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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.
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
- Received June 24, 2002; revised and accepted July 19,
2002.
Reprint requests: Pak H. Chung, M.D., The Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, 505 East 70 Street, New York, New York 10021 (FAX: 212-746-8208; E-mail: pakchu @ med.cornell.edu).
[a]The Institute of East-West Medicine. [b]The Department of Internal Medicine, Weill Medical College of Cornell Unversity. [c]The Center for Reproductive Medicine and Infertility.
0015-0282/02/$22.00
PII S0015-0282(02)04348-0
- 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 �-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 �-endorphin and other neuropeptides have been implicated (20-22).
- Acupuncture was shown by Petti et al. (20) to cause a significant
increase in �-endorphin levels during treatment, which lasted for up to
24 hours. �-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
�-lipoprotein. Further cleavage of �-lipoprotein yields neuropeptides
including �-endorphin. Aleem et al. (26, 27) demonstrated the presence
of immunoreactive �-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 �-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 �-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
�-endorphin in ovarian follicular fluid of healthy ovulatory women
revealed much higher levels than that in circulating plasma (35). The
highest level of �-endorphin was noted to be in the preovulatory
follicle.
- Because acupuncture treatment impacts on �-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 �-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.
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