It has been well documented that infertility causes stress (60-65), and stress reduction may, in turn, improve fertility (66). However, the relationship between stress and infertility is that of a vicious cycle. Social stigmatization, decreased self-esteem, unmet reproductive potential of sexual relationship, physical and mental burden of treatment, and the lack of control on treatment outcome are just some of the factors that can lead to psychological stress in any couple pursuing infertility treatment. In turn, stress may lead to the release of stress hormones and influence mechanisms responsible for a normal ovulatory menstrual cycle through its impact on the hypothalamic-pituitary-ovarian axis.

The use of acupuncture for reducing anxiety and stress possibly through its sympathoinhibitory property and impact on B-endorphin levels has been reviewed (67, 68), and the efficacy of acupuncture in depression has also been studied (69). Because the pharmacological side effects of anxiolytic and antidepressant drugs on infertility treatment outcome are largely unknown, acupuncture may provide an excellent alternative for stress reduction in women undergoing infertility treatment.

Discussion

The practice of acupuncture to treat identifiable patho-physiological conditions has been a subject of intense research. The underlying physiologic mechanisms of acupuncture such as the release of opioids and other peptides in the central peripheral nervous system, and its inhibition of the sympathetic nervous system have been increasingly established. Promising results from credible trials have emerged for the use of acupuncture in treating various pain syndromes, substance abuse, and chemotherapy-induced nausea and vomiting.

Although the definitive role of acupuncture in the treatment of female infertility is yet to be established, its neuroendocrine effect on the hypothalamic-pituitary-ovarian axis and the preliminary clinical data reviewed here justifies further clinical trials to systematically examine the efficacy of acupuncture in treating various conditions related to female infertility such as ovulatory dysfunction associated with PCOS. The peripheral impact of acupuncture in improving uterine artery blood flow and hence endometrial thickness also provides encouraging data regarding its potential positive effect on implantation.

Whether these potential beneficial effects of acupuncture on the reproductive system can be translated into improving infertility treatment outcomes will eventually mandate randomized controlled studies of adequate design. Because acupuncture is nontoxic and relatively affordable, its indications as an adjunct in assisted reproduction or as an alternative for women who are intolerant, ineligible, or contraindicated for conventional hormone induction of ovulation deserves serious research and exploration.

References 1. NIH Consensus Development Panel of Acupuncture. Acupuncture. JAMA 1998;280:1518-24.

2. Dundee JW, Ghaly RG, Lynch GA, Fitzpatrick KT, Abram WP. Acupuncture prophylaxis of cancer chemotherapy-induced sickness. J R Soc Med 1989;82:268-71.

3. Christiansen PA, Noreng M, Andersen PE, Nielsen JW. Electroacupuncture and postoperative pain. Br J Anaesth 1989;62:258-62.

4. Martelete M, Fiori AMC. Comparative study of analgesic effect of transcutaneous nerve stimulation (TNS), electroacupuncture (EA), and meperidine in the treatment of postoperative pain. Acupunct Electrother Res 1985;10:183-93.

5. Lao L, Bergman S, Langenberg P, Wong RH, Berman B. Efficacy of Chinese acupuncture on postoperative oral surgery pain. Oral Surg Med Oral Path Oral Radiol Endod 1995;79:423-8.

6. Bullock ML, Culliton PD, Olander RT. Controlled trial of acupuncture for severe recidivist alcoholism. Lancet 1989;1:1435-39.

7. Clavel-Chapelon F, Paoletti C, Banhamou S. Smoking cessation rates 4 years after treatment by nicotine gum and acupuncture. Prev Med 1997;26:25-8.

8. He D, Berg JE, Hostmark AT. Effects of acupuncture on smoking cessation or reduction for motivated smokers. Pev Med 1997;26:208-14.

9. Margolin A, Avants SK, Chang P, Kosten TR. Acupuncture for the treatment of cocaine dependence in methadone-maintained patients, Am J Addict 1993;2:194-201.

10. Patel M, Gutzwiller F, Paccaud F, Marazzi A. A meta-analysis of acupuncture for chronic pain. Int J Epidemiol 1989;18:900-6.

11. Shlay JC, Chaloner K, Max MB, Flaws B, Reichelderfer P, Wentworth D, et al. Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized control trial. JAMA 1998;280:1590-5.

12. Tier Riet G, Kleijnen J, Knipschild P. Acupuncture and chronic pain: a criteria based meta-analysis. J Clin Epidemiol 1990;43:1191-9.

13. Chez RA, Jonas WB. Complementary and alternative medicine. Part II: Clinical studies in gynecology. Obstet Gynecol Surv 1997;52:709-16.

14. Wu XJ, Cui YL, Yang BY, Zhou QM, Observations on the effect of He-Ne laser acupoint radiation in chronic pelvic inflammation. J Tradit Chin Med 1987;7:263-5.

15. Beal MW. Acupuncture and acupressure. Applications to women’s reproductive health care. J Nurse Midwifery 1999;44:217-30.

16. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998;280:1569-75.

17. World Health Organization. A proposed standard international acupuncture nomenclature: report of a WHO scientific group. Geneva, Switzerland: World Health Organization, 1991.

18. McCaig CD. Sinal neurite reabsorption and regrowth in vitro depend on the polarity of an applied electric field. Development 1987;100:31-41.

19. Mayer DJ, Price DD, Rafil A. Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone. Brain Res 1977;121:368-72.

20. Petti F, Bangrazi A, Liguori A, Reale G, Ippoliti F. Effects of acupuncture on immune response related to opioids-like peptides. J Tradit Chin Med 1998;18:55-63.

21. Ulett GA, Han S, Han JS. Electroacupuncture: mechanisms and clinical application, Biol Psychiatry 1998;44:129-38.

22. Ku Y, Chang Y. Beta-endorphin and GABA-mediated depressor effect of specific electroacupuncture surpasses pressor response of emotional circuit. Peptides 2001;22:1465-70.

23. Facchinetti F, Storchi AR, Petraglia F, Volpe A, Genazzani AR. Expression of proopiomelanocortin-related eptides in human follicular fluid. Peptides 1988;9:1089-92.

24. Gallinelli A, Garuti G, Matteo ML, Genazzani AR, Facchinetti F. Expression of proopiomelanocortin gene in human ovarian tissue. Hum Reprod 1995;10:1085-9.

25. DeBold CD, Menefee JK, Nicholson WE, Orth DN. Proopiomelanocortin gene is expressed in many normal human tissues and intumors not associated with ectopic adrenocorticotropin syndrome. Mol Endocrinol 1988;2:862-70.

26. Aleem FA, Eltabbakh GH, Omar RA, Couthren AL. Ovarian follicular fluid beta-endorphin levels in normal and polycystic ovaries. Am J Obstet Gynecol 1987;156:1197-200.

27. Aleem FA, Omar RA, Eltabbakh GH. Immunoreative beta-endorphin in human ovaries. Fertial Steril 1986;45:507-11.

28. Ferin M, Van de Wiele RL. Endogenous opioid peptides and the control of the menstrual cycle. Eur J Obstet Gynecol Repro Biol 1984;10:365-73.

29. Quigley ME, Sheeham KL, Casper RF, Yen SSC. Evidence for an increased opioid inhibition of luteinizing hormone secretion in hyperprolactinemic patients with pituitary microadenoma. J Clin Endocrinol Metabol 1980;50:427-46.

30. Ching M. Morphine suppresses the proestrous surge of GnRH in pituitary portal plasma of rats. Endocrinology 1983;112:2209-11.

31. Orstead KM, Spics HG. Inhibition of hypothalamic gonadotropin releasing hormone release by endogenous opioid peptides in the female rabbit. Neuroendocrinology 1987;46:14-23.

32. Kalra SP, Horvath T, Naftolin F, Xu B, Pu S, Kalra PS. The interactive language of the hypothalamus for the gonadotropin releasing hormone (GNRH) system. J Neuroendocrinol 1997;9:569-76.

33. Pau KY, Spies HG. Neuroendocrine signals in the regulation of gonadotropin-releasing hormone secretion. Chin J Physiol 1997;40:181-96.

34. Rossmanith WG, Mortola JF, Yen SSC. Role of endogenous opioid peptides in the initiation of the mid-cycle luteinizing hormone surge in normal cycling women. J Clin Endocrinol Metab 1988;67:695-700.

35. Petraglia F, DiMeo G, Storchi R, Segre A, Facchinette F, Szalay S, et al. Proopiomelanocortin-related peptides and methionine enkephalin in human follicular fluid: changes during the menstrual cycle. Am J Obstet Gynecol 1987;157:142-6.

36. Lin JH, Liu SH, Chan WW, Wu LS, Pi WP. Effects of electroacupuncture and gonadotropin-releasing hormone treatments on hormone changes in anoestrous sows. Am J Chin Med 1988;16:117-26.

37. Yang SP, Yu J, He L. Release of gonadotropin-releasing hormone (GnRH) from the medio-basal hypothalamus induced by electroacupuncture in conscious female rabbits. Acupunct Electrother Res 1994;19:19-27.

38. Aso T, Motohashi T, Murata M, Nishimura T, Kakizaki K. The influence of acupuncture stimulation on plasma levels of LH, FSH, progesterone and estradiol in normally ovulating women. Am J Chin Med 1976;4:391-401.

39. Yu J, Zheng HM, Ping SM. Changes in serum FSH, LH and ovarian follicular growth during electroacupuncture for induction of ovulation [Chinese]. Chung His I Chieh Ho Tsa Chih 1989;9:199-202.

40. Mo X, Li D, Pu Y, Xi G, Le X, Fu Z. Clinical studies on the mechanism of acupuncture stimulation of ovulation. J Trad Chin Med 1993;13:115-9.

41. Cai X. Substitution of acupuncture for human chorionic gonadortropin in ovulation induction. J Tradit Chin Med 1997;17:119-21.

42. Chen BY, Yu J. Relationship between blood radioimmunoreactive beta-endorphin and hand skin temperature during the electro-acupuncture induction of ovulation. Acupunct Electrother Res 1991;16:1-5.

43. Chen BY. Acupuncture normalizes dysfunction of hypothalamic-pituitary-ovarian axis. Acupunct Electrother Res 1997;22:97-108.

44. Gerhard I, Postneek F. Auricular acupuncture in the treatment of female infertility. Gynecol Endocrinol 1992;6:171-81.

45. Stener-Victorin E. Waldenstrom U, Tagnfors U, Lundeberg T, Lundstedt G, Janson PO. Effects of electro-acupuncture on anovulation in women with polycycstic ovary syndrome. Acta Obstet Gynecol Scand 2000;79:180-8.

46. Paulus WE, Zhang M, Strehler E, El-Danasouri I, Sterzik K. Influence of acupuncture on the pregnancy rate inn patients who undergo assisted reproduction therapy. Fert Steril 2002;77:721-4.

47. Haker E, Egekvist H, Bjerring P. Effect of sensory stimulation (acupuncture) on sympathetic and parasympathetic activities in healthy subjects. J Automomic Nerv Sys 2000;79:52-9.

48. Yao T, Andersson S, Thoren P. Long-lasting cardiovascular depression induced by acupuncture-like stimulation of the sciatic nerve in unanaesthetized spontaneously hypertensive rats. Brain Res 1982;240:77-85.

49. Knardahl S, Elam M, Olausson B, Wallin BG. Sympathetic nerve activity after acupuncture in humans. Pain 1998;75:19-25.

50. Noyes N, Liu HC, Sultan K, Schattman G, Rosenwaks Z. Endometrial thickness appears to be a significant factor in embryo implantation in thickness appears to be a significant factor in embryo implantation in-vitro fertilization. Hum Reprod 1995;10:919-22.

51. Schild RL, Knoblock C, Dorn C, Fimmers R, van der Ven H, Hansmann M. Endometrial receptivity in an in vitro fertilization program as assessed by spiral artery blood flow, endometrial thickness, endometrial volume, and uterine artery blood flow. Fertil Steril 2001;75:361-6.

52. Chiang CH, Hsieh TT, Chang MY, Shiau CS, Hou HC, Hsu JJ, et al. Prediction of pregnancy rate of in vitro fertilization an embryo transfer in women aged 40 and over with basal uterine artery pulsatility index. J Assist Reprod Genet 2000;17:409-14.

53. Engmann L. Sladkevicius P, Agrawal R, Bekir J, Campbell S, Tan SL. The pattern of changes in ovarian stromal and uterine artery blood flow velocities during in vitro fertilization treatment and its relationship with outcome of the cycle. Ultrasound Obstet Gynecol 1999;13:26-33.

54. Salle B, Bied-Damon V, Benchaib M, Desperes S, Gaucherand P, Rudigoz RC. Preliminary report of an ultrasonography and colour Doppler uterine score to predict uterine receptivity in an in-vitro fertilization programme. Hum Reprod 1998;13:1669-73.

55. Aytoz A, Ubaldi F, Tournaye H, Nagy ZP, Van Steirteghem A, Devroey P. The predictive value of uterine artery blood flow measurements for uterine receptivity in an intracytoplasmic sperm injection program. Fertil Steril 1997;68:935-7.

56. Friedler S, Schenker JG, Herman A, Lewin A. The role of ultrasonography in the evaluation of endometrial receptivity following assisted reproductive treatments: a critical review. Hum Reprod Update 1996; 2:323-35.

57. Zaidi J, Pittrof R, Shaker A, Kyei-Mensah A, Campbell S, Tan SL. Assessment of uterine artery blood flow on the day of human chorionic gonadotropin administration by transvaginal color Doppler ultrasound in an in vitro fertilization program. Fertil Steril 1996;65:377-81.

58. Sher G, Fisch JD. Vaginal sildenifil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod 2000;15:806-9.

59. Stener-Victorin E, Waldenstrom U, Andersson SA, Wikland M. Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture. Hum Reprod Biol 1996;11:1314-7.

60. Schenker JG, Meirow D, Schenker E. Stress and human reproduction. Eur J Obstet Gynecol Reprod Biol 1992;45:1-8.

61. Eugster A, Vingerhoets AJ. Psychological aspects of in vitro fertilization: a review. Soc Sci Med 1999;48:575-89.

62. Domar AD, Broome A, Zuttermeister PC, Seibel M. Friedman R. The prevalence and predictability of depression in infertile women. Fertil Steril 1992;58:1158-63.

63. Domar AD, Zuttermeister PC, Friedman R. The psychological impact of infertility: a comparison with patients with other medical conditions. J Psychosom Obstet Gynaecol 1993;14:45-52.

64. Mahlstedt PP, Macduff S, Bernstein J. Emotional factors in in vitro fertilization and embryo transfer process. J In Vitro fert Embryo Transf 1987;4:232-5.

65. Seibel MM, Taymore ML. Emotional aspects of infertility. Fertil Steril 1982;37:137-45.

66. Domar AS, Seibel MM, Benson H. The mind/body program for infertility: a new behavioral treatment approach for women with infertility. Fertil Steril 1990;53:246-9.

67. Chen A. An introduction to sequential electric acupuncture (SEA) in the treatment of stress related physical and mental disorders. Acupunct Electrother Res 1992;17:273-83.

68. Dong JT. Research on the reduction of anxiety and depression with acupuncture. Am J Acupunct 1993;21:327-30.

69. Luo H, Meng F, Jia Y, Zhao X. Clinical research on the therapeutic effect of the electroacupuncture treatment in patients with depression. Psychiatry Clin Neurosci 1998;52:S338-40.

Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy ? Articles
Wolfgang E. Paulus, M.D.,[a] Mingmin Zhang, M.D.,[b] Erwin Strehler, M.D.,[a]Imam El-Danasouri, Ph.D.,[a] and Karl Sterzik, M.D.[a]

FERTILITY AND STERILITY VOL. 77, NO. 4, APRIL 2002, Copyright 2002, American Society for Reproductive Medicine, Published by Elsevier Science Inc.

Objective: To evaluate the effect of acupuncture on the pregnancy rate in assisted reproduction therapy (ART) by comparing a group of patients receiving acupuncture treatment shortly before and after embryo transfer with a control group receiving no acupuncture.

Design: Prospective randomized study.

Setting: Fertility center.

Patient(s): After giving informed consent, 160 patients who were undergoing ART and who had good quality embryos were divided into the following two groups through random selection: embryo transfer with acupuncture (n = 80) and embryo transfer without acupuncture (n = 80).

Intervention(s): Acupuncture was performed in 80 patients 25 minutes before and after embryo transfer. In the control group, embryos were transferred without any supportive therapy.

Main Outcome Measure(s): Clinical pregnancy was defined as the presence of a fetal sac during an ultrasound examination 6 weeks after embryo transfer.

Result(s): Clinical pregnancies were documented in 34 of 80 patients (42.5%) in the acupuncture group, whereas pregnancy rate was only 26.3% (21 out of 80 patients) in the control group.

Conclusion(s): Acupuncture seems to be a useful tool for improving pregnancy rate after ART. (Fertil Steril 2002;77:721- 4. 2002 by American Society for Reproductive Medicine.)

Key Words: Acupuncture, assisted reproduction, embryo transfer, pregnancy rate

Acupuncture is an important element of traditional Chinese medicine (TCM), which can be traced back for at least 4,000 years. Acupuncture has been shown to alleviate nausea and vomiting, dental pain, addiction, headache, menstrual cramps, tennis elbow, fibromyalgia, myofascial pain, osteoarthritis, carpal tunnel syndrome, and asthma. Both physiologic and psychological benefits of acupuncture have been scientifically demonstrated in recent years.

However, so far there have been only a few serious trials concerning the use of acupuncture in reproductive medicine. Publications focus primarily on acupuncture therapy for male infertility (1, 2). acupuncture may reduce blood flow impedance in the uterine arteries of infertile women (3). A positive impact of acupuncture on endocrinologic parameters and ovulation in women with polycystic ovary syndrome has been demonstrated (4). In addition, auricular acupuncture was successfully used in the treatment of female infertility (5). In the present study, we chose acupuncture points that relax the uterus according to the principles of TCM. Because acupuncture influences the autonomic nervous system, such treatment should optimize endometrial receptivity (6). Our main objective was to evaluate whether acupuncture accompanying embryo transfer increases clinical pregnancy rate.