Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 282e286

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Taiwanese Journal of Obstetrics & Gynecology

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Original Article

Effectiveness of acupuncture on pregnancy success rates for women

undergoing in vitro fertilization: A randomized controlled trial
Pinar Gursoy Guven a, Yasemin Cayir a, *, 1, Bunyamin Borekci b
a
Ataturk University Faculty of Medicine, Department of Family Medicine, Erzurum, Turkey
b
Ataturk University Faculty of Medicine, Department of Obstetrics and Gynecology, Erzurum, Turkey

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To investigate the effect of acupuncture on pregnancy success rates applied before and after
Accepted 25 November 2019 embryo transfer (ET) among women undergoing in vitro fertilization (IVF).
Materials and methods: In this randomized controlled trial, 72 infertile women undergoing IVF were
Keywords: randomized to acupuncture (AG; n ¼ 36) and control group (CG; n ¼ 36). Three sessions of acupuncture
Acupuncture were applied to AG, the first was one week before ET, the second was 30 min before ET, and the third was
Embryo transfer
30 min after ET. CG received no acupuncture. The primary outcome was pregnancy success rate (Beta-
Infertility
HCG level, clinical pregnancy, ongoing pregnancy, live birth). Secondary outcome was anxiety level (STAI-
In vitro fertilization
Pregnancy
1 state anxiety scale). Beta-HCG levels were assessed for conception 12 days after ET. Additionally, STAI-1
state anxiety scale was administered 30 min before and after ET to measure anxiety levels in both groups.
Results: The mean age was 30.9 ± 3.7 years. Positive Beta HCG was detected in 63.9% (n ¼ 23) of the AG
and 33.3% (n ¼ 12) of CG (p ¼ 0.009). Clinical pregnancy, ongoing pregnancy, and live birth rates were
higher in AG (p < 0.05). There was no difference between the groups concerning anxiety scores before ET
(p > 0.05). The mean STAI-1 score was decreasing from 57.3 ± 9.8 to 28.8 ± 3.3 in AG, while it was
decreasing from 57.0 ± 8.0 to 41,1 ± 6,8 in CG after ET (p < 0.000).
Conclusions: It was observed that three sessions of acupuncture before and after ET significantly
increased the pregnancy rates in women with unexplained infertility. It was also found that acupuncture
significantly reduced anxiety levels that occurred before ET.
© 2020 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction IVF is an invasive and expensive process. It is estimated that

pregnancy rates in IVF applications are 30e35% globally [6]. The
Infertility is an inability to achieve pregnancy after regularly success rate of IVF can be influenced by many factors such as
unprotected coitus for one year [1]. Nowadays, an alarming number woman's age, co-morbid situations, and experiences of physician
of women around the world are experiencing infertility. Infertility [7]. IVF treatment also has high costs for public finance and pa-
rates were reported as 6% in America, 10e15% in England, 15% in tients. Therefore, it is significant to increase success rate of IVF.
Australia, and 10e15% in Japan among married population [1e4]. In Before IVF process, some procedures such as complementary
Turkey, it is estimated that 10e20% of the couples are diagnosed therapies are used to improve pregnancy rates for infertile females.
with infertility. In vitro fertilization (IVF) is presently one of the last To practice acupuncture as a complementary therapy during IVF is
treatment options for infertility as an Assisted Reproductive Tech- increasing all around the world. Acupuncture has been used for
nology. Since 1978, it has become a widely accepted method of hormone regulation, increasing uterine blood flow and stimulating
treatment for infertile couples [5]. secretion of endogenous opioids [8]. However, until to now there is
no standard acupuncture protocol described for infertile women
who are in IVF process.
We conducted a randomized controlled trial to determine
whether acupuncture sessions with embryo transfer (ET) improves
* Corresponding author. Fax: þ904422361301
the success rates of pregnancy among infertile women undergoing
E-mail address: [email protected] (Y. Cayir).
1
Ataturk University, Research and Practice Center for Acupuncture and Com- in vitro fertilization.
plementary Therapy Modalities Erzurum, Turkey.

https://doi.org/10.1016/j.tjog.2020.01.018
1028-4559/© 2020 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
 P.G. Guven et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 282e286 283

Methods used. Needles were 0.25  25 mm and stainless steel. Sterile and
single-use needles were used for every acupuncture session. Depth
Study design of insertion was 1e2 cun (one cun is with of thumb). The needles
were left in place for 30 min. Adverse events were monitored for all
This trial was carried out between December-2017 and January- sessions.
2018 at Ataturk University Research and Practice Center for
Acupuncture and Complementary Therapy Modalities, Turkey. It Measurements
was performed in adherence to Helsinki Declaration which is a
guideline for clinical trials [9]. The acupuncture treatment was All patients were assessed for conception 12 days after ET with
documented in accordance with Standards for Reporting In- Beta-HCG levels. It was accepted as positive above 5.0 mIU/ml.
terventions in Clinical Trials of Acupuncture (STRICTA) [10]. It is Participants with positive Beta-HCG were monitored for clinical
illustrated in Fig. 1. Acupuncture was performed by the acupunc- pregnancy, ongoing pregnancy, and live birth rate. Additionally,
turist who has acupuncture practitioner license from Turkish STAI-1 state anxiety scale was administered before 30 min and after
Ministry of Health. The written informed consent form was ob- 30 min ET to measure anxiety levels in both groups. STAI-1 was
tained from all the participants. The study protocol was approved developed by Spielberg, and Turkish validity and reliability analysis
by the ethics committee of Ataturk University Faculty of Medicine €
of the scale was performed by Oner et al. [13,14]. STAI-1 is a self-
(Protocol number: B.30.2.ATA.0.01.00/120). This study is registered assessment questionnaire. The questionnaire contains 20 items
on the website of ClinicalTrials.gov (www.clinicaltrials.gov) with rated on 4 point. The score obtained from the reversed items is
the number of NCT 03572608. This study was supported by the subtracted from the score obtained from the non-reversed items.
Scientific Research Projects Fund of Ataturk University (Project The score obtained from the two sub-dimensions (state anxiety;
Number: TTU-2018-6422). trait anxiety) ranges between 20 and 80. Higher scores indicate that
the higher anxiety level.
Patients
Statistical analysis
From December 2017 to January 2018, a total of 95 unexplained
infertile women have visited Ataturk University Obstetric and Statistical analysis was performed using SPSS version 23.0
Gynecologic Outpatient Department seeking for IVF. Inclusion software (IBM Corp., Armonk, NY, USA). Numerical variables are
criteria were being aged 23e45 years, diagnosed unexplained expressed in mean ± standard deviation and categorical variables
infertility, and undergoing a fresh IVF. Unexplained infertility was in numbers and percentages (%). Numerical data were analyzed for
accepted as not to have any common causes of infertility using normal distribution by Skewness. Independent sample t-test and c2
standard fertility investigations. Exclusion criteria included having test were used to analyze the differences between the groups.
an underlying fertility problem, any co-morbidity or uncontrolled P < 0.05 was set as the threshold for significance.
systemic diseases such as hypertension, diabetes, chronic heart
disease or chronic renal disease that can affect the treatment Results
process, and any acupuncture treatment during the previous one-
year. After baseline evaluation by a gynecologist, eligible patients The mean age of participants was 30.9 ± 3.7 years. Both AG and
(n ¼ 76) were enrolled in the study. A total of 76 unexplained CG had similar baseline characteristics in terms of age, occupation,
infertile women were randomized to acupuncture (AG; n ¼ 38) education level, body mass index (BMI) and number of IVF
and control group (CG; n ¼ 38). The secretary in the IVF clinic (p > 0.05). Baseline characteristics of participants are shown in
generated a random allocation sequence for the participants who Table 2.
meet the inclusion criteria. Three sessions of acupuncture were IVF data of the groups is demonstrated in Table 3. According to
applied to AG, the first session was one week before ET, the second these data, there were no statistical differences in terms of
session was 30 min before ET, and the third session was 30 min gonadotropin dose, number of oocytes retrieved, number of mature
after ET. CG received no acupuncture. Four of the patients had oocytes, number of embryos collected, number of embryos trans-
incomplete data, so the results from 72 patients were used in the ferred, thickness of endometrium and estradiol level of hCG trigger
final analysis (Fig. 1). Day 3 and fresh embryo transfer were used day (P > 0.05).
in all participants. Patients were compared in terms of Beta-HCG The comparison of the pregnancy success rates between AG and
positivity, clinical pregnancy, ongoing pregnancy, and live birth CG is presented in Table 4. Positive Beta HCG was detected in 63.9%
rates and anxiety levels. (n ¼ 23) of the AG and 33.3% (n ¼ 12) of CG (p ¼ 0.009). There were
It was calculated that a sample of 77 patients provided a sta- statistically significant differences between the groups as regards
tistical power of 85% for determining a difference in Beta-HCG clinical pregnancy rate (63.9% versus 33.3%), ongoing pregnancy
positivity with an a error of 5% by G-power© program. rate (55.6% versus 30.6%), and live birth rate (52.8% versus 40.3%)
(p < 0.05).
Intervention No significant differences were determined in mean STAI-1
scores before ET between the groups (p > 0.05). STAI-1 score was
Classical body acupuncture points were used without a formal 57.3 ± 9.8, and 57.0 ± 8.0 before ET respectively among groups
Traditional Chinese Medicine (TCM) diagnosis in the AG. All (Table 5). The mean STAI-1 score was 36.1 ± 6.3 just after the second
acupuncture points were selected and localized on the basis of the acupuncture session in AG. The mean STAI-1 score was decreasing
WHO Standardized Acupuncture Point Location [11]. The points to 28.8 ± 3.3 in AG, while it was 41,1 ± 6,8 in CG after ET (p < 0.000).
selected were bilateral H-7, LI-4, GV-20, ear shenmen for the first The anxiety scores decreased significantly after the second and the
session. Bilateral CV-3,4,6, GV-20, LIV-3, ST-30, and SP-8 were third acupuncture sessions compared with baseline values
selected for the second session. Bilateral LI-4, SP-6,9, and ST-36 (p < 0.001). According to STAI-1, anxiety scores reduced in ratio
were selected for the third session. The selected acupoints and 49.7% in AG, and 27.8% in CG after ET.
the effectiveness of these acupoints based on TCM are illustrated in The results of the comparisons of the STAI-1 scores before ET
Table 1 [12]. Neither needle stimulation nor moxa-therapy was and Beta HCG test results are demonstrated in Table 6. According to
284 P.G. Guven et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 282e286

Fig. 1. CONSORT flow chart of the patients.

this analyzes, participants with high STAI-1 score showed more addition, acupuncture treatment could decrease anxiety levels that
negative pregnancy test results (p < 0.05). occur before ET.
Clinical studies have shown that acupuncture is an effective
therapy method for infertility. A recent meta-analyses indicate that
Discussion acupuncture increased the odds of clinical pregnancy by 65%
compared with CGs [8]. Villahermosa et al. conducted a study; they
The results of this clinical trial demonstrated that three sessions reported that acupuncture increased clinical pregnancy rates dur-
of acupuncture treatment could result significant increase the ing IVF treatment [15]. Acupuncture's regulator effect on hypo-
pregnancy rates in infertile women undergoing IVF treatment. In thalamicepituitaryeovarian axis may influence the ovulation,

Table 1
The effects of the each selected acupoints.

General effects of the acupoints for the each session Acupoints Effect of acupoints according to TCM

1. session H-7 Calms the shen

Reduce anxiety, calm the sprit LI-4 Clears the heat
GV-20 Pacifies the spirit, releases cramps
Ear shenmen Calms the shen
2. session CV-3,4,6 Increase and regulate Qi, regulate uterus
Facilitate cervical opening, relax uterus, decrease uterine contractions, assist GV-20 Pacifies the sprit, releases cramps
embryo implementation LIV-3 Expels wind, transforms dampness, strengthens spleen
ST-30 Promotes fertilization, regulates and tonifies chong mai
SP-8 Regulates uterus function, expels dampness
3. session LI-4 Clears the heat
Support blood circulation in the uterus, maintain implantation of the embryo, SP-6 Resolves and expels dampness, restores balance to Yin and blood
nourish embryo growth, relax the uterus, prevent uterine contractions SP-9 Expels dampness
ST-36 Strengthens the body, restores balance to Qi
 P.G. Guven et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 282e286 285

Table 2 Table 5
Comparisons of baseline features of the groups. STAI-1 scores results of the groups.

AG CG P Values STAI-1 Scores Acupuncture Control P Values

Group (n ¼ 36) Group (n ¼ 36)
n ¼ 36 n ¼ 36
Before Embryo Transfer 57.3 ± 9.8 57.0 ± 8.0 0.876
Age (year) (mean ± SD) 30.3 ± 3.4 31.5 ± 4 0.17
After Embryo Transfer 28.8 ± 3.3 41.1 ± 6.8 0.000
Occupation n(%)
Do not have 27 (%51.9) 25 (%48.1) 0.59 *statistical significance.
Have 9 (%45) 11 (%55)
Education level n(%)
<8 years 7 (%46.7) 8 (%53.3) 0.89 ET has a correlation with pregnancy possibility [22]. LIV-3 is an
8e12 years 19 (%52.8) 17 (%47.2)
effective acupuncture point for reducing pain. These points were
>12 years 10 (%47.6) 11 (%52.4)
BMI (kg/m2) (mean ± SD) 24.4 ± 3.0 23.3 ± 1.9 0.06
used in some previous study. It was shown that these acupuncture
IVF number (mean ± SD) 1.97 ± 0.8 1.83 ± 0.7 0.47 points also can facilitate ET stage by relaxing the uterus, dilating the
cervical opening, and calming the patient [12,23]. In the present
SD, Standard Deviation; BMI, body mass index.
study, the used acupuncture points before ET assisted the process
by achieving the facilitator effects.
ovarian blood flow, uterine blood flow and uterine contractions To support blood circulation in the uterus, to maintain im-
[16]. Huang et al. indicated that acupuncture increased uterine and plantation of the embryo, and to nourish growing of embryo are
ovarian blood flow and also helped the implantation of the embryo significant after the ET. To provide relaxing of the uterus may
via reducing uterine motility [17]. prevent uterine contractions, uterine bleeding and abortion in this
Acupuncture around the time of ET could improve pregnancy period. The selected points after the ET were shown that have effect
success rate through some of probable effect. Increasing uterine all of these factors. Furthermore, it is thought that modulation of
blood flow, improving endometrial receptivity, and reducing stress immune system can be achieved by acupuncture that affects the
level are known as major mechanism [18]. The acupuncture points production of cytokines. According to TCM, ST-36 is an immune
used in this trial were selected according to the principles of TCM modulator point that can trigger release of some kinds of cytokines.
and our clinical experiences. While some of these points affect Some trials have proposed that the use of LI-4 or SP-6 can trigger
ovulation via acting on central and peripheral nervous system, uterine contractions, however these points can be used before
neuroendocrine system and endocrine system modulation; a part pregnancy test. In addition, suppression in the expression of COX-2
of these points increase uterine blood flow or inhibit uterine enzyme in the uterus had been shown after needling LI-4 [5,12,15].
motility [12]. Smith et al. conducted a Delphi study in order to determine an
The selected points used one week before ET (H-7, LI-4, GV-20) acupuncture protocol as an adjunct to IVF. Most of the experts were
regulate mental status and generate homeostasis. It is known that strongly agree with usage of ST-36, CV-4, P-6, Yin Tang and GV-20
mental status of women may lead to reduced fertility. In addition, during ET. The experts of this trial recommended dosing studies
balancing homeostasis is one of the required factors for fertilization for future research of acupuncture administered during IVF [18].
[12,19]. We believe that our study described a new effective treatment
CV-3,4,6, LIV-3, ST-30, and SP-8 which were used just before ET protocol by practicing the acupuncture points which of them were
have effect on facilitation of embryo implementation. CV-3,4,6 also suggested by acupuncture experts.
have regulating effect on uterus [12,20,21]. ET is a painful proced- Anxiety is a physiological response of human body to traumatic
ure. In a previous study, it was demonstrated that the pain during and stressful events. Anxiety is also known as a complicating and
reducing factor for fertility. A study suggested that more than 80%
of women had anxiety in duration of infertility [24]. Anxiety may
Table 3 lead to a reduction in pregnancy success rates during IVF [25]. It is
IVF data of the groups.
very significant to relieve anxiety and increase the outcomes of IVF
AG (n ¼ 36) CG (n ¼ 36) P values treatment. A few of trials have suggested that acupuncture plays an
Dose of gonadotropin (mg) 230.55± 225.73± 0.671 important role in managing anxiety in patients with infertility
(mean ± SD) without causing any serious side effects [26]. Some studies have
Number of oocytes retrieved 11.7 ± 7.1 10.9 ± 5.2 0.630 demonstrated that acupuncture creates an anxiolytic effect via
(mean ± SD)
increasing endogenous opioids [5,27]. In particular, the release of
Number of mature oocytes 8.4 ± 5.8 8.9 ± 4.1 0.700
(mean ± SD) endorphins in the central nervous system affects the secretion of
Number of embryos collected 4.8 ± 2.0 5.1 ± 1.9 0.485 gonadotropins. This creates a positive effect on the emotional state,
(mean ± SD) which is an effective factor in ovulation and menstrual cycle
Number of embryos transferred 1.4 ± 0.6 1.5 ± 0.7 0.632 changes [8]. Our findings are in line with all these research. In our
(mean ± SD)
Thickness of endometrium (mm) 9.9 ± 1.5 9.±1.0 0.283
study, a decrease of close to 50% in mean anxiety scores was
(mean ± SD)
Estradiol level of hCG trigger day 2695 ± 1648 3134 ± 1640 0.304
(pg/mL) (mean ± SD) Table 6
Comparisons of the STAI-1 scores before ET and pregnancy test results.

Table 4 Groups Pregnancy Test n STAI-1 Score Before P value

Pregnancy success rates. ETMean ± SD

AG (n ¼ 36) Beta HCG Positive 23 56.8 ± 10.88 0.688

AG (n ¼ 36) CG (n ¼ 36) P Value
Beta HCG Negative 13 58.23 ± 8.21
Beta HCG positivity rate n (%) 23 (63.9) 12 (33.3) 0.009* CG (n ¼ 36) Beta HCG Positive 12 49.92 ± 5.76 0.000*
Clinical pregnancy rate n (%) 23 (63.9) 12 (33.3) 0.009* Beta HCG Negative 24 60.54 ± 6.57
Ongoing pregnancy rate n (%) 20 (55.6) 11 (30.6) 0.032* Total (n ¼ 72) Beta HCG Positive 35 54,46 ± 9,9 0,011*
Live birth rate n (%) 19 (52.8) 10 (27.8) 0.031* Beta HCG Negative 37 59,73 ± 7,1

*statistical significance. SD, Standard Deviation; *statistical significance.

286 P.G. Guven et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 282e286

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