{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:08:27Z","timestamp":1790690907130,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Until recently, oral dydrogesterone has only been established in fresh in vitro fertilization (IVF) cycles, whereas its role in luteal phase support (LPS) for frozen embryo transfer (FET) cycles remains unclear. The aim of this study is to determine whether oral dydrogesterone as LPS in FET cycles results in pregnancy rates comparable to vaginal progesterone, focusing primarily on ongoing pregnancy rates, but also on clinical pregnancy, miscarriage, and live birth rates. Methods: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five databases (Embase, MEDLINE\u00ae, APA PsycInfo, Global Health, and HMIC) and two additional sources were searched from inception to November 28, 2024. Only randomized controlled trials (RCTs) were included. A common effects model combined risk estimates, and heterogeneity was assessed using I2. Study quality was evaluated with Risk of Bias 2 (RoB2), and evidence certainty was graded using GRADE. Results: Overall, five RCTs with a total of 636 women were included in the meta-analysis. The comparison between oral dydrogesterone and vaginal progesterone for LPS did not yield significant differences for any of the outcomes studied. For ongoing pregnancies, the pooled odds ratio (OR) was 0.90 (95% CI: 0.59\u20131.35), with no heterogeneity (I2 = 8.7%). For miscarriage events, the OR was 1.41 (95% CI: 0.63\u20133.13, I2 = 0). For clinical pregnancies, the OR was 0.94 (95% CI: 0.62\u20131.42, I2 = 49.2%), with heterogeneity attributed to dosage. For live births, the pooled OR was 1.08 (95% CI: 0.67\u20131.75, I2 = 0%). Two studies were assessed as high risk of bias, two as low risk, and one as moderate. The GRADE assessment indicated low to moderate certainty of evidence. Conclusions: Oral dydrogesterone and vaginal progesterone yield comparable reproductive outcomes for LPS in FET cycles. Given its ease of administration, dydrogesterone may serve as a viable alternative in future FET protocols. However, further RCTs are needed to assess its efficacy against other progesterone administration routes.<\/jats:p>","DOI":"10.3390\/jcm14093238","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T04:20:26Z","timestamp":1746591626000},"page":"3238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Oral Dydrogesterone Versus Vaginal Progesterone for Luteal Phase Support in Frozen\u2013Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6921-0573","authenticated-orcid":false,"given":"Konstantinos","family":"Stavridis","sequence":"first","affiliation":[{"name":"2nd Department of Obstetrics and Gynecology, \u201cAretaieion\u201d University Hospital, 11528 Athens, Greece"},{"name":"Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6256-2127","authenticated-orcid":false,"given":"Dimitrios","family":"Balafoutas","sequence":"additional","affiliation":[{"name":"2nd Department of Obstetrics and Gynecology, \u201cAretaieion\u201d University Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1379-894X","authenticated-orcid":false,"given":"Theodoros","family":"Kalampokas","sequence":"additional","affiliation":[{"name":"2nd Department of Obstetrics and Gynecology, \u201cAretaieion\u201d University Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0415-0386","authenticated-orcid":false,"given":"Vassiliki","family":"Benetou","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Samoli","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Vlahos","sequence":"additional","affiliation":[{"name":"2nd Department of Obstetrics and Gynecology, \u201cAretaieion\u201d University Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8851-5798","authenticated-orcid":false,"given":"Maria-Iosifina","family":"Kasdagli","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ref_1","unstructured":"Human Fertilisation and Embryology Authority (2018). Fertility Treatment 2014\u20132016 Trends and Figures, HFEA."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1093\/humrep\/deaa250","article-title":"20 years of the European IVF-monitoring Consortium registry: What have we learned? A comparison with registries from two other regions","volume":"35","author":"Wyns","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_3","first-page":"233","article-title":"Assisted reproductive technology in Europe, 2011: Results generated from European registers by ESHRE","volume":"31","author":"Lokshin","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.rbmo.2020.11.013","article-title":"The freeze-all strategy after IVF: Which indications?","volume":"42","author":"Bourdon","year":"2021","journal-title":"Reprod. Biomed. Online"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1056\/NEJMoa1705334","article-title":"Transfer of fresh versus frozen embryos in ovulatory women","volume":"378","author":"Shi","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_6","first-page":"CD011184","article-title":"Fresh versus frozen embryo transfers in assisted reproduction","volume":"3","author":"Wong","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.fertnstert.2021.04.013","article-title":"Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: A randomized clinical trial","volume":"116","author":"Devine","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00404-022-06674-2","article-title":"The optimal route of progesterone administration for luteal phase support in a frozen embryo transfer: A systematic review","volume":"308","author":"Almohammadi","year":"2023","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"240","DOI":"10.4274\/tjod.galenos.2020.01460","article-title":"Comparison of intramuscular versus subcutaneous aqueous progesterone for luteal phase support in artificially prepared frozen embryo transfer cycles","volume":"17","author":"Turgut","year":"2020","journal-title":"Turk. J. Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejogrb.2005.02.019","article-title":"Preference and acceptability of oral versus vaginal administration of misoprostol in medical abortion with mifepristone","volume":"123","author":"Arvidsson","year":"2005","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_11","first-page":"2212","article-title":"Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: A randomized clinical trial","volume":"33","author":"Griesinger","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3109\/09513590.2015.1110136","article-title":"A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization (IVF) cycles","volume":"32","author":"Saharkhiz","year":"2016","journal-title":"Gynecol. Endocrino."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1093\/humrep\/dex023","article-title":"A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization","volume":"32","author":"Tournaye","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7326\/0003-4819-151-4-200908180-00135","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"151","author":"Moher","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Higgins, J.P., Savovi\u0107, J., Page, M.J., Elbers, R.G., and Sterne, J.A. (2019). Assessing risk of bias in a randomized trial. Cochrane Handbook for Systematic Reviews of Interventions, Wiley.","DOI":"10.1002\/9781119536604.ch8"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102030","DOI":"10.1016\/j.jogoh.2020.102030","article-title":"Oral dydrogesterone vs. micronized vaginal progesterone gel for luteal phase support in frozen-thawed single blastocyst transfer in good prognosis patients","volume":"50","author":"Ozer","year":"2021","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jrsm.1411","article-title":"Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments","volume":"12","author":"McGuinness","year":"2021","journal-title":"Res. Synth. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jclinepi.2010.07.015","article-title":"GRADE guidelines: 3. Rating the quality of evidence","volume":"64","author":"Balshem","year":"2011","journal-title":"J. Clin. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.31083\/j.ceog5001008","article-title":"Randomized Clinical Trial Comparing Oral Dydrogesterone to Micronized Vaginal Progesterone for Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycle","volume":"50","author":"Neto","year":"2023","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.rbmo.2022.06.027","article-title":"Oral, vaginal or intramuscular progesterone in programmed frozen embryo transfer cycles: A pilot randomized controlled trial","volume":"45","author":"Pabuccu","year":"2022","journal-title":"Reprod. Biomed. Online"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00404-016-4217-4","article-title":"Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer cycles: A randomized clinical trial","volume":"295","author":"Zarei","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.apjr.2016.10.002","article-title":"Oral dydrogesterone for luteal support in frozen-thawed embryo transfer artificial cycles: A pilot randomized controlled trial","volume":"5","author":"Rashidi","year":"2016","journal-title":"Asian Pac. J. Reprod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/09513590701584857","article-title":"Modulating fertility outcome in assisted reproductive technologies by the use of dydrogesterone","volume":"23","author":"Patki","year":"2007","journal-title":"Gynecol. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00404-020-05900-z","article-title":"Dydrogesterone in the treatment of endometriosis: Evidence mapping and meta-analysis","volume":"304","author":"Peng","year":"2021","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.fertnstert.2018.03.034","article-title":"Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: A new standard?","volume":"109","author":"Griesinger","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jsbmb.2005.08.012","article-title":"Oral dydrogesterone versus intravaginal micronised progesterone as luteal phase support in assisted reproductive technology (ART) cycles: Results of a randomised study","volume":"97","author":"Chakravarty","year":"2005","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/09513590.2019.1645110","article-title":"A Phase III randomized controlled trial of oral dydrogesterone versus intravaginal progesterone gel for luteal phase support in in vitro fertilization (Lotus II): Results from the Chinese mainland subpopulation","volume":"36","author":"Yang","year":"2020","journal-title":"Gynecol. Endocrinol."},{"key":"ref_28","first-page":"148","article-title":"Oral dydrogesterone vs. vaginal progesterone capsules for luteal-phase support in women undergoing embryo transfer: A systematic review and meta-analysis","volume":"22","author":"Barbosa","year":"2018","journal-title":"JBRA Assist. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejogrb.2014.11.002","article-title":"Oral dydrogesterone versus vaginal progesterone gel in the luteal phase support: Randomized controlled trial","volume":"186","author":"Tomic","year":"2015","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.earlhumdev.2008.12.016","article-title":"Dydrogesterone use during pregnancy: Overview of birth defects reported since 1977","volume":"85","year":"2009","journal-title":"Early Hum. Dev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1093\/humrep\/dex285","article-title":"Frozen embryo transfer: A review on the optimal endometrial preparation and timing","volume":"32","author":"Mackens","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/humrep\/dev339","article-title":"A fresh look at the freeze\u2014All protocol: A SWOT analysis","volume":"31","author":"Blockeel","year":"2016","journal-title":"Hum. Reprod."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/3238\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:28:31Z","timestamp":1760030911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/3238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":32,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14093238"],"URL":"https:\/\/doi.org\/10.3390\/jcm14093238","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,7]]}}}