ABORM

Dieterle IVF ICSI

Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study

Stefan Dieterle, M.D., Gao Ying, M.D., Wolfgang Hatzmann, M.D., and Andreas Neuer, M.D.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Witten/Herdecke, Dortmund, Germany; and b Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Objective: To determine the effect of luteal-phase acupuncture on the outcome of IVF/intracytoplasmic sperm injection (ICSI).
Design: Randomized, prospective, controlled clinical study.
Setting: University IVF center.
Patient(s): Two hundred twenty-five infertile patients undergoing IVF/ICSI.
Intervention(s): In group I, 116 patients received luteal-phase acupuncture according to the principles of traditional Chinese medicine. In group II, 109 patients received placebo acupuncture.
Main Outcome Measure(s): Clinical and ongoing pregnancy rates.
Result(s): In group I, the clinical pregnancy rate and ongoing pregnancy rate (33.6% and 28.4%, respectively) were significantly higher than in group II (15.6% and 13.8%).
Conclusion(s): Luteal-phase acupuncture has a positive effect on the outcome of IVF/ICSI.

Download Whole Article in PDF Here

Acu Stim Embryo Transfer

<-- Back to Research Page

Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer

Caroline Smith, Ph.D., Meaghan Coyle, B.Hlth.Sc. (Acup.), and Robert J. Norman, M.D.

School of Health Science, The University of South Australia; b Department of Obstetrics and Gynecology, The University of Adelaide; c Research Centre for Reproductive Health, The Queen Elizabeth Hospital, University of Adelaide; and d Repromed, Adelaide, South Australia, Australia

Objective: To evaluate the effects of acupuncture on clinical pregnancy rates for women undergoing ET.
Design: Single-blind, randomized controlled trial using a noninvasive sham acupuncture control.
Setting: Repromed, The Reproductive Medicine Unit of The University of Adelaide.
Patient(s): Women undergoing IVF.
Intervention(s): Women were randomly allocated to acupuncture or noninvasive sham acupuncture with the placebo needle. All women received three sessions, the first undertaken on day 9 of stimulating injections, the
second before ET, and the third immediately after ET.
Main Outcome Measure(s): The primary outcome was pregnancy. Secondary outcomes were implantation, ongoing pregnancy rate at 18 weeks, adverse events, and health status.
Result(s): Two hundred twenty-eight subjects were randomized. The pregnancy rate was 31% in the acupuncture group and 23% in the control group. For those subjects receiving acupuncture, the odds of achieving a pregnancy were 1.5 higher than for the control group, but the difference did not reach statistical significance. The ongoing pregnancy rate at 18 weeks was higher in the treatment group (28% vs. 18%), but the difference was not statistically significant.
Conclusion(s): There was no significant difference in the pregnancy rate between groups; however, a smaller treatment effect can not be excluded. Our results suggest that acupuncture was safe for women undergoing ET.

Download Whole Article in PDF Here

Westergaard Embryo Transfer

<-- Back to Research Page

Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial

Lars G. Westergaard, M.D., Ph.D., Qunhui Mao, M.D., Marianne Krogslund, Steen Sandrini, Suzan Lenz, M.D., Ph.D., and Jørgen Grinsted, M.D., Ph.D.

Fertility Clinic Trianglen, Hellerup; b Holistic Acupuncture Clinic, Frederiksberg C; and c Sandrini Acupuncture I/S, Varde, Denmark

Objective: To evaluate the effect of acupuncture on reproductive outcome in patients treated with IVF/intracytoplasmic sperm injection (ICSI). One group of patients received acupuncture on the day of ET, another group on ET day and again 2 days later (i.e., closer to implantation day), and both groups were compared with a control group that did not receive acupuncture.
Design: Prospective, randomized trial.
Setting: Private fertility center.
Patient(s): During the study period all patients receiving IVF or ICSI treatment were offered participation in the study. On the day of oocyte retrieval, patients were randomly allocated (with sealed envelopes) to receive acupuncture on the day of ET (ACU 1 group, n 95), on that day and again 2 days later (ACU 2 group, n 91), or no acupuncture (control group, n 87).
Intervention(s): Acupuncture was performed immediately before and after ET (ACU 1 and 2 groups), with each session lasting 25 minutes; and one 25-minute session was performed 2 days later in the ACU 2 group.
Main Outcome Measure(s): Clinical pregnancy and ongoing pregnancy rates in the three groups.
Result(s): Clinical and ongoing pregnancy rates were significantly higher in the ACU 1 group as compared with controls (37 of 95 [39%] vs. 21 of 87 [26%] and 34 of 95 [36%] vs. 19 of 87 [22%]). The clinical and ongoing pregnancy rates in the ACU 2 group (36% and 26%) were higher than in controls, but the difference did not reach statistical difference.
Conclusion(s): Acupuncture on the day of ET significantly improves the reproductive outcome of IVF/ICSI, compared with no acupuncture. Repeating acupuncture on ET day 2 provided no additional beneficial effect.

Download Whole Article in PDF Here

Advisory Board

Advisory Board: Partners Involved in the Process

Shiao-Ting Jing, L.Ac., O.M.D.

Shiao-Ting Jing comes from a family of several generations of traditional Chinese medicine. Her grandfather was a famous local doctor of gynecology in He Bei Province. Unfortunately, his valuable book was burned in the Chinese Cultural Revolution, and Dr. Jing's mother did not have a chance to finish learning from him.

Dr. Jing loved medicine from a very young age. After completing eight years of medical school training in western and traditional Chinese practices, she decided to become an OB/Gyn. She studied at GanSu College of Traditional Chinese Medicine Hospital, under Professor Zhang Ren Yi, a seventh-generation OB/Gyn doctor of Chinese medicine. Dr. Zhang used traditional methods to train Dr. Jing, who observed and palpated pulse quality, practiced facial diagnosis, and mixed herbal formulas. She learned a great deal from this unique and valuable clinical experience, to treat patients with infertility, menopause, endometriosis, uterine myoma, PCOS, dysfunctional uterine bleeding, etc., having great success as a young doctor.

Unfortunately, Dr. Jing lost her cousin to an autoimmune condition, which resulted in kidney failure. She grieved for a long time following this incident, and sought a famous doctor to train her in treating this condition. In 1988, she went to a Beijing University affiliated hospital, DongZhiMen, to study with Professors Shang Xin Men and Lü Ren He, who were experts in auto-immune disorders, including kidney failure. She practiced as the primary intern, treating many patients under the guidance of these professors. She also played a key role in the research on the use of both types of medicine to prevent and treat kidney infection and failure, which won awards countrywide. As part of her training, Dr. Jing also taught and supervised graduating interns at the university.

After three years of work and study, Dr. Jing started working at Beijing Immunology Hospital as a chief physician. In 1992, she followed her husband in moving to Los Angeles , beginning to treat patients in 1993, and opening a busy private practice in 1994.

TEACHING EXPERIENCE: Currently on the faculty of both Yo San University of Traditional Chinese Medicine, Los Angeles and Emperor's College of Traditional Oriental Medicine, Santa Monica; former Clinic Supervisor, Yo San University Clinic.

SPECIAL SKILLS: Expert in Chinese herbal formulas, acupuncture, nutrition, and integration of Chinese medicine with western medical treatments to care for all patients' conditions; specialized focus on treatment of gynecological conditions such as infertility, menopause, endometriosis, dysmenorrhea; auto-immune diseases, pediatric conditions and general pain management.

Steven Mavros, L.Ac., MAOM

Steven received his Bachelors in Psychology from the University of Pennsylvania and began his Oriental Medical training interning at YueYang Hospital in Shanghai. There he got to see first hand how powerful medicine can be when you combine the ancient Eastern ways with modern Western medicine. He went on to complete his Masters in Acupuncture and Oriental Medicine at the New England School of Acupuncture in Watertown, Mass.

Steven started his career in the free clinics of Dimock Hospital and the AIDS Care Project in Boston before opening a private practice in Philadelphia, PA. He now co-owns the Healing Arts Center of Philadelphia, a group wellness center that integrates mainstream and complimentary medicine all under one roof.

Though he maintains a varied practice, his main focus of infertility has led him to be featured in Philadelphia Magazine, Philly Style, and CBS Health Watch. He pioneered bringing Acupuncture to all 5 major fertility clinics in the Philadelphia area and has helped bridge the gap between the local Reproductive Endocrinology and Acupuncture communities.

Dr. Daoshing Ni, D.O.M, L.Ac., Ph.D, Dipl.C.H.

Dr. Dao is a Licensed Acupuncturist in the State of California and is a Diplomat of Chinese Herbology NCCA. Dr. Dao has been active in the TCM profession as well as professional organizations. He was an examiner for the California Acupuncture Committee and also participated in the Chinese Herbology Exam development for NCCA. Well known and respected for his special interest in reproductive and gynecological conditions. Dr. Dao is a member of the American Society for Reproductive Medicine, Pacific Coast Fertility Society, and American Association of Oriental Medicine.

Gerald Williams, LAc (CA), DA (RI) MSTOM

Gerald Williams was born in London England and has lived in America for over 20 years; he and his wife have two beautiful girls and one new infant son. It was during the early years of marriage struggling with their own pains of reproductive issues that he began to explore the causes and alternate treatments for infertility.

Gerald holds a Masters of Science in Traditional Oriental Medicine from the Pacific College of Oriental Medicine, San Diego California. He is board certified in Acupuncture and Herbal Medicine to practice in California as well as nationally. During his extensive world travels in Europe, Africa and Asia, Gerald has explored and studied with numerous nature based medical experts.

While attending the Xiamen University in Fujian China, Gerald was able to study hundreds of patients, participated in clinical rounds and practice first hand with some of the leading TCM specialists. Gerald’s clinical teaching involved patient treatment of conditions including, infertility, oncology, autoimmune and endocrine disorders.

Gerald is also certified by Harvard Medical School’s, Mind-Body Medical Institute in Mind-Body Medicine, having trained personally with the institute’s director Dr. Herbert Benson, M.D. Gerald has also worked with the Scripps hospital executive health center in La Jolla California as a specialist mind-body consultant. He has been featured on numerous national and local television and radio programs.

Gerald is a clinical director at the Reproductive Wellness clinic in San Diego. The fruition of his efforts is the offering of comprehensive integrated mind-body treatment and training programs specializing in women’s reproductive health.

Acu Infertility Role

<-- Back to Research Page

Role of acupuncture in the treatment of female infertility

Raymond Chang, M.D.[a,b] Pak H. Chung, M.D.[b] and Zev Rosenwaks, M.D.[c]

The Institute of East-West Medicine and the Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, New York, New York

FERTILITY AND STERILITY® VOL. 78, NO. 6, DECEMBER 2002
Copyright ©2002 American Society for Reproductive Medicine
Published by Elsevier Science Inc., Printed on acid-free paper in U.S.A.

Objective: To review existing scientific rationale and clinical data in the utilization of acupuncture in the treatment of female infertility.

Design: A MEDLINE computer search was performed to identify relevant articles.

Result(s): Although the understanding of acupuncture is based on ancient medical theory, studies have suggested that certain effects of acupuncture are mediated through endogenous opioid peptides in the central nervous system, particularly ß-endorphin. Because these neuropeptides influence gonadotropin secretion through their action on GnRH, it is logical to hypothesize that acupuncture may impact on the menstrual cycle through these neuropeptides. Although studies of adequate design, sample size, and appropriate control on the use of acupuncture on ovulation induction are lacking, there is only one prospective randomized controlled study examining the efficacy of acupuncture in patients undergoing IVF. Besides its central effect, the sympathoinhibitory effects of acupuncture may impact on uterine blood flow.

Conclusion(s): Although the definitive role of acupuncture in the treatment of female infertility is yet to be established, its potential impact centrally on the hypothalamic-pituitary-ovarian axis and peripherally on the uterus needs to be systemically examined. Prospective randomized controlled studies are needed to evaluate the efficacy of acupuncture in the female fertility treatment. (Fertil Steril® 2002;78:1149-53. ©2002 by American Society for Reproductive Medicine.)

Key Words: Acupuncture, female infertility, in vitro fertilization

Acupuncture as a therapeutic intervention has been extensively studied and is increasingly practiced in the United States. A recent survey of acupuncture released by an NIH Consensus Development panel (1) indicated that although there are inherent problems of design, sample size, and appropriate controls in the acupuncture literature, promising data exist for the use of acupuncture in treating nausea and vomiting (2), postoperative pain (3-5), addiction (6-9), and general pain syndromes (10-12). As a medical technique, acupuncture has also been reported as an adjunct in the treatment of various gynecologic problems (13-15).

Although conventional treatment options for female infertility have been well established, there have been few systematic reviews of complementary or alternative approaches to the treatment of infertility. In light of an increasing trend in the use of complementary and alternative medicine (16) and common inquiry and utilization of such approaches by patients suffering from infertility, we intend to review the existing scientific rationale and clinical data based on which acupuncture may exert an influence on the outcome of female fertility.

In examining the potential usefulness of acupuncture in enhancing female fertility, it is appropriate first to give some theoretical background for acupuncture. Although the theory of acupuncture stems from underlying traditional Chinese medicine premises that would define etiologies for infertility in terms of energy disturbance of imbalances, or organ deficiencies and excesses, we intend to review the existing literature by examining modern medical aspects of the central and peripheral modes of action of acupuncture as they impact on the hypothalamic-pituitary-ovarian axis and the pelvic organs, respectively. Moreover, the effect of acupuncture on anxiety and stress and ensuing potential indirect effects on female fertility will also be discussed.

Background

Acupuncture is the manipulation of thin metallic needles inserted into anatomically defined locations on the body to affect bodily function. The US Food and Drug Administration has recently removed acupuncture needles from the category of experimental medical devices and now regulates them just like it does other devices, such as surgical scalpels and hypodermic needles, under good manufacturing practices and single-use standard of sterility (1).

The general theory of acupuncture is based on the premise that there are patterns of energy flow (Qi) through the body, which are essential for health. Disruption of this flow is believed to be responsible for disease. Acupuncture can correct imbalances of flow at identifiable points close to the skin.

According to the proposed international acupuncture nomenclature by The World Health Organization in 1991 (17), the meridian system consists of 20 meridians interconnecting about 400 acupoints. These acupoints correspond to specific areas on the surface of the body, which demonstrate higher electrical conductance because of the presence of higher density of gap junctions along cell borders. They act as converging points (or sinks) for electromagnetic fields. A higher metabolic rate, temperature, and calcium ion concentration, are also observed at these points. In principle, positive (anode) pulse stimulation of a point inhibits the organ function, whereas negative (cathode) pulse stimulation enhances that function (18). This forms the basis of electroacupuncture, which applies small electrical needles inserted in specific acupoints.

Effects of acupuncture on the hypothalamic-pituitary-ovarian axis and menstrual cycle

Although traditional Chinese medicine understanding of acupuncture is based on ancient medical theory, a modern and scientific neuroendocrine perspective has begun to evolve in the past two decades. Mayer et al. (19) first reported that acupuncture analgesia was induced through endorphin production and antagonized by the narcotic antagonist naloxone. Other studies similarly suggested that certain effects of acupuncture are mediated through the nervous system, within which ß-endorphin and other neuropeptides have been implicated (20-22).

Acupuncture was shown by Petti et al. (20) to cause a significant increase in ß-endorphin levels during treatment, which lasted for up to 24 hours. ß-endorphin is derived from its precursor protein pro-opiomelanocortin, which is present in abundant amounts in neuronal cells of the arcuate nucleus of the hypothalamus, pituitary, medulla, and in peripheral tissues including intestines and ovaries (23-25). Pro-opiomelanocortin cleaves to form adrenocorticotropic hormone and ß-lipoprotein. Further cleavage of ß-lipoprotein yields neuropeptides including ß-endorphin. Aleem et al. (26, 27) demonstrated the presence of immunoreactive ß-endorphin in follicular fluids of both normal and polycystic ovaries.

The influence on gonadotropin secretion and the menstrual cycle by endogenous opioid peptides is believed to be mediated by their action on GnRH secretion (28). The hypothalamic ß-endorphin center and the GnRH pulse generator, in fact, are both situated within the arcuate nucleus. Quigley et al. (29) first reported an increased opioid inhibition of LH secretion in hyperprolactinemic patients with pituitary microadenomas. Ching (30) and Orstead and Spics (31), respectively, showed that opioid peptides suppress GnRH release in rats and rabbits.

The role of these neuropeptides, including ß-endorphin, in the regulation of GnRH secretion in humans has recently been reviewed by Kalra et al. (32) and Pau and Spies (33). Rossmanith et al. (34) demonstrated the role of opioid peptides in the initiation of the mid-cycle LH surge in normal cycling women. Meanwhile, measurement of ß-endorphin in ovarian follicular fluid of healthy ovulatory women revealed much higher levels than that in circulating plasma (35). The highest level of ß-endorphin was noted to be in the preovulatory follicle.

Because acupuncture treatment impacts on ß-endorphin levels, which in turn affect GnRH secretion and the menstrual cycle, it is logical to hypothesize that acupuncture may influence ovulation and fertility. Animal studies have revealed that acupuncture treatment normalized GnRH secretion and affected peripheral gonadotropin levels (36, 37). Various investigators have shown that in normally ovulatory or anovulatory women, acupuncture also influenced plasma levels of FSH, LH, E2, and P (38-40). Acupuncture as a surrogate for hCG in ovulation induction was successfully used by Cai (41). Chen and Yu (42) showed that electroacupuncture normalized they hypothalamic-pituitary-ovarian axis, and in another study Chen (43) reported that 6 of 13 anovulatory cycles responded to acupuncture treatment.

A series published from the University of Heidelberg in Germany (44) used auricular acupuncture on 45 infertile women suffering from ovulatory dysfunction such as oligomenorrhea and luteal phase defect. The control group received medical treatment including bromocriptine, dexamethasone, levothyroxine, clomiphene citrate (CC), and gonadotropin. Although the investigators concluded that resumption of ovulatory cycles occurred significantly more often in the acupuncture group compared to the control group, pregnancy rates were not different between the two groups. However, interpretation of study data was very difficult due to the heterogeneity of the patient population and treatment modalities. Moreover, seven pregnancies in the acupuncture group were actually achieved with hormone treatment 6 months after acupuncture was stopped.

Another study by Stenver-Victorin et al. (45) evaluated the use of electroacupuncture for ovulation induction on 24 oligo/amenorrheic women with polycycstic ovarian syndrome (PCOS). The percentage of ovulatory cycles in all subjects was shown to improve from 15% (in a total of 3 months before treatment) to 66% up to 3 months after treatment. Responsive patients were noted to have significantly lower body mass index (BMI), waist-to-hip circumference ratio, serum T concentration, serum T/sex hormone-binding globulin ratio, and serum basal insulin level. They suggested that, in these selected patients with PCOS, acupuncture could be considered as an alternative or adjunct to pharmacological ovulation induction.

A recent prospective randomized controlled study by Paulus et al. (46) compared pregnancy rates in a total of 160 patients undergoing IVG. Acupuncture was performed in 80 patients 25 minutes before and after ET. After controlling confounding variables, clinical pregnancy rate for the acupuncture group (42.5%) was significantly higher than the control group (26.3%).

Peripheral effects of acupuncture

In addition to the central modulation of the hypothalamic-pituitary-ovarian axis, the effects of acupuncture on the autonomic nervous system have been well documented (47). In the early 1980s, Yao et al. (48) reported long-lasting cardiovascular depression induced by acupuncture stimulation of the sciatic nerve in unanesthetized hypertensive rats. In the human, acupuncture was also shown to be sympathoinhibitory. After acupuncture, sympathetic nerve activity as measured by norepinephrine level, skin temperature, blood pressure, and pain tolerance threshold was shown to be decreased (49).

Endometrial thickness, morphology, and uterine artery blood flow have been implicated as important parameters for success of implantation of human embryos (50-57). Despite conflicting results in the utilization of these parameters during various stages of treatment to predict outcome in IVF, it is generally believed that adequate endometrial thickness is required to optimize pregnancy rate. Because endometrial thickness is a function of uterine artery blood flow, Sher and Fisch (58) reported a novel method of using vaginal sildenafil in an attempt to improve uterine artery blood flow and endometrial development in patients undergoing IVF.

With its central sympathoinhibitory effect, acupuncture may contribute to reduce uterine artery impedance and therefore, increase blood flow to the uterus. In fact, Sterner-Victorin et al. (59) demonstrated this when they performed acupuncture in 10 infertile women who were down-regulated by GnRH analog to avoid the effect of endogenous hormone on the uterine artery blood flow.

Pulsatility index in the uterine artery and skin temperature (on the forehead and lumbosacral area) were evaluated in three time periods-before, right after, and 2 weeks after acupuncture treatment (twice a week for 4 weeks). Pulsatility index and skin temperatures were found to be significantly decreased and increased, respectively, both right after and 14 days after acupuncture treatment. This effect was hypothesized to be caused by central inhibition of sympathetic activity.

Acupuncture and stress reduction

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 ß-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.

Appropriate training, credentialing, and certification of acupuncture practitioners by state agencies can facilitate the integration of acupuncture into the treatment of female infertility, and healthcare in general. The NIH Consensus Conference (1) agreed that this is necessary to allow the public and other health practitioners to identify qualified acupuncture practitioners. With the help of the US Department of Education, issues of training and licensure of non-physician and physician practitioners have been addressed. There is sufficient evidence to acupuncture's value to expand its use into conventional medicine and treatment of female infertility, and to encourage further studies of its underlying mechanisms as well as to establish its clinical value.

References

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

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.

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

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.

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.

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

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.

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

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.

Acu ART Paulus

<-- Back to Research Page

Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy

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] Christian-Lauritzen-Institut, Ulm, Germany

FERTILITY AND STERILITY® VOL. 77, NO. 4, APRIL 2002
Copyright ©2002 American Society for Reproductive Medicine
Published by Elsevier Science Inc., Printed on acid-free paper in U.S.A.

Received June 5, 2001; revised and accepted October 16, 2001.
Reprint requests: Wolfgang E. Paulus, M.D., Christian-Lauritzen-Institut, Frauenstr. 51, D-89073, Ulm, Germany (FAX: ++49-731-9665130; E-mail: paulus@reprotox.de).
[a] Department of Reproductive Medicine, Christian-Lauritzen-Institut.
[b] Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical University, Wuhan, People's Republic of China.
0015-0282/02/$22.00
PII S0015-0282(01)03273-3

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). Electroacupuncture may reduce blood flow impedance in the uterine arteries of infertile women (3). A positive impact of electroacupuncture 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.

Materials and Methods

This study was a prospective randomized trial at the Christian-Lauritzen-Institut in Ulm, Germany. It was approved by the ethics committee of the University of Ulm. A total of 160 healthy women undergoing treatment with in vitro fertilization (IVF; n = 101) or intracytoplasmic sperm injection (ICSI; n = 59) were recruited into the study. The age of the patients ranged from 21 to 43 (mean age: 32.5 = 4.0 years). The cause of infertility was the same for both groups (Table 1). Only patients with good embryo quality were included in the study. Using a computerized randomization method, patients were assigned into either the acupuncture group or the control group.

Table 1
Descriptive data on acupuncture and control group (mean ± SD or total number).


	Control group	Acupuncture group	Statistics
	(n = 80)	(n = 80)	Statistics

Age of patients (years)	32.1 ± 3.9	32.8 ± 4.1	NS
No. of previous cycles	2.0 ± 2.0	2.1 ± 2.1	NS
No. of transferred embryos	2.1 ± 0.5	2.2 ± 0.5	NS
IVF (n)	54	47	NS
ICSI (n)	26	33	NS
No. of cycles with male factor infertility	46	47	NS
No. of cycles with tubal disease	21	22	NS
No. of cycles with polycystic ovaries	2	2	NS
No. of cycles with unknown cause of infertility	11	9	NS
Endometrial thickness (mm)	9.9 ± 2.7	9.1 ± 2.4	NS
Plasma estradiol on day of embryo transfer (pg/mL)	1001 -± 635	971 ± 832	NS
Pulsatility index of uterine arteries (PI) before embryo transfer	2.00 ± 0.56	2.02 ± 0,45	NS
Pulsatility index of uterine arteries (PI) after embryo transfer	2.19 ± 0.52	2.22 ± 0,44	NS
Pregnant	21/80 (26.3%)	34/80 (42.5%)	P=.03

NS = not significant (P>.05).
Paulus. Acupuncture in ART. Fertil Steril 2002.

Ovarian stimulation, oocyte retrieval, and in vitro culture were performed as previously described (7). Transvaginal ultrasound-guided needle aspiration of follicular fluid was performed 36 to 38 hours after hCG administration. Immediately after follicle puncture, the oocytes were retrieved, assessed, and fertilized in vitro. Sperm preparation and culture conditions did not differ for either group.

In cases of severe male subfertility, ICSI was preferred, as described in the literature (8). Forty-eight hours after the IVF or ICSI procedure, embryos were evaluated according to their appearance as type 1 or 2 (good), type 3 or 4 (poor), as described in literature (9).

Just before and after embryo transfer, all patients underwent ultrasound scans of the uterus using a 7-MHz transvaginal probe (LOGIQ 400 Pro, GE Medical Systems Ultra-sound Europe, Solingen, Germany). Pulsed Doppler curves of both uterine arteries were measured by one observer. The pulsatility index (PI) for each artery was calculated electronically from a smooth curve fitted to the average waveform over three cardiac cycles.

A maximum of three embryos, in accordance with German law, were transferred into the uterine cavity on day 2 or 3 after oocyte retrieval. For embryo replacement, the patient was placed in a dorsal lithotomy position, with an empty bladder. The cervix was exposed with a bivalved speculum, then washed with culture media prior to embryo transfer. Labotect Embryo Transfer Catheter Set (Labotect GmbH, Go¨ ttingen, Germany) was used for atraumatic replacement owing to the curved guiding cannula with a ball end, allowing the set to be used reliably even with difficult anatomic conditions. The metallic reinforced inner catheter shaft al lowed safe passage through the cervical canal. When the catheter tip lay close to the fundus, the medium containing the embryos was expelled and the catheter withdrawn gently. After this procedure, the patient was placed at bed rest for 25 minutes. All oocyte retrievals and embryo transfers were performed by one examiner using the same method. The examiner was not aware of the patient's treatment group (control or acupuncture).

At the time of the embryo transfer, blood samples (10 mL) were obtained from the cubital vein. Plasma estrogen was determined by an immunometric method using the IMMULITE 2000 Immunoassay System (DPC Diagnostic Product Corporation, Los Angeles, CA).

Luteal phase support was given by transvaginal progesterone administration (Utrogest®, 200 mg, three times per day; Kade, Berlin, Germany). Progesterone administration was initiated on the day after oocyte retrieval and was continued until the serum ß-hCG measurement 14 to 16 days after transfer and, in cases of pregnancy, until gestation week 8.

Each patient in the experimental group received an acupuncture treatment 25 minutes before and after embryo transfer. Sterile disposable stainless steel needles (0.25 X 25 mm) were inserted in acupuncture point locations. Needle reaction (soreness, numbness, or distention around the point = Deqi sensation) occurred during the initial insertion. After 10 minutes, the needles were rotated in order to maintain Deqi sensation. The needles were left in position for 25 minutes and then removed. The depth of needle insertion was about 10 to 20 mm, depending on the region of the body undergoing treatment. Before embryo transfer, we used the following locations: Cx6 (Neiguan), Sp8 (Diji), Liv3 (Taichong), Gv20 (Baihui), and S29 (Guilai).

After embryo transfer, the needles were inserted at the following points: S36 (Zusanli), Sp6 (Sanyinjiao), Sp10 (Xuehai), and Li4 (Hegu).

In addition, we used small stainless needles (0.2 X 13 mm) for auricular acupuncture at the following points, without rotation: ear point 55 (Shenmen), ear point 58 (Zhigong), ear point 22 (Neifenmi), and ear point 34 (Naodian). Two needles were inserted in the right ear, the other two needles in the left ear. The four needles remained in the ears for 25 minutes. The side of the auricular acupuncture was changed after embryo transfer. The patients in the control group also remained lying still for 25 minutes after embryo transfer. All treatments were performed by the same well-trained examiner, in the same way.

The primary point of the study was to determine whether acupuncture improves the clinical pregnancy rate after IVF or ICSI treatment. Student's t-test was used as a corrective against any possible imbalance between the two groups regarding the following variables: age of patient, number of previous cycles, number of transferred embryos, endometrial thickness, plasma estradiol on day of transfer, method of treatment (IVF or ICSI), and blood flow impedance in the uterine arteries (pulsatility index). Chi-square test was used to compare the two groups. All statistical analyses were carried out using the software package Stathttp://easternharmonyclinic.com/medart/graphics (Manugistics, Inc., Rockville, MD).

Results

A total of 160 patients was recruited for the study. Patients who failed to conceive during the first treatment cycle were not reentered into the study. According to the randomization, 80 patients were treated with acupuncture, and 80 patients underwent the usual therapy without acupuncture.

As Table 1 shows, there were no statistically significant differences between the two groups with respect to the following covariants: age of patient, number of previous cycles, number of transferred embryos, endometrial thickness, plasma estradiol on day of transfer, or method of treatment (IVF or ICSI). Clinical indications for ART were the same for patients of both groups. The blood flow impedance in the uterine arteries (pulsatility index) did not differ between the groups before and after embryo transfer.

The analysis shows that the pregnancy rate for the acupuncture group is considerably higher than for the control group (42.5% vs 26.3%; P=.03).

Discussion

The acupuncture points used in this study were chosen according to the principles of TCM (10): Stimulation of Taiying meridians (spleen) and Yangming meridians (stomach, colon) would result in better blood perfusion and more energy in the uterus. Stimulation of the body points Cx6, Liv3, and Gv20, as well as stimulation of the ear points 34 and 55, would sedate the patient. Ear point 58 would influence the uterus, whereas ear point 22 would stabilize the endocrine system.

The anesthesia-like effects of acupuncture have been studied extensively. Acupuncture needles stimulate muscle afferents innervating ergoreceptors, which leads to increased ß-endorphin concentration in the cerebrospinal fluid (11). The hypothalamic ß-endorphinergic system has inhibitory effects on the vasomotor center, thereby reducing sympathetic activity. This central mechanism, which involves the hypothalamic and brainstem systems, controls many major organ systems in the body (12). In addition to central sympathetic inhibition by the endorphin system, acupuncture stimulation of the sensory nerve fibers may inhibit the sympathetic outflow at the spinal level. By changing the concentration of central opioids, acupuncture may also regulate the function of the hypothalamic-pituitary-ovarian axis via the central sympathetic system (13).

Kim et al. (14) suggested that Li4 acupuncture treatment could be useful in inhibiting the uterus motility. In their rat experiments, treatment on the Li4 acupoint suppressed the expression of COX-2 enzyme in the endometrium and myometrium of pregnant and nonpregnant uteri.

Stener-Victorin et al. (3) reduced high uterine artery blood flow impedance by a series of eight electroacupuncture treatments, twice a week for 4 weeks. They suggest that a decreased tonic activity in the sympathetic vasoconstrictor fibers to the uterus and an involvement of central mechanisms with general inhibition of the sympathetic outflow may be responsible for this effect. In our study, we could not see any differences in the pulsatility index between the acupuncture and control group before or after embryo transfer. This may be due to a different acupuncture protocol and the selected sample of patients with high blood flow impedance of the uterine arteries (PI ≥ 3.0) in the Stener-Victorin et al. study.

As we could not observe any significant differences in covariants between the acupuncture and control groups, the results demonstrate that acupuncture therapy improves pregnancy rate.

Further research is needed to demonstrate precisely how acupuncture causes physiologic changes in the uterus and the reproductive system. To rule out the possibility that acupuncture produces only psychological or psychosomatic effects, we plan to use a placebo needle set as a control in a future study.

References

Siterman S, Eltes F, Wolfson V, Lederman H, Bartoov B. Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study. Andrologia 2000;32:31-9.

Bartoov B, Eltes F, Reichart M, Langzam J, Lederman H, Zabludovsky N. Quantitative ultramorphological analysis of human sperm: fifteen years of experience in the diagnosis and management of male factor infertility. Arch Androl 1999;43:13-25.

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 1996;11:1314 -7.

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

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

Stener-Victorin E, Lundeberg T, Waldenstrom U, Manni L, Aloe L, Gunnarsson S, Janson PO: Effects of electro-acupuncture on nerve growth factor and ovarian morphology in rats with experimentally induced polycystic ovaries. Biol Reprod 2000;63:1497-503.

Strehler E, Abt M, El-Danasouri I, De Santo M, Sterzik K. Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome. Fertil Steril 2001;75: 332-6.

Palermo GD, Schlegel PN, Colombero LT, Zaninovic N, Moy F, Rosenwaks Z. Aggressive sperm immobilization prior to intracytoplasmic sperm injection with immature spermatozoa improves fertilization and pregnancy rates. Hum Reprod 1996;11:1023-9.

Plachot M, Mandelbaum J: Oocyte maturation, fertilization and embryonic growth in vitro. Br Med Bull 1990;46:675-94.

10.

Maciocia G. Obstetrics and gynecology in Chinese medicine. New York: Churchill Livingstone, 1998.

11.

Hoffmann P, Terenius L, Thoren P. Cerebrospinal fluid immunoreactive beta-endorphin concentration is increased by voluntary exercise in the spontaneously hypertensive rat. Regul Pept 1990;28:233-9.

12.

Andersson SA, Lundeberg T. Acupuncture-from empiricism to science: functional background to acupuncture effects in pain and disease. Med Hypotheses 1995;45:271-81.

13.

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.

14.

Kim J, Shin KH, Na CS. Effect of acupuncture treatment on uterine motility and cyclooxygenase-2 expression in pregnant rats. Gynecol Obstet Invest 2000;50:225-30.

EA Ovu Induction

<-- Back to Research Page

Relationship Between Blood Radioimmunoreactive Beta-Endorphin and Hand Skin Temperature During The Electro-Acupuncture Induction of Ovulation

By

Chen Bo Ying M.D. Lecturer of Neurobiology. Institute of Acupuncture Research, and Yu Jin, MD., Prof of Gynecology Obstetricus and Gynecology Hospital, Shanghai Medical University. Shanghai, People's Republic of China

(Received October 24, 1990; Accepted with revisions,
December 8, 1990)

Source: ACUPUNCTURE & ELECTRO-THERAPEUTICS RES.,
Vol. 16, pp. 1-5,1991

Abstract: Thirteen cycles of anovulation menstruation in 11 cases were treated with Electro-Acupuncture (EA) ovulation induction. In 6 of these cycles which showed ovulation, the hand skin temperature (HST) of these patients was increased after EA treatment. In the other 7 cycles ovulation was not induced. There were no regular changes in HST of 5 normal subjects. The level of radioimmunoreactive beta-endorphin (rß-E) fluctuated, and returned to the preacupunctural level in 30 min. after withdrawal of needles in normal subjects. After EA, the level of blood rß-E in cycles with ovulation declined or maintained the range of normal subjects. But the level of blood rß-E and increase of HST after EA (r=-0.677, P <0.01). EA is able to regulate the function of the hypothalamic pituitary-ovarian axis. Since a good response is usually accompanied with the increase of HST, monitoring HST may provide a rough but simple method for prediciting the curative effect of EA. The role of rß-E in the mechanism of EA ovulation induction was discussed.

KEY WORDS: Electro-Acupuncture (EA), Hand Skin Temperature (HST), radioimmunoreactive beta-endorphin (rß-E), ovulation, radioimmunoassay (RIA)
INTRODUCTION

In our previous work, it has been demonstrated that EA is an effectual method of ovulation induction (1). The present work studied the relationship between the curative effect of EA and the changes of the HST and the level of blood beta-endorphin.

MATERIALS AND METHODS

Selection and Treatment of Cases

Eleven cases of chronically anovulatory patients including 9 cases of polycystic ovarian disease (PCO), 1 case of hypogonadotropic amenorrhea and case of oligomenorrhea were treated with EA in 13 menstruation cycles. They were 22 to 35 years of age and their courses of disease were 3 to 12 years. The basic body temperature (BBT) of these patients was monophase for at least 3 months. Each patient accepted the vaginal dropping cell examination twice or more a week. The results showed that the eosinocyte index (EI) of 10 cases was less than 30% and the EI of 1 case was more than 70%.

On the 10th day of each menstruation cycle, the patients were treated with EA. "Guanyuan" "Zhongji," "Sanyinjiao" and both sides of "Zigong" points were stimulated for 30 min. at 8:00 AM, OD for 3 days. The stimulation parameters were 7-10mA and 4-5HZ with G6805 model generator. The electric current of EA was bearable for every patient. Before and after the EA, HST was measured by a semiconduct thermometer and blood samples were collected from the forearm vien of patients for ß-E RIA. Five healthy woman voluteers with normal menstruation cycle were selected as controls. They were 31 to 35 years old and the menstruation cycle was 28 days. BBT showed change of biphase. All of them were healthy in premenorrhea and did not take any drug one month before EA. The stimulation points and parameters of EA were the same as above mentioned.

Plasma ß-Enorphin Radioimmunoassay

The blood samples were added to 100ug/ml bacitracin for inhibiting blood aminopeptidase and centrifuged at 3,000g for 15 min. The plasma was stored at -40°C.

The sensitive radioimmunoassay was performed as a routine in our lab (2,3), to determine the concentration of ß-E in the samples of plasma. Each estimative tube was added 0.1ml 1:8000 rabbit ß-E antiserum, 0.1ml[125]I-ß-E . That is 0.03ml sheep antiserum to rabbit gamma-globulin diluted 20-fold with RIA buffer was added to each tube, than shaken and incubated at 0-4°C for 24 hours, and centrifuged at 3,000g for 15 min. The supernatant was poured out and the precipitate was counted for radioactivity in Model FH 408 gamma counter. ß-E contents were quantitated according to the standard curve which was performed at the same time with the sample tubes. The least detected quantity of RIA was 10pg/tube.

RESULTS

Clinical Observation

It was adopted standards of ovulation that BBT showed biphase and EI became cyclic variation. Six of 13 menstruation cycles treated with EA showed ovulation, while the other 7 cycles failed to do so. No EA effect was found in normal control subjects.

In the 13 anovulatary cycles, increased HST occurred in 6 cycles, of which 5 cycles showed ovulation after EA treatment. 7 cycles manifested decreased HST and only one of them produced ovulation (Table 1). No regular change was seen in HST in normal subjects.

Table l. Effect of EA Induction of Ovulation in 13 Cycles

Changes of HST	Ovulation	No Ovulation	Total

Increased	5*	1	6
Decreased	1	6	7

* P<0.05 as estimated by X[2] test

Change of Plasrna rß-E

In normal menstruation cycles the level of plasma rß-E before and after EA fluctuated and returned to the preacupural level after 30 minutes.

In the 13 anovulatory cycles the level of plasma rß-E on the 10th day of the cycles was higher but not statistically significant from that of normal subjects.

After EA the plasma rß-E contents of 6 cycles with ovulation either declined or maintained within the range of normal. And the plasma level of 7 cycles that failed to show ovulation after EA were significantly higher than those of normal subjects and 6 ovulatory cases as estimated by t test (P<0.05), (Table 2).

Table 2. Changes of blood ß-E level before and after EA* (pg/ml)

Group of cases	No. of cycles	Before EA	After EA

Ovulation	6	65.59 ± 24.15	38.86 ± 10.11
No ovulation	7	65.59 ± 24.15	80.09 ± 22.16**
Normal	5	38.84 ± 10.13	41.52 ± 6.40

*The values in this table are Mean ± SE
**P<0.05

Cycles which showed increase of HST after EA were associated with a declination of plasma rß-E Ievel but in cycles where HST decreased, the plasma rß-E level elevated after EA. There was a negative correlation between changes of plasma rß-E and HST as measured by rank correlation (r=0.677, P<0.01).

Discussion

According to our clinical practice of using EA to cure barreness, the curative effect was related to the changes of patients' HST. In general, provided that the body temperature was normal and the environmental temperature was constant round 25°C, the HST may reflect the state of sympathetic system of a patient.

From present results, it seems that the successful rate of EA ovulation induction was higher in patients with the depression of sympathetic activity. In normal subject whether HST increased or declined, no influence in ovulation was found. These results suggest that the relationship of ovulation and HST in normal women is different from that in anovulatory patients. Yen and his colleagues (4) first reported that enogenous opioid peptides can inhibit pituitary pulse secreting LH. Fumiko, Akio and Michael reported in succession that morphine, ß-E and dynorphin can also depress LH pulse secretion (5,6,7). These substances may exert their action via regulating the secretion of LH-RH in hypothalmus. EA can affect the central opioid peptide level (2,8,9) thus it may regulate the function of hypothalamic-pituitary-ovarian axis via brain endogenous opiod peptides, such as ß-E and dynorphin etc.

In this study 11 cycles were PCO and the blood LH level in these cycles was marked higher than that of normal subjects. EA may promote the release of ß-E in the brain and reduce LH-RH secretion from hypothalamus. Therefore, the blood LH content released from the pituitary was decreased. This might be one of the mechanisms of EA ovulation induction.

The injection of ß-E into rat cerebellomedullary cisterm resulted in the increase of blood epinephrine (E), norepinephrine (NE) and dopamine (DA) levels, and there was a positive correlation in the dose of ß-E and the levels of blood E, NE, and DA (10). The result suggests that control ß-E may influence the activity of the sympathetic system. Our study showed that the sympathetic activity in normal subjects was not affected and the level of blood ß-E was relatively stable. Thus EA was not able to influence the normal ovulatory cycles. In anovulatory patients, especially in PCO cases, EA can depress sympathetic activity resulting in the increase of HST and the lowering the level of blood ß-E.

These results suggest that in anovulatory cases the hyperactive sympathetic system can be depressed by EA and the function of the hypothalamus-pituitary-ovarian axis can be regulated by EA via central sympathetic system. This might be another possible mechanism of EA ovulation induction.

Our study also suggest that measuring HST my provide a rough but simple method for predicting the effect of EA ovulation induction.

ACKNOWLEDGEMENT

This report has been directed by Prof. He Lian Fang.

REFERENCES

1.	Yu Jin, Zheng Hua-Mei, Chen Bo-Yeng, Relationship of hand temperature and blood ß-endorphinelike immunoreactive substance with electroacupuncture induction of ovulation, Acupuncture Research vol. 11 (2), pp. 86-90, 1986.
2.	Chen Bo-Ying, Pan Xiao-Ping, Jiang Cheng-Chuan, Chen Shang-Qun, Correlation of pain threshold and level of ß-endoprphin like immuno-reactive substance in human CST during electroacupuncture analgesia, Acta Physiologica Sinica vol. 36 (2), pp. 193-197, 1984.
3.	He Xiao-Ping, Chen Bo-Ying, Zhu Jin-Ming, Cao Xiao-Ding, Change of Leu-enkephalin and ß-endorphin-like immunoreactivity in the Hippocampus after electroconvulsive shock and electroacupuncture, Acupuncture & Electro-Therapeutics Res., Int. J., vol. 14 (1), pp.131-139, 1989.
4.	Quigley, M.E., Sheeham, K.L., Casper, R.F. and Yen, S.S.C., Evidence for an increased opioid inhibition of luteinizing hormone secretion in hyperprolactinemic patients with pituitary microadenoma, J. Clin. Endocrinol, Metabol, vol.50 (3), pp. 427-436, 1980.
5.	Fumiki Kinoshita, Yoshikatsu Nakai, Hideki Katakami, Hiroo Imura, Suppressive effect of dynorphin (1-13) on luteinizing hormone release in conscious rat, Life Sci. vol. 30 (22), pp. 1915-1919, 1982.
6.	Akio Adabori, Charles A. Barraclough, Effect of morphine on luteinizing hormone secretion and catecholmine turnover in the hypothalamus of estrogen-treated rats, Brain Res. vol. 362 (2) pp. 221-226, 1986.
7.	K. Michael Orstead, Harold G. Spics, Inhibition of hypothalamic gonadotropin releasing hormone release by endogenous opioid peptides in the female rabbit, Neuroendocrinology, vol. 46 (1), pp. 14-23, 1987.
8.	Richard S.S., Cheng, S, Pomeranz, B., Electroacupuncture analgesia could be mediated by least two pain relieving endorphin and non-endorphin systems, Life Sci., vol. 25 (22), pp. 1951-1968, 1979.
9.	Chen Bo-ying, Wang De-Ling, Pan Xiao-Ping, Changes of opiate likesubstances (OLS) level in perfusate of periaqueductal gray (PAG) after electroacupuncture and brain stimulation, Acta Physiologica Sinica vol. 34 (4), pp.385-391, 1982.
10.	Glen R. Van Loon, Nathan M. Appel, Doris Ho, ß-endorphin-induced stimulation of central sympathetic outflow: ß-endorphin increases plasma concentration of epinephrine, norepinephrine, and dopamine in rats, Endocrinology, vol. 109 (1), pp. 46-53, 1981.