Xiao-Ke Wu1, Elisabet Stener-Victorin2, Hong-Ying Kuang3, Hong-Li Ma3, Jing-Shu Gao3, Liang-Zhen Xie3, Li-Hui Hou3, Zhen-Xing Hu4, Xiao-Guang Shao5, Jun Ge6, Jin-Feng Zhang7, Hui-Ying Xue8, Xiao-Feng Xu9, Rui-Ning Liang10, Hong-Xia Ma11, Hong-Wei Yang12, Wei-Li Li13, Dong-Mei Huang14, Yun Sun15, Cui-Fang Hao16, Shao-Min Du17, Zheng-Wang Yang18, Xin Wang19, Ying Yan20, Xiu-Hua Chen21, Ping Fu22, Cai-Fei Ding23, Ya-Qin Gao24, Zhong-Ming Zhou25, Chi Chiu Wang26, Tai-Xiang Wu27, Jian-Ping Liu28, Ernest H Y Ng29, Richard S Legro30, Heping Zhang31. 1. Committee of Reproductive Medicine, World Federation of Chinese Medicine Societies, Beijing, China2Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China. 2. Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China3Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. 3. Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China. 4. Outpatient Department, Xuzhou Maternal and Children's Hospital, Xuzhou, China. 5. Centre for Reproductive Medicine, Dalian Maternal and Children's Centre, Dalian, China. 6. Department of Infertility, Tanggu District Maternal and Children's Hospital, Tianjin, China. 7. Department of Obstetrics and Gynecology, Shanxi Province Hospital of Chinese Medicine, Taiyuan, China. 8. Centre for Reproductive Medicine, Huaian Maternal and Children's Hospital, Huaian, China. 9. Department of Gynecology, Suzhou City Hospital of Chinese Medicine, Suzhou, China. 10. Department of Gynecology, Second Hospital, Jiangxi University of Chinese Medicine, Nanchang, China. 11. Department of Chinese Medicine, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. 12. Department of Infertility, Liwan District Hospital of Chinese Medicine, Guangzhou, China. 13. Department of Obstetrics and Gynecology, Affiliated Hospital, Anhui University of Chinese Medicine, Hefei, China. 14. Institute of Integrated Traditional and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 15. Department of Gynecology, Wenzhou City Hospital of Chinese Medicine, Wenzhou, China. 16. Centre for Reproductive Medicine, Yuhuangding Hospital, Yantai, China. 17. Department of Obstetrics and Gynecology, Daqing Longnan Hospital, Daqing, China. 18. Department of Obstetrics and Gynecology, First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, China. 19. Department of Obstetrics and Gynecology, First Affiliated Hospital, Liaoning University of Chinese Medicine, Shenyang, China. 20. Department of Gynecology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. 21. Department of Traditional Technology, Guangdong Province Hospital of Chinese Medicine, Guangzhou, China. 22. Department of Gynecology, Hangzhou City Hospital of Chinese Medicine, Hangzhou, China. 23. Centre for Reproductive Medicine, Zhejiang Province Hospital of Integrative Medicine, Hangzhou, China. 24. Centre for Reproductive Medicine, Daqing Oilfield General Hospital, Daqing, China. 25. Department of Obstetrics and Gynecology, Hubei Province Hospital of Chinese Medicine, Wuhan, China. 26. Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong, China27Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China28School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China. 27. Chinese Clinical Trial Registry, Shenzhen, China. 28. Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. 29. Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong, China. 30. Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China32Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey. 31. Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
Abstract
Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.
RCT Entities:
Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.
Authors: Richard S Legro; Allen R Kunselman; Robert G Brzyski; Peter R Casson; Michael P Diamond; William D Schlaff; Gregory M Christman; Christos Coutifaris; Hugh S Taylor; Esther Eisenberg; Nanette Santoro; Heping Zhang Journal: Contemp Clin Trials Date: 2012-01-13 Impact factor: 2.226
Authors: Lisa M Pastore; Christopher D Williams; Jeffrey Jenkins; James T Patrie Journal: J Clin Endocrinol Metab Date: 2011-08-03 Impact factor: 5.958
Authors: Richard S Legro; Xiaoke Wu; Kurt T Barnhart; Cynthia Farquhar; Bart C J M Fauser; Ben Mol Journal: Hum Reprod Date: 2014-09-12 Impact factor: 6.918
Authors: Hong-Ying Kuang; Yan Li; He-Ping Zhang; Richard S Legro; Elisabet Stener-Victorin Journal: Chin J Integr Med Date: 2018-05-11 Impact factor: 1.978