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The impact of acupuncture on IVF success rates: A
randomised controlled trial
K. Gillerman, A.
AQ1 Kulkarni, A. Shah, A. Gudi, Roy Homburg
Homerton Fertility Centre, Homerton
AQ2 University Hospital, Homerton Row, Hackney, London E9 6SR, UK
Abstract Background: Clinical trials to assess the benefits of acupuncture on in vitro fertilisation (IVF) treatment have
differed in study design, protocol, outcome measures and commercial bias. This heterogeneity has
precluded any firm conclusion regarding the efficacy, or otherwise, of acupuncture in this field. To address
this, 15 international acupuncturists with experience in treating women during IVF participated in Delphi
questionnaires and reached a consensus protocol to be used in future research. We were among the first to
adopt this newly agreed standard protocol. The aim of this study was to address whether the agreed
acupuncture consensus protocol is beneficial for IVF outcomes and may be offered to women undergoing
IVF. Methods: An randomised controlled trial, in which 157 women were randomised to receive either
acupuncture treatment three times in the treatment cycle in addition to our standard IVF protocol (n=79)
or no acupuncture treatment (n=78) in their first or second IVF cycle. They were between 23 and 43 years
with body mass index below 30. The study group (n=79) received acupuncture based on the Delphi
consensus protocol, between days 6 and 8 of ovarian stimulation, and twice on the day of embryo transfer,
before and after transfer. The IVF practitioner was blinded to the randomisation. The primary end point
was live birth. Results: Fifteen out of 79 women in the intervention group withdrew from the study
compared to 9/78 women from the control group (P<0.001). A per-protocol analysis revealed that the rate
of live births (27/64, 42% vs. 11/69, 15.94%, P=0.001) and positive pregnancy tests (34/64, 53% vs. 19/69,
27.53%, P=0.013) were significantly higher in the acupuncture group compared with the control group.
Conclusion: The results of this study imply that acupuncture may be offered as a possible method of
improving IVF outcome. This study followed a widely approved consensus protocol hoping to settle
disagreement in the literature and resolve previous disparity.
Trial Registration: ClinicalTrials NCT02683967.
Keywords: acupuncture, IVF, live birth, pregnancy rate
Address for correspondence: Roy Homburg, Homerton Fertility Centre, Homerton University Hospital,Homerton Row, Hackney, London E9 6SR, UK.
E-mail: royhomburg@gmail.com
BACKGROUND
Acupuncture is an ancient Chinese system of diagnosis
and treatment which is said to help a variety of conditions
including infertility. The delicate underlying mechanisms
of acupuncture have been explained and described in the
traditional Chinese medicine (TCM) language and in later
years its possible physiological background has been
repeatedly discussed.
This is an open access journal, and articles are distributed under the terms of the
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others to remix, tweak, and build upon the work non-commercially, as long as
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Access this article online
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DOI:
10.4103/fsr.fsr_37_18
For reprints contact: reprints@medknow.com
How to cite this article: Gillerman K, Kulkarni A, Shah A, Gudi A, Homburg
R. The impact of acupuncture on IVF success rates: A randomised
controlled trial. Fertil Sci Res 2019;xx:xx.
Original Article
FSR_37_18R1_OA
© 2019 Fertility Science and Research | Published by Wolters Kluwer - Medknow 1
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There are increasing numbers of women reporting delays
in conceiving. For the past 10 years, the number of
assisted reproductive technology (ART) procedures has
increased significantly despite the often great personal
costs of ART. Over the last 2 decades, the use of
acupuncture in female infertility as an adjuvant to
conventional treatment in ART has been widely used.
In vitro fertilisation (IVF) is associated with significant
stress, which affects not only the outcome of the
treatment but also the general well-being of the couple
undergoing the procedure. There is a growing body of
evidence that acupuncture reduces the stress of IVF and
also improves its success rate.
[1,2]
The first clinical trial
which suggested the efficacy of acupuncture in improving
the clinical pregnancy rate in IVF was published in 1999.
[3]
In spite of dozens of clinical trials and reviews which
aimed to assess investigating the benefits of acupuncture
in various aspects of IVF, they all differ significantly in
their study design, acupuncture timing, protocol and final
outcome measures.
[4-6]
This lack of standardisation and
extreme heterogeneity prevent us reaching a conclusion
whether acupuncture is beneficial to IVF treatments, or
otherwise, and should be offered to women undergoing
IVF. For that reason, an adequately designed and
conducted randomised controlled trial (RCT) in
acupuncture is needed.
To address this,15 international acupuncturists experienced
in treating women with acupuncture during IVF
participated in three rounds of Delphi questionnaires
and reached a consensus for the use of TCM manual
acupuncture, with 86% agreement. Such consensus
offers guidance for further future research. We were
among the first to adopt and use the consensus protocol.
Recently, we were pleased to find out that a study
[7]
also
realized the importance of a standard protocol and used the
Delphi consensus in their trial. Our study presents a single-
centre RCT and its aims and objectives were to compare
acupuncture and IVF with IVF alone.
METHODS
The objective was to determine the clinical effectiveness
of acupuncture in improving live birth and pregnancy
rates in women undergoing IVF.
Study setting
This study was a single-centre RCT in a IVF centre of a
public university. As our study was a part of the patient’s
standard IVF care, the acupuncture sessions were
performed at the fertility centre so as to accommodate
the patient schedule.
Inclusion criteria
This included women under the age of 43 years with a
body mass index <30 undergoing their first or second
IVF cycle (with a fresh or frozen/thawed embryo
replacement).
Exclusion criteria
Women receiving donor eggs, body mass index ≥30 or
currently having acupuncture or any other form of
complementary and alternative medicine or having a
contraindication to acupuncture, such as those with
human immunodeficiency virus or hepatitis C positive,
were excluded.
PATIENTS
Eligible couples AQ3
were identified from the clinic database if
they fulfilled the inclusion criteria. Written informed
consent was obtained before randomisation. Ethical
approval was given by a local ethics committee (13/
LO/1356) and the trial was registered (NCT02683967).
Randomisation
Computer randomisation was performed by an
independent worker in blocks of 10 and distributed in
individual, consecutively numbered opaque envelopes
immediately before the start of the IVF cycle following
signed consent. Randomisation allocated couples to either
the acupuncture group to receive acupuncture three times
during the cycle of IVF (n=79) or to the control group in
which couples received only IVF but no acupuncture
(n=78) [Figure 1]. (To avoid disappointment, the patients
randomised to the control group were offered three free
acupuncture sessions to be used in a following IVF cycle
should they be unsuccessful.)
Power calculation
We anticipated a study participation rate of 50% of those
eligible. On the basis of a predicted live birth rate of 20%
in the controls and 40% in the acupuncture group, 79
patients were required in each group for a power of 80%
and a significance level of P<0.001.
Acupuncture protocol (based on Delphi consensus)
The first acupuncture treatment was manually administered
between days 6 and 8 of the stimulated cycle in a style
according to TCM. Chosen points during the stimulation
phase include core points ST29, CV4, CV6, SP6, SP10 and
up to five individualised additional points based on TCM
pattern differentiation. Most of the point locations were
mainly in the lower abdomen and some inthe legs and hands
(all performed bilaterally).
Gillerman, et al.: Acupuncture and IVF
2Fertility Science and Research | Vol xx | Issue xx | Month 2019
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The duration of needling was approximately 25 minutes
using disposable stainless-steel acupuncture needles
(0.25 × 30 mm and 0.20 × 40 mm, Phoenix Medical,
Chelmsford, UK). The needles were inserted to a depth
varying from 10 ± 5 to 25 ± 5 mm at the acupoints
depending on the location and patient’s physical figure.
The practitioner (with 20 years of experience) maintained
Deqi which is a needling sensation interpreted as a flow of Qi
or the arrival of energy. This additional manual stimulation
was performed during the initial treatment on days 6 to 8
and during the pre-embryo transfer treatment. The second
and third treatments were performed on the day of embryo
transfer −before and immediately after embryo transfer.
Points used for pre-transfer included SP8, SP10,LR3, ST29,
CV4 and one selected from HT7/PC6/YinTang
(depending on presentation of women). Points used
post-transfer included GV20, KD3, ST36, SP6 and PC6.
Points Shenmen (auricular) and Zigong (lower abdomen)
were used on the day of ET
AQ4 .
An acupuncture protocol describing the timing and
acupoints for each session is stored with all
acupuncture equipment so that the practitioner can
check and ensure consistency and accuracy during the
treatment. The checklist of the detailed information of the
procedure is attached in Appendix 1.
Acupuncture points
Points on the innervations area to the uterus and ovaries
in the abdominal muscles and in the leg were utilised as
well as fertility defined points thought to improve blood
circulation to the ovaries and the blood flow to the uterus
and hence thought to improve follicular and endometrial
responsiveness. Additional points were performed to
manage stress.
IVF protocols
The IVF protocol that was used was decided by the
attending clinician according to the departmental
guidelines. Basically, predicted low and normal
responders received long GnRH agonist protocols with
a starting FSH dose of 225 to 300 IU, whereas women
predicted to be high responders received a GnRH
antagonist protocol and a starting dose of FSH of 150
IU. Frozen/thawed embryos were replaced in an embryo
replacement cycle applying the use of estradiol 2 mg three
times daily and then vaginal progesterone starting the day
before replacement.
Analysis
The results were analysed on an intention-to-treat (ITT)
and per-protocol basis. The results were stratified
according to age, duration of infertility, type of cycle
Figure 1: Consort diagram.
Gillerman, et al.: Acupuncture and IVF
Fertility Science and Research | Vol xx | Issue xx | Month 2019 3
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(fresh or frozen), first or second IVF cycle and type of
infertility [Table 1]. All results were faithfully recorded on
a clinical research file designed especially for the purpose
and, when completed, transferred to SPSS (Statistical
Package for the Social Sciences
AQ5 ).
Statistical analysis
A Chi-squared test and t-test were used to determine the
differences between the acupuncture and control groups
and compare the two arms of the study for both an ITT
and per-protocol analysis. Chi-squared test was used for
the secondary end points wherever applicable. As the
dependent variables were categorical and not quantitative,
we used these analysis methods.
RESULTS
One hundred fifty-seven women were randomly allocated
to the intervention and the control groups. The
intervention group (n=79) was programmed for full
acupuncture treatment, whereas the control group
(n=78) did not receive any acupuncture treatment.
Either fresh or frozen/thawed embryo cycles were
included. Of the 79 women allocated to the
intervention group, 15 withdrew from the study (did
not do the acupuncture treatment at all, did not finish
the full treatment or had cancelled cycles), compared to
nine women from the control group [Figure 1]. The
number of dropouts in the acupuncture and the
Appendix 1: Checklist for items in STRICTA 2010
Item Detail Page
number
1. Acupuncture rationale(Explanations and
examples)
1a) Style of acupuncture (e.g. Traditional Chinese Medicine, Japanese, Korean, Western
medical, Five Element, ear acupuncture, etc)
3,6
1b) Reasoning for treatment provided, based on historical context, literature sources, and/or
consensus methods, with references where appropriate
3
1c) Extent to which treatment was varied 6
2. Details of needling(Explanations and
examples)
2a) Number of needle insertions per subject per session (mean and range where relevant) 6
2b) Names (or location if no standard name) of points used (uni/bilateral) 6,7
2c) Depth of insertion, based on a specified unit of measurement, or on a particular tissue
level
6
2d) Response sought (e.g. de qi or muscle twitch response) 6
2e) Needle stimulation (e.g. manual, electrical) 6
2f) Needle retention time 6
2g) Needle type (diameter, length, and manufacturer or material) 6
3. Treatment regimen(Explanations and
examples)
3a) Number of treatment sessions 6
3b) Frequency and duration of treatment sessions 6
4. Other components of treatment
(Explanations and examples)
4a) Details of other interventions administered to the acupuncture group (e.g. moxibustion,
cupping, herbs, exercises, lifestyle advice)
4b) Setting and context of treatment, including instructions to practitioners, and information
and explanations to patients
5
5. Practitioner background(Explanations and
examples)
5) Description of participating acupuncturists (qualification or professional affiliation, years in
acupuncture practice, other relevant experience)
6
6. Control or comparator interventions
(Explanations and examples)
6a) Rationale for the control or comparator in the context of the research question, with
sources that justify this choice
4
6b) Precise description of the control or comparator. If sham acupuncture or any other type
of acupuncture-like control is used, provide details as for Items 1 to 3 above.
5,7
Table 1: Basal data of acupuncture and control groups (per-protocol analysis)
AcupunctureN=64 ControlN=69 Significance
Mean (SD) Mean (SD) P
Age 32.88 (17.160) 34.93 (4.142) 0.337
Attempt 1.25 (0.508) 1.25 (0.715) 0.974
BMI 24.08 (3.375) 22.97 (15.976) 0.6
AFC 11.96 (23.481) 14.03 (14.03) 0.524
AMH (pmol/L) 18.04 (15.419) 16.40 (11.152) 0.488
No. of oocytes 11.75 (6.702) 10.06 (5.888) 0.124
EmbryosTransferred 1.56 (0.500) 1.67 (0.475) 0.221
%%P
Diagnosis 10.9% anovulation50% unexplained17.2% tubal6.2%
male1.6% endometriosis10.9% DOR
14.5% anovulation34.8% unexplained27.5% tubal15.9%
male0% endometriosis5.8% DOR
0.164
Protocol 44.1% agonist44.1% antagonist11.8% frozen 56.3% agonist35.2% antagonist8.5% frozen 0.349
Cycle 57.8% fresh42.2% frozen 62.3% fresh37.7 % frozen 0.596
AFC =antral follicle count, AMH =anti-Mullerian hormone, BMI =body mass index, DOR =diminished ovarian reserve.
Gillerman, et al.: Acupuncture and IVF
4Fertility Science and Research | Vol xx | Issue xx | Month 2019
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control group was significantly different (X
2
(1) =12.67, P
<0.001). A set of Chi-square tests of independence was
performed for both ITT and per-protocol analysis. The
ITT analysis showed that rates of live birth 27/79
(34.60%) and positive pregnancy tests 35/79 (44.30%)
were significantly higher in the acupuncture group
compared to the control group in which rates of live
birth were 11/78 (14.10%) and rates of positive pregnancy
tests were 19/78 (24.36%), P<0.001.
After excluding the dropouts from each group, a set of
Chi-square tests of independence was performed to
examine any differences between the acupuncture and
the control groups (per protocol) regarding basal
parameters [Table 1] and rates of live births,
miscarriages and positive pregnancy tests [Table 2].
The rates of live births (X
2
(1) =11.207, P=0 .001)
and positive pregnancy tests (X
2
(1) =6.237, P=0.013)
were found to be significantly higher in the acupuncture
group compared to the control group [Table 2]. No
statistically significant difference was found between
the groups in the miscarriage rates. There were no
significant differences in the results of fresh and frozen
cycles.
Safety and adverse effects
Acupuncture was performed based on professional
standards of practice using disposable needles. There
were no adverse events; on the contrary, patients from
the acupuncture group filled a quality-of-life
questionnaire and reported better quality of life and
relief from the IVF symptoms after they had had the
acupuncture sessions.
DISCUSSION
In this study, we have shown that rates of live birth and
positive pregnancy tests are significantly higher following
a consensus acupuncture protocol for women undergoing
IVF treatment compared with a control group.
Acupuncture has been extensively studied to examine its
effect on live birth and pregnancy rates. However, debate
continues as different studies have used different
protocols and their outcomes are contradictory. Hence,
even with such extensive literature, no definitive
conclusions regarding the value of acupuncture for IVF
can be made. Analysing all studies so far with live birth as
the primary outcome, different timings of acupuncture
could be identified. One of the first RCTs was published
in 1999 suggesting that acupuncture improved the clinical
pregnancy rate in IVF.
[3]
In this study, 157 women
undergoing IVF were randomised to acupuncture or
controls before oocyte retrieval and a significantly
higher pregnancy rate was observed in the acupuncture
group. Since the RCT by Paulus et al.,
[8]
in which 25
minutes of acupuncture was performed before and after
embryo transfer with improved pregnancy rates in the
acupuncture group, several RCTs
[9-14]
and observational
studies
[15,16]
have been conducted to assess the effect of
acupuncture on live birth when applied around the time of
embryo transfer. However, the results have been highly
contradictory. While some RCTs showed improved
pregnancy rates,
[10,13,14]
others showed no difference
between the acupuncture and the control groups.
[9,11,12]
Another RCT divided women <40 years undergoing
IVF/intracytoplasmic sperm injection into two groups
and performed acupuncture in one group in three
sessions (each lasting for 25 minutes), with the first
session of 5 to 7 days before oocyte aspiration, second
session of 2 to 3 days before egg retrieval and third session
shortly after embryo transfer. The control group had no
intervention. The number of women recruited in this
preliminary study was limited; however, they concluded
that their results did not support a positive effect of
acupuncture on IVF.
[17]
Another negative RCT
randomised 228 women into an acupuncture group
where they received acupuncture on day 9 of ovarian
stimulation, before and after embryo transfer and a
placebo group with non-invasive sham acupuncture.
They could not show any significant difference in the
pregnancy rates between the two groups.
[18]
Assessing subjective outcome AQ6
like pain, anxiety and
general well-being, normally suggests the use of
appropriate placebo controls as otherwise the results
may be biased by the women’s pre-judgement about
the effect of acupuncture. However, while assessing
objective outcomes like pregnancy rates, they are
unlikely to be affected by the woman’s expectations
and hence use of placebo control is questioned.
[19]
Furthermore, the method of non-penetrating needle
technique (Streitberger) cannot be considered as a
placebo as it has an acupressure effect, hence one must
remember that ‘inert’placebos are not inert and the
validity of such trials is questionable.
[18]
After due
consideration and heeding the advice of Manheimer,
[19]
we decided that no placebo should be employed and a
control arm of no additional treatment would provide the
most reliable results.
Controversial evidence is available for the use of
acupuncture in the luteal phase of IVF. Although one
RCT with 225 women supported use of acupuncture in
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the luteal phase to improve pregnancy rate,
[20]
another
systematic review showed no benefits and suggested that
luteal phase acupuncture should not be offered until
further evidence is obtained.
[5]
Does acupuncture improve live birth in IVF?
A recent systematic review and meta-analysis of 24 trials
with 5807 participants has shown that although the
pooled clinical pregnancy rates were higher in the
acupuncture group, the live birth rates were not
significantly different than the control group.
[4]
However, the live birth rates were found to be higher
with acupuncture when the studies using Streitberger
controls were excluded. Further differences were seen
when different timings of acupuncture were analysed.
They concluded that acupuncture around the time of
oocyte aspiration or controlled ovarian hyper-stimulation
might be more effective in improving the pregnancy
outcome in IVF.
[4]
This meta-analysis was recently re-
evaluated in view of the marked heterogeneity. After
removing a few trials, no significant benefit of
acupuncture could be shown.
[21]
Also another
systematic review in 2012 analysed 17 trials and
showed no significant difference in clinical pregnancy,
biochemical pregnancy, ongoing pregnancy or live birth
rate between the acupuncture and the control groups.
[22]
Hence, the evidence regarding the efficacy of acupuncture
to improve clinical pregnancy rates is controversial. In
spite of 40 clinical trials and nine systematic reviews, the
debate still continues.
Problem with protocols used in different studies
As the effect of acupuncture differs along the menstrual
cycle, acupuncture applied at different time points
produces different results. Hence, different studies
using acupuncture at different time points are likely to
produce different effects and are not comparable. Even
slight alteration in the regimen might produce significant
changes in the results. Although some trials have used
acupuncture only around oocyte aspiration
[3]
or around
embryo transfer,
[9-14,23]
some have used it at different
time points throughout the IVF treatment including
ovarian stimulation, oocyte aspiration and embryo
transfer.
[17,18]
Significant differences are noted not
only in the timing but also in the acupuncture points
used in the different studies.Therefore, it has been agreed
that the quality of clinical acupuncture studies is
moderate, suffers from lack of standardisation and
extreme heterogeneity and that an adequately designed
and conducted RCT in acupuncture is needed.
[24]
For
that reason, this RCT is important as it is among the first
to follow such an appropriately designed protocol which
was achieved as an agreed consensus by experts in that
field. The importance of using this newly derived
consensus protocol is to be able to establish evidence
based data and settle disagreement in the literature to
resolve previous disparity. We believe this is the strength
of this RCT. A limitation of the present study is the
analysis of a relatively small group.
CONCLUSION
We have shown that using the acupuncture consensus
protocol in women undergoing IVF has a positive effect
on IVF outcome. This RCT is among the first studies to
follow the agreed protocol and has demonstrated the
positive effect of acupuncture on IVF success rates.
Therefore, we suggest that acupuncture may be offered
to women undergoing IVF treatments in an attempt to
improve their treatment outcome. More studies following
this consensus protocol are required in future to verify its
results.
Financial support and sponsorship
None.
Conflicts on interest
There are no conflicts of interest.
REFERENCES
1. de Lacey S, Smith CA, Paterson C. Building resilience: A preliminary
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Author Queries???
AQ1: Please provide the full name and signed copyright form of the authors.
AQ2: Please check the affiliation and correspondence for correctness.
AQ3: The section head "Subjects" has been changed to "Patients." Please check.
AQ4: Please expand ET, GnRH, FSH.
AQ5: Please provide manufacturer's details for Statistical Package for the Social Sciences.
AQ6: Please check the sentence "Assessing subjective outcome ..." for clarity.
AQ7: Details in references 10 and 17 have been checked and fixed as per the Google search. Please check for correctness.
AQ8: Please check the details provided in refs. 23 for correctness.
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