Role of Acupuncture in the
treatment of Female Infertility
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 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.
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