title: A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg.
abstract: OBJECTIVE
  Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method?
  
  
  CONCLUSIONS
  Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population.
  
  
  BACKGROUND
  LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception.
  
  
  METHODS
  This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014.
  
  
  METHODS
  A total of 330 healthy fertile women aged 18-45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered.
  
  
  RESULTS
  There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others.
  
  
  CONCLUSIONS
  This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception.
  
  
  CONCLUSIONS
  A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women.
  
  
  BACKGROUND
  This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest.
  
  
  BACKGROUND
  This study was registered on ANZCTR, Trial ID ACTRN12611001037998.
  4 October 2011.
  10 January 2012.
authors.affiliation: Department of Reproductive Health and Research, World Health Organisation, Geneva, Switzerland festinma@who.int.
authors.forename: Mario P R
authors.initials: MP
authors.lastname: Festin
authors.affiliation: Human Reproduction Unit, Department of Obstetrics and Gynaecology, University of Campinas, Campinas, Brazil.
authors.forename: Luis
authors.initials: L
authors.lastname: Bahamondes
authors.affiliation: Department of Reproductive Health and Research, World Health Organisation, Geneva, Switzerland.
authors.forename: Thi My Huong
authors.initials: TM
authors.lastname: Nguyen
authors.affiliation: Department of Reproductive Health and Research, World Health Organisation, Geneva, Switzerland.
authors.forename: Ndema
authors.initials: N
authors.lastname: Habib
authors.affiliation: Department of Obstetrics and Gynaecology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Manopchai
authors.initials: M
authors.lastname: Thamkhantho
authors.affiliation: Department of Obstetrics and Gynaecology, National University Hospital, Singapore, Singapore.
authors.forename: Kuldip
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Obstetrics and Gynaecology, National University Hospital, Singapore, Singapore.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Gosavi
authors.affiliation: Department of Obstetrics and Gynaecology, Albert Szent-Gyorgyi Medical Centre, University of Szeged, Szeged, Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Bartfai
authors.affiliation: Department of Obstetrics and Gynaecology, Albert Szent-Gyorgyi Medical Centre, University of Szeged, Szeged, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Bito
authors.affiliation: Human Reproduction Unit, Department of Obstetrics and Gynaecology, University of Campinas, Campinas, Brazil.
authors.forename: M Valeria
authors.initials: MV
authors.lastname: Bahamondes
authors.affiliation: Independent Consultant.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kapp
mesh_terms: D000293:Adolescent; D000328:Adult; D003075:Coitus; D044363:Contraception, Postcoital / Q000379:methods*; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011247:Pregnancy; D012725:Sexual Behavior
chemical_list: D003280:Contraceptives, Oral, Synthetic; D016912:Levonorgestrel
keywords: anaemia; contraception; effectiveness; oral levonorgestrel; pericoital
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