Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer Caroline Smith, Ph.D.,a Meaghan Coyle, B.Hlth.Sc. (Acup.),b and Robert J. Norman, M.D.c,d
a School of Health Science, The University of South Australia; b Department of Obstetrics and Gynecology, The University ofAdelaide; 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. (Fertil Steril 2006;85:1352– 8. 2006 by American Society for Reproductive Medicine.) Key Words: Acupuncture, clinical trial, embryo transfer, pregnancy rate
Some couples might choose to try complementary and alter-
controlled. Successful IVF and ET require optimal endome-
native medicines before they commence infertility treatment
trial receptivity at the time of implantation. Blood flow
or might choose to use it as an adjunct while undergoing
impedance in the uterine arteries as measured by transvagi-
infertility treatment. Acupuncture has long been used for
nal ultrasonography expressed as a resistance index, the
gynecological and obstetric problems, such as amenorrhea,
pulsatility index, is considered to be a useful method for
menorrhagia, morning sickness, and problems during labour
assessing uterine receptivity. In one small, uncontrolled
and delivery and is one complementary and alternative
study of electro-acupuncture, lower pulsatility index values
medicine considered by some women to assist with infertil-
ity treatment. Classic acupuncture refers to the insertion offine needles into specific points of the body. This treatment
There have been two randomized controlled trials of acu-
has a history dating back 2,500 years and treats illness by
puncture administered to women undergoing IVF In
restoring a balance in the flow of Qi (energy) in the human
the trial undertaken by Paulus et al. 160 healthy women
body. Acupuncture today involves modes of stimulation,
undergoing IVF or intracytoplasmic sperm injection (ICSI)
such as acupressure, transcutaneous electrical nerve stimu-
in Germany were randomized to receive acupuncture or no
lation, moxibustion, ear acupuncture, and the use of lasers.
acupuncture. Acupuncture was administered 25 minutes be-fore and after ET. Needles were inserted, and the Deqi
There have been few randomized controlled trials of acu-
needling sensation was obtained. Needles were retained for
puncture in the area of reproductive medicine. Two studies
25 minutes before and after the transfer, and acupuncture
of acupuncture for male infertility concluded that
points were used to move Chi and Blood and calm Chi.
acupuncture might be a useful treatment for men with poor
Treatment used a fixed combination of body and auricular
sperm density; however, these studies were small and un-
acupuncture points. A higher pregnancy rate was found inthe acupuncture group compared with the control group
Received September 15, 2005; revised and accepted December 10,
(42.5% vs. 26.3%, PϽ.03). However, bias might have arisen
from inadequate blinding, and insufficient details were re-
Supported by research funds from Repromed and the University of South
ported on the sample and effect size.
Reprint requests: Caroline Smith, Ph.D., The Australian Centre for Natural
Quintero evaluated the effectiveness of acupuncture as
Health and Wellness, 2 The Parade, Norwood, SA 5006, Australia(E-mail: caroline.smith@acnhw.com.au).
an adjunct to IVF. Seventeen women were randomized to
Fertility and Sterilityா Vol. 85, No. 5, May 2006
Copyright 2006 American Society for Reproductive Medicine, Published by Elsevier Inc.
receive acupuncture or sham acupuncture in a double-blind,
All women received three treatment sessions. The first
crossover trial; however, only seven women completed the
took place on day 9 of stimulating injections, and the second
study. Two women in each group achieved an ongoing
and third were immediately before and after ET. The time
pregnancy. Of the seven who crossed over to the other
from randomization to ET varied (depending on women’s
treatment arm, two women in the acupuncture group
response to stimulation); however, the mean length of time
achieved an ongoing pregnancy, compared with one in the
sham acupuncture group. Although the investigators found
A structured interview was used to determine the infertil-
that acupuncture significantly reduced the amount of gonad-
ity diagnosis from a traditional Chinese medicine (TCM)
otropin used (PϽ.05), no effect on the pregnancy rate was
perspective. This included a tongue examination, palpation
of the radial pulse, and a history of symptoms. Diagnosis
In two retrospective clinical studies Magarelli et al.
was made with the approach described in Maciocia The
explored the effects of acupuncture on IVF outcomes, using
patterns identified included kidney yang, kidney yin, blood
the protocols reported by Sterner-Victorin et al. and
deficiency, blood stagnation, damp, and Qi stagnation
Paulus et al. Magarelli et al. reported higher preg-
The acupuncture treatment protocol was based on the pro-
nancy rates (51% vs. 36%, PϽ.05) and lower miscarriage
tocol reported by Paulus et al. Two modifications were
rates (8% vs. 20%, PϽ.05) among those subjects receiving
made: an initial acupuncture treatment was administered
acupuncture compared with subjects in the comparison
before ET, and two acupuncture points were excluded (liver
group. The second study explored the influence of acupunc-
4 and governing vessel 20). Acupuncture was administered
ture stimulation among subjects described as “poor respond-
with point selection based on the TCM diagnosis. Points
ers to IVF.” Fifty-seven subjects received acupuncture, and
were needled bilaterally, and Acuglide (Helio Medical Sup-
94 received no acupuncture. A significant increase in the
plies, San Jose, CA) 0.18 mm ϫ 30 mm needles were
pregnancy rate was found for subjects receiving acupuncture
inserted with a guide tube to tissue level and stimulated
(53% vs. 38%, PϽ.01) Methodological limitations, such
manually to elicit the Deqi response (needling sensation).
as selection bias, might have influenced the study findings.
The number of needles inserted ranged from 6 to 14 for thefirst treatment and were 13 and 10 in the second and third
The research to date suggests that acupuncture might have
treatments, respectively. Needles were retained for 25 min-
a role in increasing pregnancy rates among women under-
utes per treatment. Two acupuncturists administered acu-
going IVF. There is clearly a need for a larger, pragmatic,
puncture treatments, with the majority being administered by
well-designed, randomized controlled trial to determine the
the primary acupuncture researcher (M.C.).
effectiveness of acupuncture on pregnancy rates amongwomen undergoing IVF. In this article we report the findings
For women in the control group, sham acupuncture points
from a randomized controlled trial evaluating the effect of
were used. These were located close to but not on the real
acupuncture on pregnancy rates for women undergoing ET.
acupuncture points. These included points located on thefoot anterior to the junction of the third and fourth metatar-
MATERIALS AND METHODS
sals, 4 cun (anatomical units) below and two fingerbreadthslateral to the knee, 2 cun above kidney 3 between the spleen
Women undergoing IVF or ICSI were recruited from Re-
and kidney meridians, 3 cun lateral to the midline level with
promed, The Reproductive Medicine Unit of The University
conception vessel 5 and 7, and 2 cun above the wrist crease
of Adelaide. Women with a planned ET were eligible for
between the lung and pericardium meridians.
inclusion; women previously randomized to the trial wereexcluded. Eligible women were identified by a research
The Streitberger (Asiamed, Pullach, Germany) placebo
nurse and were provided with information about the study.
needle (0.30 mm ϫ 30 mm) was used Because the tip
The trial also received media coverage, resulting in some
of the needle is blunted, skin penetration did not occur.
women self-referring to the study. Recruitment took place
Needles were manually “stimulated” by lifting and thrusting
between May 2003 and January 2005 and was approved by
the handle of the needle and by running a fingernail along the
the Women’s and Children’s Hospital’s research and ethics
handle. The acupuncturist held the placebo needle in place
with one hand while “stimulating” the needle with the otherhand. Each point was stimulated bilaterally for approxi-
Information on demographics, fertility history, and health
mately 3 minutes. Treatment duration was approximately 25
status was collected from subjects. Subjects were randomly
minutes. This noninvasive sham procedure was selected
allocated to a study group by selection of the next sealed
because it closely resembles a style of TCM acupuncture
envelope in the sequence for each stratification by number of
IVF cycles (first, second, third, fourth, fifth or more) andmaternal age (Ͻ35 years, 35–37 years, 38 to 39 years, and
The primary outcome was pregnancy, defined as the num-
Ն40 years). Randomization was in balanced, variable blocks
ber of couples achieving a clinical pregnancy (demonstration
of random size (2, 4, 6) prepared by a researcher not involved
of fetal heart activity on ultrasound scan). Secondary out-
in the trial. Women were allocated to receive treatment with
comes were implantation (defined as demonstration of a
acupuncture or with noninvasive sham acupuncture.
gestational sac on ultrasound scan and calculated as a per-
centage of the total embryos transferred), ongoing pregnancy
with the most common reasons for infertility attributed to
rate at 18 weeks, adverse events, and health status according
male infertility and tubal factors. The SF36 scores were
to the MOS 36 Short Form Health Survey (SF36)
lower for women in the study cohort on the social function,vitality, mental health, and emotional role function domains
Assessment of health status at the time of trial entry and
compared with the South Australian population; however,
after ET was made with the SF36. The SF36 is a multi-item
higher scores were seen on the physical function and phys-
scale measuring eight key health concepts: physical func-
ical role function domains compared with the South Austra-
tioning, role limitation due to physical health problems,
lian population No differences existed between the two
bodily pain, general health, vitality, social functioning, role
groups, suggesting that the randomization produced compa-
limitation due to emotional problems, and mental health
well-being. The possible score range is 0 –100, with 100being the best possible score. The posttreatment question-naire included an evaluation of any adverse effects and an
Pregnancy Outcome
assessment of which group subjects thought they were allo-
presents the primary and secondary outcomes. Grad-
ing was performed on all embryos with the score developedby Cummins et al. 1986 No difference in the grading of
The power analysis was based on data presented by Paulus
embryos was found between groups. The pregnancy rate,
et al. which reported a pregnancy rate of 42.5% in the
defined as fetal heart rate on ultrasound scan, was 31% in the
treatment group and 26% in the control group. For women
acupuncture group and 23% in the control group. For those
undergoing IVF at Repromed, the pregnancy rate was 30%
subjects receiving acupuncture, the odds of achieving a
this was used for the control group pregnancy
pregnancy was 1.5 higher than the control group but again
rate. A trial of 114 women per group would detect a differ-
did not reach statistical significance. The pregnancy rate was
ence between groups, assuming a power of 80%, two-sided
also not found to differ between groups among women aged
testing at the 5% significance level.
Ͻ35 years (50% vs. 33%, PϽ.11). The ongoing pregnancy
Data were analyzed with commercial software (Statistical
rate at 18 weeks was higher in the treatment group, but the
Package for the Social Sciences 11.5.1; SPSS, Chicago, IL).
difference was not statistically significant (28% vs. 18%).
The initial analysis examined the demographic and baseline
Subjects’ health status did not differ between groups.
characteristics of women randomized to the trial. Any dif-
Overall, however, the SF36 scores declined over the study
ferences in prognostic variables were taken into account in
intervention for the physical function, bodily pain, mental
subsequent analyses of the major outcome variables. The
main analyses undertook an “intention-to-treat” approachand compared differences in the primary study outcome
No difference was found between groups for other study
measure between the two groups. Comparisons were made
endpoints: number of oocytes retrieved (weighted mean dif-
between groups with 2 tests and by constructing relative
ference 0.84, 95% CI Ϫ0.64 to 2.32), fertilization rate (RR
risks (RRs); 95% confidence intervals (CIs) were based on
1.08, 95% CI 0.99 to 1.17), number of embryos transferred
differences between groups. Levels of significance were
(weighted mean difference 0.04, 95% CI Ϫ0.17 to 0.25), and
reported at PϽ.05 and PϽ.01.
biochemical pregnancy rate (RR 1.16, 95% CI 0.87 to 1.56). Side Effects
Of the 469 women assessed for eligibility, 215 declined to
Subjects were asked whether they had experienced any side
participate, and a small number were identified as being
effects after any of their treatments. These were categorized
ineligible Of the 228 subjects randomized, an
into positive and negative side effects. The most frequently
intention-to-treat analysis was performed on the primary
reported side effects were relaxation (51% vs. 67%), feeling
endpoint, pregnancy outcome. Thirty-six women (15%)
calm and peaceful (55% vs. 64%), or feeling energized (10%
were unable to comply with the treatment protocol because
vs. 12%). Subjects in the control group were more likely to
their cycle was cancelled or the ET was not undertaken.
report relaxation as a side effect of acupuncture (PϽ.05).
Seven women with a cancelled cycle were excluded from
To examine the effect of blinding, subjects were asked
which group they thought they had been allocated to. Twenty-
The mean age of women participating in the trial was 36
six subjects (11%) correctly guessed their group allocation
years The majority of subjects were receiving their
. Of the 16 subjects who correctly guessed that they
first fertility cycle, had a body mass index in the overweight
were in the treatment group, the reasons given included
category, were nonsmokers (90%), were currently drinking
feeling positive, calm, relaxed, or better (6 women); gut
alcohol (67%), were employed outside the home (85%), and
feeling (3); positive thinking (3); point location (e.g., time
had finished high school (83%). The majority of women
taken to locate the points, accuracy in placement of nee-
(69%) had not received acupuncture previously. More than
dles) (2); and 1 subject guessed her group allocation. Of
50% of women reported a history of infertility Ͼ2 years,
the 10 subjects who correctly guessed that they were in
RCT of acupuncture at ET Assessed for eligibility: 469 Randomized: 228
Cycle cancelled: 9 Pregnant: 8 Egg collection earlier than expected: 6 Egg collection after trial ceased: 2 Interpreter required: 1
Smith. RCT of acupuncture at ET. Fertil Steril 2006.
the control group, the reasons included the placement of
We examined whether previous experience of acupuncture
needles (e.g., focus on feet, placement of needles, and
would lead subjects to correctly identify their group allocation.
points used) (6); gut feeling (1); never had acupuncture
This analysis was based on 71 subjects (32 in the treatment
before (1); to avoid disappointment (1); and 1 subject
group and 39 in the control group). After the first treatment 73%
of subjects were unsure of their group allocation, and after thethird treatment 68% were unsure of their group allocation.
After the third treatment, a difference was found between
Participants with previous acupuncture experience were not
subjects’ perception of their group allocation (PϽ.05). Of the
more likely to be able to correctly guess their group allocation
24 subjects who correctly guessed that they were in the treat-
ment group, the reasons for their decision included feelinggood, relaxed, calm, positive, happier, warm, or better (12); thetreatment itself (e.g., points chosen, time to locate points, sense
DISCUSSION
of accuracy in the method or care of treatment administration)
The results from this study did not show a significant increase
(4); positive thinking (4); and other reasons (4). Of the 10
in the pregnancy rate between acupuncture and sham acupunc-
subjects who correctly guessed that they were in the control
ture groups; however, a smaller treatment effect can not be
group the reasons for their decision included a lack of sensa-
excluded. Our results suggest that acupuncture was safe for
tions (4); needle placement (3); and other reasons (3). Participant demographic and baseline characteristics. True acupuncture Noninvasive sham acupuncture Characteristic (n ؍ 110) (n ؍ 118) P Note: Values are mean (SD) or n (%). Smith. RCT of acupuncture at ET. Fertil Steril 2006.
The study might have been underpowered, with the sample size
egg collection, transfer of embryos of varying quality (the Paulus
calculation based on the effect size of the Paulus study. Our results
study transferred good-quality embryos only), and there were also
suggest a smaller treatment effect from acupuncture with a post
minor variations in treatment protocol.
hoc power effect of 27.4%, requiring a sample size of 484 subjects. Our study can not be directly compared with the Paulus study
Compared with other clinical trials of acupuncture, our
our study protocol included a first treatment administered before
study included a larger sample size. Other strengths of this
RCT of acupuncture at ET Primary and secondary outcomes by group. Noninvasive sham Risk ratio Pregnancy outcome acupuncture acupuncture P Grading of embryo 1 Implantation achieved (defined as demonstration of a gestational sac on ultrasound) Pregnancy achieved (all women)
(fetal heart on ultrasound) Pregnancy at 18 weeks SF36 mean (SD) Note: Values are n (%) or mean (SD). Smith. RCT of acupuncture at ET. Fertil Steril 2006.
trial include high compliance and low loss to follow-up;
The pregnancy rate for women in the control group of the
loss to follow-up was associated with the IVF cycle being
study was lower than the overall pregnancy rate at Re-
cancelled rather than their being any association with
promed. This might have been influenced by the age of
acceptability of the research. Both groups were also com-
subjects in the study and an overrepresentation of women
parable for sociodemographic characteristics and repro-
with poor pregnancy outcomes from previous IVF cycles.
Data from Repromed indicate that our study might have been
Subjects’ views on study group allocation. True acupuncture Noninvasive sham acupuncture Perceived group allocation (n ؍ 109) (n ؍ 118) P Smith. RCT of acupuncture at ET. Fertil Steril 2006.
underrepresented by younger women (46.5% vs. 38.6%) and
trial; Kristyn Willson (The University of Adelaide) and Ms. Kerena Eckert
overrepresented by women aged 35–39 years (30.9% vs.
(The University of South Australia) for their statistical support; and CarolHorn, acupuncturist.
35.0%) and Ͼ40 years (22.5% vs. 26.3%), who are lesslikely to have a positive outcome
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Acknowledgments: The authors thank all the women participating in the
trial; the staff at Repromed who contributed to the implementation of the
RCT of acupuncture at ET