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Semin Reprod Med 2017; 35(04): 353-358
DOI: 10.1055/s-0037-1606570
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acupuncture for Infertility in Women with Polycystic Ovary Syndrome: What Does It Add?

Elisabet Stener-Victorin
1   Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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Publication History

Publication Date:
16 October 2017 (online)

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Abstract

Acupuncture is a nonpharmacological therapy to induce ovulation in women with polycystic ovary syndrome (PCOS), but not until recently there has been a study reporting the live birth rate following ovulation induction by acupuncture or its potential as an adjuvant to pharmacological ovulation induction. Clomiphene citrate, the first-line treatment for ovulation induction in women with PCOS, was twice as effective at achieving live birth, with no effect of acupuncture alone or in combination with clomiphene. Thus, the findings from the recent randomized control trial do not support acupuncture as an infertility treatment, alone or in combination, in women with PCOS. The recent trial has important clinical implications not only for women with PCOS with an active wish for pregnancy but also for those with no active wish of pregnancy, as acupuncture induces ovulation to a higher degree than no treatment and also relieves other PCOS-related symptoms. This narrative review dissects possible mechanism of action of acupuncture on reproductive function, it discusses stimulation parameters, it discusses the recent findings on live birth, and it also discusses the control situation in potential future acupuncture trials.

Keywords

polycystic ovary syndrome - infertility - acupuncture - electrical stimulation - ovulation - testosterone
 

  • References

  • 1 Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev 2015; 36 (05) 487-525
    CrossrefPubMedGoogle Scholar
  • 2 Roos N, Kieler H, Sahlin L, Ekman-Ordeberg G, Falconer H, Stephansson O. Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study. BMJ 2011; 343: d6309
    CrossrefPubMedGoogle Scholar
  • 3 Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012; 33 (06) 981-1030
    CrossrefPubMedGoogle Scholar
  • 4 Legro RS, Barnhart HX, Schlaff WD. , et al; Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356 (06) 551-566
    CrossrefPubMedGoogle Scholar
  • 5 Legro RS, Brzyski RG, Diamond MP. , et al; NICHD Reproductive Medicine Network. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 2014; 371 (02) 119-129
    CrossrefPubMedGoogle Scholar
  • 6 Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 2008; 23 (03) 462-477
    CrossrefPubMedGoogle Scholar
  • 7 Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 2008; 89 (03) 505-522
    CrossrefPubMedGoogle Scholar
  • 8 Smith JF, Eisenberg ML, Millstein SG. , et al; Infertility Outcomes Program Project Group. Fertility treatments and outcomes among couples seeking fertility care: data from a prospective fertility cohort in the United States. Fertil Steril 2011; 95 (01) 79-84
    CrossrefPubMedGoogle Scholar
  • 9 Bovey M, Lorenc A, Robinson N. Extent of acupuncture practice for infertility in the United Kingdom: experiences and perceptions of the practitioners. Fertil Steril 2010; 94 (07) 2569-2573
    CrossrefPubMedGoogle Scholar
  • 10 Jedel E, Labrie F, Odén A. , et al. Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Endocrinol Metab 2011; 300 (01) E37-E45
    CrossrefPubMedGoogle Scholar
  • 11 Johansson J, Redman L, Veldhuis PP. , et al. Acupuncture for ovulation induction in polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Endocrinol Metab 2013; 304 (09) E934-E943
    CrossrefPubMedGoogle Scholar
  • 12 Pastore LM, Williams CD, Jenkins J, Patrie JT. True and sham acupuncture produced similar frequency of ovulation and improved LH to FSH ratios in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2011; 96 (10) 3143-3150
    CrossrefPubMedGoogle Scholar
  • 13 Maliqueo M, Benrick A, Alvi A. , et al. Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome. Mol Cell Endocrinol 2015; 412: 159-169
    CrossrefPubMedGoogle Scholar
  • 14 Mannerås L, Cajander S, Lönn M, Stener-Victorin E. Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS. Am J Physiol Regul Integr Comp Physiol 2009; 296 (04) R1124-R1131
    CrossrefPubMedGoogle Scholar
  • 15 Mannerås L, Jonsdottir IH, Holmäng A, Lönn M, Stener-Victorin E. Low-frequency electro-acupuncture and physical exercise improve metabolic disturbances and modulate gene expression in adipose tissue in rats with dihydrotestosterone-induced polycystic ovary syndrome. Endocrinology 2008; 149 (07) 3559-3568
    CrossrefPubMedGoogle Scholar
  • 16 Feng Y, Johansson J, Shao R. , et al. Hypothalamic neuroendocrine functions in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of low-frequency electro-acupuncture. PLoS One 2009; 4 (08) e6638
    CrossrefPubMedGoogle Scholar
  • 17 Lim CE, Ng RW, Xu K. , et al. Acupuncture for polycystic ovarian syndrome. Cochrane Database Syst Rev 2016; 5 (05) CD007689
    PubMedGoogle Scholar
  • 18 Wu XK, Stener-Victorin E, Kuang HY. , et al; PCOSAct Study Group. Effect of acupuncture and clomiphene in Chinese women with polycystic ovary syndrome: a randomized clinical trial. JAMA 2017; 317 (24) 2502-2514
    CrossrefPubMedGoogle Scholar
  • 19 Sato A, Sato Y, Uchida S. Reflex modulation of visceral functions by acupuncture-like stimulation in anesthetized rats. Int Congr Ser 2002; 1238: 111-123
    CrossrefPubMedGoogle Scholar
  • 20 Kagitani F, Uchida S, Hotta H, Aikawa Y. Manual acupuncture needle stimulation of the rat hindlimb activates groups I, II, III and IV single afferent nerve fibers in the dorsal spinal roots. Jpn J Physiol 2005; 55 (03) 149-155
    CrossrefPubMedGoogle Scholar
  • 21 Kaufman MP, Waldrop TG, Rybicki KJ, Ordway GA, Mitchell JH. Effects of static and rhythmic twitch contractions on the discharge of group III and IV muscle afferents. Cardiovasc Res 1984; 18 (11) 663-668
    CrossrefPubMedGoogle Scholar
  • 22 Andersson S, Lundeberg T. Acupuncture--from empiricism to science: functional background to acupuncture effects in pain and disease. Med Hypotheses 1995; 45 (03) 271-281
    CrossrefPubMedGoogle Scholar
  • 23 Feng Y, Johansson J, Shao R, Mannerås-Holm L, Billig H, Stener-Victorin E. Electrical and manual acupuncture stimulation affect oestrous cyclicity and neuroendocrine function in an 5α-dihydrotestosterone-induced rat polycystic ovary syndrome model. Exp Physiol 2012; 97 (05) 651-662
    CrossrefPubMedGoogle Scholar
  • 24 Langevin HM, Schnyer R, MacPherson H. , et al; Executive Board of the Society for Acupuncture Research. Manual and electrical needle stimulation in acupuncture research: pitfalls and challenges of heterogeneity. J Altern Complement Med 2015; 21 (03) 113-128
    CrossrefPubMedGoogle Scholar
  • 25 Kuang H, Li Y, Wu X. , 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
    PubMedGoogle Scholar
  • 26 Sato A, Sato Y, Shimura M, Uchida S. Calcitonin gene-related peptide produces skeletal muscle vasodilation following antidromic stimulation of unmyelinated afferents in the dorsal root in rats. Neurosci Lett 2000; 283 (02) 137-140
    CrossrefPubMedGoogle Scholar
  • 27 Higashimura Y, Shimoju R, Maruyama H, Kurosawa M. Electro-acupuncture improves responsiveness to insulin via excitation of somatic afferent fibers in diabetic rats. Auton Neurosci 2009; 150 (1-2): 100-103
    CrossrefPubMedGoogle Scholar
  • 28 Torres-Rosas R, Yehia G, Peña G. , et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med 2014; 20 (03) 291-295
    CrossrefPubMedGoogle Scholar
  • 29 Stener-Victorin E. Hypothetical physiological and molecular basis for the effect of acupuncture in the treatment of polycystic ovary syndrome. Mol Cell Endocrinol 2013; 373 (1-2): 83-90
    CrossrefPubMedGoogle Scholar
  • 30 Stener-Victorin E, Kobayashi R, Kurosawa M. Ovarian blood flow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats. Auton Neurosci 2003; 108 (1-2): 50-56
    CrossrefPubMedGoogle Scholar
  • 31 Stener-Victorin E, Kobayashi R, Watanabe O, Lundeberg T, Kurosawa M. Effect of electro-acupuncture stimulation of different frequencies and intensities on ovarian blood flow in anaesthetized rats with steroid-induced polycystic ovaries. Reprod Biol Endocrinol 2004; 2 (01) 16
    CrossrefPubMedGoogle Scholar
  • 32 Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 1984; 7: 309-338
    CrossrefPubMedGoogle Scholar
  • 33 Yao T, Andersson S, Thorén P. Long-lasting cardiovascular depression induced by acupuncture-like stimulation of the sciatic nerve in unanaesthetized spontaneously hypertensive rats. Brain Res 1982; 240 (01) 77-85
    CrossrefPubMedGoogle Scholar
  • 34 Stener-Victorin E, Fujisawa S, Kurosawa M. Ovarian blood flow responses to electroacupuncture stimulation depend on estrous cycle and on site and frequency of stimulation in anesthetized rats. J Appl Physiol (1985) 2006; 101 (01) 84-91
    CrossrefPubMedGoogle Scholar
  • 35 Sverrisdóttir YB, Mogren T, Kataoka J, Janson PO, Stener-Victorin E. Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth?. Am J Physiol Endocrinol Metab 2008; 294 (03) E576-E581
    CrossrefPubMedGoogle Scholar
  • 36 Fagius J. Sympathetic nerve activity in metabolic control--some basic concepts. Acta Physiol Scand 2003; 177 (03) 337-343
    CrossrefPubMedGoogle Scholar
  • 37 Ojeda S, Lara H. Role of the Sympathetic Nervous System in the Regulation of Ovarian Function. Berlin: Springer-Verlag; 1989
    Google Scholar
  • 38 Sir-Petermann T, Maliqueo M, Angel B, Lara HE, Pérez-Bravo F, Recabarren SE. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod 2002; 17 (10) 2573-2579
    CrossrefPubMedGoogle Scholar
  • 39 Reaven GM, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities--the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996; 334 (06) 374-381
    CrossrefPubMedGoogle Scholar
  • 40 Dissen GA, Garcia-Rudaz C, Ojeda SR. Role of neurotrophic factors in early ovarian development. Semin Reprod Med 2009; 27 (01) 24-31
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Semenova II. Adrenergic innervation of ovaries in Stein-Leventhal syndrome [in Russian, Abstract in English]. Vestn Akad Med Nauk SSSR 1969; 24 (09) 58-62
    PubMedGoogle Scholar
  • 42 Heider U, Pedal I, Spanel-Borowski K. Increase in nerve fibers and loss of mast cells in polycystic and postmenopausal ovaries. Fertil Steril 2001; 75 (06) 1141-1147
    CrossrefPubMedGoogle Scholar
  • 43 Carmina E, Orio F, Palomba S, Longo RA, Lombardi G, Lobo RA. Ovarian size and blood flow in women with polycystic ovary syndrome and their correlations with endocrine parameters. Fertil Steril 2005; 84 (02) 413-419
    CrossrefPubMedGoogle Scholar
  • 44 Greiner M, Paredes A, Araya V, Lara HE. Role of stress and sympathetic innervation in the development of polycystic ovary syndrome. Endocrine 2005; 28 (03) 319-324
    CrossrefPubMedGoogle Scholar
  • 45 Dissen GA, Garcia-Rudaz C, Paredes A, Mayer C, Mayerhofer A, Ojeda SR. Excessive ovarian production of nerve growth factor facilitates development of cystic ovarian morphology in mice and is a feature of polycystic ovarian syndrome in humans. Endocrinology 2009; 150 (06) 2906-2914
    CrossrefPubMedGoogle Scholar
  • 46 Schlaich MP, Straznicky N, Grima M. , et al. Renal denervation: a potential new treatment modality for polycystic ovary syndrome?. J Hypertens 2011; 29 (05) 991-996
    CrossrefPubMedGoogle Scholar
  • 47 Stener-Victorin E, Jedel E, Janson PO, Sverrisdottir YB. Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am J Physiol Regul Integr Comp Physiol 2009; 297 (02) R387-R395
    CrossrefPubMedGoogle Scholar
  • 48 Leonhardt H, Hellström M, Gull B. , et al. Serum anti-Müllerian hormone and ovarian morphology assessed by magnetic resonance imaging in response to acupuncture and exercise in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial. Acta Obstet Gynecol Scand 2015; 94 (03) 279-287
    CrossrefPubMedGoogle Scholar
  • 49 Stener-Victorin E, Holm G, Janson PO, Gustafson D, Waern M. Acupuncture and physical exercise for affective symptoms and health-related quality of life in polycystic ovary syndrome: secondary analysis from a randomized controlled trial. BMC Complement Altern Med 2013; 13 (01) 131
    CrossrefPubMedGoogle Scholar
  • 50 Zheng YH, Wang XH, Lai MH, Yao H, Liu H, Ma HX. Effectiveness of abdominal acupuncture for patients with obesity-type polycystic ovary syndrome: a randomized controlled trial. J Altern Complement Med 2013; 19 (09) 740-745
    CrossrefPubMedGoogle Scholar
  • 51 Streitberger K, Kleinhenz J. Introducing a placebo needle into acupuncture research. Lancet 1998; 352 (9125): 364-365
    CrossrefPubMedGoogle Scholar
  • 52 MacPherson H, Hammerschlag R, Coeytaux RR. , et al. Unanticipated insights into biomedicine from the study of acupuncture. J Altern Complement Med 2016; 22 (02) 101-107
    CrossrefPubMedGoogle Scholar
  • 53 Benedetti F, Amanzio M, Baldi S, Casadio C, Maggi G. Inducing placebo respiratory depressant responses in humans via opioid receptors. Eur J Neurosci 1999; 11 (02) 625-631
    CrossrefPubMedGoogle Scholar
  • 54 Benedetti F, Arduino C, Amanzio M. Somatotopic activation of opioid systems by target-directed expectations of analgesia. J Neurosci 1999; 19 (09) 3639-3648
    CrossrefPubMedGoogle Scholar
  • 55 Sherman KJ, Cherkin DC, Ichikawa L. , et al. Treatment expectations and preferences as predictors of outcome of acupuncture for chronic back pain. Spine 2010; 35 (15) 1471-1477
    CrossrefPubMedGoogle Scholar
  • 56 Wechsler ME, Kelley JM, Boyd IO. , et al. Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med 2011; 365 (02) 119-126
    CrossrefPubMedGoogle Scholar
  • 57 Witt CM, Aickin M, Baca T. , et al; Effectiveness Guidance Documents Collaborators. Effectiveness guidance document (EGD) for acupuncture research - a consensus document for conducting trials. BMC Complement Altern Med 2012; 12: 148
    CrossrefPubMedGoogle Scholar
  • 58 Stener-Victorin E, Waldenström U, Tägnfors U, Lundeberg T, Lindstedt G, Janson PO. Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand 2000; 79 (03) 180-188
    CrossrefPubMedGoogle Scholar
  • 59 Benrick A, Kokosar M, Hu M. , et al. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture. FASEB J 2017; 31 (08) 3288-3297
    CrossrefPubMedGoogle Scholar
  • 60 Billhult A, Stener-Victorin E. Acupuncture with manual and low frequency electrical stimulation as experienced by women with polycystic ovary syndrome: a qualitative study. BMC Complement Altern Med 2012; 12: 32
    PubMedGoogle Scholar
  • 61 Stener-Victorin E, Maliqueo M, Soligo M. , et al. Changes in HbA1c and circulating and adipose tissue androgen levels in overweight-obese women with polycystic ovary syndrome in response to electroacupuncture. Obes Sci Pract 2016; 2 (04) 426-435
    PubMedGoogle Scholar