About 10–15% of couples have difficulty conceiving at some point in their reproductive lives and thus have to seek specialist fertility care. One of the most commonly used treatment options is
With rapid economic development, lifestyle changes, and increased environmental pollution, the incidence of infertility has gained increased worldwide attention. Almost 10–15% of couples have suffered from infertility and seek specialist fertility care worldwide [
CAM has been defined as diagnosis, treatment, and/or prevention which complements mainstream medicine by contributing to a common whole, satisfying a demand not met by orthodoxy or diversifying the conceptual frameworks of medicine [
CAM mainly contains the following methods: (i) alternative medical system: TCM (traditional Chinese medicine), Ayurveda, and homeopathy; (ii) mind-body intervention: meditation and biofeedback; (iii) biologically based therapies: herbal therapy and special diet therapy; (iv) manipulative and body-based methods: chiropractic and massage; and (v) energy therapies [
Acupuncture and moxibustion treatment are one of the traditional Chinese practices widely used in China and some Asian countries. In China, practitioners of acupuncture and moxibusion regard the human body as a whole network based on the theories of meridian, viscera, and Qi-Blood. Acupuncture is a therapy of inserting, manipulating, and retaining very fine needles in specific “acupoints” and has been used in China for centuries to regulate the female reproductive system [
Some studies show that acupuncture is helpful in improving the success rate of assisted reproductive techniques. Some potential mechanisms for its effects on fertility have been proposed [
In 2002, Paulus et al. first published the results of the randomized controlled trial investigating the effects of acupuncture on pregnancy rates of IVF patients. In this trial, 160 healthy women undergoing IVF or intracytoplasmic sperm injection (ICSI) were randomized to receive acupuncture or no acupuncture. Acupuncture was administered 25 minutes before and after ET. Higher pregnancy rates were found in the acupuncture group compared with the group that did not undergo acupuncture (42.5% versus 26.3%;
Although some evidence exists on the beneficial effects of acupuncture on IVF success rates, there are still some controversies about the benefits from acupuncture treatment. Some recent clinical trials have shown negative results. Andersen et al. administrated real or placebo acupuncture on the day of ET in 635 patients and found no difference of pregnancy rates in the two groups and implied that the effect of acupuncture in pregnancy rates was only a placebo effect [
In addition to the efficacy of acupuncture therapy for IVF-ET patients, the security of acupuncture therapy for IVF-ET patients is also arousing researchers’ much attention. The risks of administrating acupuncture during the period of IVF-ET have been widely investigated and have been proved to be minimal [
Summary of randomized studies of the effect of acupuncture on IVF outcomes.
Study ID | Design | Sample size | Interventions | Outcomes | Limitation |
---|---|---|---|---|---|
20 | RCT | 273 | Treatment arm: acupuncture intervention |
Treatment arm: PR, 39% [37 of 95] |
Not mentioned blindness |
|
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19 | RCT | 160 | Treatment arm: acupuncture intervention |
Treatment arm: PR, 42.5% [34 of 80] |
Not mentioned blindness |
|
|||||
21 | Single-blind, RCT | 228 | Treatment arm: acupuncture intervention |
Treatment arm: PR, 31% [33 of 107] |
Single-blind trial |
|
|||||
22 | RCT | 225 | Treatment arm: acupuncture intervention |
Treatment arm: PR, 33.6% [39 of 116] |
Not mentioned blindness |
|
|||||
37 | Single-blind, RCT | 150 | Treatment arm: acupuncture intervention |
Treatment arm: PR, 50% [39 of 78] |
Single-blind trial |
|
|||||
59 | RCT | 44 | Treatment arm: acupuncture intervention |
Treatment arm: PR, 30% [9 of 30] |
Not mentioned blindness |
|
|||||
35 | Double-blind, RCT | 370 | Treatment arm: acupuncture intervention |
Treatment arm: PR, 55.1 [102 of 185]# |
|
|
|||||
36 | Double-blind, RCT | 226 | Treatment arm: acupuncture intervention |
There were no significant differences in outcomes of PR, OPR, LBR, and IR in the placebo acupuncture group than in the real acupuncture group | Small sample size |
|
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34 | Double-blinded, RCT | 635 | Treatment arm: acupuncture intervention |
There were no significant differences in outcomes of OPR and LBR and IR between the placebo acupuncture group and the real acupuncture group | |
|
|||||
39 | RCT | 416 | Treatment arm: acupuncture intervention |
There was no significantly increased PR in the acupuncture group than in the control group | Not mentioned blindness |
|
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44 | Double-blinded, RCT | 160 | Treatment arm: acupuncture intervention |
CPR had no significant difference between the true acupuncture group and the sham acupuncture group | Small sample size |
|
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32 | RCT | 66 | Treatment arm: acupuncture intervention |
The fertilization rate, cleavage rate, and the rate of high-quality embryos were all significantly higher in the acupuncture group than in the control group | Not mentioned blindness |
Note: RCT: randomized clinical trial; PR: pregnancy rate; OPR: ongoing pregnancy rate; LBR: live birth rate; IR: implantation rate; FR: fertilization rate; CR: cleavage rate.
Regarding the potential mechanisms of acupuncture effect on fertility, the following points deserve careful consideration. The first point is that acupuncture may mediate the release of neurotransmitters, which may influence the menstrual cycle, ovulation, and fertility by stimulating the secretion of gonadotrophin-releasing hormone. Acupuncture was well known for its effect of releasing
The second point is that acupuncture may promote blood flow to the uterus by inhibiting uterine central sympathetic nerve activity and may promote the endometrial receptivity. A successful implantation of human embryos into the uterine cavity was effected by several important parameters, such as endometrial thickness, morphology, and uterine artery blood flow. High arterial blood flow impedance and low uterine perfusion result in low implantation rate [
Clinicians generally considered that acupuncture in early pregnancy will cause a strong contraction of the uterus, leading to miscarriage. “Acupuncture Figure of Bronze Acupoints (medical records of acupuncture in the ancient China)” also has a medical record that documented that needling the acupoints of Hegu and Sanyinjiao could cause abortion. But, some clinical and animal studies gained exactly the opposite results in recent. They demonstrated a lower miscarriage rate in those patients treated with acupuncture than those patients treated without acupuncture during the period of IVF. Some studies have supported that one possible mechanism of acupuncture on IVF outcomes is to decrease the miscarriage rate in those patients treated with acupuncture than those patients treated without acupuncture during the period of IVF [
The last point is that acupuncture can alleviate anxiety and stress of infertility patients. Psychological stress or stressful life events may negatively influence the clinical pregnancy rates [
In summary, even though numerous studies have been performed in this area, the discrepancy between the positive outcomes and negative outcomes about acupuncture’s effect on patients undergoing IVF-ET was still unknown. The possible reasons for these different outcomes might be related to differences in the study design and acupuncture protocol. Another possible reason is related to the number of studied patients being small, and hence the power of the findings is too low for the results to be considered reliable. A study with a larger number of patients was thus needed to clarify this point.
Moxibustion originated from the periods of spring and autumn and the Warring States in ancient China. Moxibustion could warm meridians, relieve pain, and promote blood circulation by burning compressed herbal material at the acupoints. Modern studies confirmed that moxibustion can regulate functional activity of whole body’s organs and enhance immune function, increasing the chance of pregnancy [
Chinese medicine is a medical system that has existed for an estimated 3000 years. Near the turn of the last century, the Chinese systematized various Chinese medicine practices into one unified medical system that could best be integrated with Western medicine and called it traditional Chinese medicine (TCM). TCM includes a series of traditional medical practices originating in China. It is considered as a complementary and alternative medical system in most of the Western countries while remaining as a form of primary care throughout most of Asian countries. TCM is a comprehensive system for the assessment, as well as for the preventative health care and maintenance. TCM theory is extremely complex and originated thousands of years ago through meticulous observation of nature, the cosmos, and the human body. The major theories of TCM include the Yin-yang, the Five Elements, Qi and Blood, and Zang-fu organ theories. In TCM, the understanding of the human body is based on the holistic understanding of the universe as described in Daoism, and the treatment of illness is based primarily on the diagnosis and differentiation of syndromes. The typical TCM therapies include Chinese herbal medicine (CHM) and acupuncture. CHM acts on Zang-fu organs internally, and acupuncture is accomplished by stimulating certain areas of the external body.
Some studies show that 17% of the couples had utilized herbal therapy for infertility in the United States and 46% of patients undergoing IVF admitted regular use of CHM in Irish [
Recently, some RCTs have shown that adjuvant treatment with CHM during IVF-ET could significantly increase pregnancy rate [
Summary of the effect of randomized studies of CHM on IVF outcomes.
Study ID | Design | Sample size | Interventions | Outcomes | Composition | Limitation |
---|---|---|---|---|---|---|
90 | RCT | 400 | Treatment arm: CHM |
Treatment arm: PR, 59.41% [101 of 170] |
(1) Tiaojing Zhuyun pill: |
Not mentioned blindness |
|
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91 | RCT | 244 | Treatment arm: CHM |
Treatment arm: PR, 47.37% [36 of 76] |
(1) Zhongyu I: |
Not mentioned blindness |
|
||||||
93 | RCT | 220 | Treatment arm: CHM |
Treatment arm: PR, 52.73% [58 of 110] |
(1) Yishen Angong I: |
Not mentioned blindness |
|
||||||
94 | RCT | 207 | Treatment arm: CHM |
Treatment arm: PR, 54.46% [55 of 101] |
(1) Cuhuangti Granule: |
Not mentioned blindness |
|
||||||
95 | RCT | 200 | Treatment arm: CHM |
Treatment arm: PR, 45% [45 of 100] |
Antai I: |
Not mentioned blindness |
|
||||||
97 | RCT | 160 | Treatment arm: CHM |
Treatment arm: PR, 60.0% [48 of 80] |
Bubao Decoction: |
Not mentioned blindness |
|
||||||
98 | Single-blind RCT | 122 | Treatment arm: CHM |
Treatment arm: PR, 39.34% [24 of 61] |
Erzhi Tiangui Granule: |
Single-blind trial |
|
||||||
99 | RCT | 100 | Treatment arm: CHM |
Treatment arm: PR, 16.0% [8 of 50] |
Zishen Huoxue decoction: |
Not mentioned blindness |
|
||||||
100 | RCT | 98 | Treatment arm: CHM |
Treatment arm: PR, 40.74% [21 of 50] |
Bushen Huatan decoction: |
Not mentioned blindness |
|
||||||
101 | RCT | 82 | Treatment arm: CHM |
Treatment arm: PR, 63.4% [26 of 41] |
(1) Jinghou Zengzhi Granule: |
Not mentioned blindness |
|
||||||
102 | RCT | 82 | Treatment arm: CHM |
Treatment arm: PR, 39.34% [17 of 42] |
Quyu Jiedu Granule: |
Not mentioned blindness |
|
||||||
103 | RCT | 80 | Treatment arm: CHM |
Treatment arm: PR, 62% [31 of 50] |
Shoutai pill: |
Not mentioned blindness |
|
||||||
104 | RCT | 80 | Treatment arm: CHM |
Treatment arm: PR, 57.5% [23 of 40] |
Shoutai pill: |
Not mentioned blindness |
|
||||||
105 | RCT | 80 | Treatment arm: CHM |
Treatment arm: PR, 47.6% [20 of 42] |
Erzhi Tiangui Granule: |
Not mentioned blindness |
|
||||||
106 | RCT | 72 | Treatment arm: CHM |
Treatment arm: PR, 83.33% [30 of 36] |
Radix codonopsis (Dangshen), Astragalus (Huangqi), Herba taxilli (Shangjisheng), White paeony root (Baishao |
Not mentioned blindness |
|
||||||
107 | Single-blind RCT | 70 | Treatment arm: CHM |
Treatment arm: PR, 65.7% [23 of 35] |
Dane Fukang Jiangao: |
Single-blind trial |
|
||||||
88 | RCT | 64 | Treatment arm: CHM |
Treatment arm: PR, 36.11% [13 of 36] |
Erzhi Tiangui Granule: |
Not mentioned blindness |
|
||||||
109 | RCT | 63 | Treatment arm: CHM |
Treatment arm: PR, 43.5% [14 of 31] |
(1) CHM decoction I: |
Not mentioned blindness |
|
||||||
110 | RCT | 61 | Treatment arm: CHM |
Treatment arm: PR, 56.7% [17 of 31] |
Erzhi Daotan decoction: |
Not mentioned blindness |
|
||||||
111 | RCT | 60 | Treatment arm: CHM |
Treatment arm: PR, 73.33% [22 of 30] |
Bushen Tiaojing decoction: |
Not mentioned blindness |
|
||||||
112 | RCT | 58 | Treatment arm: CHM |
Treatment arm: PR, 73.33% [22 of 30] |
Bushen Tiaojing decoction: |
Not mentioned blindness |
Note: CHM: Chinese herbal medicine; PR: pregnancy rate;
In addition, some researchers put forward artificial cycle sequential therapies of CHM according to the different stages of the menstrual cycle as a treatment method for IVF patients [
Summary of the effect of the clinical studies of artificial cycle sequential therapies with CHM on IVF outcomes.
Study ID | Design | Sample size | Interventions | Outcomes | Composition | Limitation |
---|---|---|---|---|---|---|
121 | Single-blind RCT | 60 | Treatment arm: CHM + COH |
Treatment arm: PR, 46.7% [14 of 30] |
Period: |
Not mentioned drop-out rate |
|
||||||
122 | RCT | 160 | Treatment arm: CHM + COH |
Treatment arm: PR, 63.5% [40 of 63] |
Follicular phase: |
Not mentioned blindness |
|
||||||
123 | RCT | 100 | Treatment arm: CHM + COH |
Treatment arm: PR, 50% [25 of 50] |
The basic prescription: |
Not mentioned blindness |
|
||||||
125 | RCT | 58 | Treatment arm: CHM + COH |
Treatment arm: PR, 26.7% [8 of 30] |
Follicular phase: |
Not mentioned blindness |
|
||||||
126 | RCT | 42 | Treatment arm: CHM + COH |
Treatment arm: PR, 38.1% [8 of 21] |
Follicular phase: |
Not mentioned blindness |
|
||||||
127 | RCT | 53 | Treatment arm: CHM + COH |
Treatment arm: PR, 48.0% [12 of 25] |
The basic prescription: |
Not mentioned blindness |
|
||||||
128 | Observational studies | 480 | Treatment arm: CHM | PR, 10.8% [52 of 480] | Period: |
No control group |
Note: CHM: Chinese herbal medicine; COH: control ovarian hyperstimulation; PR: pregnancy rate;
Although enormous studies have proved that CHM have a postivve effect on pregnancy outcome for those patients undergoing IVF-ET, there still have some opposite opinions about the benefits from CHM [
There are some potential mechanisms of CHM effect on IVF outcomes, including improving the quality of oocytes and embryos and inhibiting the damage to the fetus from harmful antibodies by strengthening maternal immune action [
Chinese medicine has a theory of “the same homology both of the medicine and food.” With the development of society, the consciousnesses of modern health concept and health care are constantly strengthened, and diet therapy as a prevention and auxiliary treatment method has been widely accepted by the public. Diet therapy as one of the characteristic therapies of Chinese medicine has played an important role in auxiliary treatment for IVF-ET [
Patients should prepare for the treatment of IVF-ET before 1-2 months of starting treatment, including physical preparation and psychological preparation. Some dietetic therapies of TCM are suitable to these patients during this period, such as some bone soups made of some kinds of CHM, including DangShen, HuangQi, ShanYao, ShiHu, and so on. In addition, dietetic therapy of TCM could help the growth of the follicles to have a sufficient number, improve the quality of eggs, accelerate the growth of endometrium synchronously, and protect ovarian function and embryos [
Enema therapy using CHM is also known as anorectal drug delivery method which consists of pouring CHM into the rectum where it remains for four to five hours to make the CHM fully absorbed through the intestinal mucosa to treat some specific diseases. It is often used in the treatment of infertility to improve the pregnancy rate. One study observed 131 cases of IVF-ET failed patients treated with uterine lavage or treated with uterine lavage combined with retention enema of CHM; results showed that the clinical pregnancy rate (48.5% versus 29.2%,
The goals of adjuvant therapy with CHM are premise to ensure the safety of IVF-ET and maximize regulation of the overall health of patients and alleviate the adverse reaction during the period of IVF-ET treatment, then improving the clinical pregnancy rate and live birth rate. The mechanisms of adjuvant therapy with CHM in IVF patients may be as follows: (1) reduced ovarian blood flow resistance and increased ovarian perfusion, thus promoting the follicular development and improving the quality of oocyte [
CHM and acupuncture are commonly used to treat subfertile women with IVF as one of the complementary and alternative therapies; psychotherapy and temperature therapy are also commonly used in IVF-ET treatment as a kind of the complementary and alternative therapies.
Infertility patients with IVF-ET treatment are special groups; they suffer several pressures from family, society, high cost of medical care, and urgent desire of pregnancy, which easily leads to stress, anxiety, and depression. All of these bad emotions will cause reproductive endocrine dysfunction, leading to adverse effect on the development and maturation of follicles and the outcomes of medical care [
We should take some actions to reduce psychological pressure and increase compliance of patients undergoing IVF-ET, in order to improve the success rate of IVF-ET. The psychological interventions were widely used to relieve the pressure of patients as a popular CAM therapy. Psychological interventions include psychological counseling, supportive psychotherapy, the insight therapy or reasoning treatment, beliefs therapy, relaxation therapy, systematic desensitization therapy, behavioral therapy, and group therapy. Psychological interventions are varied, while the relaxation therapy is the usual recommended. Relaxation therapy leads to smooth emotion by relaxing the body step by step. All of these interventions belong to relaxation therapy, such as Chinese qigong, Indian yoga, Japanese meditation, German autogenic training, and American progressive relaxation training. Some studies suggested that psychological intervention can reduce the anxiety and depression of those patients undergoing IVF-ET, relieve the negative impacts on psychology, and improve the pregnancy rate than those patients who did not receive psychological intervention [
Summary of the effect of the clinical studies of psychological intervention on IVF outcomes.
Study |
Design | Sample size | Interventions | Outcomes | Limitation |
---|---|---|---|---|---|
148 | RCT | 420 | Treatment arm: psychological intervention |
Treatment arm: PR, 44.83% [39 of 125] |
|
|
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158 | Nonrandomized clinical trial | 110 | Treatment arm: psychological intervention |
Treatment arm: PR, 38.18% [21 of 55] |
Not mentioned drop-out rate |
|
|||||
149 | RCT | 210 | Treatment arm: psychological intervention through the treatment |
Treatment arm: PR, 53.33% [56 of 105] |
Not mentioned drop-out rate |
|
|||||
150 | RCT | 286 | Treatment arm: psychological intervention |
Treatment arm: PR, 40.79% [62 of 152] |
Not mentioned drop-out rate |
|
|||||
159 | RCT | 100 | Treatment arm: psychological intervention |
Treatment arm: PR, 35.7% [15 of 42] |
Small sample size |
|
|||||
151 | RCT | 268 | Treatment arm: psychological intervention |
Treatment arm: PR, 41.67% [80 of 192] |
Not mentioned drop-out rate |
|
|||||
152 | RCT | 207 | Treatment arm: psychological intervention |
Treatment arm: PR, 44.5% [49 of 108] |
Not mentioned drop-out rate |
|
|||||
153 | RCT | 385 | Treatment arm: psychological intervention |
Treatment arm: PR, 64.56% [122 of 189] |
|
|
|||||
154 | RCT | 218 | Treatment arm: IKAP intervention |
Treatment arm: PR, 54.0% [65 of 120] |
Not mentioned drop-out rate |
|
|||||
155 | RCT | 447 | Treatment arm: psychological intervention |
Treatment arm: PR, 43.5% [121 of 278] |
Not mentioned drop-out rate |
|
|||||
156 | RCT | 268 | Treatment arm: psychological intervention |
Treatment arm: PR, 46.32% [89 of 129] |
|
|
|||||
157 | RCT | 1060 | Treatment arm: psychological intervention |
Treatment arm: PR, 51.71% [320 of 590] |
Not mentioned drop-out rate |
Note: PR: pregnancy rate; IKAP: information-knowledge-attitude-practice;
Temperature is the key factor which influences the outcomes of IVF-ET, but what temperature is suitable for IVF remains controversial. Temperature therapy focuses on finding the most suitable temperature to promote the growth and development of the fertilized egg by adjusting the temperature during the period of IVF-ET. The temperature is different in different stages of IVF-ET, including ovary transfer temperature, oocyte maturation temperature, fertilization and embryo culture temperature, operating temperature of gamete and embryo
(I) Ovarian transport temperature: ovarian
Complementary and alternative medicine has been widely accepted in many Western countries; more and more infertile women select CAM as an adjuvant treatment to promote the pregnancy rate of IVF-ET treatment; Chinese herbal medicine and acupuncture are the most commonly used as the main therapies of TCM. In addition to TCM, there are psychological therapies, temperature therapies, and other alternative therapies which were used for the treatment of IVF-ET. All of these therapies of CAM can contribute to improve the pregnancy rate of IVF-ET patients in different degrees. Although all of current studies about CAM therapies are in the initial stage, there are many shortcomings, such as small size, low quality, and lack of uniform standard in clinical trial; superficial and unsystematic research for the mechanism in the experiment cannot provide a high-quality evidence for clinical application. Therefore, CAM therapy as a promising therapy for the patients with IVF-ET treatment is worthy of further research in the near future.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The study was funded by (1) the National Clinical Trial Base for Chinese Medicine (JDZX2012036), (2) the Project of Excellent Innovation Talents by Heilongjiang University of Chinese Medicine, and (3) the China Postdoctoral Science Foundation Special Funded Project (2013T60397).