings, the Ante La Duda, Pregunta [When in Doubt, Ask] campaign was launched to promote awareness of Z-CAN services among those who chose to prevent pregnancy during the Zika outbreak. Our results underscore the importance of conducting formative research to develop communication initiatives, while also demonstrating that it is feasible to perform these activities as part of an emergency response.

OBJECTIVE: To estimate expulsion rates among women with postpartum intrauterine device (IUD) placement by timing of insertion, IUD type, and delivery method. DATA SOURCES: We searched PubMed, Cochrane Library, and ClinicalTrials.gov from 1974 to May 2018. METHODS OF STUDY SELECTION: We searched databases for any published studies that examined postpartum placement of a copper IUD or levonorgestrel intrauterine system and reported counts of expulsions. We assessed study quality using the U.S. Preventive Services Task Force evidence grading system. We calculated pooled absolute rates of IUD expulsion and estimated adjusted relative risks (RRs) for timing of postpartum placement, delivery method, and IUD type using log-binomial multivariable regression model. TABULATION, INTEGRATION, AND RESULTS: We identified 48 level I to II-3 studies of poor to good quality. Pooled rates of expulsion varied by timing of IUD placement, ranging from 1.9% with interval placements (4 weeks postpartum or greater), 10.0% for immediate placements (10 minutes or less after placental delivery), and 29.7% for early placements (greater than 10 minutes to less than 4 weeks postpartum). Immediate and early postpartum placements were associated with increased risk of expulsion compared with interval placement (adjusted RR 7.63, 95% CI 4.31-13.51; adjusted RR 6.17, 95% CI 3.19-11.93, respectively). Postpartum placement less than 4 weeks after vaginal delivery was associated with an increased risk of expulsion compared with cesarean delivery (adjusted RR 5.19, 95% CI 3.85-6.99). Analysis of expulsion rates at less than 4 weeks postpartum also indicated that the levonorgestrel intrauterine system was associated with a higher risk of expulsion (adjusted RR 1.91, 95% CI 1.50-2.43) compared with CuT380A. CONCLUSION: Postpartum IUD expulsion rates vary by timing of placement, delivery method, and IUD type. These results can aid in counseling women to make an informed choice about when to initiate their IUD and to help institutions implement postpartum contraception programs.

Potential drug interactions with hormonal contraceptives are an important public health concern. A public meeting on "Drug Interactions With Hormonal Contraceptives: Public Health and Drug Development Implication" was hosted by the United States Food and Drug Administration (FDA). The meeting endeavored to provide an opportunity for the FDA to seek input from experts on the public health concerns associated with the use of hormonal contraceptives and interacting drugs that might affect efficacy and safety, including pharmacokinetic/pharmacodynamic considerations, in the design of drug interaction studies of hormonal contraceptives for drug development and approaches to translating the results of drug interaction information into informative labeling and communication. The input received could be used to refine FDA's thinking on hormonal contraceptives drug interaction study design and interpretation and labeling communication of drug interaction risk. This meeting benefited from strong and diverse participation from the Center for Drug Evaluation and Research at the FDA, Centers for Disease Control and Prevention, National Institutes of Health, Swedish Medical Products Agency, pharmaceutical industry, and representatives of academia. This report provides a summary of the key discussion based on the presentations and panel discussion.

BACKGROUND: Prevention of unintended pregnancy is a primary strategy to reduce adverse pregnancy and birth outcomes related to Zika virus infection. The Zika Contraception Access Network (Z-CAN) aimed to build a network of health-care providers offering client-centred contraceptive counselling and the full range of reversible contraception at no cost to women in Puerto Rico who chose to prevent pregnancy during the 2016-17 Zika virus outbreak. Here, we describe the Z-CAN programme design, implementation activities, and baseline characteristics of the first 21 124 participants. METHODS: Z-CAN was developed by establishing partnerships between federal agencies, territorial health agencies, private corporations, and domestic philanthropic and non-profit organisations in the continental USA and Puerto Rico. Private donations to the National Foundation for the Centers for Disease Control and Prevention (CDCF) secured a supply of reversible contraceptive methods (including long-acting reversible contraception), made available to non-sterilised women of reproductive age at no cost through provider reimbursements and infrastructure supported by the CDCF. To build capacity in contraception service provision, doctors and clinic staff from all public health regions and nearly all municipalities in Puerto Rico were recruited into the programme. All providers completed 1 day of comprehensive training in contraception knowledge, counselling, and initiation and management, including the insertion and removal of long-acting reversible contraceptives (LARCs). Z-CAN was announced through health-care providers, word of mouth, and a health education campaign. Descriptive characteristics of programme providers and participants were recorded, and we estimated the factors associated with choosing and receiving a LARC method. As part of a Z-CAN programme monitoring plan, participants were invited to complete a patient satisfaction survey about whether they had obtained free, same-day access to their chosen contraceptive method after receiving comprehensive counselling, their perception of the quality of care they had received, and their satisfaction with their chosen method and services. FINDINGS: Between May 4, 2016, and Aug 15, 2017, 153 providers in the Z-CAN programme provided services to 21 124 women. 20 110 (95%) women received same-day provision of a reversible contraceptive method. Whereas only 767 (4%) women had used a LARC method before Z-CAN, 14 259 (68%) chose and received a LARC method at their initial visit. Of the women who received a LARC method, 10 808 (76%) women had used no method or a least effective method of contraception (ie, condoms or withdrawal) before their Z-CAN visit. Of the 3489 women who participated in a patient satisfaction survey, 3068 (93%) of 3294 women were very satisfied with the services received, and 3216 (93%) of 3478 women reported receiving the method that they were most interested in after receiving counselling. 2382 (78%) of 3040 women rated their care as excellent or very good. INTERPRETATION: Z-CAN was designed as a short-term response for rapid implementation of reversible contraceptive services in a complex emergency setting in Puerto Rico and has served more than 21 000 women. This model could be replicated or adapted as part of future emergency preparedness and response efforts. FUNDING: National Foundation for the Centers for Disease Control and Prevention.

Correct and consistent use of contraception decreases the risk of unintended pregnancy; yet, outdated policies or practices can delay initiation or hinder continuation of contraceptive methods. To promote the quality of, and access to, family planning services, WHO created a series of evidence-based guidance documents for family planning, known as WHO’s Four Cornerstones of Family Planning Guidance (Fig. 1). The Medical eligibility criteria for contraceptive use (MEC), first published in 1996,1 provides guidance on the safety of various contraceptive methods in users with specific health conditions or characteristics (i.e. who can use a contraceptive method safely). The Selected practice recommendations for contraceptive use (SPR) is the second cornerstone,2 outlining how to safely and effectively use contraceptive methods. These two documents can serve as a reference for policymakers and program managers as they develop their own national family planning policies in the context of local needs, values, and resources. The two other cornerstone documents—the Decision making tool for family planning clients and providers3 and Family planning: a global handbook for providers4—provide guidance to healthcare providers for applying these recommendations in practice.

The US Medical Eligibility Criteria for Contraceptive Use (US MEC) and the US Selected Practice Recommendations for Contraceptive Use (US SPR) were first adapted by the Centers for Disease Control and Prevention (CDC) from their World Health Organization counterparts in 2010 and 2013, respectively [1], [2]. These evidence-based guidance documents provide critically important information for health care providers on the safety of contraceptive methods for women with specific characteristics or medical conditions (US MEC) and on common but sometimes complex clinical issues regarding how to use contraceptive methods in select circumstances (US SPR). Through knowledge and use of the contraception guidance, providers are helping women select and use safe and effective contraceptive methods. Some of these methods may not otherwise have been considered due to patient or provider concerns about potential risks given the patient's particular characteristics or underlying medical condition, or their use may have been delayed due to unnecessary tests prior to initiation. The US MEC and US SPR remove unnecessary medical barriers to access and use of effective contraceptive methods; this is especially important for women with medical conditions associated with heightened risk during pregnancy [1]. | Between August 2014 and August 2015, CDC conducted a formal process to update the 2010 US MEC and the 2013 US SPR. Through this process, CDC identified topics warranting systematic reviews of published evidence to help inform recommendation updates and to serve as a basis for the addition of new topics to the existing guidance. Systematic reviews were then conducted, presented and discussed at a meeting of national family planning experts, and CDC determined the final recommendations. As part of this review process, gaps in the evidence were identified for which research is needed to further inform the recommendations. In this paper, we list these research gaps (Tables 1 and 2) and explore three of the topics in depth.

Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities. Since 2015, Zika virus has been spreading through much of the World Health Organization's Region of the Americas, including U.S. territories. Zika virus is spread through the bite of Aedes aegypti or Aedes albopictus mosquitoes, by sex with an infected partner, or from a pregnant woman to her fetus during pregnancy. CDC estimates that 41 states are in the potential range of Aedes aegypti or Aedes albopictus mosquitoes, and on July 29, 2016, the Florida Department of Health identified an area in one neighborhood of Miami where Zika virus infections in multiple persons are being spread by bites of local mosquitoes. These are the first known cases of local mosquito-borne Zika virus transmission in the continental United States.(dagger) CDC prevention efforts include mosquito surveillance and control, targeted education about Zika virus and condom use to prevent sexual transmission, and guidance for providers on contraceptive counseling to reduce unintended pregnancy. To estimate the prevalence of contraceptive use among nonpregnant and postpartum women at risk for unintended pregnancy and sexually active female high school students living in the 41 states where mosquito-borne transmission might be possible, CDC used 2011-2013 and 2015 survey data from four state-based surveillance systems: the Behavioral Risk Factor Surveillance System (BRFSS, 2011-2013), which surveys adult women; the Pregnancy Risk Assessment Monitoring System (PRAMS, 2013) and the Maternal and Infant Health Assessment (MIHA, 2013), which surveys women with a recent live birth; and the Youth Risk Behavior Survey (YRBS, 2015), which surveys students in grades 9-12. CDC defines an unintended pregnancy as one that is either unwanted (i.e., the pregnancy occurred when no children, or no more children, were desired) or mistimed (i.e., the pregnancy occurred earlier than desired). The proportion of women at risk for unintended pregnancy who used a highly effective reversible method, known as long-acting reversible contraception (LARC), ranged from 5.5% to 18.9% for BRFSS-surveyed women and 6.9% to 30.5% for PRAMS/MIHA-surveyed women. The proportion of women not using any contraception ranged from 12.3% to 34.3% (BRFSS) and from 3.5% to 15.3% (PRAMS/MIHA). YRBS data indicated that among sexually active female high school students, use of LARC at last intercourse ranged from 1.7% to 8.4%, and use of no contraception ranged from 7.3% to 22.8%. In the context of Zika preparedness, the full range of contraceptive methods approved by the Food and Drug Administration (FDA), including LARC, should be readily available and accessible for women who want to avoid or delay pregnancy. Given low rates of LARC use, states can implement strategies to remove barriers to the access and availability of LARC including high device costs, limited provider reimbursement, lack of training for providers serving women and adolescents on insertion and removal of LARC, provider lack of knowledge and misperceptions about LARC, limited availability of youth-friendly services that address adolescent confidentiality concerns, inadequate client-centered counseling, and low consumer awareness of the range of contraceptive methods available.

OBJECTIVE: To examine whether the co-administration of hormonal contraceptives (HC) and psychotropic drugs commonly used to treat anxiety and/or depression results in safety or efficacy concerns for either drug. METHODS: We searched PubMed and Cochrane libraries for clinical or pharmacokinetic [PK] studies that examined co-administration of any HC with psychotropic drugs (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs], oral benzodiazepines, bupropion, mirtazapine, trazadone, buspirone, hydroxyzine, monoamine oxidase inhibitors [MAOIs], or atypical antipsychotics) in reproductive aged women. RESULTS: Of 555 articles identified, 22 articles (18 studies) met inclusion criteria. We identified five studies on SSRIs, four on TCAs, one on bupropion, three on atypical antipsychotics and five on oral benzodiazepines. No articles met inclusion criteria for SNRIs, mirtazapine, trazadone, buspirone, hydroxyzine or MAOIs. Overall, clinical studies did not demonstrate differences in unintended pregnancy rates when HCs were administered with and without psychotropic drugs or in psychotropic drug treatment outcomes when psychotropic drugs were administered with and without HCs. PK studies did not demonstrate changes in drug exposure related to contraceptive safety, contraceptive effectiveness or psychotropic drug effectiveness for most classes of psychotropic drugs. However, limited PK data raise concern for HCs increasing systemic exposure of amitriptyline and imipramine (both TCAs), theoretically posing safety concerns. CONCLUSION: Limited quality and quantity evidence on use of psychotropic drugs and HCs suggests low concern for clinically significant interactions, though no data exist specifically for non-oral formulations of HC. Given the high frequency of use for both HCs and psychotropic drugs among reproductive age women in the US, this review highlights a need for further research in this area.

The 2016 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) comprises recommendations for the use of specific contraceptive methods by women and men who have certain characteristics or medical conditions. These recommendations for health care providers were updated by CDC after review of the scientific evidence and consultation with national experts who met in Atlanta, Georgia, during August 26-28, 2015. The information in this report updates the 2010 U.S. MEC (CDC. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR 2010:59 [No. RR-4]). Notable updates include the addition of recommendations for women with cystic fibrosis, women with multiple sclerosis, and women receiving certain psychotropic drugs or St. John's wort; revisions to the recommendations for emergency contraception, including the addition of ulipristal acetate; and revisions to the recommendations for postpartum women; women who are breastfeeding; women with known dyslipidemias, migraine headaches, superficial venous disease, gestational trophoblastic disease, sexually transmitted diseases, and human immunodeficiency virus; and women who are receiving antiretroviral therapy. The recommendations in this report are intended to assist health care providers when they counsel women, men, and couples about contraceptive method choice. Although these recommendations are meant to serve as a source of clinical guidance, health care providers should always consider the individual clinical circumstances of each person seeking family planning services. This report is not intended to be a substitute for professional medical advice for individual patients. Persons should seek advice from their health care providers when considering family planning options.

OBJECTIVES: St. John's wort (SJW) is a known strong inducer of the cytochrome P450 (CYP) 3 A4 enzyme, and both the ethinyl estradiol and progestin components of hormonal contraceptives are substrates of CYP3A4. This systematic review examined whether the co-administration of SJW and hormonal contraceptives leads to significant safety or efficacy concerns. STUDY DESIGN: Systematic review. METHODS: PubMed and Cochrane Library databases were searched for articles of any comparative study design (clinical or pharmacokinetic) that examined potential interactions between SJW and hormonal contraceptives in women of reproductive age. RESULTS: Of the 48 identified articles, four studies met inclusion criteria and compared use of combined oral contraceptives (COCs) alone to the use of COCs co-administered with SJW. Two studies demonstrated no change in markers of ovulation, but one study demonstrated increased follicular growth and probable ovulation when COCs were co-administered with SJW. Three studies demonstrated an increased risk of breakthrough bleeding with COCs and SJW. Three studies showed changes in at least one pharmacokinetic parameter that suggested a significantly decreased exposure to hormone concentrations when COCs were co-administered with SJW. The only study that did not demonstrate any significant pharmacokinetic differences examined a SJW product containing a low amount of hypericin. CONCLUSION: Limited evidence showing increased risk of ovulation and breakthrough bleeding raises concern for decreased contraceptive efficacy when COCs are co-administered with SJW. The pharmacokinetic evidence is mixed but suggests that SJW administration may be associated with weak to moderate induction of the metabolism of COCs.

OBJECTIVES: To investigate levonorgestrel (LNG)-releasing and copper-bearing (Cu) intrauterine device (IUD) safety among breastfeeding women and, for Cu-IUD use, breastfeeding performance and infant health. STUDY DESIGN: Systematic review METHODS: We searched PubMed, Embase, Cochrane Library and clinicaltrials.gov for articles through January 2016. We included studies of Cu-IUD or LNG-IUD users comparing IUD-specific (perforation, expulsion) and other contraceptive-related (infection, removal/cessation due to bleeding/pain, and other adverse events) outcomes for breastfeeding versus non-breastfeeding women. We also included studies of breastfeeding women comparing contraceptive-related outcome for IUD-users versus other contraceptive-method users. Finally, we included studies comparing breastfeeding outcomes among Cu-IUD users to users of other non-hormonal contraceptives or no contraception. RESULTS: Of 548 articles identified, 23 (16 studies) met inclusion criteria. Two studies suggested the risk of IUD perforation was 6-10 times higher among breastfeeding versus non-breastfeeding women. Seven studies suggested risks for other adverse events were similar or lower among breastfeeding versus non-breastfeeding women. Three studies among breastfeeding women found no increased risk of adverse events in IUD users versus non-users. Breastfeeding performance and infant growth were similar for Cu-IUD users and users of other non-hormonal methods or no contraception. CONCLUSION: Overall, risks for adverse events among IUD users, including expulsion, pain and removals were similar or lower for breastfeeding women versus non-breastfeeding women. Uterine perforation with IUDs, while rare, appeared more frequent among breastfeeding women. No evidence indicated Cu-IUD use in breastfeeding women influences breastfeeding performance or infant growth.

BACKGROUND: Women with depressive or bipolar disorders are at an increased risk for unintended pregnancy. OBJECTIVE: To examine the safety of hormonal contraception among women with depressive and bipolar disorders. METHODS: We searched for articles published through January 2016 on the safety of using any hormonal contraceptive method among women with depressive or bipolar disorders, including those who had been diagnosed clinically or scored above threshold levels on a validated screening instrument. Outcomes included changes in symptoms, hospitalization, suicide, and modifications in medication regimens such as increase or decrease in dosage or changes in type of drug. RESULTS: Of 2376 articles, six met inclusion criteria. Of three studies that examined women clinically diagnosed with depressive or bipolar disorder, one found that oral contraceptives (OCs) did not significantly change mood across the menstrual cycle among women with bipolar disorder, whereas mood did significantly change across the menstrual cycle among women not using OCs; one found no significant differences in the frequency of psychiatric hospitalizations among women with bipolar disorder who used depot medroxyprogesterone acetate (DMPA), intrauterine devices (IUDs), or sterilization; and one found no increase in depression scale scores among women with depression using and not using OCs, for both those treated with fluoxetine and those receiving placebo. Of three studies that examined women who met a threshold for depression on a screening instrument, one found that adolescent girls using combined OCs (COCs) had significantly improved depression scores after 3 months compared with placebo, one found that OC users had similar odds of no longer being depressed at follow-up compared with non-users, and one found that COC users were less frequently classified as depressed over 11 months than IUD users. CONCLUSIONS: Limited evidence from six studies found that OC, levonorgestrel-releasing (LNG)-IUD, and DMPA use among women with depressive or bipolar disorders was not associated with worse clinical course of disease compared with no hormonal method use.

BACKGROUND: Women who use combined hormonal contraceptives and cigarettes have an increased risk for cardiovascular (CV) events. We reviewed the literature to determine whether women who use hormonal contraceptives (HC) and electronic cigarettes (e-cigarettes) also have an increased risk. STUDY DESIGN: Systematic review. METHODS: We searched for articles reporting myocardial infarction (MI), stroke, venous thromboembolism, peripheral arterial disease, or changes to CV markers in women using e-cigarettes and HC. We also searched for indirect evidence, such as CV outcomes among e-cigarette users in the general population and among HC users exposed to nicotine, propylene glycol, or glycerol. RESULTS: No articles reported on outcomes among e-cigarette users using HC. Among the general population, 13 articles reported on heart rate or blood pressure after e-cigarette use. These markers generally remained normal, even when significant changes were observed. In 3 studies, changes were less pronounced after e-cigarette use than cigarette use. One MI was reported among 1,012 people exposed to e-cigarettes in these studies. One article on nicotine and HC exposure found both exposures to be significantly associated with acute changes to heart rate, though mean heart rate remained normal. No articles on propylene glycol or glycerol and HC exposure were identified. CONCLUSION: We identified no evidence on CV outcomes among e-cigarette users using HC. Limited data reporting mostly acute outcomes suggested that CV events are rare among e-cigarettes users in the general population, and that e-cigarettes may affect heart rate and blood pressure less than conventional cigarettes. There is a need for research assessing joint HC and e-cigarette exposure on clinical CV outcomes.