{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:44:44Z","timestamp":1792413884067,"version":"4.4.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012899","name":"Lanzhou University","doi-asserted-by":"publisher","award":["\u4e0d\u3002071100132"],"award-info":[{"award-number":["\u4e0d\u3002071100132"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022817","name":"Lanzhou University Second Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022817","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic endometritis (CE) is associated with recurrent reproductive failure (RRF), but the optimal treatment strategy remains uncertain. This study evaluated the efficacy and safety of doxycycline plus medroxyprogesterone acetate (MPA) in women with RRF and CE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>This prospective cohort study included 330 women with RRF and CE diagnosed by CD138 immunohistochemistry. According to the treatment received, patients were classified into the doxycycline group or the doxycycline plus MPA group, with 165 women in each group. The primary outcome was the histological cure rate of CE after one treatment course. Secondary outcomes included pregnancy rate, live birth rate, pregnancy loss rate, ongoing pregnancy rate, and adverse events. Multivariable Poisson regression with robust variance was used to adjust for potential confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the primary efficacy population, CE cure occurred in 117 of 158 patients (74.1%) receiving doxycycline and 130 of 160 (81.2%) receiving doxycycline plus MPA [adjusted risk difference [aRD], 6.1; 95% CI, \u22123.2\u201315.4; adjusted risk ratio [aRR], 1.08; 95% CI, 0.96\u20131.22;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.202]. Pregnancy occurred in 97 of 158 patients (61.4%) and 126 of 160 (78.8%) (aRD, 16.5 percentage points; 95% CI, 6.5\u201326.5; aRR, 1.27; 95% CI, 1.09\u20131.47;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002). Adverse events occurred in 12 of 165 patients (7.3%) in each group and were all mild.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Doxycycline plus MPA did not significantly improve the CE cure rate in women with RRF and CE, but was associated with a higher pregnancy rate without an increase in adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2400080514 (31\/01\/2024)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1913511","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:37:48Z","timestamp":1790228268000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical efficacy and pregnancy outcomes of doxycycline plus medroxyprogesterone acetate therapy for chronic endometritis in women with recurrent reproductive failure: a prospective cohort study"],"prefix":"10.3389","volume":"13","author":[{"given":"Fei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, The Second Hospital of Lanzhou University","place":["Lanzhou, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongrui","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Public Health, Lanzhou University","place":["Lanzhou, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The Second Hospital of Lanzhou University","place":["Lanzhou, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The Second Hospital of Lanzhou University","place":["Lanzhou, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The Second Hospital of Lanzhou University","place":["Lanzhou, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaolong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Lanzhou University","place":["Lanzhou, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The Second Hospital of Lanzhou University","place":["Lanzhou, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.23736\/S2724-606X.24.05549-0","article-title":"Immune biomarkers in cases of recurrent pregnancy loss and recurrent implantation failure","volume":"77","author":"Cavalcante","year":"2025","journal-title":"Minerva Obstet Gynecol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e39584","DOI":"10.1016\/j.heliyon.2024.e39584","article-title":"Revolutionized attitude toward recurrent pregnancy loss and recurrent implantation failure based on precision regenerative medicine","volume":"10","author":"Motlagh Asghari","year":"2024","journal-title":"Heliyon"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1427454","DOI":"10.3389\/fimmu.2024.1427454","article-title":"Chronic endometritis and recurrent reproductive failure: a systematic review and meta-analysis","volume":"15","author":"Ticconi","year":"2024","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.fertnstert.2019.11.025","article-title":"Definitions of infertility and recurrent pregnancy loss: a committee opinion","volume":"113","year":"2020","journal-title":"Fertil Steril"},{"key":"B5","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1111\/jog.13937","article-title":"Review: chronic endometritis and its effect on reproduction","volume":"45","author":"Kimura","year":"2019","journal-title":"J Obstet Gynaecol Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5935\/1518-0557.20230015","article-title":"Endometriosis and infertility: the hidden link between endometritis, hormonal imbalances and immune dysfunctions preventing implantation!","volume":"27","author":"Bouic","year":"2023","journal-title":"JBRA Assist Reprod"},{"key":"B7","doi-asserted-by":"publisher","first-page":"980511","DOI":"10.3389\/fmed.2022.980511","article-title":"Impact of antibiotic treatment for chronic endometritis on pregnancy outcomes in women with reproductive failures (RIF and RPL): a systematic review and meta-analysis","volume":"9","author":"Liu","year":"2022","journal-title":"Front Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.22074\/ijfs.2020.5779","article-title":"Chronic endometritis: old problem, novel insights and future challenges","volume":"13","author":"Puente","year":"2020","journal-title":"Int J Fertil Steril"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e13369","DOI":"10.1111\/aji.13369","article-title":"Diagnosis of chronic endometritis: how many CD138+ cells\/HPF in endometrial stroma affect pregnancy outcome of infertile women?","volume":"85","author":"Li","year":"2021","journal-title":"Am J Reprod Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1007\/s10815-020-01955-8","article-title":"Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review","volume":"37","author":"Buzzaccarini","year":"2020","journal-title":"J Assist Reprod Genet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.ajog.2018.02.012","article-title":"The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology","volume":"218","author":"Moreno","year":"2018","journal-title":"Am J Obstet Gynecol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1002\/ijgo.70115","article-title":"High prevalence of chronic endometritis in women with nonstructural abnormal uterine bleeding and benefits of antimicrobial treatment on blood loss pattern: a prospective, observational study","volume":"170","author":"Cicinelli","year":"2025","journal-title":"Int J Gynaecol Obstet"},{"key":"B13","doi-asserted-by":"publisher","first-page":"102034","DOI":"10.1016\/j.jogoh.2020.102034","article-title":"Impact of antibiotic treatment for chronic endometritis on unexplained recurrent pregnancy loss","volume":"50","author":"Gay","year":"2021","journal-title":"J Gynecol Obstet Hum Reprod"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e12719","DOI":"10.1111\/aji.12719","article-title":"Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure","volume":"78","author":"Kitaya","year":"2017","journal-title":"Am J Reprod Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.fertnstert.2008.12.131","article-title":"Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization","volume":"93","author":"Johnston-MacAnanny","year":"2010","journal-title":"Fertil Steril"},{"key":"B16","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.fertnstert.2018.03.017","article-title":"Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis","volume":"110","author":"Vitagliano","year":"2018","journal-title":"Fertil Steril"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3073","DOI":"10.1007\/s43032-021-00583-6","article-title":"Combination of dydrogesterone and antibiotic versus antibiotic alone for chronic endometritis: a randomized controlled trial study","volume":"28","author":"Qu","year":"2021","journal-title":"Reprod Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.maturitas.2009.10.011","article-title":"Progestational effects of dydrogesterone in vitro, in vivo and on the human endometrium","volume":"65","author":"Schindler","year":"2009","journal-title":"Maturitas"},{"key":"B19","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1046\/j.1365-2362.2000.0300s3006.x","article-title":"Molecular mechanisms of dissociative glucocorticoid activity","volume":"30","author":"Bamberger","year":"2000","journal-title":"Eur J Clin Invest"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4055","DOI":"10.1210\/jc.84.11.4055","article-title":"Dissociative glucocorticoid activity of medroxyprogesterone acetate in normal human lymphocytes","volume":"84","author":"Bamberger","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"B21","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.mce.2017.05.015","article-title":"Medroxyprogesterone acetate drives M2 macrophage differentiation toward a phenotype of decidual macrophage","volume":"452","author":"Tsai","year":"2017","journal-title":"Mol Cell Endocrinol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.3390\/ijms26031295","article-title":"Exploring the immunological aspects and treatments of recurrent pregnancy loss and recurrent implantation failure","volume":"26","author":"Garmendia","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"hoad023","DOI":"10.1093\/hropen\/hoad023","article-title":"ESHRE good practice recommendations on recurrent implantation failure","volume":"2023","author":"Cimadomo","year":"2023","journal-title":"Hum Reprod Open"},{"key":"B24","doi-asserted-by":"publisher","first-page":"5683","DOI":"10.1038\/s41467-020-19414-4","article-title":"Single-cell analysis of developing and azoospermia human testicles reveals central role of sertoli cells","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat Commun"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e12782","DOI":"10.1111\/aji.12782","article-title":"Chronic endometritis in patients with unexplained infertility: prevalence and effects of antibiotic treatment on spontaneous conception","volume":"79","author":"Cicinelli","year":"2018","journal-title":"Am J Reprod Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/j.fertnstert.2018.12.007","article-title":"Correlation between hysteroscopy findings and chronic endometritis[J]","volume":"111","author":"Song","year":"2019","journal-title":"Fertil Steril"},{"key":"B27","doi-asserted-by":"publisher","first-page":"69","DOI":"10.4103\/0974-2727.105584","article-title":"Evaluation of endometrium for chronic endometritis by using syndecan-1 in abnormal uterine bleeding","volume":"4","author":"Kannar","year":"2012","journal-title":"J Lab Physicians"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e13669","DOI":"10.1111\/aji.13669","article-title":"Effect of different antibiotic therapies on the reproductive outcomes of fresh embryo transfer for chronic endometritis: a retrospective cohort study","volume":"89","author":"Liu","year":"2023","journal-title":"Am J Reprod Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.ajog.2025.07.045","article-title":"Doxycycline vs levofloxacin combined with tinidazole for treating chronic endometritis: a randomized controlled trial","volume":"234","author":"Liu","year":"2026","journal-title":"Am J Obstet Gynecol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12958-025-01478-w","article-title":"Between evidence and expectation: a retrospective cohort study on chronic endometritis in repeated implantation failure and recurrent pregnancy loss","volume":"23","author":"Lastinger","year":"2025","journal-title":"Reprod Biol Endocrinol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1186\/s12884-024-06422-1","article-title":"Reproductive factors and subsequent pregnancy outcomes in patients with prior pregnancy loss","volume":"24","author":"Yang","year":"2024","journal-title":"BMC Pregnancy Childbirth"},{"key":"B32","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.fertnstert.2019.09.001","article-title":"Evaluation of peripheral and uterine immune status of chronic endometritis in patients with recurrent reproductive failure","volume":"113","author":"Li","year":"2020","journal-title":"Fertil Steril"},{"key":"B33","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.fertnstert.2019.05.015","article-title":"Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method","volume":"112","author":"Liu","year":"2019","journal-title":"Fertil Steril"},{"key":"B34","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1186\/s12905-024-03221-w","article-title":"Chronic endometritis multiplies the recurrence risk of endometrial polyps after transcervical resection of endometrial polyps: a prospective study","volume":"24","author":"Huang","year":"2024","journal-title":"BMC Womens Health"},{"key":"B35","doi-asserted-by":"publisher","first-page":"111855","DOI":"10.1016\/j.mce.2023.111855","article-title":"Glucocorticoids and medroxyprogesterone acetate synergize with inflammatory stimuli to selectively upregulate CCL20 transcription[J]","volume":"563","author":"Moliki","year":"2023","journal-title":"Mol Cell Endocrinol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1186\/s12905-022-02033-0","article-title":"Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study","volume":"22","author":"Liu","year":"2022","journal-title":"BMC Womens Health"},{"key":"B37","doi-asserted-by":"publisher","first-page":"T1","DOI":"10.1530\/JME-19-0212","article-title":"90 YEARS OF PROGESTERONE: new insights into progesterone receptor signaling in the endometrium required for embryo implantation","volume":"65","author":"DeMayo","year":"2020","journal-title":"J Mol Endocrinol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1913511\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:10:30Z","timestamp":1792411830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1913511\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":37,"alternative-id":["10.3389\/fmed.2026.1913511"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1913511","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"1913511"}}