Discussion
Infertility can be defined as the condition in which a woman cannot become pregnant despite having a normal married life for about 1 year. Not being able to become pregnant continuously who have not pregnant in the past, was called primary infertility, and if a couple had conceived experience but was not pregnant even a year after the miscarriage or delivery, it was called secondary infertility [
7].
In Korea, the number of patients claiming health insurance due to infertility increased by 4.2% annually from 162,000 in 2008 to 191,000 in 2012 [
8]. In 2012, the number of patients suffering infertility per 100,000 population by age, was the highest in women aged 30–34 (
n = 3,658), followed by women aged 35–39 (
n = 1,920), and women aged 25–29 (
n = 1,352) [
8].
In Western medicine the major cause of infertility is ovulation disorder (15%), followed by oviduct and abdominal abnormalities (30% to 40%), and male factors (30% to 40%), and in some cases the cause is unknown [
1]. Infertile patients may receive internal medication, and/or surgical procedures depending on the causes of ovulation disorders, endometriosis, oviduct factors, aging, genetic factors, and cancer status of patients [
9].
Oriental medicine puts more emphasis on functional aspects such as uterine deficiency cold, deficiency of Qi and blood, menstrual irregularities, yin deficiency, and Chiljeongsang than on organic aspects such as uterine or ovarian abnormalities [
10]. While Western medicine puts more emphasis on the causes and on organic aspects [
10]. The cause of male infertility has been reported to be mainly kidney essence deficiency, and it was recognized as stagnation of Qi, dampness-phlegm, blood stasis, damp-heat, and trauma [
11].
Research on infertility has been conducted in oriental medicine, as Kwon et al [
12] reported in 2006, on studies in the last 3 years, she described the success in infertility treatments which are published every year in overseas journals through cooperation with oriental medicine and Western medicine [
12]. The combination of phycological treatment in oriental medicine was reported to be helpful in continuing infertility treatment, so it is necessary to study oriental medicine infertility treatment more systematically in the future [
12].
In this review, studies on acupuncture research for infertility published in the last decade were analyzed in order to present the direction of acupuncture research to help acupuncture treatment of infertility in the future.
There were 18 infertility studies selected for analysis according to the cause and treatment method of infertility. Acupoint used based on this were analyzed according to the cause, and most commonly used in infertility treatment.
In the study of infertility treatment using acupuncture, polycystic ovarian syndrome (PCOS) was the most common cause of infertility, followed by premature ovarian failure (POF), varicocele, tubal obstruction, ovulation failure, and thin endometrium (
Fig. 2). Considering that male factors account for 30–40% of the causes of infertility [
1], studies on male infertility are needed in the future.
As a result of analyzing infertility treatment studies using acupuncture according to the treatment method (
Table 3), the types of acupuncture used were acupuncture, electroacupuncture, and laser acupuncture. In addition to acupuncture, studies were conducted in parallel with moxibustion, herbal medicine, and Western medicine. There were 3 studies on the use of acupuncture alone, including varicocele, 1 case with electroacupuncture alone, and 1 case with laser acupuncture alone. Other than that, in most cases, various herbal treatments, and Western medicine were used in parallel. However, in the case of varicocele, which is the cause of male infertility, there are only studies using acupuncture alone, so it is thought that studies using various oriental medicine treatments for male infertility are needed in the future.
PCOS is 1 of the most common endocrine abnormalities in women of childbearing age and is a complex syndrome caused by functional abnormalities in the hypothalamus-pituitary gland-ovarian axis, and adrenal glands. It refers to a series of symptoms such as menstrual disorders such as oligomenorrhea, amenorrhea, anovulation, infertility, hirsutism, and ovarian features with polycystic findings [
13].
Zhuo et al [
14] reported that endometrial thickness increased in the group treated with acupuncture compared with the group taking clomiphene (
p < 0.01), and that the ovulation rate was significantly improved [88.0% in the acupuncture group compared with 70.0% in the group taking clomiphene group (
p < 0.05)]. Ma et al [
15] reported that the treatment rate for ovulation disorder was 69.6% in the group taking clomiphene, 66.7% in the acupuncture group, and 86.2% in the group taking clomiphene + acupuncture group, so clomiphene + acupuncture treatment groups had significantly higher treatment rates (
p < 0.05). The acupuncture group and the acupuncture + clomiphene treatment group had fewer side effects (
p < 0.05). Xu et al [
16] reported that in the group taking clomiphene the ovulation rate was 80.0%, and the clomiphene + acupuncture treatment group was 93.3%, the pregnancy rate was 33.3% in the group taking clomiphene, and 43.3% in the group taking clomiphene + acupuncture treatment. The ovulation rate and pregnancy rate were significantly higher in the group taking clomiphene + acupuncture treatment (
p < 0.05).
Yin et al [
17] reported that the ovulation rate and pregnancy rate after treatment were most successful (in the order) Western medication + herbal medicine + electroacupuncture treatment group, Western medication + herbal medicine group, and Western medication alone group (
p < 0.05, in all groups). In the case of luteinized unruptured follicle, there were no cases in the group using Western medication + herbal medicine + electroacupuncture treatment, 3 cases (7.5%) in the group Western medication + herbal medicine and 5 cases (12.5%) in the group Western medication alone.
Jiang et al [
18] reported that endometrial thickness was better in the acupuncture + moxibustion + herbal medicine group, and the clomiphene + acupuncture + moxibustion + herbal medicine group compared with the clomiphene alone group, but there was no difference between the 2 groups (
p > 0.05). As for the pregnancy rate, the acupuncture + moxibustion + herbal medicine group had the highest rate (
p < 0.05), and the miscarriage rate was the lowest in the clomiphene + acupuncture + moxibustion + herbal medicine group (
p < 0.01), it was judged that it was more effective to take both Western medication and oriental treatment including acupuncture than to take Western medication alone.
In the case of using electroacupuncture, Budihastuti et al [
19] reported on follicle growth; the group that combined electroacupuncture treatment and lifestyle management had an average follicle measurement of 16.13 ± 2.43 mm which was significantly larger than the group who addressed lifestyle management alone which was 13.72 ± 1.20 mm (
p = 0.001). Yu et al [
20] reported that the ovulation rate and pregnancy rate were higher in the group who received clomiphene + electroacupuncture treatment compared with the group that received clomiphene alone. Lin et al [
21] reported that in the case of endometrial thickness, there was a significant difference between the group who received Western medication alone (0.14 ± 0.08 mm), compared with the group which received Western medication + electroacupuncture + ginger moxibustion treatment (0.21 ± 0.13 mm;
p < 0.01). The pregnancy rate was significantly different between the group who received Western medication alone (30.30%) and the group who received Western medication + electroacupuncture + ginger moxibustion treatment (56.25%;
p < 0.05), and the early miscarriage rate was determined to be significantly lower in the Western medication + electroacupuncture + ginger moxibustion treatment group (10.53%) than in the Western medication alone group (50.00%;
p < 0.05).
The causes of hyperinsulinemia in patients with PCOS may include genetic factors, or acquired factors, of which obesity is the most important cause. It has been reported that abdominal obesity plays an important role in the pathophysiology of hyperinsulinemia in patients with PCOS [
22].
In the case of catgut embedding, Qin et al [
23] reported that the waist-to-hip ratio and body mass index (BMI) were improved in the group who received herbal medicine + catgut embedding, and in the group using catgut embedding alone, compared with the herbal medicine alone group (
p < 0.05), and there was no significant difference between these 2 groups (
p > 0.05). In the case of pregnancy rate, it was highest in the herbal medicine + catgut embedding group compared with the other groups in the study (
p > 0.05). Since most of the Korean studies on research using catgut embedding are focused on the musculoskeletal system, facial paralysis, and plastic surgery [
24], research on infertility treatment using catgut embedding is required in the future.
In the case of laser acupuncture, El-Shamy et al [
25] reported that the group who received laser acupuncture treatment insulin resistance were significantly reduced than placebo treatment group (
p < 0.05). But there was no significant change in follicle stimulating hormone (FSH) levels (both,
p > 0.05).
A method to correct insulin and glucose metabolism by using an agent that increases insulin sensitivity in patients with insulin-resistant polycystic ovary syndrome was reported in a Cochrane Database System Review in 2003 [
26]. However, in 2008, even in patients with PCOS whose insulin resistance had not been proven on examination, it has been suggested that use of insulin response improving agent should be considered such as metformin primarily [
27].
Rouhani et al [
28] reported that in the group who received metformin + electroacupuncture + herbal medicine showed the greatest decrease in body fat and BMI compared with the groups receiving metformin only, metformin + electroacupuncture group and metformin + electroacupuncture + herbal medicine group. High density lipoprotein and low-density lipoprotein decreased in the metformin + electroacupuncture group, and metformin + electroacupuncture + herbal medicine group so it was judged that the combination treatment with acupuncture and oriental medicine treatment could treat metabolic complications and overweight problems better than metformin alone.
POF is a syndrome characterized by amenorrhea accompanied by hypergonadotropin induced hypogonadism before the age of 40, it is divided into primary and secondary POF according to menstrual history [
29].
Xu et al [
30] reported that the cured and effective rates (due to POF) of the electroacupuncture + heat-sensitive moxibustion group was 72.5% which was superior to that of the Western medication group (37.5%;
p < 0.05). Li et al [
31] reported that the treatment and remarkably effective rates were seen in the Western medication group of 75.8%, and in the catgut embedding + Western medication group 81.8% (
p < 0.05).
About 30–40% of female infertility is due to oviduct and abdominal factors. Oviduct factors include damage and closure of the oviduct (which is usually accompanied by pelvic inflammatory diseases or previous pelvic or oviduct surgery) [
32]. If an obstruction was observed on the hysterosalpingography, a selective hysterosalpingogram can be performed to attempt an opening, because obstruction of the oviduct is a reversible blockage [
33].
Tian et al [
34] reported that the total effective rate of infertility in the group treated with retention enema + herbal medicine was 45.71%, whilst the group treated with herbal medicine was 77.14%, and the group treated with acupuncture + moxibustion was 85.71%, but there was no statistical difference between the herbal medicine group and the acupuncture + moxibustion group (
p > 0.05).
Infertility due to ovulation failure refers to infertility caused by a disorder in the ovulation process that occurs when the mature follicle ruptures and the egg is released from the ovary. It is the easiest type of infertility to diagnose and the most treatable (accounting for 30–40% of female infertility factors) [
32].
Zheng et al [
35] reported that the ovulation rate was 59.3% in the acupuncture + herbal medicine therapy group, 55.6% in the acupuncture treatment group, and 53.3% in the Western medication group. The difference was not significant between the 3 groups (
p > 0.05). The endometrial thickness in the periovulatory period significantly increased as compared with the thickness before treatment in the acupuncture + herbal medicine therapy group (
p < 0.05), and in the acupuncture treatment group (
p < 0.05). The total effective rate was 88.9% in the acupuncture + herbal medicine therapy group, and was 92.6% in the acupuncture treatment group, which was higher than in the Western medication group which was 56.7% (both,
p < 0.01). There was no adverse reaction in the acupuncture + herbal medicine therapy group and the acupuncture treatment group.
The incidence of infertility due to uterine factors is approximately 5–10% [
32], it is thought that there is the most appropriate endometrial thickness for implantation and endometrial thickness for implantation affects the pregnancy rate [
36].
If the thickness of the endometrium before ovulation was less than 6 mm, pregnancy would be impossible, and if the thickness is less than 8 mm, the possibility of preclinical miscarriage increases, and the shape of the endometrium on ultrasound is related to whether or not pregnancy has established [
37].
You et al [
38] reported that the average endometrial thickness in the electroacupuncture + warm-needle moxibustion group increased from 5.23 ± 1.57 mm to 8.31 ± 2.80 mm after treatment, while the average endometrial thickness in the Western medication group increased from 5.27 ± 0.99 mm to 8.32 ± 1.97 mm after treatment, and the difference were statistically significant in both groups (
p < 0.05). After treatment for 3 menstrual cycles, the pregnancy rate of those who received electroacupuncture + warm-needle moxibustion was 25%, and in the Western medication group it was 15%.
There are several causes of male infertility, but varicocele is relatively common in men, especially young men [
39]. Varicocele can cause male infertility by causing hormonal dysfunction, increased testicular temperature, regurgitation of toxic metabolites in the adrenal or kidneys, and testicular hypoxia. Surgical correction through varicocelectomy using microsurgery can reduce DNA damage in the sperm nucleus, as well as improve other indicators of semen analysis [
40].
Ketabchi et al [
41] reported that the acupuncture treatment group had a significant increase in the percentage of normal-shaped and motility sperm in comparison with the control group. Pregnancy rates in the acupuncture treatment group was significantly better than control group. Kucuk et al [
42] reported that sperm concentration and motility improved significantly in the subinguinal microscopic varicocelectomy group, and the acupuncture treatment group after treatment. The increase in sperm concentration was higher in the acupuncture treatment group compared with the subinguinal microscopic varicocelectomy group (
p = 0.039).
The most commonly used acupoint for each cause of infertility are as follows: SP6, CV4, CV3, CV6, ST36, EX-CA1, ST29, SP10, BL23, CV12 for PCOS, SP6, BL20, BL23, BL32, EX-CA1 for POF, CV6, CV4, CV3, KI13, ST29 for remaining causes of infertility, ST29, BL23, BL32, CV3, CV4, VC6 for varicocele (
Table 5).
Among the most commonly used acupoint CV4, CV3, CV6, SP6, and BL23 were used the most, and KI13 was also widely used. So, the function of the uterus is dominated by Ren channels and Chong channels, and is dominated not only by the heart but also by the Foot-three Yin meridians (spleen, liver, kidney) [
43] can be inferred from the point of view.
We determined that the treatment effect for infertility significantly improved in the group using acupuncture treatment compared with the control group, or the group taking Western medicine alone, but there was a limitation in that there were more cases of using an acupuncture, moxibustion and herbal medicine combination of treatments than cases of using acupuncture alone.
In addition, considering that studies have been conducted focusing on PCOS among the causes of infertility, more diverse studies on infertility, and active studies on male infertility are needed in the future.