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Adjuvant acupuncture reduces first trimester pregnancy loss after IVF

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Background: The objective of this study was to de-termine the effects of acupuncture treatment as an adjunctive therapy on the outcome of in vitro fertili-zation (IVF)/Intracytoplasmic Sperm Injection (ICSI). Material/Methods: We conducted a retrospective study of 238 patients who underwent conventional IVF/ ICSI alone or in conjunction with acupuncture over a course of 2 years. Patients in the two treatment groups were matched in terms of age and diagnosis. Acupuncture was administered in two sessions 5 to 7 days prior to and on the day of embryo transfer. Re-sults: There were no differences between the two groups in terms of fertilization rate, pregnancy or implantation rates, and endometrial thickness. The number of oocytes retrieved (P < 0.005) and the number of first trimester miscarriages were signifi-cantly lower in the group receiving acupuncture (P < 0.001). Conclusions: Acupuncture reduces miscar-riage rates in patients undergoing IVF/ICSI possibly secondary to stress relief.
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Open Journal of Obstetrics and Gynecology, 2012, 2, 283-286 OJOG
doi:10.4236/ojog.2012.23059 Published Online September 2012 (http://www.SciRP.org/journal/ojog/
)
Adjuvant acupuncture reduces first trimester pregnancy
loss after IVF
Naseem M. Khorram
1
, Susan Horton
2
, Vicken Sahakian
2
, Richard Chacon
2
, Omid Khorram
1*
1
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, USA
2
Department of Obstetrics and Gynecology, Pacific Fertility Center, Westwood, USA
Email:
*
okhorram@obgyn.humc.edu
Received 25 April 2012; revised 30 May 2012; accepted 11 June 2012
ABSTRACT
Background: The objective of this study was to de-
termine the effects of acupuncture treatment as an
adjunctive therapy on the outcome of in vitro fertili-
zation (IVF)/Intracytoplasmic Sperm Injection (ICSI).
Material/Methods: We conducted a retrospective study
of 238 patients who underwent conventional IVF/
ICSI alone or in conjunction with acupuncture over a
course of 2 years. Patients in the two treatment
groups were matched in terms of age and diagnosis.
Acupuncture was administered in two sessions 5 to 7
days prior to and on the day of embryo transfer. Re-
sults: There were no differences between the two
groups in terms of fertilization rate, pregnancy or
implantation rates, and endometrial thickness. The
number of oocytes retrieved (P < 0.005) and the
number of first trimester miscarriages were signifi-
cantly lower in the group receiving acupuncture (P <
0.001). Conclusions: Acupuncture reduces miscar-
riage rates in patients undergoing IVF/ICSI possibly
secondary to stress relief.
Keywords: Acupuncture; IVF/ICSI; Pregnancy Rates;
Implantation Rate; Miscarriage
1. INTRODUCTION
Acupuncture, an ancient Chinese treatment, is based on
the energy flow of Qi. Disease results when this energy
flow is disrupted, and can subsequently be treated via
stimulation of specific points on the body that balance
this energy flow [1]. In recent studies, the use of acu-
puncture in conjunction with in vitro fertilization (IVF)
treatments has produced mixed results with both positive
and no effects. In relation to female infertility, acupunc-
ture is believed to stimulate β-endorphin secretion which
in turn stimulates blood flow to the uterus and ovaries [2].
The principle mechanisms by which acupuncture could
improve the outcome of IVF are thought to be: modula-
tion of neuroendocrine factors; increased blood flow to
the uterus and ovaries; cytokine modulation; and reduc-
tion of stress and anxiety [3].
In a randomized controlled study Paulus et al. [4]
reported a higher pregnancy rate in women who received
acupuncture both before and after embryo transfer was
reported. This study was limited due to lack of a placebo
control group [4,5]. In a retrospective study by Magarelli
et al. [6] higher pregnancy rates (51% vs 36%, P < 0.05)
as well as lower miscarriage rates (8% vs 20%, P < 0.05)
among poor responder women who received acupuncture
was reported. In a subsequent study by the same inves-
tigators significantly higher pregnancy rates for good
prognosis patients receiving acupuncture (53% vs 38%,
P < 0.01) was reported [7]. However, in a study con-
ducted by Wang et al. [8] where acupuncture treatments
were only performed during the follicular and luteal
phase but not on the day of embryo transfer no difference
in pregnancy rates was found. The aim of this study was
to determine the effects of acupuncture treatment deli-
vered by a single acupuncturist as an adjunctive therapy
on the outcome of IVF/ICSI and the resultant pregnan-
cies in two groups of women matched for age and diag-
nosis.
2. MATERIALS AND METHODS
This study was a retrospective analysis using data col-
lected at Pacific Fertility Center over a two year course.
Data was obtained from 127 patients having IVF/ICSI in
conjunction with acupuncture, and another 111 patients
undergoing IVF/ICSI alone. Being a retrospective chart
analysis the study was considered as IRB exempt. Pa-
tients in the study were derived from the practices of two
physicians working in the same center and using the
same embryology laboratory with one physician refer-
ring all their patients for acupuncture and the other phy-
sician not referring their patients for acupuncture. Both
physicians are board certified reproductive endocrinolo-
*
Corresponding author.
Published Onlin
e September 2012 in SciRes. http://www.scirp.org/journal/ojog
N. M. Khorram et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 283-286
284
gists using the same stimulation protocols and medica-
tions for controlled ovarian hyperstimulation. The stimu-
lation protocol consisted of oral contraceptive suppres-
sion for one month followed by Leuprolide acetate for
down regulation. For controlled ovarian hyperstimulation
a combination of recombinant FSH and HMG prepara-
tion (1:1 or 2:1 ratio) was used. Luteal support was pro-
vided with progesterone in oil (50 mg/ml IM, daily) and
vaginal suppository (50 mg daily). A single acupuncturist
administered the treatment. A minimum of two acupunc-
ture treatments were given 5 to 7 days prior to and on the
day of embryo transfer. The acupuncture protocol con-
sisted of three groups of acupuncture points, each group
promoting fertility in a different way. These groups were
Eight Extraordinary Vessel points, Twelve Meridian acu-
puncture points, and Auricular points. Additionally, each
session incorporated acu-points selected to treat specific
presenting symptoms related to side effects of the ferti-
lity medications.
The first group of points inserted pertains to the deep
lying Extraordinary Vessels. The combination of Peri-
carium Six and Spleen Four opens the Chong Mai, the
Sea of Blood, which promotes blood flow to the uterus.
The combination points Lung 7 and Kidney 6 open the
Ren Mai, the Receiving Vessel, tonifying all aspects of
reproduction and fertility. The second group of points is
related to the meridians located more superficially on the
body. Stomach 36, Spleen 6, Kidney 3, Ren 4 (concep-
tion vessel 4), Stomach 28, Liver 3 and Large Intestine 4
all work together to activate and strengthen Qi and
Blood.
The data were then analyzed documenting seven vari-
ables including the clinical outcome, as well as age,
diagnosis, endometrial thickness, number of oocytes re-
trieved, percent fertilization, and implantation rates. The
implantation rate was calculated by dividing the number
of gestational sacs on the ultrasound by the number of
embryos transferred. All pregnancies were followed for
the first trimester. Data was analyzed using the Sigma
Stat software. The Chi-square and student’s t-test were
used to compare the various end points in the two study
groups.
3. RESULTS
Table 1 demonstrates the demographics of the two study
groups. As shown there were no differences in terms of
age or infertility diagnosis or percentage of patients
undergoing Intracytoplasmic Sperm Injection (ICSI)
between the two groups. Outcome data are shown in
Table 2. There were no significant differences between
the groups in terms of endometrial thickness, percent
fertilization, or pregnancy rates. The number of oocytes
retrieved in the control group was significantly higher
Table 1. Diagnosis and age of patients in acupuncture and
control groups.
Control
(n = 111)
Acupuncture
(n = 127)
P
Average Age
36.61 ± 0.41 36.83 ± 0.51 NS
Ovulatory Dysfunction
8.3% 11% NS
Male Factor
33% 38.5% NS
Tubal Disease
13% 9.7% NS
Unexplained
16.2% 20% NS
Age Factor
8.3% 5.3% NS
Endometriosis
21% 15.8% NS
Table 2. End points analyzed in acupuncture and control
groups.
Control
(n = 111)
Acupuncture
(n = 127)
P
Endometrial Thickness
(mm)
8.73 ± 0.21 8.29 ± 0.19 NS
Mean Number of
Oocytes Retrieved
13.55 ± 0.88 10.57 ± 0.60 0.005
Percent Fertilization
66.36% ± 2.09% 68.97% ± 2.29% NS
Implantation Rate
34.74% ± 3.29% 31.12% ± 3.28% NS
Pregnancy Rate
45.45% ± 0.04% 39.37% ± 0.04% NS
Miscarriage Rate
40% ± 0.07% 31.8% ± 0.07% 0.001
than acupuncture group (P < 0.005). First trimester mis-
carriage rates were significantly lower (P < 0.001) in the
acupuncture group as compared with the control group.
The 95% confidence interval for the difference between
the two means (miscarriage) was determined to be
0.280 to +0.117 making it plausible that μ
1
and µ
2
are
nearly equal and the null hypothesis can be accepted.
4. DISCUSSION
In this study comparing two well-matched groups un-
dergoing IVF/ICSI alone or in conjunction with acu-
puncture no differences in terms of endometrial thickness,
fertilization, or pregnancy rates was observed. However,
the rates of first trimester miscarriage rates were signifi-
cantly lower in the acupuncture group.
Patients undergoing IVF are often times under great
emotional stress, and it has been found that stress can
reduce fertility [9], and increase miscarriages [10].
Acupuncture can help eliminate mental stress [11,12]
even in the setting of patients undergoing IVF [13]. In
our study subjects receiving acupuncture reported feeling
relaxed after the treatment sessions, possibly indicating
reduced stress in this group. The reduction in stress indu-
ced by acupuncture has been associated with higher β-
Copyright © 2012 SciRes. OJOG
N. M. Khorram et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 283-286
285
endorphin secretion [14]. At the time of embryo transfer
uterine contraction frequency is increased [15], and acu-
puncture has been shown to reduce uterine contractions
[16] and thereby increase pregnancy rates [17]. The re-
duction of uterine contractions might be another potential
mechanism for reduction of miscarriage rates found in
our study. In a systematic online review and meta-ana-
lysis of seven trials involving 1366 women undergoing
IVF and IVF in conjunction with acupuncture treatments
on day of embryo transfer [18] an increase in clinical
pregnancy (odds ratio 1.65, 95% confidence interval 1.27
to 2.14; number needed to treat (NNT) 10 (7 to 17);
seven trials), ongoing pregnancy (1.87, 1.40 to 2.49;
NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to
2.64; NNT 9 (6 to 17); four trials) was reported. While
the miscarriage rates were not specified, live birth rates
were determined to be higher in the acupuncture group.
Stener et al. [19] also reported a higher take home baby
rate per embryo transfer in the acupuncture group (41%
versus 19.4%, P < 0.05). The miscarriage rate in this
study was determined to be non-significantly lower in
the acupuncture group, (10.7% vs 31.6%). Magarelli et
al. [20] found statistically lower ectopic pregnancy rates
in the acupuncture group (P 0.05) with no differences
in implantation and fertilization rates or number of
oocytes retrieved. Stener-Victorin et al. [19] also showed
a significantly
higher implantation rate per embryo
transfer (27.2% vs 16.3%, P < 0.05) in the acupuncture
group. The reason for the lower number of oocytes
retrieved in the acupuncture group in our study is
unknown. If acupuncture increases blood flow to the
ovary we would have expected to retrieve higher number
of oocytes in the acupuncture group. The reported dif-
ferences in outcomes in the various acupuncture studies
are related to heterogeneity of the patients studied, the
timing and manner of acupuncture administered. To con-
trol for these variables multi-center randomized pro-
spective trials using the same protocols will be needed to
address the beneficial or lack of effect of acupuncture as
an adjunct to IVF/ICSI. The effects of acupuncture on
uterine blood flow, contractions and correlation with
stress level will need to be assessed in such trials.
5. ACKNOWLEDGEMENTS
The authors thank Ms. Hye Jin Park for manuscript preparation.
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