Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study

Objective To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management.

This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed.

The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05].

CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management. Similar content being viewed by others Data Availability The corresponding author has full access to all data in the study and ultimately determines the decision to submit for publication.

Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med 2020;382:1244–1256. Horne AW, Saunders PTK. SnapShot: Endometriosis. Cell 2019;179:1677. Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet 2010;27:441–447. Da Broi MG, Navarro PA. Oxidative stress and oocyte quality: ethiopathogenic mechanisms of minimal/mild endometriosis-related infertility. Cell Tissue Res 2016;364:1–7. Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand 2017;96:659–667. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update 2019;25:592–632. Endometriosis Association of Gynecology and Obstetrics Branch, Chinese Medical Association. Guideline for the diagnosis and treatment of endometriosis. Chin J Obstet Gynecol (Chin) 2015;50:161–169. Rossi AC, Prefumo F. The effects of surgery for endometriosis on pregnancy outcomes following in vitro fertilization and embryo transfer: a systematic review and meta-analysis. Arch Gynecol Obstet 2016;294:647–655. Kong S, Zhang YH, Liu CF, Tsui I, Guo Y, Ai BB, et al. The complementary and alternative medicine for endometriosis: a review of utilization and mechanism. Evid Based Complement Alternat Med 2014;2014:146383. Meresman 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. Meng W, Ta N, Wang F. Add-on effect of Guizhi Fuling Formula to mifepristone for endometriosis: a meta-analysis of randomized controlled trials. Medicine (Baltimore) 2019;98:e16878. Shan J, Cheng W, Zhai DX, Zhang DY, Yao RP, Bai LL, et al. Meta-analysis of Chinese traditional medicine Bushen Huoxue Prescription for endometriosis treatment. Evid Based Complement Alternat Med 2017;2017:5416423. Zhao RH. Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy of endometriosis-associated infertility. Chin J Integr Med 2019;25:243–245. Xiong T. Study on the construction of endometriosis TCM chronic disease management program and management tool [(Dissertation)]. Beijing: Beijing University of Chinese Medicine;2021. Gao 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. Dong P, Ling L, Hu L. Systematic review and meta-analysis of traditional Chinese medicine compound in treating infertility caused by endometriosis. Ann Palliat Med 2021;10:12631–12642. Flower A, Liu JP, Lewith G, Little P, Li Q. Chinese herbal medicine for endometriosis. Cochrane Database Syst Rev 2012;CD006568. Hung HH, Lai JN, Chen WC, Chen YH, Chiu LT, Chen HY. Evaluation of the efficacy of traditional Chinese medicine for the reproductive and pregnancy outcomes in women with endometriosis: a nationwide population-based study. Taiwan J Obstet Gynecol 2021;60:685–689. Liao YH, Lin JG, Lin CC, Tsai CC, Lai HL, Li TC. Traditional Chinese medicine treatment associated with female infertility in Taiwan: a population-based case-control study. Evid Based Complement Alternat Med 2020;2020:3951741. Zhao 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. Zhang YJ. A study on the mechanism of Huoxue Xiaoyi Decoction in the treatment of endometriosis based on β 2-AR/Treg signaling pathway [Dissertation]. Beijing: China Academy of Chinese Medical Sciences;2022. Chang B, Liu Y, Hu J, Tang Z, Qiu Z, Song Z, et al. Bupleurum Chinense DC improves CUMS-induced depressive symptoms in rats through upregulation of the cAMP/PKA/CREB signalling pathway. J Ethnopharmacol 2022;289:115034. Liang Y, Kang L, Qi Z, Gao X, Quan H, Lin H. Salvia Miltiorrhiza solution and its active compounds ameliorate human granulosa cell damage induced by H2O2. Exp Ther Med 2021;21:64. Huang C, He X, Luo W, Chen H, Huang Y. Combined chitosan and Dan-shen Injection for long-term tubal patency in fallopian tube recanalization for infertility. Drug Deliv Transl Res 2019;9:738–747. Lu J, Li W, Gao T, Wang S, Fu C, Wang S. The association study of chemical compositions and their pharmacological effects of Cyperi Rhizoma (Xiangfu), a potential traditional Chinese medicine for treating depression. J Ethnopharmacol 2022;287:114962. Li XH, Liu YR, Jiang DH, Tang ZS, Qian DW, Song ZX, et al. Research on the mechanism of Chinese herbal medicine Radix Paeoniae Rubra in improving chronic pelvic inflammation disease by regulating PTGS2 in the arachidonic acid pathway. Biomed Pharmacother 2020;129:110052. Liu Z, Zhao RH. Study on network pharmacology of Huoxue Xiaoyi Formula in treating endometriosis. J Shandong Univ Tradit Chin Med (Chin) 2021;45:354–361. Shi G. A study on the mechanism of Huoxue Xiaoyi Decoction on regulation of apoptosis and autophagy of ovarian granulosa cells in endometriosis rats [Dissertation]. Beijing: China Academy of Chinese Medical Sciences;2020. Wu TS, Cui YY, Sun WW, Zhao RH, Xu C. Effects of Huoxuexiaoyi Recipe on endometrial receptivity in mice models with endometriosis. Hebei Med J (Chin) 2017;39:965–967,972. Yang YH, Zhao RH, Wu TS, Cui YY, Sun WW, Xu C. Effects of Huoxue Xiaoyi Formula on expressions of HOXA10 of mice with endometriosis hypofunction pregnancy. Liaoning J Tradit Chin Med (Chin) 2016;43:2639–2642. Li TT, Sun WW, Zhao RH, Yu YW. Effect of Huoxue Xiaoyi Recipe on TCF-β/Smads signaling pathway of pelvic adhesions of endometriosis rats. Chin J Integr Med Tradit West (Chin) 2018;38:712–716. Sun WW, Chang H, Cui YY, Wu TS, Zhao RH. Effect of Huoxue Xiaoyi Decoction on expression of osteopontin and tumor necrosis factor-α in endometriosis rats. Jilin J Chin Med (Chin) 2019;39:512–515. Cui YY, Sun WW, Zhao RH, Xu C, Wu TS. Effects of Huoxue Xiaoyi Fang on embryo development after IVF-ET in endometriosis model mice. J Reprod Med (Chin) 2016;25:166–171. Sun WW, Chang H, Zhao RH. Effect of Huoxue Xiaoyi Prescription on fertility and early pregancy toxicity of rats with endometriosis. Drug Evaluat Res (Chin) 2019;42:648–652. Sun WW, Chang H, Zhao RH. Preliminary study of Huoxue Xiaoyi Fang on the fetal-perinatal developmental toxicity of rats with endometriosis. Jilin J Chin Med (Chin) 2020;40:1500–1504. Hou RJ, Zhang YJ, Yang XC, Hang T, Zhao RH. Experience in treating primary infertility with Liuhe Dingzhong Decoction. China J Tradit Chin Med Pharm (Chin) 2022;37:6933–6935. An DD, Zhao RH. Introduction of Fuyang method in application of endometriosis. Guangming J Chin Med (Chin) 2015;30:713–715. Nie X, Sheng W, Hou D, Liu Q, Wang R, Tan Y. Effect of hyperin and icariin on steroid hormone secretion in rat ovarian granulosa cells. Clin Chim Acta 2019;495:646–651. Liu B, Wang JL, Wang XM, Zhang C, Dai JG, Huang XM, et al. Reparative effects of lycium barbarum polysaccharide on mouse ovarian injuries induced by repeated superovulation. Theriogenology 2020;145:115–125. Yang L, Lei L, Zhao Q, Gao Z, Xu X. Lycium barbarum polysaccharide improves the development of mouse oocytes vitrified at the germinal vesicle stage. Cryobiology 2018;85:7–11. Hui Y, Zhao S, Gu J, Hang C. Analysis of factors related to fertility after endometriosis combined with infertility laparoscopic surgery. Medicine (Baltimore) 2020;99:e20132. Sindan N, Bhandari A, Sindan N, Kc R, Xia E, Lin Y. Clinical factors influencing the pregnancy outcome after laparoscopic treatment in endometriosis-associated infertility patients: a retrospective study. Am J Transl Res 2021;13:2399–2409. Zhao RH, Sun WW, Liu Y, Dai ZQ. Chinese medicine in management of chronic disease endometriosis. Chin J Integr Med 2020;26:88–91. Collinet P, Fritel X, Revel-Delhom C, Ballester M, Bolze PA, Borghese B, et al. Management of endometriosis: CNGOF/HAS clinical practice guidelines—short version. J Gynecol Obstet Hum Reprod 2018;47:265–274. Author information Authors and Affiliations Contributions Yand XC and Liu Y contributed equally to this work. Yang XC and Liu Y wrote the manuscript and reviewed the literature. Sun WW, Shi G collected, assembled and analyzed the data. Wu Y, Xu C, Meng QW, Hao ZP and Han Q collected and assembled the data. Zhao RH designed and conceived the study and revised the manuscript. All of the authors approved the final manuscript. Corresponding author Ethics declarations The authors declare that there is no conflict of interest regarding the publication of this paper. Additional information Supported by Capital’s Funds for Health Improvement and Research (No. 2018-1-4151), and Project of “Hundred Thousand” Talents Project of TCM Inheritance and Innovation (Qihuang Project) Qihuang Scholars (Letter [2018] No.284, Department of Human Education, National Administration of Traditional Chinese Medicine) Rights and permissions About this article Cite this article Yang, Xc., Liu, Y., Sun, Ww. 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. 29, 971–979 (2023). https://doi.org/10.1007/s11655-023-3736-z Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11655-023-3736-z