{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:29:30Z","timestamp":1792794570484,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Uppsala University, Uppsala Family Planning fund","id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ferring pharmaceuticals AB, Malm\u00f6, Sweden"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Does supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Progesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Women, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100\u2009mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>There were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102\u20132.428, P\u2009=\u20090.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012\u20132.108, P\u2009=\u20090.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024\u20132.188, P\u2009=\u20090.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>The study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5\/6 embryos compared to Day 2\/3 embryos.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Supplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malm\u00f6, Sweden. The authors have no personal conflicting interests to declare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>NL4152.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION DATE<\/jats:title>\n                    <jats:p>5 December 2013.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATE OF FIRST PATIENT\u2019S ENROLMENT<\/jats:title>\n                    <jats:p>18 February 2013.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deac181","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T10:45:32Z","timestamp":1660646732000},"page":"2366-2374","source":"Crossref","is-referenced-by-count":35,"title":["Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos\u2014a randomized controlled trial"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8818-4531","authenticated-orcid":false,"given":"K","family":"W\u00e5nggren","sequence":"first","affiliation":[{"name":"Division of Obstetrics and Gynaecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet , Stockholm, Sweden"},{"name":"Department of Women\u2019s and Children\u2019s Health, Uppsala University , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Dahlgren Granbom","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynaecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S I","family":"Iliadis","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Uppsala University , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Gudmundsson","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Uppsala University , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Stavreus-Evers","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Uppsala University , Uppsala, Sweden"},{"name":"The Centre for Reproductive Biology in Uppsala, CRU , Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"2022100305584002200_deac181-B1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.rbmo.2012.10.012","article-title":"Increasing vaginal progesterone gel supplementation after frozen-thawed embryo transfer significantly increases the delivery rate","volume":"26","author":"Alsbjerg","year":"2013","journal-title":"Reprod Biomed Online"},{"key":"2022100305584002200_deac181-B2","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.rbmo.2018.08.022","article-title":"Progesterone levels on pregnancy test day after hormone replacement therapy-cryopreserved embryo transfer cycles and related reproductive outcomes","volume":"37","author":"Alsbjerg","year":"2018","journal-title":"Reprod Biomed Online"},{"key":"2022100305584002200_deac181-B3","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1034\/j.1600-0412.2003.00128.x","article-title":"Embryo transfer by midwife or gynecologist: a prospective randomized study","volume":"82","author":"Bjuresten","year":"2003","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2022100305584002200_deac181-B4","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.fertnstert.2010.05.019","article-title":"Luteal phase progesterone increases live birth rate after frozen embryo transfer","volume":"95","author":"Bjuresten","year":"2011","journal-title":"Fertil Steril"},{"key":"2022100305584002200_deac181-B5","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/0002-9378(73)90073-2","article-title":"The effect of estradiol replacement therapy on early pregnant luteectomized patients","volume":"117","author":"Csapo","year":"1973","journal-title":"Am J Obstet Gynecol"},{"key":"2022100305584002200_deac181-B6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0090-6980(73)90030-0","article-title":"The effect of luteectomy-induced progesterone-withdrawal on the oxytocin and prostaglandin response of the first trimester pregnant human uterus","volume":"4","author":"Csapo","year":"1973","journal-title":"Prostaglandins"},{"key":"2022100305584002200_deac181-B7","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/0002-9378(72)90181-0","article-title":"The significance of the human corpus luteum in pregnancy maintenance. 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