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Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support
Journal of Integrative Medicine xxx (xxxx) xxx
Contents lists available at ScienceDirect
Journal of Integrative Medicine journal homepage: www.jcimjournal.com/jim www.journals.elsevier.com/journal-of-integrative-medicine
Commentary
Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support Sherman Gu a,b,⇑, Arthur Yin Fan c,d a
Federation of Chinese Medicine & Acupuncture Societies of Australia Ltd (FCMA), Melbourne, Victoria 3150, Australia Knox Chinese Healing & Myotherapy, Wantirna South, Victoria 3152, Australia American TCM Association, Vienna, VA 22182, USA d McLean Center for Complementary and Alternative Medicine, PLC, Vienna, VA 22182, USA b c
a r t i c l e
i n f o
Article history: Received 29 October 2019 Accepted 12 December 2019 Available online xxxx Keywords: Acupuncture Randomized controlled trial Polycystic ovary syndrome Fertilization in vitro Traditional Chinese medicine
a b s t r a c t Two reports of trials investigating the potential effect of acupuncture in increasing live birth rate (LBR) in women with polycystic ovary syndrome (PCOS) or those undergoing in vitro fertilization (IVF) were published by Journal of American Medical Association in 2017 and 2018 respectively. The trial investigators did not recommend acupuncture for the women with PCOS or IVF based on their findings. This paper raises the concern that the findings that acupuncture did not increase LBR for women with PCOS or undergoing IVF may be the result of methodological flaws in the studies and unintended bias such as use of an invalid control intervention and underestimation of the true acupuncture effect. Therefore, their findings may not be a valid reflection of acupuncture’s effect in improving LBR in women with these clinical conditions. Please cite this article as: Gu S, Fan AY. Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support. J Integr Med. 2020; xx(x): xxx–xxx Ó 2020 Shanghai Changhai Hospital. Published by ELSEVIER B.V. All rights reserved.
1. Introduction Acupuncture has been used for management of a variety of conditions including chronic pain, women with infertility and its use in supporting in vitro fertilization (IVF) globally over several decades [1–3]. Researchers have sought to find solid scientific evidence of the effect of acupuncture through randomized controlled trials (RCTs), which are considered the gold standard for evaluating the efficacy of an intervention. The Journal of American Medical Association (JAMA) published two RCT reports: Wu et al. [4], in 2017, used electro-acupuncture for treatment of Chinese women with infertility associated with polycystic ovary syndrome (PCOS), and Smith et al. [5], in 2018, employed acupuncture to support women undergoing IVF. Whilst it is pleasing that the trial investigators have sought to subject acupuncture to scientific investigation, we are concerned that their findings that acupunc⇑ Corresponding author at: Federation of Chinese Medicine & Acupuncture Societies of Australia Ltd (FCMA), Melbourne, P.O. Box 526, Glen Waverley, Victoria 3150, Australia. E-mail addresses: [email protected], [email protected] (S. Gu).
ture did not increase live birth rate (LBR) for women with PCOS or undergoing IVF may be the result of methodological flaws in the studies, and unwanted bias. This paper discusses these methodological flaws and argues that because of these, the conclusion that acupuncture is not efficacious in increasing LBR in women with PCOS or undergoing IVF, based on these two studies, is not a valid one. 2. Invalid control intervention The control acupuncture protocol of Wu et al. in 2017 [4] involved using acupuncture needles to achieve 5 mm depth skin penetration at fixed locations on the upper arms. It was a verum superficial acupuncture (shallow needling technique) procedure, which is not an appropriate control since superficial acupuncture is one of the acupuncture techniques noted in ancient Chinese medicine practice (Maoci or Fuci in Chinese ancient classic) and does have a physiological effect. The effect of an active control intervention should have been validated as an appropriate comparator to the experimental intervention. Superficial acupuncture techniques, including Japanese-style acupuncture in which the
https://doi.org/10.1016/j.joim.2020.01.007 2095-4964/Ó 2020 Shanghai Changhai Hospital. Published by ELSEVIER B.V. All rights reserved.
Please cite this article as: S. Gu and A. Y. Fan, Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support, Journal of Integrative Medicine, https://doi.org/10.1016/j.joim.2020.01.007
2
S. Gu, A.Y. Fan / Journal of Integrative Medicine xxx (xxxx) xxx
needling technique is similar with Maoci or Fuci needling techniques mentioned above, are widely used by many contemporary acupuncturists, especially in the Western countries, for various treatments including gynecological conditions [6–8]. There is no evidence that superficial needling does not produce a biomedical effect. In fact, the control acupuncture plus placebo medication group had a 16.8% LBR in the Wu et al.’s study published in 2017. This was more than three times higher than their estimated LBR, which was 5% for the sample size calculation in the control acupuncture plus placebo medication arm [9]. The trial investigators claimed this was due to a nonspecific effect or placebo [10]. Interestingly, this figure was not dissimilar to the LBR found in another RCT, conducted by one of the Wu’s study team members, which reported a 19.1% cumulative LBR with clomiphene citrate (CC) alone in 2014 [11]. Although use of insulin-sensitizing agent such as metformin or dietary supplement such as inositol could improve the clinical pregnancy rate in women with PCOS [12,13], CC has been used as a first-line medication for infertility associated with PCOS [14]. Furthermore, a nonspecific effect (a concept from the pharmacological perspective) is not equal to no effect or placebo. With respect to acupuncture as a nonpharmacological therapy, nonspecific effects are a part of its effectiveness in addition to more specific biomedical effects [6]. It is inappropriate to conclude that the acupuncture treatment was inefficacious because no significant difference was detected when an invalid comparator was used in the trial.
in the Smith’s 2018 study was much lower than the average LBR (18.0% vs 32.7%) recorded in the Australian and New Zealand Assisted Reproductive Database [20]. These could be due to altered selection bias or performance bias during the trial.
3. Underestimate of the true acupuncture effect
Conflicts of interest
Similar to the Smith’s study in 2006 [15], the acupuncture treatment protocol in their 2018 study [5] was too short to be efficacious in increasing the pregnancy rate for women undergoing IVF [16]. In addition to the short length of the acupuncture treatment, only 65.5% of the participants completed the full three sessions of acupuncture treatment. The study power might have been compromised by this high noncompliance rate. The Smith’s 2018 study also reported that there was a substantially higher number of women undergoing blastocyst stage of embryo transfer (days 5–6 of embryo) in the control group as compared to the treatment group (P = 0.02) [5]. Although the trial investigators admitted the blastocyst stage embryo transfer could have higher rates of pregnancy and LBR than the cleavage stage of embryo transfer (days 2–3 of embryo), no adjustment was made in the data analysis when post-hoc exploratory analysis was performed in the Smith’s 2018 study. In addition, current treatment standards recommend that dosage of medications for PCOS treatment and IVF procedure should be tailored to an individual patient’s condition such as age and ovarian reserve [17,18]. The Smith’s 2018 study included a total of 230 participants with PCOS; neither the follicle stimulation nor acupuncture protocol was individually tailored in these cohorts. The true acupuncture effect of this trial could have been underestimated by the short treatment duration, poor compliance rate of treatment protocol, imbalance of the embryo transfer stage between groups, and non-individualized treatment protocol. 4. Departure from the approved and published trial protocol The Smith’s 2018 study planned to recruit only those women with potential low LBR in four IVF centers [19]. However, this inclusion criterion was changed halfway through the trial and 12 IVF centers were invited to participate in the trial [5]. The potential impact of this departure from trial protocol remains unknown. However, the pregnancy rate at the acupuncture treatment group of the Smith’s 2018 study was significantly lower than that in the Smith’s 2006 study (25.7% vs 31.0%) [15] and the overall LBR
5. Conclusion Findings from the studies of Wu et al. 2017 and the Smith et al. 2018 were limited and their conclusions were possibly erroneous due to study design flaws and/or bias. Consequently, their findings cannot be considered a valid answer to the question of whether acupuncture is efficacious in increasing LBR in women with infertility due to PCOS or who are undergoing IVF. Additional welldesigned RCTs with appropriate controls are needed to answer this question. Funding The authors declare that no funder supported this study for study design and conduct, collection, analysis and interpretation of data, preparation of the article, or submission of the article for publication. Author contributions SG and AYF drafted, revised and finalized the manuscript.
The authors declare that they have no conflicts of interest. References [1] MacPherson H, Vickers A, Bland M, Torgerson D, Corbett M, Spackman E, et al. Acupuncture for chronic pain and depression in primary care: a programme of research. Southampton (UK): NIHR Journals Library; 2017. [2] Huang DM, Huang GY, Lu FE, Stefan D, Andreas N, Robert G. Acupuncture for infertility: is it an effective therapy?. Chin J Integr Med 2011;17(5):386–95. [3] Nandi A, Shah A, Gudi A, Homburg R. Acupuncture in IVF: a review of current literature. J Obstet Gynaecol 2014;34(7):555–61. [4] Wu XK, Stener-Victorin E, Kuang HY, Ma HL, Gao JS, Xie LZ, et al. Effect of acupuncture and clomiphene in Chinese women with polycystic ovary syndrome: a randomized clinical trial. JAMA 2017;317(24):2502–14. [5] Smith CA, de Lacey S, Chapman M, Ratcliffe J, Norman RJ, Johnson NP, et al. Effect of acupuncture vs sham acupuncture on live births among women undergoing in vitro fertilization: a randomized clinical trial. JAMA 2018;319 (19):1990–8. [6] Li YM. Puzzles and hypotheses of acupuncture. Zhongguo Zhong Xi Yi Jie He Za Zhi 2013;33(11):1445–8 [Chinese with abstract in English]. [7] Wang S. Sweet acupuncture, a type of comfortable acupuncture. Zhong Yi Yao Dao Bao 2017;23(5):7–8 [Chinese]. [8] Wayne PM, Kerr CE, Schnyer RN, Legedza AT, Savetsky-German J, Shields MH, et al. Japanese-style acupuncture for endometriosis-related pelvic pain in adolescents and young women: results of a randomized sham-controlled trial. J Pediatr Adolesc Gynecol 2008;21(5):247–57. [9] Kuang H, Li Y, Wu X, Hou L, Wu T, Liu J, et al. Acupuncture and clomiphene citrate for live birth in polycystic ovary syndrome: study design of a randomized controlled trial. Evid Based Complement Alternat Med 2013;2013:527303. [10] Wu XK, Stener-Victorin E, Zhang H. Acupuncture for infertility in polycystic ovary syndrome—reply. JAMA 2017;318(15):1502. [11] Legro RS, Zhang H. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 2014;371(2):119–29. [12] Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2014;11:CD006105. [13] Regidor PA, Schindler AE, Lesoine B, Druckman R. Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Horm Mol Biol Clin Investig 2018;34(2). [14] Vause TDR, Cheung AP. Ovulation induction in polycystic ovary syndrome. J Obstet Gynaecol Can 2010;32(5):495–502. [15] Smith C, Coyle M, Norman RJ. Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril 2006;85 (5):1352–8. [16] Gu S. Acupuncture for women undergoing in vitro fertilization. JAMA 2018;320 (13):1384–5.
Please cite this article as: S. Gu and A. Y. Fan, Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support, Journal of Integrative Medicine, https://doi.org/10.1016/j.joim.2020.01.007
S. Gu, A.Y. Fan / Journal of Integrative Medicine xxx (xxxx) xxx [17] Di Paola R, Garzon S, Giuliani S, Laganà AS, Noventa M, Parissone F, et al. Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman’s age and markers of ovarian reserve. Arch Gynecol Obstet 2018;298(5):1029–35. [18] Reyes-Muñoz E, Sathyapalan T, Rossetti P, Shah M, Long M, Buscema M, et al. Polycystic ovary syndrome: implication for drug metabolism on assisted reproductive techniques—a literature review. Adv Ther 2018;35(11):1805–15.
3
[19] Smith CA, de Lacey S, Chapman M, Ratcliffe J, Norman RJ, Johnson N, et al. Acupuncture to improve live birth rates for women undergoing in vitro fertilization: a protocol for a randomized controlled trial. Trials 2012;18 (13):60. [20] Chambers GM, Paul RC, Harris K, Fitzgerald O, Boothroyd CV, Rombauts L, et al. Assisted reproductive technology in Australia and New Zealand: cumulative live birth rates as measures of success. Med J Aust 2017;207(3):114–8.
Please cite this article as: S. Gu and A. Y. Fan, Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support, Journal of Integrative Medicine, https://doi.org/10.1016/j.joim.2020.01.007
Contents lists available at ScienceDirect
Journal of Integrative Medicine journal homepage: www.jcimjournal.com/jim www.journals.elsevier.com/journal-of-integrative-medicine
Commentary
Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support Sherman Gu a,b,⇑, Arthur Yin Fan c,d a
Federation of Chinese Medicine & Acupuncture Societies of Australia Ltd (FCMA), Melbourne, Victoria 3150, Australia Knox Chinese Healing & Myotherapy, Wantirna South, Victoria 3152, Australia American TCM Association, Vienna, VA 22182, USA d McLean Center for Complementary and Alternative Medicine, PLC, Vienna, VA 22182, USA b c
a r t i c l e
i n f o
Article history: Received 29 October 2019 Accepted 12 December 2019 Available online xxxx Keywords: Acupuncture Randomized controlled trial Polycystic ovary syndrome Fertilization in vitro Traditional Chinese medicine
a b s t r a c t Two reports of trials investigating the potential effect of acupuncture in increasing live birth rate (LBR) in women with polycystic ovary syndrome (PCOS) or those undergoing in vitro fertilization (IVF) were published by Journal of American Medical Association in 2017 and 2018 respectively. The trial investigators did not recommend acupuncture for the women with PCOS or IVF based on their findings. This paper raises the concern that the findings that acupuncture did not increase LBR for women with PCOS or undergoing IVF may be the result of methodological flaws in the studies and unintended bias such as use of an invalid control intervention and underestimation of the true acupuncture effect. Therefore, their findings may not be a valid reflection of acupuncture’s effect in improving LBR in women with these clinical conditions. Please cite this article as: Gu S, Fan AY. Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support. J Integr Med. 2020; xx(x): xxx–xxx Ó 2020 Shanghai Changhai Hospital. Published by ELSEVIER B.V. All rights reserved.
1. Introduction Acupuncture has been used for management of a variety of conditions including chronic pain, women with infertility and its use in supporting in vitro fertilization (IVF) globally over several decades [1–3]. Researchers have sought to find solid scientific evidence of the effect of acupuncture through randomized controlled trials (RCTs), which are considered the gold standard for evaluating the efficacy of an intervention. The Journal of American Medical Association (JAMA) published two RCT reports: Wu et al. [4], in 2017, used electro-acupuncture for treatment of Chinese women with infertility associated with polycystic ovary syndrome (PCOS), and Smith et al. [5], in 2018, employed acupuncture to support women undergoing IVF. Whilst it is pleasing that the trial investigators have sought to subject acupuncture to scientific investigation, we are concerned that their findings that acupunc⇑ Corresponding author at: Federation of Chinese Medicine & Acupuncture Societies of Australia Ltd (FCMA), Melbourne, P.O. Box 526, Glen Waverley, Victoria 3150, Australia. E-mail addresses: [email protected], [email protected] (S. Gu).
ture did not increase live birth rate (LBR) for women with PCOS or undergoing IVF may be the result of methodological flaws in the studies, and unwanted bias. This paper discusses these methodological flaws and argues that because of these, the conclusion that acupuncture is not efficacious in increasing LBR in women with PCOS or undergoing IVF, based on these two studies, is not a valid one. 2. Invalid control intervention The control acupuncture protocol of Wu et al. in 2017 [4] involved using acupuncture needles to achieve 5 mm depth skin penetration at fixed locations on the upper arms. It was a verum superficial acupuncture (shallow needling technique) procedure, which is not an appropriate control since superficial acupuncture is one of the acupuncture techniques noted in ancient Chinese medicine practice (Maoci or Fuci in Chinese ancient classic) and does have a physiological effect. The effect of an active control intervention should have been validated as an appropriate comparator to the experimental intervention. Superficial acupuncture techniques, including Japanese-style acupuncture in which the
https://doi.org/10.1016/j.joim.2020.01.007 2095-4964/Ó 2020 Shanghai Changhai Hospital. Published by ELSEVIER B.V. All rights reserved.
Please cite this article as: S. Gu and A. Y. Fan, Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support, Journal of Integrative Medicine, https://doi.org/10.1016/j.joim.2020.01.007
2
S. Gu, A.Y. Fan / Journal of Integrative Medicine xxx (xxxx) xxx
needling technique is similar with Maoci or Fuci needling techniques mentioned above, are widely used by many contemporary acupuncturists, especially in the Western countries, for various treatments including gynecological conditions [6–8]. There is no evidence that superficial needling does not produce a biomedical effect. In fact, the control acupuncture plus placebo medication group had a 16.8% LBR in the Wu et al.’s study published in 2017. This was more than three times higher than their estimated LBR, which was 5% for the sample size calculation in the control acupuncture plus placebo medication arm [9]. The trial investigators claimed this was due to a nonspecific effect or placebo [10]. Interestingly, this figure was not dissimilar to the LBR found in another RCT, conducted by one of the Wu’s study team members, which reported a 19.1% cumulative LBR with clomiphene citrate (CC) alone in 2014 [11]. Although use of insulin-sensitizing agent such as metformin or dietary supplement such as inositol could improve the clinical pregnancy rate in women with PCOS [12,13], CC has been used as a first-line medication for infertility associated with PCOS [14]. Furthermore, a nonspecific effect (a concept from the pharmacological perspective) is not equal to no effect or placebo. With respect to acupuncture as a nonpharmacological therapy, nonspecific effects are a part of its effectiveness in addition to more specific biomedical effects [6]. It is inappropriate to conclude that the acupuncture treatment was inefficacious because no significant difference was detected when an invalid comparator was used in the trial.
in the Smith’s 2018 study was much lower than the average LBR (18.0% vs 32.7%) recorded in the Australian and New Zealand Assisted Reproductive Database [20]. These could be due to altered selection bias or performance bias during the trial.
3. Underestimate of the true acupuncture effect
Conflicts of interest
Similar to the Smith’s study in 2006 [15], the acupuncture treatment protocol in their 2018 study [5] was too short to be efficacious in increasing the pregnancy rate for women undergoing IVF [16]. In addition to the short length of the acupuncture treatment, only 65.5% of the participants completed the full three sessions of acupuncture treatment. The study power might have been compromised by this high noncompliance rate. The Smith’s 2018 study also reported that there was a substantially higher number of women undergoing blastocyst stage of embryo transfer (days 5–6 of embryo) in the control group as compared to the treatment group (P = 0.02) [5]. Although the trial investigators admitted the blastocyst stage embryo transfer could have higher rates of pregnancy and LBR than the cleavage stage of embryo transfer (days 2–3 of embryo), no adjustment was made in the data analysis when post-hoc exploratory analysis was performed in the Smith’s 2018 study. In addition, current treatment standards recommend that dosage of medications for PCOS treatment and IVF procedure should be tailored to an individual patient’s condition such as age and ovarian reserve [17,18]. The Smith’s 2018 study included a total of 230 participants with PCOS; neither the follicle stimulation nor acupuncture protocol was individually tailored in these cohorts. The true acupuncture effect of this trial could have been underestimated by the short treatment duration, poor compliance rate of treatment protocol, imbalance of the embryo transfer stage between groups, and non-individualized treatment protocol. 4. Departure from the approved and published trial protocol The Smith’s 2018 study planned to recruit only those women with potential low LBR in four IVF centers [19]. However, this inclusion criterion was changed halfway through the trial and 12 IVF centers were invited to participate in the trial [5]. The potential impact of this departure from trial protocol remains unknown. However, the pregnancy rate at the acupuncture treatment group of the Smith’s 2018 study was significantly lower than that in the Smith’s 2006 study (25.7% vs 31.0%) [15] and the overall LBR
5. Conclusion Findings from the studies of Wu et al. 2017 and the Smith et al. 2018 were limited and their conclusions were possibly erroneous due to study design flaws and/or bias. Consequently, their findings cannot be considered a valid answer to the question of whether acupuncture is efficacious in increasing LBR in women with infertility due to PCOS or who are undergoing IVF. Additional welldesigned RCTs with appropriate controls are needed to answer this question. Funding The authors declare that no funder supported this study for study design and conduct, collection, analysis and interpretation of data, preparation of the article, or submission of the article for publication. Author contributions SG and AYF drafted, revised and finalized the manuscript.
The authors declare that they have no conflicts of interest. References [1] MacPherson H, Vickers A, Bland M, Torgerson D, Corbett M, Spackman E, et al. Acupuncture for chronic pain and depression in primary care: a programme of research. Southampton (UK): NIHR Journals Library; 2017. [2] Huang DM, Huang GY, Lu FE, Stefan D, Andreas N, Robert G. Acupuncture for infertility: is it an effective therapy?. Chin J Integr Med 2011;17(5):386–95. [3] Nandi A, Shah A, Gudi A, Homburg R. Acupuncture in IVF: a review of current literature. J Obstet Gynaecol 2014;34(7):555–61. [4] Wu XK, Stener-Victorin E, Kuang HY, Ma HL, Gao JS, Xie LZ, et al. Effect of acupuncture and clomiphene in Chinese women with polycystic ovary syndrome: a randomized clinical trial. JAMA 2017;317(24):2502–14. [5] Smith CA, de Lacey S, Chapman M, Ratcliffe J, Norman RJ, Johnson NP, et al. Effect of acupuncture vs sham acupuncture on live births among women undergoing in vitro fertilization: a randomized clinical trial. JAMA 2018;319 (19):1990–8. [6] Li YM. Puzzles and hypotheses of acupuncture. Zhongguo Zhong Xi Yi Jie He Za Zhi 2013;33(11):1445–8 [Chinese with abstract in English]. [7] Wang S. Sweet acupuncture, a type of comfortable acupuncture. Zhong Yi Yao Dao Bao 2017;23(5):7–8 [Chinese]. [8] Wayne PM, Kerr CE, Schnyer RN, Legedza AT, Savetsky-German J, Shields MH, et al. Japanese-style acupuncture for endometriosis-related pelvic pain in adolescents and young women: results of a randomized sham-controlled trial. J Pediatr Adolesc Gynecol 2008;21(5):247–57. [9] Kuang H, Li Y, Wu X, Hou L, Wu T, Liu J, et al. Acupuncture and clomiphene citrate for live birth in polycystic ovary syndrome: study design of a randomized controlled trial. Evid Based Complement Alternat Med 2013;2013:527303. [10] Wu XK, Stener-Victorin E, Zhang H. Acupuncture for infertility in polycystic ovary syndrome—reply. JAMA 2017;318(15):1502. [11] Legro RS, Zhang H. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 2014;371(2):119–29. [12] Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2014;11:CD006105. [13] Regidor PA, Schindler AE, Lesoine B, Druckman R. Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Horm Mol Biol Clin Investig 2018;34(2). [14] Vause TDR, Cheung AP. Ovulation induction in polycystic ovary syndrome. J Obstet Gynaecol Can 2010;32(5):495–502. [15] Smith C, Coyle M, Norman RJ. Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril 2006;85 (5):1352–8. [16] Gu S. Acupuncture for women undergoing in vitro fertilization. JAMA 2018;320 (13):1384–5.
Please cite this article as: S. Gu and A. Y. Fan, Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support, Journal of Integrative Medicine, https://doi.org/10.1016/j.joim.2020.01.007
S. Gu, A.Y. Fan / Journal of Integrative Medicine xxx (xxxx) xxx [17] Di Paola R, Garzon S, Giuliani S, Laganà AS, Noventa M, Parissone F, et al. Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman’s age and markers of ovarian reserve. Arch Gynecol Obstet 2018;298(5):1029–35. [18] Reyes-Muñoz E, Sathyapalan T, Rossetti P, Shah M, Long M, Buscema M, et al. Polycystic ovary syndrome: implication for drug metabolism on assisted reproductive techniques—a literature review. Adv Ther 2018;35(11):1805–15.
3
[19] Smith CA, de Lacey S, Chapman M, Ratcliffe J, Norman RJ, Johnson N, et al. Acupuncture to improve live birth rates for women undergoing in vitro fertilization: a protocol for a randomized controlled trial. Trials 2012;18 (13):60. [20] Chambers GM, Paul RC, Harris K, Fitzgerald O, Boothroyd CV, Rombauts L, et al. Assisted reproductive technology in Australia and New Zealand: cumulative live birth rates as measures of success. Med J Aust 2017;207(3):114–8.
Please cite this article as: S. Gu and A. Y. Fan, Controversial conclusions from two randomized controlled trials for acupuncture’s effects on polycystic ovary syndrome or in vitro fertilization support, Journal of Integrative Medicine, https://doi.org/10.1016/j.joim.2020.01.007