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6. Traditional Chinese Medicine for Assisted Reproductive Technology
6.1 Introduction
In 1978, Dr. Patrick Steptoe, an expert in gynecology and laparoscopic surgery, and embryologist Dr. Robert Edwards successfully applied in vitro fertilization–embryo transfer (IVF–ET) technology resulting in and the first case of test-tube baby in the world, which was a big milestone and opened up a new way to treat infertile couples with assisted reproductive technology (ART). At present, ART has been expanded significantly in its clinical applications, incorporating various advances in ovarian physiology, reproductive endocrinology cryobiology, genetics, embryo culture, and transfer techniques [1].
However, there are still many challenges in ART. Currently, the average global clinical pregnancy rates with ART is running between 30% and 40%, and the take-home baby rates are even much lower [2]. Some patients are still unable to achieve successful pregnancy outcomes after repetitive trials at various ART practices. Therefore, they may face with the serious consequences of lifelong infertility [3]. There are many other problems needed to be solved, such as poor ovarian response, advanced reproductive age, diminished ovarian reserve (DOR), and recurrent implantation failure, all of which should be overcome in order to boost live birth rates with ART.
Traditional Chinese medical science (TCMS) has a long and extensive history. Traditional Chinese medical science has applied methods for curing infertility, and its efficacies have been clinically affirmed. This chapter reviews TCMS approaches for fertility treatment or to support ART success.
6.2 Traditional Chinese Medicine Science
6.2.1 Reproduction
Per TCMS “kidneys control reproduction,” “menstruation is based on kidneys,” and “menstruation is from kidneys.” With abundant and vigorous kidney energy, full kidney essence, unblocked Ren and Chong channels, and harmonious vital energy and blood, the menstruation will be symphonious, and women can get pregnant. However, with insufficient kidney energy and insufficient kidney essence, women may suffer from the disorder of vital energy and blood and cannot get pregnant. Therefore, tonifying the kidney and regulating menstruation are important treatment approaches for infertility in TCMS.
Many studies have shown that the use of TCMS in IVF can enhance clinical pregnancy rate [4, 5]. TCMS already has rich record of accomplishment and perfect theoretical system in gynecology and obstetrics. Theories such as “regulating menstruation before infertility treatment” and “two kinds of essences should be met to achieve pregnancy” play important roles for guiding modern medical treatment [5].
6.2.2 Assisted Reproductive Technology
- 1.
Controlled ovarian stimulation (COS): Tonifying the kidney, invigorating the spleen, and draining dampness can significantly reduce the risk of ovarian hyperstimulation syndrome (OHSS), alleviate the severity of OHSS, and increase the chance of fresh embryo transfer in patients at high risk for OHSS [6]. Periodic traditional Chinese medicine (TCM) treatment before COS by tonifying the kidney and regulating menstrual cycles in women with predicted poor ovarian response can improve ovarian response, which may involve the regulation of the hypothalamus–pituitary–ovary axis and ovarian microenvironment [7]. The combination of kidney-tonifying TCM can significantly reduce the dose of gonadotropins (Gn), improve the ovarian response, increase the number of oocytes retrieved, and improve oocyte quality, which result in increased pregnancy rates [8]. The mechanism of action of tonifying the kidney and activating blood circulation in diminished ovarian reserve patients is intended to regulate reproductive hormones, inhibit the apoptosis of ovarian granulosa cells, and promote ovarian angiogenesis [9].
- 2.
Embryo transfer: It is very important to improve endometrial receptivity, and therefore TCMS believes that viscera, menstruation, vital energy and blood, and uterus and Chong, Ren, Du, and Dai channels are the physiological bases of female reproductive system. Among them, the kidney, menstruation, uterus, and Chong and Ren channels are the central lines. According to TCM theory, kidney vacuity and essence depletion cause reproductive problems. In addition, liver dysfunction leads to inability of storing and regulating blood; dysfunction of spleen in transportation causes inability of producing blood and absorbing blood. All of these components are involved in the main pathogenesis of low endometrial receptivity. We should apply vital energy-enhancing, blood-replenishing, and liver and kidney-tonifying TCM in ART to optimize endometrial receptivity, to improve embryo implantation and pregnancy rates [10].
- 3.
Prevention of miscarriages: TCMS emphasizes that the pathogenesis of miscarriage is due to the damage to Chong and Ren channels and instability of embryo due to various causes of disease. Therefore, tonifying the spleen and kidney is the key to prevent miscarriage [11]. It is found that the Modified An Dian Laing Tian Tang has a significant effect in treatment of threatened abortion due to spleen and kidney deficiency in ART patients. It can promote embryo development and reduce excitability of myometrium by regulating the endocrine system and result in strengthen vigor and prevent miscarriage [12]. The research showed that TCM, such as using Gu Tai Tang and Sheng Qi Shou Tai Wan, is effective treatment for late threatened abortion in ART patients [13].
In short, further studies are needed regarding how to standardize and expand the TCM in every aspect of IVF–ET. It is necessary to make further efforts and research on combining the theory of TCMS and the research methodology of Western medicine to provide new and cost-effective treatment alternatives for women undergoing ART cycles.
6.3 Traditional Chinese Medicine
Traditional Chinese medicine is also known as Han medicine. It is considered a valuable treasure of Chinese culture, and TCM has made great contributions to the prosperity of the Chinese nation. The treatment concepts of TCM are finding more acceptance worldwide. Traditional medicine has attracted more and more attention from the international community. Traditional Chinese medicine is mentioned as “Chinese materia medica” in ancient Chinese books. The earliest Chinese monograph on science of Chinese pharmacology is Sheng Nong’s Herbal Classic written during the Han Dynasty. Tang Materia Medica issued by the government in the Tang Dynasty is the earliest pharmacopoeia in the world. Valuable Prescriptions for Emergency and Supplement to Valuable Prescriptions for Emergency compiled by Sun Simiao in the Tang Dynasty are the culmination of experience in diagnosis and treatment before the Tang Dynasty and have great influence on doctors of later ages. Compendium of Materia Medica written by Li Shizhen in the Ming Dynasty summarizes the drug experience before the sixteenth century and makes great contributions to the development of pharmacology in later ages.
6.3.1 Infertility
Traditional Chinese medicine and pharmacology have a long history in infertility treatment. According traditional Chinese medicine theory, the pathogenesis of infertility is the deficiency of the kidney [14]. In this section, we will present TCM formulas for infertility.
6.3.1.1 ART
Among infertile women receiving treatment of ART, 53.9% of them were diagnosed with kidney–Yang deficiency by doctors of TCM [15]. Wenshen’antai Decoction, including prepared Rehmannia root, pulp of Cornus, seed of Chinese dodder, Sichuan teasel, fried Eucommia ulmoides, Loranthus parasiticus, Morinda officinalis, glossy privet fruit, Angelica sinensis, root of red-rooted Salvia, Scutellaria baicalensis, and some others should be decocted in water for oral intake one dose twice per day. The decoction should be commenced on the second day after embryo transfer and continued for 5–7 days. Then the components which will nourish the blood and promote the blood circulation, such as root of red-rooted Salvia. Angelica sinensis should be removed from the decoction, and the decoction should be taken for another 5–7 consecutive days. In a relevant study, progesterone or human chorionic gonadotropin (HCG) was also administered to 40 patients with history of IVF–ET failure after the embryo transfer. Compared with the control group only taking Western medicine, the result shows Wenshen’antai Decoction can enhance the pregnancy rate of the second embryo transfer of patients who experienced embryo implantation failure (P < 0.05); moreover, it can increase the pregnancy rate of patients who experienced multiple implantation failures (P < 0.01) [16]. Li et al. [16] found that Wenshen’antai Decoction with prepared Rehmannia root, pulp of Cornus, glossy privet fruit, and Angelica sinensis can nourish blood and Yin and tonify the liver and kidney; seed of Chinese dodder, Sichuan teasel, fried Eucommia ulmoides, Loranthus parasiticus, and Morinda officinalis can warm the uterus and kidney, nourish the bone marrow, strengthen Chong and Ren channels, promote pregnancy, and prevent miscarriage; largehead Atractylodes rhizome can tonify the spleen and prevent miscarriage; Scutellaria baicalensis can clear heat, relieve fidgetiness, and prevent miscarriage; and root of red-rooted Salvia can promote blood circulation, remove blood stasis, cool blood, and calm the nerves, which not only improves blood circulation of endometrium but also relieves mental anxiety and tension. Cooperation of the medicinal materials can strengthen Chong and Ren channels, warm the kidney, and promote pregnancy, which will create a good internal environment for the uterus and enhance the affinity between embryo and the uterus.
6.3.1.2 Tubal Factor
- 1.
Enema with TCM and Western medicine: Use 20 ml normal saline to dissolve 4000 units of chymotrypsin; then draw 16 units of gentamicin, 10 mg dexamethasone injection, and 20 ml red-rooted salvia injection to inject into rectum. Then inject metronidazole sodium chloride injection in the same way.
- 2.
Application of hot compresses of TCM on abdomen: Hot compress of TCM consists of monkshood 15 g, cassia Twig 10 g, Sichuan pepper 10 g, green Chinese onion 3, Ephedra 5 g, ginger 10 g, garden balsam stem 15 g, Impatiens 15 g, Angelica sinensis 10 g, Sanguis draconis 3 g, frankincense 3 g, myrrh 3 g, borneol 1 g, camphor 1 g, and appropriate amount of vinegar.
- 3.
Prescriptions of TCM as an oral medication: Angelica sinensis 10 g, root of red-rooted Salvia 10 g, Chinese honey locust spine 10 g, Leonurus japonicus houtt 10 g, Fructus liquidambaris 10 g, Herba lycopi 10 g, seed of cowherb 10 g, Fructus aurantii 10 g, red peony root 10 g, medicinal Cyathula root 10 g, Akebia quinata 5 g, Angelica Sinensis 5 g, and sliced Cornus cervi 5 g.
For patients with severe hydrosalpinx, the following medicinal materials shall be added: Rhizoma Sparganii treated with vinegar 5 g, Curcuma zedoaria treated with vinegar 5 g, and endothelium corneum gigeriae galli 5 g.
For patients with severe heat and dampness, the following medicinal materials shall be added: Shuteria pampaniniana 5 g, Herba Patriniae 5 g, and raw Coix seed 5 g.
For patients with kidney–Qi deficiency, the following medicinal materials shall be added: seed of Chinese dodder 10 g and teasel 10 g; for patients with kidney–Yang deficiency, the following medicinal materials shall be added: Fluoritum 5 g, Morinda officinalis 5 g, and raspberry 5 g.
6.3.1.3 Ovarian Factor
Ovarian follicular development disorders, such as polycystic ovary syndrome, luteinized unruptured follicle syndrome, anovulation, and others, are common causes of infertility. In TCM, treatment for ovarian follicular development disorder mainly focuses on treating “kidney deficiency.” Deficiency of kidney essence is the key pathogenesis of ovarian follicular development disorder. Kidney deficiency causes blood stasis, which blocks Chong and Ren channels and the uterus. Without adequate nutrition, oocytes cannot be matured and excreted. Therefore, kidney nourishing and essence replenishing should be emphasized in the treatment. Yin nourishing and supporting Yang should be carried out at the same time. Both Yin and Yang should be nourished. Meanwhile, the right amount of blood nourishing and blood circulation-activating and blood stasis-removing medicines with appropriate compatibility should be used to treat both symptoms and root causes of disease [18]. In a study by Zhang et al. [19], PCOS patients receiving IVF–ET were randomly allocated to TCM group and control group, with 30 patients in each group. Compared to the control group, the patients in TCM arm took TCM formula (Fluoritum 30 g, seed of Chinese dodder 30 g, fruit of Chinese wolfberry 15 g, Eucommia ulmoides 15 g, Angelica sinensis 12 g, root of red-rooted Salvia 15 g, Radix Achyranthis Bidentatae 15 g, white peony root 12 g, Rhizoma Cyperi 12 g, and licorice 6 g) to tonify kidney and activate blood circulation in the process of COS. Their results showed that there was significantly higher rates of fertilization and embryo cleavage and greater high-quality embryo rate and clinical pregnancy rate in TCM arm as compared to those in the control group (P < 0.05). However, there was no significant difference in the number of eggs retrieved between the two groups (P > 0. 05).
6.3.1.4 Prevention of Ovarian Hyperstimulation Syndrome
Ovarian hyperstimulation syndrome (OHSS) is a dreaded complication of ART. Patients with severe OHSS present with hemoconcentration, hydrothorax and ascites, liver and kidney function damage, thrombosis, adult respiratory distress syndrome, and even death. In the view of TCM, the mechanism of OHSS is a large amount of kidney essence lost, which results in the emptiness of the uterus and loss of nourishment in Chong and Ren channels. Disorder of vital energy and blood and disorder of viscera function result in the occurrence of pathological products such as blood stasis and phlegm. The two disorders can interact with each other, which causes vicious circle and results in severe disorder of viscera function, vital energy, and blood, finally causing abdominal distention and edema [20]. Niu et al. [21] used kidney-tonifying and blood circulation-activating prescription to induce ovulation in 56 PCOS patients with clomiphene citrate. Control group only used HCG to induce ovulation. Their results demonstrated that kidney-tonifying and blood circulation-activating TCM (prepared Rehmannia root 10 g, monkshood 5 g, seed of Chinese dodder 15 g, fruit of Chinese wolfberry 15 g, Poria cocos 15 g, longspur Epimedium 15 g, Ligusticum wallichii 10 g, Angelica sinensis 10 g, peach kernel 10 g, safflower Carthamus 10 g, Gleditsia sinensis 15 g, pangolin 10 g) can significantly reduce the incidence of OHSS without affecting the ovulation rate and the pregnancy rate. For OHSS treatment, Zhao Rong et al. [22] used luteinizing granules (prepared Rehmannia root, Chinese yam, fruit of Chinese wolfberry, pulp of Cornus, seed of Chinese dodder, deer horn glue, tortoise plastron, Codonopsis pilosula, largehead Atractylodes rhizome, hyacinth bean, Coix seed, Poria cocos, and some others) combined with conventional luteal support treatment, which is compared with using luteal support treatment only. The cure rate of the test group was 90.9%, and the total effective rate was 100%; the cure rate and total effective rate in the control group were 61.5% and 80.8%. These differences were statistically significant favoring TCM co-treatment (P < 0.05). The authors mentioned that largehead Atractylodes rhizome and Poria cocos can invigorate the spleen and drain dampness; Chinese yam can strengthen the spleen and tonify the kidney; hyacinth bean and Coix seed can clear damp and promote diuresis and be helpful in treating the symptoms; seed of Chinese dodder and deer horn glue can warm and tonify kidney Yang; prepared Rehmannia root, fruit of Chinese wolfberry, tortoise plastron, and pulp of Cornus can nourish kidney Yin, which achieves the purpose of reinforcing Yang from Yin. The prescription treats both symptoms and root causes of OHSS.
6.3.1.5 Western Medicine
Supplementing modern ART with diagnosis and treatment of TCM plays an affirmative role in areas such as ovarian stimulation, increasing IVF success rate, increasing endometrial receptivity, and preventing complications of ART like OHSS. However, TCM is not standardized, lacking unified and objective diagnosis and treatment standards and also lacking evidence-based medicine research, poor theoretical repeatability, and insufficient theoretical depth. These aspects of TCM may lead to some concerns regarding its clinical applications. At present, the research on TCMS and TCM in ART is developing rapidly. It is believed that the combined treatment of TCM and Western medicine can be used widely. Traditional Chinese and Western medicines can complement each other advantages, to improve the treatment efficiency and quality of ART.
6.4 Acupuncture and Moxibustion
6.4.1 Definitions and Types
Acupuncture and moxibustion are the general designation of acupuncture therapy and moxibustion therapy. These are important components of TCMS, which include acupuncture theory, acupoints, acupuncture and moxibustion technology, and related instruments. These are the result of a valuable heritage developed on the basis of the cultural and scientific tradition of Chinese nation.
Acupuncture therapy refers to stabbing needling instruments (acupuncture needles in general) into patient’s body in a certain angle with the guidance of TCMS and stimulates the specific parts of the human body by using acupuncture manipulation techniques, such as twirling needles and lifting and thrusting needles, to achieve the purpose of treating diseases.
Moxibustion therapy is intended to cauterize, smoke, and press certain acupoints on the surface of the human body with prefabricated moxibustion cones and moxibustion herbs through thermal stimulation to prevent and treat diseases. There are many types of acupuncture and moxibustion, and the most common types are acupuncture therapy, electroacupuncture therapy, and moxibustion therapy
6.4.2 Mechanism of Action
6.4.2.1 Dredging the Channels
The fundamental and direct therapeutic effect of acupuncture and moxibustion is to treat or prevent main and collateral channel block so that they can play their normal physiological functions. The main and collateral channels are “distributed in viscera, limbs, and joints.” One of its main physiological functions is to enable vital energy and blood circulation. Blocked main and collateral channels will block vital energy and blood circulation, which clinically manifest as pain, numbness, swelling, and ecchymosis. Acupuncture and moxibustion can unblock main and collateral channels and recover normal vital energy and blood circulation by corresponding acupoints and acupuncture manipulation techniques, and by also inducing bleeding by pricking with three-edged needles.
6.4.2.2 Regulating the Balance Between Yin and Yang
The ultimate purpose of acupuncture and moxibustion treatment is to keep the balanced status of Yin and Yang. The mechanism of disease can be summarized as the imbalance of Yin and Yang. The acupuncture and moxibustion regulate the balance between Yin and Yang through Yin and Yang attributes of the main and collateral channels, compatibility of channels and acupoints, and acupuncture manipulation techniques.
6.4.2.3 Strengthening the Body Immunity to Eliminate Pathogenic Factors
The mechanism of acupuncture and moxibustion in strengthening the body immunity to eliminate pathogenic factors is to strengthen the human body’s vital energy and eliminate pathogenic factors. The occurrence, development, and prognosis of disease are the process of the battle between the vital energy and the pathogenic factor. Acupuncture and moxibustion treatment play their roles in strengthening the body immunity to eliminate pathogenic factors.
6.4.3 Clinical Applications in ART and Infertility
6.4.3.1 Acupuncture and Moxibustion to Improve Ovarian Function
Improving Ovarian Endocrine Function
Wu et al. [23] found that 3-month electroacupuncture treatment was ineffective in patients with premature ovarian insufficiency . This treatment consisted of acupoint prescription I, UB33 (bilateral); acupoint prescription II, REN4; ST25 (bilateral); and ST29 (bilateral). The two acupoint prescriptions were acupunctured alternately every other day. The results suggested that acupuncture and moxibustion may significantly improve the endocrinologic function of patients with premature ovarian insufficiency by reducing FSH and LH levels while increasing estradiol (E2) levels (P < 0.01). FSH, LH, and E2 levels were not statistically significant between the month that the acupuncture and moxibustion treatment ended and the third-month follow-up visit. Therefore, the potential treatment effects were temporary. Mi et al. [24] treated 30 patients with poor ovarian response with transcutaneous electrical nerve stimulation (TENS). The main acupoints selected were REN4, REN3, SP6, EX-CA1, ST25, UB23, DU3, and DU4. After 3 months of treatment, patients’ serum levels of FSH, LH, and E2 were significantly different from those before treatment.
Xu Yin et al., [25] treated 40 patients with ovulatory infertility by using electroacupuncture and moxa moxibustion on acupoints such as EX-CA1, REN4, and REN3 combined with activating acupoints with eight methods of intelligent turtle once a day for 3 months. They found that FSH and LH levels significantly decreased, and E2 levels significantly increased after treatment compared with the levels before treatment.
Promoting Follicular Development
Zhou et al. [26] randomly divided 63 DOR patients into treatment group and control group before they received IVF–ET treatment. The treatment group was treated with acupuncture and moxibustion sequential therapy according to menstrual cycle by stages. Acupoints selected for premenopausal period were REN6, REN4, GB34, and LIV3; acupoints selected for menstrual period were EX-B8 and DU4; acupoints selected for postmenopausal period were SP6, KID3, UB23, and UB17; and acupoints selected for ovulatory period were REN6, REN4, EX-CA1, ST36, and KID7. They found that the number of oocytes retrieved, the number of fertilized oocytes, the number of high-quality embryos, the embryo implantation rate, and the clinical pregnancy rate significantly increased in treatment group compared with control group.
Cui et al. [27] randomly divided 66 PCOS patients who were about to receive IVF–ET treatment into observation group and control group. Both groups used GnRH agonist long protocol for COS. The observation group received additional electroacupuncture intervention. The main acupoints selected were REN4, REN3, SP6, EX-CA1, and KID3. The authors noted that fertilization rate, cleavage rate, and high-quality embryo rate were significantly higher in observation group than the control group.
Lian et al. [28] randomly divided 66 IVF–ET patients diagnosed with kidney deficiency with the age 35 to 42 years old into observation group and control group. All patients received GnRH agonist long protocol. The observation group started with electroacupuncture treatment on the fifth day of menstruation, and the acupoints selected were SP6, EX-CA1, REN3, and REN4. For the control group, the same acupoints were selected for fake acupuncture. Electroacupuncture treatment was carried out every other day until the day of oocyte retrieval. High-quality oocyte rate and high-quality embryo rate were higher in observation group than in the control group.
Ovulation Induction
Yin et al. [29] treated 40 patients with anovulatory infertility with electroacupuncture, and the selected acupoints were DU4, REN4, SP6, EX-CA1, and ST36. After treatment, the ovulation rate was 45%. Total pregnancy rate within the first year after the treatment was 22.5%.
Zhang et al. [30] selected 50 patients with anovulatory disorder and randomly divided them into study group and control group. The study group was treated with acupuncture on ovarian acupoints by handle-twisting and lifting–thrusting method. Patients of the control group were given basic clinical treatment. They found that the rate of successful ovulation in the study group was 80%, which was significantly higher than the control group, in which the rate of successful ovulation was 40%.
Sheng et al. [31] randomly divided 138 infertile patients into treatment and control groups. The control group adopted long-term ovulation induction schedule. The treatment group added acupuncture and moxibustion therapy. The acupoints selected were REN8, REN3, REN4, EX-CA1, ST36, PC6, and SP6. Their results demonstrated that the ovulation rate and the pregnancy rate of the treatment group were significantly higher than those of the control group.
Improving Endometrial Receptivity
Xu et al. [32] randomly divided 176 patients undergoing frozen-thawed embryo transfer (FET) with history of recurrent implantation failure into observation group and control group. Both groups received conventional endometrial preparation before FET. The observation group was also given TENS from the tenth day of menstruation. There were significant differences in endometrial thickness, biochemical pregnancy rate, clinical pregnancy rate, and embryo implantation rate between the two groups, favoring TENS addition to conventional FET preparation. This study suggests that TENS can improve endometrial receptivity of patients with recurrent implantation failure.
Li et al. [33] randomly divided 90 patients suffering from failed IVF–ET cycles due to poor endometrial development of unknown reasons into observation group and control group. The observation group was intervened with transcutaneous electrical nerve stimulation from the fifth day of menstruation, and the acupoints selected were ST25, KID12, EX-CA1, and SP6. The observation and control groups both treated by GnRH agonist long protocol. By comparing the endometrial thickness, endometrial pattern, and blood flow parameters of the two groups, they suggest that transcutaneous electrical nerve stimulation can promote endometrial growth, improve endometrial receptivity, promote embryo implantation, and enhance clinical pregnancy rate.
Yan et al. [34] randomly divided 108 patients undergoing IVF/ICSI treatment into three groups: acupuncture group, placebo acupuncture group, and control group. Patients received acupuncture treatment 24 hours before embryo transfer and 30 minutes after embryo transfer in acupuncture group, and the acupoints selected were Group I, ST29, SP8, EX-CA1, and SP10 and Group II, ST36, KID3, UB23, and REN4. Patients receive acupuncture treatment on acupoints unrelated to embryo transfer in placebo acupuncture group. There is no acupuncture treatment in control group. They found that acupuncture can improve the endometrial blood flow and improve pregnancy rates in IVF patients.
The Analgesic Effect of Acupuncture and Moxibustion During the Oocyte Retrieval Process
Kou et al. [35] selected 462 patients receiving IVF–ET and divided them into three groups, meperidine alone, acupuncture-combined anesthesia, and intravenous anesthesia, and compared the analgesic effect and adverse reaction among the three groups. For the group of acupuncture-combined anesthesia, patients received intramuscular injection of meperidine in 50 mg 30 minutes before the operation and then received acupuncture. The acupoints selected were DU20, EX-CA1 (ear), SJ8 (ipsilateral), PC6, ST36, and SP6. The needles were retained until the end of the operation. Acupuncture-combined anesthesia and intravenous anesthesia could both alleviate patients’ degree of pain and adverse reaction during the oocyte retrieval, reduce the need for other sedatives, and enhance the oocyte retrieval rate without direct effects on pregnancy results.
Chen et al. [36] randomly divided 106 IVF–ET patients into meperidine group, ear acupuncture group 1, and ear acupuncture group 2, to compare the analgesic effects of the three groups. The acupoints selected were Shen Men point and internal genitalia point in ear acupuncture group 1 and were heart point and subcortex point in ear acupuncture group 2. The electroacupuncture stimulation was applied to both groups, and the needles were retained until the end of operation. Finally, it was reported that electroacupuncture on ear acupoints is safe and effective for analgesia during the oocyte retrieval procedure. Analgesic effects were not significantly different between electroacupuncture stimulation on Shen Men point and internal genitalia point and electro acupuncture stimulation on heart point and subcortex point.
Acupuncture and Moxibustion to Reduce IVF-Associated Complications
He et al. [37] randomly divided 304 infertile ART patients into study group and control groups. GnRH-agonist long protocol was used for COS. Patients in study group were treated with acupuncture from the first day of COS until the day of embryo transfer. The control group did not receive acupuncture treatment. The main acupoints selected were REN4, REN3, EX-CA1, ST29, PC6, LI4, ST36, SP8, and SP6. The OHSS incidence rate of the study group was lower than that of the control group, and the difference was statistically significant (P < 0.05).
Yang [38] selected 102 patients with high risk of OHSS and randomly assigned them into acupuncture ovulation induction group (study group) and ovulation induction group (control group). COS was achieved with GnRH agonist long protocol in both groups. The study group started receiving assisted traditional acupuncture treatment from the first day of COS to the day of oocyte retrieval. The main acupoints selected were Zhongyuan, REN3, REN4, EX-CA1, ST29, LI4, ST36, SP9, SP6, and KID3. The results show that the traditional acupuncture-assisted treatment can reduce the incidence of severe OHSS during the IVF–ET treatment. It may improve local microenvironment and metabolism of the ovary by reducing inflammatory response of human body and secretion of inflammatory factors.
6.4.4 Expectations and Concerns
In recent years, more research has focused on the application of acupuncture and moxibustion in reproductive medicine. These techniques may have unique advantages in improving ovarian response and endometrial receptivity and also in reduction of COS complications and in decreasing the dose of gonadotropins. However, there are still some concerns, which need to be addressed: First, most of the researchers only pay attention to the follicular development, oocyte retrieval, and embryo implantation but ignore preconceptional care. Secondly, there are few follow-up studies to investigate the long-term efficacies of acupuncture and moxibustion, such as clinical pregnancy rate and live birth rate. Thirdly, there is a lack of high-quality, multicenter randomized controlled trials with a large sample size with a unified inclusion, exclusion, and efficacy determination criteria. In addition, therapeutic protocols reported in most clinical studies are the combinations of acupuncture and modern therapy, which cannot well-reflect the characteristics of traditional acupuncture and moxibustion. In recent years, most of the research is focused on applications of acupuncture and moxibustion to affect clinical outcomes of IVF-ET, but there are no efforts to investigate the real mechanisms of action of these technologies. This will limit the further clinical applications of acupuncture and moxibustion since they are still not justified for Western clinical practice. At present, animal testing is the main route of the exploring the mechanisms of acupuncture and moxibustion, although the related animal studies are very few. Moreover, the most common animal model selected is mouse, which is quite different from human beings in terms of reproduction. Exploring the mechanism of acupuncture and moxibustion is a unique significance for further effectively applying it in IVF–ET or for infertility.
6.5 Other Traditional Chinese Medicine Approaches
Besides TCMS, TCM, acupuncture, and moxibustion, there are other TCM-assisted treatments which can be used in the field of ART, such as naprapathy, cupping therapy, chiropractic, ear acupuncture therapy, enema therapy, navel paste made of TCM, and music therapy of five elements of TCMS. The treatment for female infertility includes five aspects: kidney deficiency, disorder of liver and kidney, liver stagnation, internal retention of phlegm and dampness, and kidney deficiency and blood stasis.
Among them, naprapathy is a therapy, which combines modern medical theory and applies naprapathy manipulation to act on specific parts and acupoints of human body under the guidance of traditional Chinese medical theory, in order to prevent and treat diseases. From the perspective of traditional medicine, naprapathy can regulate the balance between Yin and Yang, unblock main and collateral channels, activate vital energy and blood circulation, nourish muscles and bones, and improve viscera functions. Viscera naprapathy takes effect by adjusting nerves and body fluid and can dilate blood vessels, promote blood flow, and improve the microcirculation.
The basic function of naprapathy manipulation are as follows: (1) unblock main and collateral channels and activate vital energy and blood circulation; (2) adjust viscera; (3) regulate tendons and remove stasis; and (4) bone setting and restoration.
Naprapathy therapy can promote the recovery of ovarian function and adjust endocrine disorders and basal body temperature abnormalities [39]. Naprapathy therapy can stimulate the main and collateral channels and regulate vital energy, blood circulation, and viscera functions, which result in abundant kidney essence, normal dredging function of the liver, unblocked vital energy and blood circulation, and symphonious Chong and Ren channels. Moxibustion can also stimulate Ren channel to connect to Sanyin channel, which will enhance the uterus’ ability of gestating fetus [40].
Zhang et al. [41] reported that abdominal naprapathy may promote ovarian function by regulating vital energy and blood circulation, tonifying the liver and kidney, conditioning Chong and Ren channels, soothing the liver, and relieving depression. Therefore, it is significantly effective in the treatment of patients with corpus luteum maldevelopment, thin and weak body, and spleen–kidney deficiency.
Cupping therapy is a method that removes air in cups by burning and air exhaustion to create negative pressure in the cups, which can make cups adhere to acupoints or body surface of locations needing cupping therapy. This method makes congestion and blood stasis form on local skin, in order to prevent and treat diseases.
It is stated in Plain Questions: On Dermal Parts, “Since twelve channels are part of the skin, incidence of every disease is certainly shown on skin.” Twelve dermal parts are closely related to main and collateral channels and viscera. Cupping therapy acts on the skin surface and then reaches the muscle, which can activate vital energy and blood circulation, promote blood circulation, and remove blood stasis. Modern medicine believes that cupping therapy causes a series of neuroendocrine changes and regulates the permeability of blood vessel wall, and influences diastolic and retractile function of blood vessels, which result in improved local blood circulation [42]. The main function of cupping therapy is to activate vital energy and blood circulation, to dispel pathogenic cold, to relieve pain, and to reduce swelling.
Chiropractic is a method of acting on the spine and surrounding muscles with various manipulations by physicians to achieve treatment purpose [43]. The chiropractic treatment keeps the spinal cord stage of lumbar vertebra consistent with that of pelvic organs, which makes the uterus prepared for pregnancy [44]. Some researchers believe slight anatomical position changes in the spine can cause pain in the neck, shoulders, waist, and legs and result in muscle spasm and poor blood and lymphatic circulation. Chiropractic treatment can restore normal physiological and anatomical position, thus alleviating muscle spasm, regulating nerve reflex, strengthening blood and lymphatic circulation, enhancing metabolism of tissue, relieving swelling and pain, and promoting rapid repair of damaged tissue [45, 46]. This method mainly treats infertility caused by lumbar vertebral bone injuries or lumbar vertebral diseases.
Ear acupuncture refers to the method of stimulating auricle acupoints by acupuncture to prevent and treat diseases and diagnosing diseases by observing and touching ears, preventing and treating diseases by stimulating auricle. In addition to traditional acupuncture carried out with acupuncture needles, there are more than 20 ear acupoint-stimulating methods, such as electric stimulating method, needle imbedding method, bloodletting method, injection method, magnet therapy method, ear clip method, drug application method, plaster application method, pellet pressing method, and laser method. Egyptian paleontologists documented that women used needles and braids on auricle to practice contraception in ancient Egypt. Hippocrates, an ancient Greek physician, reported that the bloodletting method was used to alleviate impotence and activate ejaculation [47].
Zhang et al. [48] used body acupuncture and ear acupuncture intervention before and after embryo transfer. With respect to body acupuncture, the acupoints selected before transplantation were PC6, SP8, LIV3, DU20, and ST29; the acupoints selected after embryo transfer were ST36, SP6, SP10, and LI4. Mild reinforcing and attenuating manipulation were used. With respect to ear acupuncture, ear acupoints, namely, HT7, EX-CA1, endocrine acupoint, and brain point, were acupunctured without twirling needle before and after embryo transfer. The non-acupuncture control group was the same as the normal treatment cycle. The results showed the pregnancy rate of the acupuncture group (46%) was significantly higher than that of the control group (26%).
Enema with traditional Chinese medicine including solution can be absorbed directly by the rectum and then act on pelvic organs, which may have benefits in endometriosis and chronic pelvic inflammatory disease treatment.
Wu [49] claimed that enema with TCM as an assisted treatment for endometriosis patients after laparoscopic operation is safe and effective, with high pregnancy rate. For infertile patients with tubal obstruction, enema therapy reduces the drug’s gastrointestinal reaction, makes drug locally and directly absorbed, promotes blood circulation, increases tubal peristalsis, improves internal pelvic environment, causes tubal adhesions to release, and enhances the pregnancy rates.
Lu et al. [50] achieved good results in treating tubal obstruction by enema with TCM. For patients with chronic pelvic inflammation, they are often diagnosed with stagnation of vital energy and blood stasis and dampness–heat type by TCM. It means dampness and heat are retained in the lower energizer and block main and collateral channels of the uterus and vital energy and blood of the uterus, which form vital energy and blood stasis and obstruction in main and collateral channels and finally develop adhesions and masses. Combining enema therapy of TCM can effectively promote blood circulation to remove blood stasis, unblocking main and collateral channels, softening hardness to dissipate stagnation, and clearing heat and promoting diuresis with laparoscopic surgery. Pregnancy rate of infertile patients with chronic pelvic inflammation can be further enhanced [51].
Navel compressing with traditional Chinese medicine, including Eucommia ulmoides, Fennel fruit, China berry fruit, monkshood root, Radix Achyranthis Bidentatae, teasel, licorice, Illicium verum, tall Gastrodia fruit, freshwater sponge, Fructus Psoraleae, desert-living Cistanche, prepared Rhizome of adhesive Rehmannia, Herba cynomorii, fossil fragments, hippocampus, Chinese eaglewood, frankincense, Fructus caryophylli, myrrh, Radix aucklandiae, Cervi cornu pantotrichum, is also practiced. The herbal medicines should be decocted into ointment, dissolved into liquid by heat, and pasted to the navel. The ointment should be changed every 3–5 days. It can nourish the liver, kidney, and blood and warm channels, in order to treat infertility caused by deficiency of the liver and kidney.
The traditional music therapy in China takes the “harmony of music and human” and “unity of nature and human” as an ideal state. It emphasizes the balance of Yin and Yang and the inter-promoting relation among the heart, liver, spleen, lungs, and kidneys and promotes the balance of Yin and Yang in the human body, harmonization of vital energy and blood, and emotional comfort by orthodox and gentle five musical sounds and six tonalities in traditional music to treat diseases. The theory is pointed out in The Yellow Emperor’s Canon of Internal Medicine, including that there are five elements (wood, fire, earth, metal, and water) in the world and they generate five musical sounds (Jue, Zhi, Gong, Shang, and Yu). There are five seasons (spring, summer, long summer, autumn, and winter) on the earth, and they produce five stages (birth, growth, change, collection, and store). Human has five internal organs (liver, heart, spleen, lungs, and kidneys) and five kinds of emotions (anger, joy, thought, worry, and fear). All of these reflect the organic connection between human and nature. It is also recorded that “Jue” is the sound of wood which is connected to the liver; “Zhi” is the sound of fire which is connected to the heart; “Gong” is the sound of earth which is connected to the spleen; “Shang” is the sound of metal which is connected to the lungs; and “Yu” is the sound of water which is connected to the kidneys. This is the principle of five-sound therapy. Therefore, according to the theory of five-sound therapy, the mode of motion of vital energy inside the living body is influenced by acoustic oscillations of different musical modes to comply with spreading of vital energy of wood, rising of vital energy of fire, placidity of vital energy of earth, adduction of vital energy of metal, and decline of vital energy of water, respectively. All of these result in harmonious and orderly circulation of vital energy and blood and steady state of viscera function operation [52].
The clinical diagnoses of patients with recurrent spontaneous abortion are mainly due to deficiency of spleen and kidney. “Gong” is the sound of earth, which is connected to the spleen; “Yu” is the sound of water which is connected to the kidneys. According to the theory of midnight–midday ebb flow, vital energy and blood of spleen channel are vigorous at 10:00 a.m. (Sishi) every day. In order to enhance the efficacy of treatment, the patients should listen to music of Gong at 10 a.m. Vital energy and blood of kidney channel are vigorous at 5:00 p.m. (Youshi) every day, so the patients should listen to music of Yu at 5 p.m. Many research results show that anxiety is the only emotional factor that can cause pregnancy complications. The evidences suggest that complications of pregnancy, such as recurrent abortion, pregnancy-induced hypertension, premature delivery, and prolonged labor, may be associated with emotional factors during pregnancy, at least related to the stressful emotional conditions, which indicates that emotional stress in pregnant women can affect the fetal development and labor and delivery [53].
6.6 Conclusion
Traditional Chinese medicine is based on thousands of years of tradition and experience. There should be mechanistic and outcome-based studies in many applications and techniques we discussed in this chapter. In order to assure their real-life applications and their combination with Western medicine, more studies are required. We provide a supplemental file listing the English and Chinese names of the herbal substances, most of which are mentioned in this chapter.
