Surrogate post-coital testing for contraceptive efficacy against human sperm activity in the ovine vaginal model†.

High unintended pregnancy rates are partially due to lack of effective nonhormonal contraceptives; development of safe, effective topical vaginal methods will address this need. Preclinical product safety and efficacy assessment requires in vivo testing in appropriate models. The sheep is a good model for the evaluation of vaginally delivered products due to its close similarities to humans. The study objective was to develop an ovine model for efficacy testing of female nonhormonal contraceptives that target human sperm. Fresh human semen was pooled from male volunteers. Nonpregnant female Merino sheep were treated with control or vaginal contraceptive product (IgG antibody with action against sperm or nonoxynol-9 [N9]). Pooled semen was added to the sheep vagina and mixed with product and vaginal secretions. Microscopic assessment of samples was performed immediately and progressive motility (PM) of sperm was compared between treatments. Cytokines CXCL8 and IL1B were assessed in vaginal fluid after instillation of human semen. No adverse reactions or elevations in proinflammatory cytokines occurred in response to human semen. N9 produced signs of acute cellular toxicity while there were no cellular changes after IgG treatment. N9 and IgG had dose-related effects with the highest dose achieving complete sperm immobilization (no sperm with PM). Surrogate post-coital testing of vaginally administered contraceptives that target human semen was developed in an ovine model established for vaginal product preclinical testing. This expanded model can aid the development of much needed nonhormonal topical vaginal contraceptives, providing opportunities for rapid iterative drug development prior to costly, time-intensive human testing.

Use of effective contraception following provision of the progestogen-only pill for women presenting to community pharmacies for emergency contraception (Bridge-It): a pragmatic cluster-randomised crossover trial.

BACKGROUND: Unless women start effective contraception after oral emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies. We hypothesised that pharmacist provision of the progestogen-only pill as a bridging interim method of contraception with emergency contraception plus an invitation to a sexual and reproductive health clinic, in which all methods of contraception are available, would result in increased subsequent use of effective contraception. METHODS: We did a pragmatic cluster-randomised crossover trial in 29 UK pharmacies among women receiving levonorgestrel emergency contraception. Women aged 16 years or older, not already using hormonal contraception, not on medication that could interfere with the progestogen-only pill, and willing to give contact details for follow-up were invited to participate. In the intervention group, women received a 3-month supply of the progestogen-only pill (75 µg desogestrel) plus a rapid access card to a participating sexual and reproductive health clinic. In the control group, pharmacists advised women to attend their usual contraceptive provider. The order in which each pharmacy provided the intervention or control was randomly assigned using a computer software algorithm. The primary outcome was the use of effective contraception (hormonal or intrauterine) at 4 months. This study is registered, ISRCTN70616901 (complete). FINDINGS: Between Dec 19, 2017, and June 26, 2019, 636 women were recruited to the intervention group (316 [49·6%], mean age 22·7 years [SD 5·7]) or the control group (320 [50·3%], 22·6 years [5·1]). Three women (one in the intervention group and two in the control group) were excluded after randomisation. 4-month follow-up data were available for 406 (64%) participants, 25 were lost to follow-up, and two participants no longer wanted to participate in the study. The proportion of women using effective contraception was 20·1% greater (95% CI 5·2-35·0) in the intervention group (mean 58·4%, 48·6-68·2), than in the control group (mean 40·5%, 29·7-51·3 [adjusted for recruitment period, treatment group, and centre]; p=0·011).The difference remained significant after adjusting for age, current sexual relationship, and history of effective contraception use, and was robust to the effect of missing data (assuming missingness at random). No serious adverse events occurred. INTERPRETATION: Provision of a supply of the progestogen-only pill with emergency contraception from a community pharmacist, along with an invitation to a sexual and reproductive health clinic, results in a clinically meaningful increase in subsequent use of effective contraception. Widely implemented, this practice could prevent unintended pregnancies after use of emergency contraception. FUNDING: National Institute for Health Research (Health Technology Assessment Programme project 15/113/01).

The use of emergency contraceptive pills in India: A meta-analysis.

BACKGROUND: Unplanned pregnancies are a major public health concern. In India, 33% of an estimated 48.1 million pregnancies end in induced abortions. Emergency contraceptive pills (ECPs) can prevent pregnancy after sexual intercourse, have been part of India's family planning program since 2002-2003 and are available as over-the-counter drugs. While there are concerns about the overuse of ECPs, the pattern of use of ECPs in India is unknown. OBJECTIVES: The objective is to determine the proportion of women who have ever used ECPs and repeatedly used ECPs and also to assess the reasons for use and nonuse of EC pills along with factors associated with the use. METHODS: A systematic review of ECP use in India was conducted by electronically searching three databases-PubMed, Popline, and Google Scholar. All studies were published between 2001 and 2017, and the electronic search was last conducted in July 2018. The proportion of use was calculated using meta-analysis, and the other factors were assessed by narratively synthesizing the findings. Thirty-three articles met the inclusion criteria. RESULTS: The pooled proportion of women who ever used ECPs was 6% (95% confidence interval, 0.03-0.10). The proportion of repeat use ranged from 12% to 69%. Five studies reported reasons for not using ECPs, and the most common reasons were religious/cultural beliefs followed by fear of side effects and inadequate knowledge. Studies to understand sociodemographic and other factors affecting the use of ECPs in India are lacking. There are significant concerns about the quality of the studies. The definition of repeat use of ECPs is inconsistent across papers. Furthermore, judgmental attitudes of health-care providers were apparent in some papers. CONCLUSION: The review highlights important research and program gaps.

A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive.

INTRODUCTION: The levonorgestrel oral emergency contraceptive is well tolerated and effective, however its use is still limited, mainly due to safety concerns. OBJECTIVE: This systematic review and meta-analysis aimed to summarize current evidence regarding the adverse events, and their prevalence, reported during the use of oral levonorgestrel emergency contraceptives. METHODS: Four electronic databases and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched. Studies that reported or investigated safety outcomes or adverse reactions during the use of levonorgestrel as an emergency oral contraceptive were included. Data on study design, demographics of levonorgestrel and the control cohort, and reported adverse effects were extracted. RESULTS: A total of 47 articles were included in this systematic review, from which it was shown that most of the adverse reactions were common and not serious. Uncommon adverse reactions identified included anorexia, ectopic pregnancy, exanthema, chloasma, miscarriage, and weight gain. Multiple serious adverse events, including convulsion, ectopic pregnancy, febrile neutropenia, stroke, abdominal hernia, anaphylaxis, cancer, ovarian cyst rupture, serious infections, and suicidal ideation, were reported. In addition, the prevalence of adverse events after a levonorgestrel 0.75 mg two-dose regimen and a levonorgestrel 1.5 mg single-dose regimen were not statistically different (p > 0.05). CONCLUSIONS: The most common adverse effects of levonorgestrel were not serious. This systematic review shows that data regarding the adverse reactions of repeated use of levonorgestrel are scarce. Studies on the multiple uses of levonorgestrel emergency contraception are still required to ensure its safety.

Reconceptualizing Measurement of Emergency Contraceptive Use: Comparison of Approaches to Estimate the Use of Emergency Contraception.

Estimated use of emergency contraception (EC) remains low, and one reason is measurement challenges. The study aims to compare EC use estimates using five approaches. Data come from Performance Monitoring and Accountability 2020 surveys from 10 countries, representative sample surveys of women aged 15 to 49 years. We explore EC use employing the five definitions and calculate absolute differences between a reference definition (percentage of women currently using EC as the most effective method) and each of the subsequent four, including the most inclusive (percentage of women having used EC in the past year). Across the 17 geographies, estimated use varies greatly by definition and EC use employing the most inclusive definition is statistically significantly higher than the reference estimate. Impact of using various definitions is most pronounced among unmarried sexually active women. The conventional definition of EC use likely underestimates the magnitude of EC use, which has unique programmatic implications.

Bills as Band-Aids: Hopes and Challenges of Expanding Pharmacists' Prescriptive Authority to Include Contraceptives.

This paper critically examines the implications of state efforts to expand prescriptive authority of pharmacists, which will allow them to prescribe various types of hormonal contraceptives. With this expansion, women no longer need to see a physician before being prescribed such contraceptives, but instead, they must answer self-assessment questionnaires at the pharmacy to ensure that their chosen method is safe and appropriate. This paper argues that while these measures to expand pharmacists' prescriptive authority will surely meet the stated goal to increase access to hormonal contraceptives, the measures may have detrimental consequences that have largely been downplayed. Studies consistently show that the OB-GYN is a significant primary care provider identified by young female patients, and some of the main reasons provided by these young women for going to the OB-GYN is to discuss, or obtain a prescription for, contraceptives. Through the expansion of pharmacists' prescriptive authority, a likely consequence is that some women will relinquish going to the OB-GYN. However, the OB-GYN provides important services beyond contraceptives, such as preventive screenings for hypertension, cardiovascular diseases, alcohol abuse, mental health, etc., and there is evidence supporting both the effectiveness and cost-benefits of these interventions. By increasing access to contraceptives, the likely result is that many women will have less interaction with a physician and will receive fewer preventive screenings. I do not wish to suggest that these bills should not pass, nor that OB-GYNs should hold contraceptives hostage, only that there are consequences to expanded prescriptive authority that must be anticipated. Further, expanding prescriptive authority obscures the real problem: some individuals have trouble accessing the health care system, not merely trouble accessing hormonal contraceptives. The expansion of prescriptive authority to include contraceptives applies a Band-Aid to treat one aspect of this problem. What is needed is not merely expanded access to hormonal contraceptives, but better access to health care in general.

Does ulipristal acetate emergency contraception (ella®) interfere with implantation?

BACKGROUND: Ulipristal acetate (UPA) 30 mg (ella®, HRA-Pharma, Paris, France) acts as an emergency contraceptive (EC) by delaying ovulation. Because it is a selective progesterone receptor modulator, an additional effect on interfering with implantation has been suggested. OBJECTIVE: This review discusses the evidence for, and against, an anti-implantation effect of UPA-EC. SOURCES OF EVIDENCE: Primary research on the effect of UPA, at a relevant dose, on endometrium, implantation, efficacy and pregnancy outcome. RESULTS: UPA-EC does not appear to have a direct effect on the embryo. Changes in endometrial histology are small and not consistent, varying among studies. While UPA-EC affects the profile of gene expression in human endometrium, the findings vary between studies, and it is not clear that these changes affect endometrial receptivity or prevent implantation. UPA at pharmacological concentrations does not appear to have any inhibitory effect on embryo attachment in in vitro systems of human endometrium. UPA-EC is not more effective at preventing pregnancy than chance alone if used after ovulation and does not increase miscarriage rates. CONCLUSIONS: An anti-implantation effect of UPA is highly unlikely at the dose used for EC. Maintaining the warning on the FDA-approved label that "it may also work by preventing implantation to the uterus" might deter some women from using EC, leaving them no option to prevent unwanted pregnancy after unprotected sexual intercourse.

Availability of ulipristal acetate: A secret shopper survey of pharmacies in a metropolitan area on emergency contraception.

OBJECTIVES: To assess levonorgestrel (LNG) and ulipristal acetate (UPA) availability in pharmacies in a metropolitan area. METHODS: A cross-sectional survey was conducted of all identified pharmacies within 25 miles of an urban medical center in Kansas City, KS. We categorized the pharmacies as dedicated commercial (national chains), store-associated (affiliated with a general merchandise or grocery store), or independent. We assessed LNG and UPA availability or time to availability if not currently stocked. RESULTS: We contacted 165 pharmacies. Of the 165 pharmacies, few stocked UPA (12/165, 7%) whereas the majority stocked oral LNG (128/165, 78%). Dedicated commercial pharmacies were more likely to carry UPA than store-associated and independent pharmacies (11/84 [13%] vs. 1/61 [1%] vs. 0/20, respectively; P = 0.016). Most pharmacies that did not stock UPA reported that they could obtain it within 24 hours (94/153, 62%). Dedicated commercial pharmacies were most likely report the ability to obtain UPA in 24 hours (P = 0.016). CONCLUSION: Few pharmacies stock UPA, the most effective form of oral emergency contraception. Enhanced communication between medical providers and pharmacists within current laws and regulations could enhance patient access to UPA.

Pharmacokinetics of the 1.5 mg levonorgestrel emergency contraceptive in women with normal, obese and extremely obese body mass index.

OBJECTIVE: To assess the pharmacokinetics (PK) of levonorgestrel after 1.5 mg oral doses (LNG-EC) in women with normal, obese and extremely obese body mass index (BMI). STUDY DESIGN: The 1.5 mg LNG dose was given to healthy, reproductive-age, ovulatory women with normal BMI (mean 22.0), obese (mean 34.4), and extremely obese (mean 46.6 kg/m2) BMI. Total serum LNG was measured over 0 to 96 h by radioimmunoassay while free and bioavailable LNG were calculated. The maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the curve (AUC) of LNG were assessed. Pharmacokinetic parameters calculated included half-life (t1/2), clearance (CL) and volume of distribution (Vss). RESULTS: Ten normal-BMI, 11 obese-BMI, 5 extremely obese-BMI women were studied. After LNG-EC, mean total LNG metrics were lower in the obese and extremely obese groups compared to normal (Cmax 10.5 and 10.5 versus 16.2 ng/mL, both p<.01; AUC 208 and 197 versus 360 h × ng/mL, both p<.05). Mean bioavailable LNG Cmax was lower in obese (7.03 ng/mL, p<.05) and extremely obese (7.53 ng/ml, p=.198) compared to normal BMI (9.39 ng/mL). Mean bioavailable LNG AUC values were lower in obese and extremely obese compared to normal (131.6 and 127.5 vs 185.0 h × ng/mL, p<.05 for both). CONCLUSIONS: Obese and extremely obese women were exposed to lower total and bioavailable LNG than normal BMI women. IMPLICATIONS: Lower 'bioavailable' (free plus albumin bound) LNG AUC in obese women may play a role in the purported reduced efficacy of LNG-EC in obese users.

Interventions for emergency contraception.

BACKGROUND: Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. This is an update of a review previously published in 2009 and 2012. OBJECTIVES: To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy. SEARCH METHODS: In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers. SELECTION CRITERIA: Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes. MAIN RESULTS: We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency.Comparative effectiveness of different emergency contraceptive pills (ECP)Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I2 = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I2 = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I2 = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I2 = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I2 = 0%, high-quality evidence).Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I2 = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I2 = 0%, high-quality evidence).Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence).Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I2 = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I2 = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I2 = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I2 = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I2 = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence). AUTHORS' CONCLUSIONS: Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA may be more effective than levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.

Prevalence and Correlates of Emergency Contraceptive Use in Transitional Albania.

OBJECTIVES: The two emergency contraceptive drugs ("morning-after pill") ulipristal acetate and levonorgestrel are available without prescription in many European countries. In Albania, ulipristal acetate is not marketed yet and levonorgestrel has still prescription-only status. The objective of this study was to assess the prevalence and socioeconomic correlates of emergency contraceptive (EMC) use, collect sales figures, and gain information on the women's way of purchasing EMCs in post-communist Albania. METHODS: For this cross-sectional study, self-administered questionnaires were made accessible to women in Albania in March 2015 by hard copy or online via social networks. Women were asked about lifetime use and last year's use of EMCs, and if they purchased EMCs with or without a prescription. Additionally, pharmacies were contacted and asked about EMC sales figures. RESULTS: Of the 205 participating women, 80.5% knew about the availability and use of EMCs, and 15.1% reported EMC use during the previous 12 months. The lifetime prevalence of use was 46.8%. Although having prescription-only status in Albania, 96% of the women bought EMCs without a physician's prescription. Knowledge was significantly lower among the lower educated women and among women residing in small cities. Use of EMCs was significantly higher in women with a weaker financial background and, compared with small cities, in those from large or mid-sized cities. The 54 participating pharmacies (3% of all Albanian pharmacies) reported selling 11 EMCs on average per month. The use of EMCs may be estimated at 0.22 defined daily doses per 1,000 inhabitants per day. Compared to January 2015, EMC sales increased by 17% in February 2016. CONCLUSIONS: Compared to other European countries, the prevalence of EMC use seems to be higher in Albania. Use and knowledge of EMCs depend on socioeconomic characteristics. It is recommended to switch EMCs to non-prescription status in transitional Albania.

Counseling and in-advance provision of levonorgestrel emergency contraceptive pills decrease the rate of unplanned pregnancy during breastfeeding: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of counseling and in-advance provision of levonorgestrel emergency contraceptive pills (LNG-ECPs) during postpartum counseling on the incidence of occurrence of unplanned pregnancy during breastfeeding. MATERIALS AND METHODS: The current study is an open-label, parallel, randomized controlled trial carried out in a university hospital in Egypt. All women who delivered and planning to birth-space and breastfeed for at least 1 year were approached for participation during a postpartum hospital stay. Eligible participants were randomly allocated to receive adequate lactational amenorrhea method (LAM) counseling Group 1 (LAM-only) or the above LAM counseling in addition to counseling and in advance provision of one packet of 0.75-mg LNG-ECPs Group 2 (LAM + EC). The two study groups were followed 6 months and the primary outcome was the unplanned pregnancy rate. RESULTS: The study included 2708 women randomized into two groups; LAM-only and LAM + EC groups. Demographic characteristics were homogenous between the groups at the time of recruitment. Unplanned pregnancy was significantly higher in LAM-only group 70 (5.3%) as compared with 5 (0.4%) in LAM-EC group (p = .0001). Also, 619 women (46.6%) used LNG-ECPs with minor side effects like nausea in 175 (28.3%) women, headache in 94 (15.2%) women, vomiting in 24 (3.9%) women. CONCLUSION: In-advance counseling and provision of LNG-ECPs for those opt to use LAM during postpartum family planning counseling can decrease the rate of unplanned pregnancy during breastfeeding and increase the initiation of long-term use of contraception.

Levonorgestrel emergency contraception and bodyweight.

Objectives: Emergency contraception (EC) provides an opportunity to avoid an unwanted pregnancy following unprotected sexual intercourse (UPSI), failure of a regular contraceptive method, or after sexual assault. Two main methods are currently available: oral pills or the copper-T intrauterine device. In recent years there has been some debate regarding the efficacy of oral therapy in obese women. In this brief commentary we review new evidence, published after the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) referral of 2014, relating to the effect of obesity on the pharmacokinetics and clinical efficacy of levonorgestrel EC in light of some of the concerns that have been raised. Methods: A PubMed literature search ("levonorgestrel" and "emergency contraception") was conducted between 1 January 2005 to 31 March 2018; results from the main clinical trials are discussed. Additional literature known to the authors and identified from the reference lists of cited publications was included. Results: Overall, it should be noted that, in studies which determined pregnancy rates across different weight or BMI categories, the overall pregnancy rate was low (1-2%) and there was no direct evidence that lower levonorgestrel plasma levels contributed to an increased pregnancy rate in obese women. This conclusion was reached by the EMA referral in 2014 and they concluded that emergency contraceptive pills (ECPs) could be taken regardless of body weight or BMI, as soon as possible after UPSI. Since the EMA review, additional evidence has been published regarding this topic. This includes PK data (which can neither support, nor deny the previously submitted meta-analyses during the Article 31 Referral procedure), or re-analyses of the previously submitted data. Conclusions: Evidence published since the EMA referral in 2014 does not change the original conclusions of the agency, which recommended that ECPs could be taken regardless of body weight or BMI, as soon as possible after UPSI.

Medical advancements: emergency contraception (EC). Medico-legal implications of EC on adolescents.

The article's main focus is documenting what the best options are in order to make sure that minors are allowed to play a key role in the management of issues arising from the use of emergency contraception. In that regard, there is a lack of clean-cut legislative measures and, although there are several legal and ethical norms designed to get parents or legal guardians involved in such decisions, there seems to be an increasingly widespread tendency to give weight to the minor's will, thus acknowledging her decision-making capacity. Lastly, the paper's authors undertake a thorough examination as to what the duties of doctors are, and the measures that need to be put in place in order to safeguard the minor patients' conditions. They arrive at the conclusion that emergency contraception is suitable for minors even in absence of the stated consent from their parents or guardians, but it is of utmost importance to implement adequate measures aimed at the provision of proper care, prevention and education.

Levonorgestrel only emergency contraceptive use and risk of ectopic pregnancy in Eldoret Kenya: a case-control study.

INTRODUCTION: ectopic pregnancy is one of the causes of maternal morbidity and mortality in sub-Saharan Africa. Levonorgestrel (LNG) only emergency contraceptive pill is a well-established emergency contraceptive pill that is administered within 72 hours after unprotected intercourse. This study aimed at determining whether or not there is a significant association between levonorgestrel emergency contraceptive use and the occurrence of ectopic pregnancy. METHODS: case-control (1:3) study among 79 women with ectopic pregnancy (cases) matched against 237 women without (controls) at Moi Teaching and Referral Hospital in Eldoret, Kenya; Sociodemographic and clinical data were collected using a questionnaire. Association between ectopic pregnancy and LNG-EC was assessed using Pearson chi-square test. The relationship between outcome and exposure (while adjusting for confounders) was assessed using logistic regression model. RESULTS: The mean age was 27.15 years. Both cases and controls were similar by age (p = 0.990), educational level (p = 0.850), marital status (p = 0.559), employment status (p = 0.186) and parity (p = 0.999). Seventy-eight (24.7%) participants had a history of miscarriage. A higher proportion of the cases had history of using LNG-EC compared to the controls (32.9% vs. 7.2%, p < 0.001). The use of LNG-EC portended more than nine times increased odds of ectopic pregnancy compared to other contraceptive methods {OR = 9.34 (95% CI: 3.9 - 16.0)}. CONCLUSION: levonorgestrel only emergency contraceptive use was associated with ectopic pregnancy. One of the limitations of this study is that we could not control for all confounders of ectopic pregnancy.

Centchroman: A safe reversible postcoital contraceptive with curative and prophylactic activity in many disorders.

Centchroman (INN: Ormeloxifene), a reversible post-coital/weekly oral contraceptive (half-life of about 168 hours), designed and developed at CDRI, Lucknow is the only non-steroidal oral contraceptive in clinical use in the world today. Synthesized in 1967 and completing pre-clinical and clinical studies in 1989, this drug was approved for marketing in 1991, social marketing in 1995 and NFPW in April 2016. It acts by preventing implantation of blastocyst in endometrium. It is the only contraceptive which neither suppresses ovulation nor interferes with the hypothalamic-pituitary-ovarian axis. It has high level of safety and is virtually free from side effects except for a delay in about 8% menstrual cycles which is not confined to any women/cycle. Besides contraception, this SERM is also clinically useful in the management of DUB, mastalgia and fibroadenoma and has promising therapeutic efficacy in a variety of cancers including breast cancer. Due to estrogenic activity, this drug also has anti-osteoporotic and cardioprotective activity. Thus, Centchroman is likely to show other curative and prophylactic activity in a wide range of other disorders.

Service Delivery Correlates of Choosing Short-Acting Contraceptives at the Time of Uterine Evacuation in Bangladesh.

CONTEXT: The World Health Organization recommends that contraceptives be offered on the day of a uterine evacuation procedure (i.e., induced abortion or postabortion care for an incomplete abortion). Short-acting methods can be initiated on the day of the uterine evacuation, regardless of procedure type. METHODS: Survey data from a facility-based sample of 479 Bangladeshi women aged 18-49 who did not intend to become pregnant in the four months following their uterine evacuation were used to examine women's choice of short-acting contraceptive methods (pill, condoms or injectable). Service delivery correlates of contraceptive choice were identified using sequential logistic regression models. RESULTS: Seventy-three percent of women chose a short-acting contraceptive method on the day of their uterine evacuation. The odds that a woman chose a short-acting method, rather than no method, were lower among those who had had a medication abortion (odds ratio, 0.1) or dilatation and curettage (0.3) than among those who had had a vacuum aspiration. The likelihood that a woman chose a specific type of short-acting method varied according to the type of uterine evacuation she had had, the facility level and the governmental or nongovernmental entity that managed the facility. CONCLUSIONS: Uterine evacuation service delivery characteristics may act as barriers to women's choosing a contraceptive method following an abortion. Training and monitoring providers may help ensure that all uterine evacuation clients have access to the full range of contraceptive information and services and that their choices, rather than service delivery factors, drive postabortion contraceptive use.

Are oral emergency contraceptives a safe and effective form of long-term birth control?

Yes, but not as effective as some other methods. Annual pregnancy rates in women using pericoital levonorgestrel 150 mcg to 1 mg range from 4.9% to 8.9%; menstrual irregularity is the most common adverse effect (strength of recommendation [SOR]: B, Cochrane review of lower-quality trials). In women younger than 35 years who have sexual intercourse 6 or fewer times per month, correct and consistent use of pericoital levonorgestrel 1.5 mg results in an annual pregnancy rate of 11% (SOR: B, one large prospective, open-label trial). Pericoital contraception is less effective than long-acting reversible contraceptives (annual pregnancy rates of 0.05%-0.8%) or perfect use of combined oral contraceptives (0.3% annual pregnancy rate), but similar to, or better than, typical use of combined oral contraception (9%) and condoms (18%).

Interventions for emergency contraception.

BACKGROUND: Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. This is an update of a review previously published in 2009 and 2012. OBJECTIVES: To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy. SEARCH METHODS: In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers. SELECTION CRITERIA: Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes. MAIN RESULTS: We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency. Comparative effectiveness of different emergency contraceptive pills (ECP)Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I2 = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I2 = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I2 = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I2 = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I2 = 0%, high-quality evidence). Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I2 = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I2 = 0%, high-quality evidence). Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence). Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I2 = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I2 = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I2 = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I2 = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I2 = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence). AUTHORS' CONCLUSIONS: Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA was more effective than levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.

The safety of available and emerging options for emergency contraception.

INTRODUCTION: Emergency contraception (EC) is a way to significantly reduce the chance of becoming pregnant after an episode of unprotected intercourse. Considerable data support the safety of all available and emerging options for EC. Areas covered: This review presents a comprehensive summary of the literature regarding the safety of EC as well as directions for further study. PubMed was searched for all relevant studies published prior to June 2017. Expertopinion: All available methods of EC (i.e., ulipristal acetate pills, levonorgestrel pills, and the copper-IUD), carry only mild side effects and serious adverse events are essentially unknown. The copper IUD has the highest efficacy of EC methods. Given the excellent safety profiles of mifepristone and the levonorgestrel IUD, research is ongoing related to use of these products for EC.