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Acupuncture and in vitro fertilization: Critique of the evidence and application to
, Lara Rosenthal
Paciﬁc College of Oriental Medicine, 915 Broadway, New York, NY 10010, USA
Rosenthal Acupuncture, 39 West 14th St., Suite 201, New York, NY 10011, USA
In vitro fertilization
Women undergoing in vitro fertilization (IVF) commonly use adjunctive therapies to improve IVF
outcomes and reduce stress, anxiety and depression. Among these acupuncture is a popular choice.
Despite 40 clinical trials and 9 systematic reviews investigating the efﬁcacy of acupuncture for improving
IVF outcomes, evidence-based guidelines are difﬁcult to devise. The methodology used in the clinical
trials does not closely resemble the use of acupuncture in real world acupuncture clinics, limiting the
applicability of this research. Since many women undergoing IVF are currently using acupuncture there is
a pressing need for a broader understanding of the use of acupuncture for female infertility. This paper
offers a critical examination of the research on acupuncture and IVF and its limitations, details the
differences between these studies and real world clinical practice, and discusses Chinese medicine theory
for improving fertility and its possible scientiﬁc mechanisms within the context of clinical practice.
Ó2012 Elsevier Ltd. All rights reserved.
Infertility is a growing problem due to the choice to havechildren
later in life and the impact of environmental and lifestyle factors on
the both the female and male reproductive systems. Many perceive
in vitro fertilization (IVF) as the last remaining hope of being able to
achieve a successful pregnancy. However live birth rates from IVF
range from 31.9% for 35e37 year old women to 12.5% for 41e42 year
olds (for fresh non-donor egg; https://www.sartcorsonline.com/
rptCSR_PublicMultYear.aspx?ClinicPKID¼0). Consequently most
women need to undergo several IVF cycles to achieve a successful
pregnancy, and manywill not succeed without the use of donor eggs.
Due to the signiﬁcant emotional and ﬁnancial stress associated with
undergoing IVF many women seek out other therapies to reduce
stress levels and improve their IVF success rates. Acupuncture is
a common choice, partly because many randomized controlled trials
(RCTs) investigating the impact of acupuncture on IVF have been
undertaken. This data is accessible to patients and biomedical
practitioners and can be used as an endorsement for the use of
acupuncture to improve IVF success.
Close examination of the scientiﬁc evidence for the use of
acupuncture to improve IVF outcomes does not however lead to
simple conclusive statements. The inability to draw clear conclu-
sions about the efﬁcacy of acupuncture for many conditions is
a pervasive problem in acupuncture research
for several reasons.
Firstly, many studies have consistently shown that placebo
acupuncture is not inert and does indeed have a therapeutically
beneﬁcial effect. Studies comparing verum (real) and placebo
acupuncture often show that both are equally as efﬁcacious, but
more efﬁcacious than no treatment or conventional treatment
Secondly, often in acupuncture RCTs the acupuncture intervention
is therapeutically suboptimal due to factors such as excluding the
use of Chinese medicine diagnosis, lack of individualized treat-
ments for subjects, and inadequate acupuncture dosage. Conse-
quently it becomes very difﬁcult to demonstrate a statistically
signiﬁcant difference between a suboptimal verum intervention
and a therapeutically beneﬁcial placebo intervention. In the RCTs
investigating the impact of acupuncture on IVF outcomes this is
of several issues that render the research data difﬁcult to
interpret and use for referral purposes and to apply to clinical
practice. This paper offers a critical examination of the research on
acupuncture and IVF and its limitations, details the differences
between these studies and real world clinical practice, and
discusses Chinese medicine theory for improving fertility and its
possible scientiﬁc mechanisms within the context of clinical
*Corresponding author. Paciﬁc College of Oriental Medicine, 915 Broadway, New
York, NY 10010, USA. Tel.: þ1 212 982 3456x216; fax: þ1 212 982 6514.
E-mail addresses: banderson@paciﬁccollege.edu (B. Anderson), lara@
lararosenthal.com (L. Rosenthal).
Tel.: þ1 212 807 6797.
Contents lists available at SciVerse ScienceDirect
Complementary Therapies in Clinical Practice
journal homepage: www.elsevier.com/locate/ctcp
1744-3881/$ esee front matter Ó2012 Elsevier Ltd. All rights reserved.
Complementary Therapies in Clinical Practice 19 (2013) 1e5
Author's personal copy
2. The research evidence
More than 40 clinical trials investigating the impact of
acupuncture on IVF outcomes have been undertaken since 1999,
and nine systematic reviews have been published in an attempt to
make general conclusions from the data.
From all this work the
evidence is still unclear about whether a women should have
acupuncture as an adjunctive therapy for IVF.
reasons why this evidence is inconclusive relate to issues like the
heterogeneity of the studies with regard to hypotheses, subject
populations, study protocols, acupuncture interventions, controls,
and outcome measures. The majority of the systematic reviews did
not take these factors into consideration and were not able to
demonstrate signiﬁcant beneﬁts of acupuncture for IVF.
However, the systematic reviews that accounted for some of
these issues in their statistical analysis methodology have
demonstrated a clinically beneﬁcial effect of acupuncture for
3. Limitations of the research
Despite the many discussions about the research into
acupuncture and IVF, there has been little critique of the
acupuncture protocols and dosage that were used in the RCTs.
is not uncommon in acupuncture research,
and reﬂects the
possibility that acupuncture is often viewed as a standardized type
of intervention, where the protocol follows linear guidelines that
a trained clinician would recommend for the purposes of a clinical
trial. Most of the reviewers for the journals that publish these
studies and the biomedical readers are also largely unaware of how
acupuncture is practiced in real world settings. Consequently there
is an almost complete absence of appreciation that there are some
very signiﬁcant limitations in these trials related to the acupunc-
ture protocols and dosage.
3.1. Problem 1: lack of diagnosis & ﬁxed protocol bias
All of the acupuncture-IVF RCTs thus far have used the same
acupuncture points (a ﬁxed protocol) for all patients. In these
studies, an obese 35 year-old with polycystic ovarian syndrome
(PCOS) is given the same acupuncture protocol as a slender 42 year-
old with elevated follicle stimulating hormone (FSH) levels. This is
incongruent with a basic principle of Chinese medicine: that proper
diagnosis is the key to successful treatment. Most people outside
the ﬁeld of Chinese medicine do not realize that Chinese medicine
includes a complex diagnostic system, which determines
acupuncture point selection. To forgo diagnosis and use a ﬁxed
acupuncture protocol is somewhat analogous to an allopathic
physician treating everyone who complains of headaches with
Chinese medicine rests on the fundamental principle of indi-
vidualized treatments, whether this be acupuncture, Chinese herbs,
or any of the other acupuncture associated therapies.
asked many questions about their main complaint and medical
history and this information is combined with several very speciﬁc
observations and palpation techniques to permit the practitioner to
formulate a diagnosis. The process of diagnosing is within the
context of Chinese medicine theory, which draws together many
different signs and symptoms to reach a summation of the overall
patient condition. Patients with the same Chinese medicine diag-
nosis may have many different biomedical diagnoses and clinical
presentations, and be treated differently in terms of acupuncture
point protocols and Chinese herbal medicine formulas. Conversely,
patients with the same biomedical diagnosis (e.g., PCOS, endome-
triosis, low ovarian reserve etc.) may have different Chinese
medicine diagnoses and would therefore receive different treat-
ments. It is the Chinese medicine diagnosis that determines correct
treatment, not the biomedical diagnosis. It is this aspect of Chinese
medicine that is least understood by other medical professionals
and the lay public. As with biomedicine, expert clinicians are often
revered for their capacity to accurately diagnose and select the
It is difﬁcult for an RCT to accommodate this aspect of Chinese
medicine. What happens in an RCT is that subjects are selected
according to a biomedical diagnostic category, in this case infer-
tility. Chinese medicine experts are asked to devise an acupuncture
protocol that would be approximately appropriate for the average
patient, which generally consists of the most commonly used
points. Indeed, some researchers have surveyed acupuncturists to
ﬁnd out what are the most commonly used acupuncture protocols
These average treatments are highly likely to give
suboptimal clinical outcomes because they are not devised specif-
ically for any of the subjects in the trial.
More recently new methodology for conducting acupuncture
RCTs has been developed using the Delphi approach.
In such trials
a panel of experts are asked to devise a ﬂow chart of questions that
permit standardization of diagnostic methodology between
different acupuncturists. Acupuncture points that must be used for
each diagnostic category and additional optional acupuncture
points are stipulated allowing the acupuncturist to individualize
the treatment for each subject. None of the acupuncture-IVF RCTs
have used this improved methodology.
3.2. Problem 2: acupuncture dosage
The most commonly tested protocol for acupuncture-IVF RCTs is
the so called ‘Paulus protocol’, modeled on the protocol of Paulus
who demonstrated that subjects that received acupuncture
25 min before and after embryo transfer (ET) had clinical pregnancy
rates of 42.5% compared to the controls who did not receive
acupuncture and had rates of 26.3%. This protocol of acupuncture
25 min before and after ET became the accepted protocol for
acupuncture in an IVF cycle, and many women undergoing IVF
request just this and/or are recommended by fertility clinics to get
this treatment regime. Somehow this protocol, even though there
was only one successful RCTat the time, became the gold standard.
Even more surprising is the fact that many attempts to repeat this
outcome have not been successful.
Part of the reason for the inability to repeat this outcomes is
related to the fact that later studies included a placebo control and
could not demonstrate any statistical difference between the
verum and placebo treatments. As discussed earlier, placebo
acupuncture has been repeatedly shown to not be inert, making
these comparisons problematic.
However, other important
factors could account for this, including ﬁxed protocol bias (all
subjects receiving the same treatment, as discussed above) and
Acupuncture dosage consists of two components: the number of
points needled in a single treatment, and the total number of
treatments that the patient receives. Although it is possible for
patients to experience beneﬁcial effects from one or two treat-
ments and/or just the stimulation of one or two points, this is more
the exception, rather than the rule. The nature and duration of the
condition is a very signiﬁcant determining factor as to the likeli-
hood that just one or two treatments will be effective. Acute
conditions of short duration in younger patients are most likely to
respond to small dosages of acupuncture. Conversely chronic
conditions of long-term duration need larger dosages of acupunc-
ture, especially in patients with multiple health issues. Generally
speaking a clinically valid dosage of acupuncture usually includes
B. Anderson, L. Rosenthal / Complementary Therapies in Clinical Practice 19 (2013) 1e52
Author's personal copy
four to ten (or more) acupuncture points given in each of six (or
more) acupuncture treatments.
As mentioned, most acupuncture-IVF RCTs used two acupunc-
ture treatments e25 min before and after ET. Some of the RCTs did
add additional treatments, but most only included one or two
additional treatments within the IVF cycle. This is a very low dosage
of acupuncture. The number of points used in each treatment was
adequate, but the total number of treatments was sub-optimal.
What compounds this issue is the fact that infertility is a complex
medical issue, often associated with either signiﬁcant previous
gynecological issues/pathology (e.g., ﬁbroids, endometriosis, fallo-
pian tube adhesions, autoimmune disease etc.) and/or with
patients whose age (often late 30s/early 40s) brings signiﬁcant
additional physiological challenges. It is therefore debatable
whether a couple of acupuncture treatments using ﬁxed protocols
will have a signiﬁcant impact on the outcome of an IVF cycle.
4. Mechanistic considerations
To be more realistic in our assessment and expectations of
acupuncture when used in conjunction with IVF we need to
consider possible mechanisms by which acupuncture could
improve IVF outcomes. Several have been proposed: improving
blood circulation to the ovaries and uterus; neuro-hormonal
modulation; cytokine modulation and improving implantation;
and reducing stress, anxiety and depression.
nisms can be thought of in terms of short-term and longer-term
beneﬁts, and correspondingly the likelihood to beneﬁt during
a single IVF cycle or more focused on longer-term beneﬁts for either
assisted or natural conception.
4.1. Treatment duration
Women that seek out acupuncture during IVF generally fall into
two categories: those that only seek treatment during an IVF cycle
(and often only receive something similar to the Paulus protocol e
25 min before and after ET); and those that seek out Chinese
medicine to help with infertility over a longer time period. In the
latter category acupuncture is used before,during, and between IVF
cycles to create an improvement in both reproductive and overall
health and thereby increase the likelihood that conception could
occur either naturally or through the use of assisted reproductive
4.2. Short-term treatment
Patients that receive a small number of treatments during an IVF
cycle are most likely beneﬁting from acupuncture due to the
improved blood circulation to the uterus and ovaries, and
by facilitating lowered stress levels and improved relaxation.
This effect of acupuncture has been observed in several
However it is also possible that if women have
not had acupuncture before, the treatment could raise stress levels,
as was demonstrated in one clinical trial.
This is likely due to the
concern around an unknown procedure involving needles that is
likely to engender some degree of pain. So advising women to
receive acupuncture before and after ET should take into consid-
eration their perceptions about acupuncture and the possibility
that this may raise stress levels. From this perspective better advice
would seem to be suggesting acupuncture treatments before an IVF
cycle to determine if the patient is comfortable with the inter-
vention. In addition, the Paulus protocol model of using acupunc-
ture 25 min before and after ET may be introducing new stresses
that reduce efﬁcacy. One study showed that when patients were
rushing through Seattle, WA, trafﬁc trying to get their acupuncture
25 min before and after the ET, the pregnancy rates were lower
than without acupuncture.
Again from the perspective of
reducing stress levels and improving relaxation, this could be
Important additional short-term beneﬁts are to ameliorate the
side effects of IVF medications. Hormonal stimulation of the ovaries
to produce multiple follicles is often associated with signiﬁcant
abdominal bloating and discomfort. The associated increased
estrogen levels also often leads to ﬂuid retention, headaches, and
mood swings. A fundamental effect of acupuncture is to reduce
stagnation both energetically and in terms of facilitating the
reduction of ﬂuid, gas, and digestive accumulations. This impact
can bring signiﬁcant amelioration of IVF medication side effects
including ovarian hyperstimulation syndrome.
4.3. Longer-term treatment
Patients that seek out longer-term treatment often want to
improve their general state of health before starting IVF to increase
their chances of success and reduce the required number of IVF
cycles. Other patients begin by just seeking out acupuncture during
an IVF cycle (before and after ET) and ﬁnd that they notice beneﬁts
from it and then decide to continue regular treatment in subse-
quent IVF cycles and/or into their pregnancy. Some patients decide
to take breaks between IVF cycles and often will continue their
acupuncture treatments with the goal of improving their overall
and reproductive health to get ready for future IVF cycles or to try to
conceive naturally. In these longer treatment situations, a different
spectrum of mechanistic possibilities becomes evident.
Acupuncture treatment may be beneﬁcial for preexisting
gynecological conditions that can be a signiﬁcant factor preventing
conception or rendering patients ineligible for IVF. Patients and
biomedical practitioners are often unaware that acupuncture can
address a wide variety of gynecological conditions, an area very
well documented in the classical and modern Chinese medicine
Some examples of conditions that can be treated
with acupuncture and are commonly seen in women undergoing
IVF include: endometriosis, ﬁbroids, PCOS, elevated FSH, adhesions,
and ovarian cysts. Acupuncture is unlikely to resolve advanced
cases of gynecological pathology where surgery may be necessary.
However, in such cases treatment can often alleviate symptoms,
work synergistically with biomedical treatments, and facilitate
successful conception. Mechanistic studies have demonstrated that
acupuncture can induce regular ovulation in women diagnosed
through modulation of endogenous regulatory
systems, including the sympathetic nervous system, the endocrine
system and the neuroendocrine system.
Patients receiving longer-term treatment also beneﬁt from the
effects of regular acupuncture on their other health issues. Chinese
medicine is holistic in the sense that treatment beneﬁts the whole
body and addresses all imbalances. This is why acupuncture clinical
trials that have included quality of life measurements often show
that patients receiving acupuncture experience a wide range of
beneﬁts and often have a general improvement in their feelings of
even if their main complaint did not signiﬁ-
cantly improve. This is attributable to the acupuncture treatment
and also to lifestyle modiﬁcations that acupuncturists routinely
recommend. For fertility patients important lifestyle recommen-
dations often include dietary changes consistent with their Chinese
medicine diagnosis, increasing sleep duration and quality, ﬁnding
appropriate forms and intensity of exercise, incorporating relaxa-
tion techniques, and reducing excessive work hours.
Longer-term treatment also provides for signiﬁcant psycho-
emotional factors to come into play. Patients undergoing IVF are
faced with understanding a complex medical procedure with many
B. Anderson, L. Rosenthal / Complementary Therapies in Clinical Practice 19 (2013) 1e53
Author's personal copy
unknown outcomes. Patients are often very knowledgeable about
the process and experience considerable anxiety over their prog-
ress and its implications for their ability to conceive. Visiting their
acupuncturist at least once per week, and usually twice per week
during the stimulation phase and ET, provides an opportunity to
discuss progress, choices, and outcome possibilities with an expe-
rienced clinician who can provide emotional support and infor-
mation. For many women going through IVF, emotional endurance
and retaining a sense of hope are central to eventual success. Their
acupuncturist can become like a coach who partners with them
through the arduous journey. All of this reduces stress and imparts
all the physiological and psychological beneﬁts associated with
5. Signiﬁcance of the research to clinical practice
Despite the fact that the Paulus protocol has been accepted as
the gold standard for acupuncture practice during an IVF cycle, we
really do not know if this is the most optimal approach to impart
short-term beneﬁts. What becomes especially difﬁcult from
a practical standpoint in clinical practice is how critical it is for
treatments to be given 25 min before and after ET. This has never
been tested against any other time frame, leading many patients
to insist on trying to have acupuncture within this narrow time
frame and likely causing undue stress that could be counterpro-
ductive. For this reason, many acupuncturists will recommend
24 h before and after ET to facilitate scheduling and reduce stress.
If the primary short-term beneﬁts are to improve blood ﬂow to
the reproductive system and reduce stress, then it would seem
logical that treatment throughout the entire cycle would also be
beneﬁcial, especially during the stimulation phase. Increased
blood circulation to the ovaries during hormonal stimulation
could potentially improve follicular development and reduce
medication side effects. For this reason acupuncturists may also
recommend a treatment 24 h before egg retrieval, and many
recommend twice weekly treatments during the whole IVF cycle
up until ET.
The question of whether acupuncture is more beneﬁcial if
undertaken for longer durations both before and throughout an IVF
cycle remains untested and unanswered. However many women
(and quite possibly the majority) who have acupuncture in
conjunction with IVF do more than just before and after ET. Most
common is acupuncture throughout the entire IVF cycle, often
twice per week, and then into pregnancy, or prior to and
throughout the next IVF cycle. Considering the possible mecha-
nisms by which acupuncture may beneﬁt women trying to
conceive (as discussed above), especially the modulation of
endogenous regulatory systems, a logical argument can be
proposed in support of the use of acupuncture before, during and
between IVF cycles. If circumstances permit it is most advisable to
start acupuncture (and Chinese herbal medicine) 3e6 months
before undergoing ART. This is discussed below in the section on
Chinese herbal medicine, which is often seen to signiﬁcantly
enhance the effect of acupuncture.
When acupuncture is performed throughout the entire IVF cycle
and into pregnancy, it is important to carefully consider using
acupuncture points that are contraindicated during pregnancy
following ET. This decision should be made based on the patient’s
Chinese medicine diagnosis. Many of the acupuncture-IVF RCTs
have included contraindicated points following ET.
One such trial,
showed that the group that received an additional acupuncture
treatment 2 days post ET
had a greater early pregnancy loss. This
is an aspect of the current research that requires further
6. Chinese herbal medicine
Chinese Herbal medicine is used extensively to treat a wide
range of gynecological conditions including both female and male
However there is relatively little research available
to make evidence informed decisions about the use of Chinese
herbal medicine for treating infertility. A recent systematic
investigating the effect of Chinese herbal medicine upon
pregnancy rates compared with ART intervention showed that
Chinese herbal medicine improved pregnancy rates 2-fold within
a 4 month period compared with fertility drug therapy or IVF. A
showed that the combination of Chinese
herbal medicine with intrauterine insemination (IUI) resulted in
statistically signiﬁcant higher pregnancy and live birth rates as
compared to IUI alone. A recent systematic review has also
demonstrated the effectiveness of Chinese herbal medicine for
Combining Chinese herbal medicine with fertility medications
must be done with caution because Chinese herbs can potentiate or
negate the effect of drugs,
and be potentially unsafe or detri-
mental. There are differing opinions within the Chinese medicine
community about the use of herbs together with IVF drugs. Some
advocate the use of Chinese herbs
while others recommend herbs
only during times when women are not taking any fertility medi-
cations (before starting IVF and between IVF cycles). Despite the
relatively small amount of evidence in support of the efﬁcacy of
Chinese herbs for improving the success of ART, some additional
guidelines for clinical practice based on experience and mecha-
nistic considerations are given below.
When there is signiﬁcant preexisting gynecological pathology
and/or the patient is in her late thirties/early forties long-term
treatment with acupuncture and/or Chinese herbal medicine is
ideally at least 3e6 months. The 3e6 month duration has been
observed clinically to be the time required to see beneﬁcial
outcomes in terms of parameters such as better follicular response
to gonadotropin stimulation during IVF and signiﬁcant lowering of
FSH levels. The effect upon follicular response may be related to the
length of time it takes for a secondary follicle to develop into
a dominant follicle, which is approximately 3 months.
months of treatment may be undertaken before (if inclusive of
Chinese herbal medicine) or in conjunction with ART (if acupunc-
ture alone). Delaying ART to include Chinese herbal medicine
treatment needs to be carefully considered in relation to the age of
the patient and the potential disadvantages of delaying ART
Shorter duration treatment with Chinese herbal medicine can
also be quite effective, especially in cases of milder pathology of
recent onset. This is relevant for women who have breaks between
IVF cycles, which may be opportune times to take Chinese herbal
medicine. A common situation is where a woman has been through
one or more unsuccessful IVF cycles and then has elevated FSH,
such that she is not able to start another cycle. This provides an
opportunity to add Chinese herbal medicine to her treatment
regime, which is often more successful in reducing FSH levels than
acupuncture treatment alone. Women who have a history of
recurrent miscarriage following IVF also often beneﬁt from even
brief periods of Chinese herbal medicine treatment, which again is
usually better than acupuncture alone.
There is a pressing need for further research into the effective-
ness of acupuncture for improving IVF outcomes. Such research
needs to examine acupuncture treatment within a context that
more closely resembles real world clinical practice. Given that
B. Anderson, L. Rosenthal / Complementary Therapies in Clinical Practice 19 (2013) 1e54
Author's personal copy
many women undergoing IVF are utilizing acupuncture and
deriving beneﬁts in addition to improving IVF outcomes,
research does not adequately inform patients or clinicians. Possible
mechanisms by which acupuncture may treat gynecological
conditions requires further exploration, and may well represent
general mechanisms by which acupuncture modulates physiology
and treats a broad spectrum of pathology.
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