{"paper_id":"fb420446-6356-41c3-b36b-86acd0702800","body_text":"Abstract\nObjective\nTo evaluate the long-term efficacy of Chinese herbal medicine (CHM) in enhancing reproductive outcomes and reducing recurrence rates among endometriosis-associated infertility women infertile women.\nMethods\nThis study is a retrospective analysis of a randomized, double-blind, placebo-controlled clinical trial implemented from May 2014 to April 2018. The study included patients with endometriosis-associated infertility who had undergone standardized laparoscopic surgery. After surgery, the participants were randomly assigned to 2 groups: the intervention group received a CHM treatment regimen, while the control group was given placebo therapy. Both groups were subjected to the same blinding procedures and received treatment for a period of 6 months. Five years after surgery, the researchers conducted follow-up with the participants and analysed the data on pregnancy outcomes and recurrence of endometriosis.\nResults\nIn this trial, a total of 202 patients with endometriosis-associated infertility (101 per group) were followed up at 5 years post-surgery for clinical pregnancy, live birth, and recurrence outcomes (101 patients per group). According to our data, pregnancies occurred in 83 (82.18%) participants in the CHM group, with a pregnancy rate of 69.02 person-years, and 70 (69.31%) participants in the placebo group, with a pregnancy rate of 42.86 person-years during pregnancy-related median follow-up of 0.75 years [interquartile range (IQR) 0.25–1.71, hazard ratio (HR) 1.451, 95% confidence interval (CI) 1.055–1.997; P=0.017]. Clinical pregnancies occurred in 80 (79.21%) participants in the CHM group, with a clinical pregnancy rate of 64.91 person-years, and in 67 (66.34%) participants in the placebo group, with a clinical pregnancy rate of 39.14 person-years over the course of a median clinical pregnancy-related follow-up of 0.83 years (IQR 0.33–1.83, HR 1.495, 95% CI 1.079–2.072; P=0.012). Live births occurred in 78 (77.23%) participants in the CHM group at a rate of 36.72 person-years and in 60 (59.41%) participants in the placebo group at a rate of 23.94 person-years during the live birth-related median follow-up of 1.79 years (IQR 1.06–3, HR 1.542, 95% CI 1.097–2.165; P=0.010). Recurrence occurred in 12 (11.88%) participants in the CHM group, with a recurrence rate of 2.95 person-years, and in 24 (23.76%) participants in the placebo group, with a recurrence rate of 7.09 person-years (HR 0.458, 95% CI 0.229–0.916; P=0.022) during the recurrence-related median follow-up of 5 years (IQR 1.0–5.0). When assessed within subgroups, the HRs of the intervention on pregnancy and recurrence were similar in participants in different layers (P interaction>0.05).\nConclusion\nCHM can improve postoperative pregnancy outcomes, shorten the time to conception, and reduce the risk of long-term recurrence in infertile patients with endometriosis after laparoscopic surgery. (Registration Number. ChiCTR2300070138)\nSimilar content being viewed by others\nData Availability\nThe datasets generated during the current study are available from the corresponding author upon reasonable request.\nReferences\nBonavina G, Taylor HS. Endometriosis-associated infertility: from pathophysiology to tailored treatment. Front Endocrinol (Lausanne) 2022;13:1020827.\nLeonardi M, Gibbons T, Armour M, Wang R, Glanville E, Hodgson R, et al. When to do surgery and when not to do surgery for endometriosis: a systematic review and metaanalysis. J Minim Invas Gynecol 2020;27:390–407.e3.\nBafort C, Beebeejaun Y, Tomassetti C, Bosteels J, Duffy JM. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev 2020;10:CD011031.\nYounis JS, Shapso N, Ben-Sira Y, Nelson SM, Izhaki I. Endometrioma surgery—a systematic review and meta-analysis of the effect on antral follicle count and anti-Müllerian hormone. Am J Obstet Gynecol 2022;226:33–51.\nZhang Y, Zhang S, Zhao Z, Wang C, Xu S, Wang F. Impact of cystectomy versus ablation for endometrioma on ovarian reserve: a systematic review and meta-analysis. Fertil Steril 2022;118:1172–1182.\nSomigliana E, Li Piani L, Paffoni A, Salmeri N, Orsi M, Benaglia L, et al. Endometriosis and IVF treatment outcomes: unpacking the process. Reprod Biol Endocrinol 2023;21:107.\nWu CQ, Albert A, Alfaraj S, Taskin O, Alkusayer GM, Havelock J, et al. Live birth rate after surgical and expectant management of endometriomas after in vitro fertilization: a systematic review, meta-analysis, and critical appraisal of current guidelines and previous meta-analyses. J Minim Invasive Gynecol 2019;26:299–311.\nBecker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al; ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum Reprod Open 2022;2022:hoac009.\nTahmasbi Rad M, Akpinar-Isci D, Nobs T, Gasimli K, Becker S. Pregnancy after laparoscopic surgery for endometriosis: how long should we wait? A retrospective study involving a long-term follow up at a university endometriosis center. Int J Gynaecol Obstet 2023;163:108–114.\nRoman H, Chanavaz-Lacheray I, Hennetier C, Tuech JJ, Dennis T, Verspyck E, et al. Long-term risk of repeated surgeries in women managed for endometriosis: a 1,092 patient-series. Fertil Steril 2023;120:870–879.\nZakhari A, Delpero E, McKeown S, Tomlinson G, Bougie O, Murji A. Endometriosis recurrence following postoperative hormonal suppression: a systematic review and meta-analysis. Hum Reprod Update 2021;27:96–107.\nKaponis A, Chatzopoulos G, Paschopoulos M, Georgiou I, Paraskevaidis V, Zikopoulos K, et al. Ultralong administration of gonadotropin-releasing hormone agonists before in vitro fertilization improves fertilization rate but not clinical pregnancy rate in women with mild endometriosis: a prospective, randomized, controlled trial. Fertil Steril 2020;113:828–835.\nMuzii L, Achilli C, Lecce F, Bianchi A, Franceschetti S, Marchetti C, et al. Second surgery for recurrent endometriomas is more harmful to healthy ovarian tissue and ovarian reserve than first surgery. Fertil Steril 2015;103:738–743.\nPascoal E, Wessels JM, Aas-Eng MK, Abrao MS, Condous G, Jurkovic D, et al. Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research. Ultrasound Obstet Gynecol 2022;60:309–327.\nYang XC, Liu Y, Sun WW, Shi G, Wu Y, Xu C, et al. Efficacy of Chinese herbal medicines on pregnancy outcomes in patients with endometriosis in long-term management: a multicenter retrospective cohort study. Chin J Integr Med 2023;29:971–979.\nZhao RH, Liu Y, Lu D, Wu Y, Wang XY, Li WL, et al. Chinese medicine sequential therapy improves pregnancy outcomes after surgery for endometriosis-associated infertility: a multicenter randomized double-blind placebo parallel controlled clinical trial. Chin J Integr Med 2020;26:92–99.\nKanellopoulos D, Karagianni D, Pergialiotis V, Nikiteas N, Lazaris AC, Iliopoulos D. The effect of endometriosis on fertility in an animal model. J Med Life 2022;15:1170–1175.\nMohammed Rasheed HA, Hamid P. Inflammation to infertility: panoramic view on endometriosis. Cureus 2020;12:e11516.\nWahl KJ, Orr NL, Lisonek M, Noga H, Bedaiwy MA, Williams C, et al. Deep dyspareunia, superficial dyspareunia, and infertility concerns among women with endometriosis: a cross-sectional study. Sex Med 2020;8:274–281.\nZondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med 2020;382:1244–1256.\nRequadt E, Nahlik AJ, Jacobsen A, Ross WT. Patient experiences of endometriosis diagnosis: a mixed methods approach. BJOG 2024;131:941–951.\nGarcia-Velasco JA, Viganò P, Somigliana E. Twenty-five years of research in endometriosis. Reprod Biomed Online 2025;50:104830.\nGao Q, Shen L, Jiang B, Luan YF, Lin LN, Meng FC, et al. Salvia miltiorrhiza-containing Chinese herbal medicine combined with GnRH agonist for postoperative treatment of endometriosis: a systematic review and meta-analysis. Front Pharmacol 2022;13:831850.\nMeresman GF, Götte M, Laschke MW. Plants as source of new therapies for endometriosis: a review of preclinical and clinical studies. Hum Reprod Update 2021;27:367–392.\nZhao RH, Hao ZP, Zhang Y, Lian FM, Sun WW, Liu Y, et al. Controlling the recurrence of pelvic endometriosis after a conservative operation: comparison between Chinese herbal medicine and Western medicine. Chin J Integr Med 2013;19:820–825.\nLi XY, Chao XP, Leng JH, Zhang W, Zhang JJ, Dai Y, et al. Risk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women. J Ovarian Res 2019;12:79.\nJiang D, Zhang X, Shi J, Tao D, Nie X. Risk factors for ovarian endometrioma recurrence following surgical excision: a systematic review and meta-analysis. Arch Gynecol Obstet 2021;304:589–598.\nSzyplowska M, Tarkowski R, Kulak K. The impact of endometriosis on depressive and anxiety symptoms and quality of life: a systematic review. Front Public Health 2023;11:1230303.\nGao X, Tang Y, Kong L, Fan Y, Wang C, Wang R. Treg cell: critical role of regulatory T cells in depression. Pharmacol Res 2023;195:106893.\nLi JM, Ni Y, Wang N, Liao Y, Yu YW, Lyu WL, et al. Genetically predicted plasma levels of amino acids and endometriosis: a mendelian randomization study. Biomed Environ Sci 2024;37:672–675.\nZhang YJ. A study on the mechanism of Huoxue Xiaoyi Decoction in the treatment of endometriosis based on β2-AR/Treg signaling pathway [Dissertation]. Beijing: China Academy of Chinese Medical Sciences; 2023.\nLin Y, Hou R, Zhang T, Chung JPW, Wang CC, Zhao R. Efficacy and safety of Chinese herbal medicine for endometriosis associated pain. Am J Chin Med 2022;50:1095–1111.\nAuthor information\nAuthors and Affiliations\nContributions\nYang XC and Han Q contributed equally to this work. Yang XC and Han Q conceived, drafted and revised the article, followed up with the subjects, and performed the mapping and analysis of the results. Zhao RH was the corresponding author and conceived and designed the study protocol. Xu R, Zhang Y, Shi G, Liu Y, Sun WW and Wu Y contributed to the follow-up of the subjects. All authors have read and approved the final manuscript for publication.\nCorresponding author\nEthics declarations\nNo conflict of interest exists in the submission of this manuscript, which is approved by all the authors for publication.\nAdditional information\nSupported by the Key Projects of the National Science and Technology Pillar Program during the 12th Five-Year Plan Period (No. 2014BAI10B08)\nRights and permissions\nAbout this article\nCite this article\nYang, Xc., Han, Q., Xu, R. et al. Chinese Herbal Medicine Improves Pregnancy Outcome and Decreases Recurrence Rate after Surgery for Endometriosis-Associated Infertility: A Retrospective Study. Chin. J. Integr. Med. (2026). https://doi.org/10.1007/s11655-026-4240-7\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s11655-026-4240-7","source_license":"public-domain-us","license_restricted":false}