--- title: "Aqueous SC progesterone vs. vaginal progesterone in IVF. | Sutter Health" description: "SC progesterone represents a novel option for luteal phase support in women undergoing IVF who prefer not to use a vaginal preparation." url: "https://www.sutterhealth.org/research/publications/aqueous-sc-progesteronevsvaginalprogesteroneinivf-1055312422" --- 1. [Home](https://www.sutterhealth.org/) / 2. [Research](https://www.sutterhealth.org/research) / 3. [Research publications](https://www.sutterhealth.org/research/publications) / 4. Aqueous SC progesterone vs. vaginal progesterone in IVF. # A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization. Baker VL, Jones CA, Doody K, Foulk R, Yee B, Adamson GD, Cometti B, DeVane G, Hubert G, Trevisan S, Hoehler F, Jones C, & Soules M. _Hum Reprod. 29(10):2212-20. doi: 10.1093/humrep/deu194. Epub 2014 Aug 6._ 2014-10-10 ## Abstract STUDY QUESTION: Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex(®)) non-inferior to vaginal progesterone (Endometrin(®)) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER: In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of -2.8% (95% confidence interval (CI) -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY: Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION: This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18-42 years, with a BMI of ≤ 30 kg/m(2), with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2-3) FSH of ≤ 15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS(®)). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: Using a PP analysis, which included all patients who received an embryo transfer (Prolutex = 392; Endometrin = 390), the ongoing pregnancy rate per retrieval for subcutaneous versus vaginal progesterone was 41.6 versus 44.4%, with a difference between groups of -2.8% (95% CI -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. In addition, rates of initial positive β-hCG (56.4% subcutaneous versus 59.0% vaginal; 95% CI -9.5, 4.3), clinical intrauterine pregnancy with fetal cardiac activity (42.6 versus 46.4%; 95% CI -10.8, 3.2), implantation defined as number of gestational sacs divided by number of embryos transferred (33.2 versus 35.1%; 95% CI -7.6, 4.0), live birth (41.1 versus 43.1%; 95% CI -8.9, 4.9) and take-home baby (41.1 versus 42.6%; 95% CI -8.4, 5.4) were comparable. Both formulations were well-tolerated, with no difference in serious adverse events. Analysis with the intention-to-treat population also demonstrated no difference for any outcomes between the treatment groups. LIMITATIONS, REASONS FOR CAUTION: The conclusions are limited to the progesterone dosing regimen studied and duration of treatment for the patient population examined in this study. WIDER IMPLICATIONS OF THE FINDINGS: Subcutaneous progesterone represents a novel option for luteal phase support in women undergoing IVF who for personal reasons prefer not to use a vaginal preparation or who wish to avoid the side effects of vaginal or i.m. routes of administration. [PubMed abstract](http://www.ncbi.nlm.nih.gov/pubmed/25100106) ## Research topics - [Disease Management](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Disease+Management%5C%22%22) - [Obstetrics and Gynecology](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Obstetrics+and+Gynecology%5C%22%22) ## Related publications [View all publications](https://www.sutterhealth.org/research-search-results?verticalKey=research_publication) - Publication ### [World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: IV. Tissue collection, processing, and storage in endometriosis research.](https://www.sutterhealth.org/research/publications/tissue-collectn-process-storage-endometriosis-res-1055312412) Fassbender A, Rahmioglu N, Vitonis AF, Viganò P, Giudice LC, D'Hooghe TM, Hummelshoj L, Adamson GD, Becker CM, Missmer SA, Zondervan KT; WERF EPHect Working Group. Fertil Steril. 102(5):1244-53. doi: 10.1016/j.fertnstert.2014.07.1209. Epub 2014 Sep 22. 2014 Nov 01 - Publication ### [A success story: impact of the United States in vitro fertilization data registry on advancing fertility care.](https://www.sutterhealth.org/research/publications/us-in-vitro-fertilization-data-registry-success-1055312413) Adamson GD. Fertil Steril. 111(3):457-458. doi: 10.1016/j.fertnstert.2019.01.031. 2019 Mar 01 - Publication ### [Improved implantation rates of day 3 embryo transfers with the use of an automated time-lapse-enabled test to aid in embryo selection.](https://www.sutterhealth.org/research/publications/improved-implantation-rates-day-3-embryo-transfers-1055312301) Adamson GD, Abusief ME, Palao L, Witmer J, Palao LM, Gvakharia M. Fertil Steril. pii: S0015-0282(15)02041-5. doi: 10.1016/j.fertnstert.2015.10.030. \[Epub ahead of print\] 2015 Nov 18 - Publication ### [World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: II. Clinical and covariate phenotype data collection in endometriosis research.](https://www.sutterhealth.org/research/publications/clin-covar-phenotype-data-collectn-endometri-res-1055312435) Vitonis AF, Vincent K, Rahmioglu N, Fassbender A, Buck Louis GM, Hummelshoj L, Giudice LC, Stratton P, Adamson GD, Becker CM, Zondervan KT, Missmer SA; WERF EPHect Working Group. Fertil Steril. 102(5):1223-32. doi: 10.1016/j.fertnstert.2014.07.1244. Epub 2014 Sep 22. 2014 Nov 01 - Publication ### [Research priorities for endometriosis: recommendations from a global consortium of investigators in endometriosis.](https://www.sutterhealth.org/research/publications/research-priorities-endometriosis-1055312479) Rogers PA, Adamson GD, Al-Jefout M, Becker CM, D'Hooghe TM, Dunselman GA, Fazleabas A, Giudice LC, Horne AW, Hull ML, Hummelshoj L, Missmer SA, Montgomery GW, Stratton P, Taylor RN, Rombauts L, Saunders PT, Vincent K, Zondervan KT; WES/WERF Consortium for Research Priorities in Endometriosis. Reprod Sci. pii: 1933719116654991. \[Epub ahead of print\] 2016 Jun 30 [View all publications](https://www.sutterhealth.org/research-search-results?verticalKey=research_publication) ```json {"@context":"https://schema.org","@type":"MedicalOrganization","name":"Sutter Health","@id":"https://www.sutterhealth.org/#medicalorganization","url":"https://www.sutterhealth.org","logo":"https://www.sutterhealth.org/static/images/sutter-health-logo.svg","address":{"@type":"PostalAddress","streetAddress":"2200 River Plaza Drive","addressLocality":"Sacramento","addressRegion":"CA","postalCode":"95833","addressCountry":"US"},"areaServed":{"@type":"AdministrativeArea","name":"California"},"sameAs":["https://www.facebook.com/SutterHealth","https://www.instagram.com/sutterhealth/","https://x.com/SutterHealth","https://www.youtube.com/sutterhealth","https://www.linkedin.com/company/sutter-health","https://en.wikipedia.org/wiki/Sutter_Health"]} ``` ```json {"@context":"https://schema.org","@type":"BreadcrumbList","@id":"https://www.sutterhealth.org/research/publications/aqueous-sc-progesteronevsvaginalprogesteroneinivf-1055312422#breadcrumblist","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https://www.sutterhealth.org/"},{"@type":"ListItem","position":2,"name":"Research","item":"https://www.sutterhealth.org/research"},{"@type":"ListItem","position":3,"name":"Research publications","item":"https://www.sutterhealth.org/research/publications"},{"@type":"ListItem","position":4,"name":"Aqueous SC progesterone vs. vaginal progesterone in IVF."}]} ``` ```json {"@context":"https://schema.org","@type":"MedicalScholarlyArticle","@id":"https://www.sutterhealth.org/research/publications/aqueous-sc-progesteronevsvaginalprogesteroneinivf-1055312422#medicalscholarlyarticle","name":"A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization.","headline":"Aqueous SC progesterone vs. vaginal progesterone in IVF.","abstract":"STUDY QUESTION: Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex(®)) non-inferior to vaginal progesterone (Endometrin(®)) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER: In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of -2.8% (95% confidence interval (CI) -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY: Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION: This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18-42 years, with a BMI of ≤ 30 kg/m(2), with \u003c3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2-3) FSH of ≤ 15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS(®)). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: Using a PP analysis, which included all patients who received an embryo transfer (Prolutex = 392; Endometrin = 390), the ongoing pregnancy rate per retrieval for subcutaneous versus vaginal progesterone was 41.6 versus 44.4%, with a difference between groups of -2.8% (95% CI -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. In addition, rates of initial positive β-hCG (56.4% subcutaneous versus 59.0% vaginal; 95% CI -9.5, 4.3), clinical intrauterine pregnancy with fetal cardiac activity (42.6 versus 46.4%; 95% CI -10.8, 3.2), implantation defined as number of gestational sacs divided by number of embryos transferred (33.2 versus 35.1%; 95% CI -7.6, 4.0), live birth (41.1 versus 43.1%; 95% CI -8.9, 4.9) and take-home baby (41.1 versus 42.6%; 95% CI -8.4, 5.4) were comparable. Both formulations were well-tolerated, with no difference in serious adverse events. Analysis with the intention-to-treat population also demonstrated no difference for any outcomes between the treatment groups. LIMITATIONS, REASONS FOR CAUTION: The conclusions are limited to the progesterone dosing regimen studied and duration of treatment for the patient population examined in this study. WIDER IMPLICATIONS OF THE FINDINGS: Subcutaneous progesterone represents a novel option for luteal phase support in women undergoing IVF who for personal reasons prefer not to use a vaginal preparation or who wish to avoid the side effects of vaginal or i.m. routes of administration.","description":"SC progesterone represents a novel option for luteal phase support in women undergoing IVF who prefer not to use a vaginal preparation.","keywords":["Disease Management","Obstetrics and Gynecology"],"datePublished":"2014-10-10","url":"https://www.sutterhealth.org/research/publications/aqueous-sc-progesteronevsvaginalprogesteroneinivf-1055312422","inLanguage":"en-US","identifier":[{"@type":"PropertyValue","propertyID":"PMID","value":"25100106"},{"@type":"PropertyValue","propertyID":"DOI","value":"10.1093/humrep/deu194"}],"sameAs":["https://pubmed.ncbi.nlm.nih.gov/25100106/","https://doi.org/10.1093/humrep/deu194"],"isPartOf":{"@type":"Periodical","name":"Hum Reprod"},"author":[{"@type":"Person","name":"Baker VL"},{"@type":"Person","name":"Jones CA"},{"@type":"Person","name":"Doody K"},{"@type":"Person","name":"Foulk R"},{"@type":"Person","name":"Yee B"},{"@type":"Person","name":"Adamson GD"},{"@type":"Person","name":"Cometti B"},{"@type":"Person","name":"DeVane G"},{"@type":"Person","name":"Hubert G"},{"@type":"Person","name":"Trevisan S"},{"@type":"Person","name":"Hoehler F"},{"@type":"Person","name":"Jones C"},{"@type":"Person","name":"Soules M"}],"sourceOrganization":{"@type":"MedicalOrganization","name":"Palo Alto Medical Foundation Research Institute"},"about":[{"@type":"DefinedTerm","name":"Disease Management","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22Disease+Management%22%5D%7D%5D&verticalKey=research_publication"},{"@type":"DefinedTerm","name":"Obstetrics and Gynecology","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22Obstetrics+and+Gynecology%22%5D%7D%5D&verticalKey=research_publication"}],"mainEntityOfPage":{"@type":"WebPage","@id":"https://www.sutterhealth.org/research/publications/aqueous-sc-progesteronevsvaginalprogesteroneinivf-1055312422","breadcrumb":{"@id":"https://www.sutterhealth.org/research/publications/aqueous-sc-progesteronevsvaginalprogesteroneinivf-1055312422#breadcrumblist"}}} ```