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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 (
Adjuvant acupuncture reduces first trimester pregnancy
loss after IVF
Naseem M. Khorram
, Susan Horton
, Vicken Sahakian
, Richard Chacon
, Omid Khorram
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, USA
Department of Obstetrics and Gynecology, Pacific Fertility Center, Westwood, USA
Received 25 April 2012; revised 30 May 2012; accepted 11 June 2012
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
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-
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.
N. M. Khorram et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 283-286
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
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
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.
(n = 111)
(n = 127)
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
16.2% 20% NS
Age Factor
8.3% 5.3% NS
21% 15.8% NS
Table 2. End points analyzed in acupuncture and control
(n = 111)
(n = 127)
Endometrial Thickness
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
and µ
nearly equal and the null hypothesis can be accepted.
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
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.
The authors thank Ms. Hye Jin Park for manuscript preparation.
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Full-text available
The aim of the present study was to evaluate the anaesthetic effect during oocyte aspiration of a paracervical block (PCB) in combination with either electro-acupuncture (EA) or intravenous alfentanil. In all, 150 women undergoing in-vitro fertilization (IVF) and embryo transfer were randomized to receive either EA plus PCB or alfentanil plus PCB. Visual analogue scales (VAS) were used to evaluate subjective experiences during oocyte aspiration, and IVF outcome parameters were recorded. No differences in pain directly related to oocyte aspiration, adequacy of anaesthesia during oocyte aspiration, abdominal pain, or degree of nausea were found between the two groups in the VAS ratings. Before oocyte aspiration, the level of stress was significantly higher in the EA group than in the alfentanil group (P < 0.05), and the EA group experienced discomfort for a significantly longer period during oocyte aspiration (P < 0.01). Compared with the alfentanil group, the EA group had a significantly higher implantation rate (P < 0.05), pregnancy rate (P < 0.05), and take home baby rate (P < 0.05) per embryo transfer. In conclusion, EA has been shown to be as good an anaesthetic method as alfentanil during oocyte aspiration, and we suggest that EA may be a good alternative to conventional anaesthesia during oocyte aspiration.
Full-text available
To evaluate the effect of acupuncture on the pregnancy rate in assisted reproduction therapy (ART) by comparing a group of patients receiving acupuncture treatment shortly before and after embryo transfer with a control group receiving no acupuncture. Prospective randomized study. Fertility center. After giving informed consent, 160 patients who were undergoing ART and who had good quality embryos were divided into the following two groups through random selection: embryo transfer with acupuncture (n = 80) and embryo transfer without acupuncture (n = 80). Acupuncture was performed in 80 patients 25 minutes before and after embryo transfer. In the control group, embryos were transferred without any supportive therapy. Clinical pregnancy was defined as the presence of a fetal sac during an ultrasound examination 6 weeks after embryo transfer. Clinical pregnancies were documented in 34 of 80 patients (42.5%) in the acupuncture group, whereas pregnancy rate was only 26.3% (21 out of 80 patients) in the control group. Acupuncture seems to be a useful tool for improving pregnancy rate after ART.
The purpose of this study was to assess the effects of acupuncture on reducing anxiety and depression in patients with chronic disease. This study was conducted on 68 cases, 11 with anxiety, 8 with depression, 49 with both anxiety and depression. Results were scored on the Hospital Anxiety and Depression Scale. The results indicated there were highly significant changes in the levels of anxiety and depression pre- and post-acupuncture, demonstrating that acupuncture is an effective method for their control.
Acupuncture might have a positive effect on the outcome of IVF and intracytoplasmic sperm injection. Further evidence is required before acupuncture can be recommended as a routine method.
To investigate the possible consequences of uterine contractions (UC) as visualized by ultrasound (US) on in-vitro fertilization (IVF)-embryo transfer outcome, we studied prospectively 209 infertile women undergoing 220 cycles of controlled ovarian stimulation. Inclusion criteria were age < or = 38 years, a morphologically normal uterus, and at least three good quality embryos transferred. Just before embryo transfer, women underwent 5 min digital recordings of the uterus using US image analysis software for UC assessment. Plasma progesterone and oestradiol concentrations were measured. Four groups were defined according to UC frequency: < or = 3.0 (n = 53), 3.1-4.0 (n = 50), 4.1-5.0 (n = 43), and > 5.0 (n = 74) UC/min respectively. Patients, controlled ovarian hyperstimulation and embryology characteristics were comparable in all groups. A stepwise decrease in clinical and ongoing pregnancy rates as well as in implantation rates occurred from the lowest to the highest UC frequency groups (53, 36, 21; 46, 32, 20; 23, 19, 10; and 14, 11, 4%; P < 0.001). Plasma progesterone and UC frequency were negatively correlated (r = -0.34, P < 0.001). Direction of UC did not affect embryo transfer outcome. As this study was controlled strictly for confounding variables and UC were assessed objectively by a computerized system, its results indicate that high frequency UC on the day of embryo transfer hinder IVF-embryo transfer outcome, possibly by expelling embryos out of the uterine cavity. The negative correlation between UC frequency and progesterone concentrations supports the uterine relaxing properties of progesterone.
Comparing stress levels in women entering IVF treatment with those of fertile controls as well as relating these levels to the outcome of IVF. State anxiety and personality profiles as well as stress hormones were studied in 22 normally menstruating women entering IVF treatment for tubal infertility. Their personality profiles as well as state anxiety scores measured before entering IVF treatment were related to the outcome of treatment. Twenty-two fertile women served as controls. Stress markers were serum prolactin and cortisol. These were estimated by radioimmunoassay. The psychological evaluation included the Karolinska Scales of Personality (KSP) and state anxiety as measured by the STAI questionnaire. Basal FSH on cycle day 3 and E2 and P4 AUC during the luteal phase were evaluated as hormonal predictors for the outcome of IVF treatment. Comparison of the personality profiles of the two groups, showed that infertile women had significantly higher scores of suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than fertile controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle. Serum cortisol, prolactin and FSH levels on cycle day 3 did not differ between the women who conceived after IVF treatment and those who did not conceive. However, significant differences were found in E2 and P4 AUC (p>0.01) in the luteal phase between those women who became pregnant and those who failed. There was a trend (p<0.06) toward higher state anxiety levels among the women who did not succeed in becoming pregnant after IVF treatment. The main findings suggest that infertile women have a different personality profile in terms of more suspicion, guilt and hostility as compared to the fertile controls, perhaps as a response to their infertility. Their stress levels in terms of circulating prolactin and cortisol levels were elevated compared to the fertile controls. Psychological stress may affect the outcome of IVF treatment since state anxiety levels among those who did not achieve pregnancy were slightly higher than among those who became pregnant.
As the pregnancy stage advances, prostaglandin (PG) concentrations increase in the uterus, being responsible for the increased uterus contractility during labor. Therefore, regulating the concentration of the PGs in the uterus is important for controlling preterm delivery. In oriental medicine traditionally, an acupuncture of LI-4 controls for the function and motility of the uterus. In this study, acupuncture treatment on the LI-4 acupoint in nonpregnant and pregnant rats was evaluated for its efficacy in the expression of COX-2 enzyme and uterus motility. Whether the rats were pregnant or not, immunohistochemical localization of the COX-2 enzyme was primarily found in the uterine endometrium with weak localization in the uterine myometrium. The level of expression in these two locations was intensified by pregnancy but reduced by the LI-4 acupuncture. The infusion of PGF(2alpha) in pregnant rats caused and increased COX-2 expression in the myometrium while it caused a decreased expression in the endometrium. The uterus motility monitored during the LI-4 acupuncture reduced to 67.0% in nonpregnant rats, and to 75.0% in pregnant rats. PGF(2alpha) infusion in pregnant rats increased uterine motility to 117.3%. The significant reduction in uterus motility in pregnant rats supports the role of LI-4 acupuncture in inhibiting the expression of COX-2 enzyme that can be used to regulate complicated preterm labor.
The objective of this review was to determine the incidence of adverse events associated with acupuncture. A search for prospective surveys of the safety of acupuncture was conducted using computerized databases (Medline, Embase, the Cochrane Library, and CISCOM), inquiries to acupuncture organizations, and our own files. Data on sample, size, types of patients duration of study, types of acupuncture, definition of adverse events, method of evaluation, and findings were extracted systematically from the retrieved reports. Nine surveys were located and included in the review. Their results were not uniform. The most common adverse events were needle pain (1% to 45%) from treatments, tiredness (2% to 41%), and bleeding (0.03% to 38%). Feelings of faintness and syncope were uncommon, with an incidence of 0% to 0.3%. Feelings of relaxation were reported by as many as 86% of patients. Pneumothorax was rare, occurring only twice in nearly a quarter of a million treatments. Although the incidence of minor adverse events associated with acupuncture may be considerable, serious adverse events are rare. Those responsible for establishing competence in acupuncture should consider how to reduce these risks.