{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:22:39Z","timestamp":1787775759064,"version":"build-2784847793"},"reference-count":11,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4]]},"abstract":"\n Background:<\/jats:title>\n Traditional letrozole or clomiphene treatment is started on cycle days 3 to 5, following a spontaneous menses or progestin-induced bleeding. If ovulation does not occur, the dose is increased following a progestin-induced bleeding. An alternative stair step protocol has been described, and if ovulation does not occur in this protocol, a higher dose is used without inducing withdrawal bleeding. There is no randomized trial comparing the traditional and stair-step letrozole protocols yet.<\/jats:p>\n <\/jats:sec>\n \n Aim:<\/jats:title>\n To compare the efficacy of traditional and stair-step protocols for ovulation induction using letrozole in women with polycystic ovary syndrome (PCOS).<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n A total of 200 eligible women were given 5 mg\/day letrozole, and those 80 who did not respond were randomized in a 1:1 ratio to stair-step or traditional letrozole therapy for up to 10 mg\/day. For the traditional protocol, higher doses of letrozole were used in each new cycle if no ovulation occurred. For the stair-step protocol, higher doses of letrozole were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. The PCOS was defined according to modified Rotterdam criteria. Participants were 18 to 35 years of age, had a body mass index of <40 kg\/m\n 2<\/jats:sup>\n , had at least one patent fallopian tube, had a normal uterine cavity, and had normal spermiogram results.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The median follicle development time was significantly longer in the traditional protocol group than in the stair-step protocol group (41 days, 95% CI (40\u201342) vs 25 days, 95% CI (25\u201326); log rank 64;\n P<\/jats:italic>\n < 0.001). Between traditional and stair step groups, the cumulative ovulation ratio (37\/40 [%93] vs 36\/40 [%90];\n P<\/jats:italic>\n = 1), endometrial thickness (9 [5\u201313] vs. 9 [5\u201311];\n P<\/jats:italic>\n = 0.005), mature follicule development (36\/40 [%90] vs 36\/40 [%90];\n P<\/jats:italic>\n = 0.549), pregnancy rates (3\/40 [%8] vs 2\/40 [%5];\n P<\/jats:italic>\n = 1), and antiestrogenic side effects were similar.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n The stair-step protocol shortens the treatment time without causing any detrimental effects on ovulation outcome.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/njcp.njcp_516_24","type":"journal-article","created":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T23:00:17Z","timestamp":1745794817000},"page":"502-507","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["A Randomized Trial of Stair-Step Letrozole versus Traditional Letrozole for Subfertile Women with Polycystic Ovary Syndrome"],"prefix":"10.4103","volume":"28","author":[{"given":"S","family":"Karakaya","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Ataturk University, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Kumtepe","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Ataturk University, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RA","family":"Al","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Ataturk University, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GNC","family":"Senocak","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Ataturk University, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EPT","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Ataturk University, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"R1-20260423","first-page":"CD010287","article-title":"Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome","volume":"5","author":"Franik","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"R2-20260423","doi-asserted-by":"crossref","first-page":"510e1","DOI":"10.1016\/j.ajog.2008.10.031","article-title":"Novel clomiphene \u201cstair-step\u201d protocol reduces time to ovulation in women with polycystic ovarian syndrome","volume":"200","author":"Hurst","year":"2009","journal-title":"Am J Obstet Gynecol"},{"key":"R3-20260423","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00404-014-3398-y","article-title":"Clomiphene citrate \u2018stair-step\u2019 protocol vs. traditional protocol in patients with polycystic ovary syndrome: A randomized controlled trial","volume":"291","author":"Deveci","year":"2015","journal-title":"Arch Gynecol Obstet"},{"key":"R4-20260423","doi-asserted-by":"crossref","first-page":"261","DOI":"10.4103\/jhrs.JHRS_15_17","article-title":"Ovulation induction using clomiphene citrate using stair-step regimen versus traditional regimen in polycystic ovary syndrome women-A randomized control trial","volume":"10","author":"Agrawal","year":"2017","journal-title":"J Hum Reprod Sci"},{"key":"R5-20260423","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/AOG.0000000000002418","article-title":"Clomiphene stair-step protocol for women with polycystic ovary syndrome","volume":"131","author":"Jones","year":"2018","journal-title":"Obstet Gynecol"},{"key":"R6-20260423","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.1111\/jog.14936","article-title":"Comparison of the efficacy of letrozole stair\u2010step protocol with clomiphene citrate stair\u2010step protocol in the management of clomiphene citrate\u2010resistant polycystic ovary syndrome patients","volume":"47","author":"Sakar","year":"2021","journal-title":"J Obstet Gynaecol Re"},{"key":"R7-20260423","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40834-019-0102-4","article-title":"Ovulation rates in a stair-step protocol with Letrozole vs clomiphene citrate in patients with polycystic ovarian syndrome","volume":"4","author":"Thomas","year":"2019","journal-title":"Contracept Reprod Med"},{"key":"R8-20260423","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1016\/S0015-0282(02)03524-0","article-title":"Prospective randomized trial comparing the effects of 2.5 and 5.0 mg of letrozole (LE) on follicular development, endometrial thickness and pregnancy rate in patients undergoing super-ovulation","volume":"78","author":"Biljan","year":"2002","journal-title":"Fertil Steril"},{"key":"R9-20260423","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1210\/clinem\/dgab232","article-title":"Clinical practice guidelines on the diagnosis and management of polycystic Ovary syndrome: A systematic Review and quality assessment study","volume":"106","author":"Al Wattar","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"R10-20260423","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1056\/NEJMoa1313517","article-title":"Letrozole versus clomiphene for infertility in the polycystic ovary syndrome","volume":"371","author":"Legro","year":"2014","journal-title":"N Engl J Med"},{"key":"R11-20260423","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1210\/jc.2005-1923","article-title":"Review: aromatase inhibitors for ovulation induction","volume":"91","author":"Casper","year":"2006","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Nigerian Journal of Clinical Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/njcp.njcp_516_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:41:39Z","timestamp":1787773299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/njcp.njcp_516_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/njcp.njcp_516_24","relation":{},"ISSN":["1119-3077","2229-7731"],"issn-type":[{"value":"1119-3077","type":"print"},{"value":"2229-7731","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-08-08","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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