{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:14:01Z","timestamp":1789820041077,"version":"4.0.1"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006259","name":"Teva Pharmaceutical Industries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006259","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>As part of the European risk management plan of a 91\u2010day extended levonorgestrel\u2010containing combined oral contraceptive (COC<jats:sub>LNG<\/jats:sub>), a study was performed to assess its safety. This analysis was conducted to examine delayed pregnancy detection and return to fertility with extended combined oral contraceptives (COC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective cohort study in new users of 91\u2010day COC<jats:sub>LNG<\/jats:sub> or 28\u2010day COC<jats:sub>LNG<\/jats:sub> within a US\u2010based healthcare claims database from 2006 to 2017. Delayed pregnancy detection during current COC<jats:sub>LNG<\/jats:sub> exposure was defined as the time between estimated pregnancy start and first prenatal care encounter. Additionally, the time between estimated pregnancy start and COC<jats:sub>LNG<\/jats:sub> discontinuation was measured. To measure return to fertility, pregnancy rates were estimated among females who discontinued treatment. 91\u2010day COC<jats:sub>LNG<\/jats:sub> users were propensity score\u2010matched to 28\u2010day COC<jats:sub>LNG<\/jats:sub> users. Hazard ratio for pregnancy was calculated using Cox proportional hazards models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 91\u2010day and 28\u2010day COC<jats:sub>LNG<\/jats:sub> users had 25\u2009593 and 76\u2009586 treatment episodes, respectively. The median time to pregnancy detection was 64.5 and 61.0\u2009days (<jats:italic>p<\/jats:italic>\u00a0=\u20090.24) in users of 91\u2010day COC<jats:sub>LNG<\/jats:sub> and 28\u2010day COC<jats:sub>LNG<\/jats:sub>. The median exposure time to treatment after estimated pregnancy start was 54.0 and 38.0\u2009days (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.01). In the fertility analysis, pregnancy rates were 54.82 (95% CI, 50.05\u201359.93) and 69.30 (95% CI, 64.98\u201373.82) per 1000 person\u2010years in extended COC<jats:sub>LNG<\/jats:sub> discontinuers and 28\u2010day COC<jats:sub>LNG<\/jats:sub> discontinuers. The adjusted hazard ratio of pregnancy was 0.77 (95% CI, 0.69\u20130.85).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Small differences were observed for pregnancy rates and delayed pregnancy detection between 91\u2010day extended COC<jats:sub>LNG<\/jats:sub> and 28\u2010day COC<jats:sub>LNG<\/jats:sub>, which may be related to the longer days' supply of extended COC<jats:sub>LNG<\/jats:sub>. Differences in the fertility analysis may be related to unmeasured residual confounding.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5497","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T10:56:21Z","timestamp":1655463381000},"page":"78-83","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Delayed pregnancy detection and return to fertility with extended levonorgestrel\u2010containing oral contraceptives: A real world setting cohort study"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3352-8480","authenticated-orcid":false,"given":"Sigal","family":"Kaplan","sequence":"first","affiliation":[{"name":"Epidemiology Teva Pharmaceutical Industries Ltd  Netanya Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8790-7243","authenticated-orcid":false,"given":"Monica L.","family":"Bertoia","sequence":"additional","affiliation":[{"name":"Epidemiology Optum  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Lass","sequence":"additional","affiliation":[{"name":"Haipharm Ltd  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8776-9434","authenticated-orcid":false,"given":"Florence T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Epidemiology Optum  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Evans","sequence":"additional","affiliation":[{"name":"Drug Safety Research Unit  Southampton UK"},{"name":"School of Pharmacy and Biomedical Sciences University of Portsmouth  Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Dhanda","sequence":"additional","affiliation":[{"name":"Drug Safety Research Unit  Southampton 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