Open access peer-reviewed chapter

Acupuncture Management in the Field of Assisted Reproductive Technology

Written By

Jie Yang, Liying Liu, Xiaoyan Zheng, Jingwen Zhang and Yuanyuan Lai

Submitted: 31 May 2023 Reviewed: 01 June 2023 Published: 27 June 2023

DOI: 10.5772/intechopen.1001948

From the Edited Volume

Recent Advances in Alternative Medicine

Cengiz Mordeniz

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Abstract

Acupuncture is an ancient traditional Chinese medical practice that involves the insertion of fine needles into specific acupuncture points to rebalance energy and improve blood circulation within the body. Assisted reproductive technology (ART) is a method used to help couples who are unable to conceive naturally fulfill their desire for parenthood. Within ART, acupuncture management is utilized as adjunctive therapy to optimize the reproductive environment and increase the chances of a successful pregnancy. Acupuncture, as an adjunctive treatment modality in ART, offers unique advantages in regulating endocrine function, enhancing blood circulation, and reducing stress. Drawing upon a decade of experience in acupuncture-assisted reproduction and previous research, this chapter provides an overview of the clinical applications of acupuncture in different stages of ART and explores its potential mechanisms of action in the treatment of male infertility and female infertility. It highlights the promising prospects of acupuncture-like adjunctive therapies in the field of ART.

Keywords

  • acupuncture
  • assisted reproductive technology
  • in vitro fertilization
  • adjunctive treatment
  • complementary medicine

1. Introduction

Infertility refers to couples who have cohabited for at least a year and have a normal sexual life without using contraceptives but are still unable to conceive [1]. Statistically, between 8 and 12 percent of reproductive couples worldwide are infertile [2]. Since the first successful use of conventional in vitro fertilization (IVF) in 1978, assisted reproductive technology (ART) has rapidly evolved and become an important means of resolving infertility, which plays a crucial role in achieving fertility [34]. ART, which includes artificial insemination (AI) and in vitro fertilization-embryo transfer (IVF-ET) and its derivatives, is a modern method for creating new life. IVF-ET involves egg donation, sperm donation, gestational carriers, ovarian stimulation, egg retrieval, embryo culture, and transfer [5, 6]. ART, the last resort if medications and surgery fail, had birthed over 8 million babies by 2020. Since reproductive medicine developed, the clinical pregnancy rate (CPR) has been 29–35% [7], whereas the live birth rate (LBR) is barely 30% [8].

As a treasure of Chinese medicine, acupuncture was accumulated through long-term medical practice by ancient people. It has the characteristics of safety, effectiveness, wide applicability, simplicity, and economy. Acupuncture has made great contributions to the prosperity and development of the Chinese nation for thousands of years and gradually plays a unique role in the world’s healthcare industry. The treatment principle of acupuncture is mainly to stimulate the acupoints of the human body through various acupuncture instruments and special treatment techniques to adjust the balance of yin and yang, promote the circulation of qi and blood, and accelerate the circulation of the meridians. Compared with other treatment methods, acupuncture has obvious advantages in the comprehensive treatment of local and systemic conditions. It can be said that the essence of acupuncture action is to initiate, promote, and adjust, rather than supplement and intervene with exogenous substances.

Acupuncture has a long history as a safe and effective physical therapy with few side effects in the treatment of infertility. In 1999, Stener-Victorin and their colleagues [9] were the first to find that electroacupuncture (EA) benefits embryo implantation, and women’s pregnancy in the process of ART and can relieve the pain of patients during oocyte retrieval. Since then, studying how and why acupuncture makes ART work better has become an important area of research in this field. Several studies have investigated the mechanisms of acupuncture in male or female infertility. For instance, acupuncture affects the female reproductive endocrine immune system by activating the hypothalamic–pituitary-ovarian (HPO) axis [10]. EA can improve sperm function by increasing the functional expression of CatSper corporate channels in sperm [11].

With our wealth of expertise gained from ten years of experience in acupuncture-assisted reproduction and extensive prior research, this chapter offers a comprehensive examination of acupuncture’s clinical applications throughout various stages of ART. It delves into the potential mechanisms underlying acupuncture’s efficacy in addressing both male and female infertility while emphasizing the optimistic outlook for acupuncture-related complementary therapies in the realm of ART.

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2. Clinical research for acupuncture management in the ART process

As the demand for safe and holistic approaches to improve fertility outcomes continues to grow, clinical research investigating the efficacy of acupuncture in the management of ART procedures has become paramount. By examining the available evidence, we aim to provide a comprehensive overview of the current understanding of acupuncture’s potential benefits and its impact on key aspects of the ART journey, including controlled ovarian hyperstimulation (COH), oocyte quality, embryo transfer, pregnancy rates, etc. The overall outlooks of clinical research for acupuncture management in ART were shown in Figure 1.

Figure 1.

The overall outlooks of clinical research for acupuncture management in ART.

2.1 Acupuncture management during the COH

COH is a medical procedure employed in ART to induce the development of multiple follicles in the ovaries, thereby increasing the likelihood of successful pregnancy for women undergoing IVF or other ART procedures. Significant advancements in COH programs have been achieved, primarily driven by the research and development of innovative therapeutic agents. However, it has become evident that overly aggressive ovarian management can have detrimental effects on a woman’s reproductive system. COH can lead to the occurrence of side effects, such as ovarian hyperstimulation syndrome (OHSS). To address these concerns, acupuncture has emerged as a valuable approach for managing the symptoms associated with COH and OHSS. By stimulating the body’s innate healing mechanisms and promoting relaxation, acupuncture offers a complementary therapy to alleviate the adverse effects.

2.1.1 Regulate hormone levels

Acupuncture has been shown to stimulate the production of endorphins, which can help regulate hormone levels and improve reproductive function. As early as 2009, a study found that the regulation of cortisol and prolactin in the acupuncture group appeared to be beneficial during the medication phase of IVF treatment, with a trend toward a more normal fertility cycle dynamic [12]. Poor ovarian response (POR) to ovarian stimulation usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes [13]. Based on our newly published systematic review, we found that acupuncture treatment during COH is questionable in improving pregnancy outcomes in POR patients. However, acupuncture can increase sex hormone levels and improve ovarian function in women with POR [14, 15].

2.1.2 Improve blood flow

Acupuncture can improve blood flow to the uterus and ovaries, which can improve the chances of success in ART procedures. Transvaginal Doppler ultrasonography advances the pathophysiological understanding of female pelvic hemodynamics [16]. The latest Doppler indices differed significantly between women with and without ovarian dysfunction and correlated significantly with markers of ovarian dysfunction, and these results support the use of Doppler ultrasound to detect ovarian dysfunction [17]. Patients undergoing IVF have a Doppler ultrasound of the uterine arteries before the day of egg retrieval, a test that is thought to be associated with success after embryo transfer [18]. Positive effects of acupuncture for infertility may be related to endorphin system inhibition of central sympathetic nerves, altered uterine blood flow and motility, and stress reduction [19].

Our previous study found a trend toward relatively high doses of acupuncture to have better results in women with poor endometrial receptivity and to significantly improve the uterine blood flow (UBF) index in this type of patient [20]. The latest study also confirms our view and recommends acupuncture as an intervention to improve UBF [21, 22]. In addition, our systematic review of studies related to the improvement of ovarian blood flow by acupuncture included 20 studies with 1611 participants of luteinized unruptured follicle syndrome, polycystic ovary syndrome (PCOS), poor ovarian insufficient (POI), premature ovarian failure (POF), and diminished ovarian reserve (DOR) patients, found acupuncture could significantly improve the ovary blood flow (OBF) parameters, including vascular resistance index and peak systolic velocity (PSV).

2.1.3 Reduce OHSS and other side effects

Acupuncture possesses noteworthy anti-inflammatory properties, rendering it beneficial in mitigating the occurrence of OHSS and countering other potential side effects associated with COH. By incorporating acupuncture into the treatment regimen, women with PCOS who undergo IVF or intracytoplasmic sperm injection (ICSI) can witness improvements in their CPR as well as ongoing pregnancy rate (OPR). Furthermore, acupuncture plays a crucial role in diminishing the risk of OHSS in this specific patient population, thereby contributing to a more favorable outcome in their assisted reproductive journey [23].

2.2 Acupuncture management around the time of oocyte retrieval or implantation

Acupuncture has demonstrated its effectiveness in alleviating mood disorders that may arise during the process of egg retrieval or transplantation, providing much-needed emotional support for patients. By incorporating acupuncture into pre- and post-procedural care, individuals undergoing these interventions can experience improvements in their overall mood and emotional well-being. Moreover, acupuncture also proves beneficial in mitigating the pain associated with the procedure, offering a non-invasive and natural approach to pain management. The strategic application of acupuncture techniques can help alleviate discomfort, reduce anxiety, and promote relaxation, thereby enhancing the overall experience for patients undergoing oocyte retrieval or transplantation.

2.2.1 Reduce emotion disorders

Multiple studies have substantiated the presence of elevated levels of state anxiety and depression in patients undergoing IVF, particularly during critical stages such as oocyte retrieval or embryo transfer [24]. It has been observed that this anxiety and depression tend to persist across multiple cycles of treatment. Encouragingly, a systematic evaluation conducted by Hullender Rubin, Smith et al. [25] indicates a noteworthy yet modest impact of acupuncture on reducing state anxiety specifically during oocyte retrieval or implantation, when compared to various control groups. Nevertheless, further high-quality evidence is essential to validate and strengthen these findings.

2.2.2 Relive pain and side effects around oocyte retrieval

We published a systematic review suggesting that acupuncture-combined analgesic therapy is more effective than utilizing conscious sedation and analgesia or non-steroidal anti-inflammatory drugs alone. In addition, there is no clear consensus on whether acupuncture applied alone during oocyte retrieval has analgesic effects, which requires further research [26]. Among these, EA is widely used for analgesia during oocyte retrieval with a mixed frequency and a fixed frequency for short-duration EA with similar analgesic effects [27, 28].

2.3 Acupuncture management for the pregnancy outcomes

Acupuncture has been used in various assisted reproductive technologies, including IVF-ET, frozen embryo transfer (FET), and ICSI, and studies have shown that acupuncture can improve biochemical and clinical pregnancies; however, no studies have yet shown that acupuncture can significantly improve LBR in patients undergoing assisted reproductive technologies. A randomized controlled study published in JAMA in 2018 showed that acupuncture was effective in improving LBRs before and after oocyte extraction or on and before and after ET, there were no overall benefits of acupuncture in improving LBRs when performed [29]. However, in two other systematic evaluations, acupuncture was found to improve clinical pregnancy during IVF [30, 31]. Another study confirmed that acupuncture before or during FET helped improve patients’ biochemical pregnancy, and clinical pregnancy outcomes and the risk of serious adverse events is very low [32]. However, no significant improvement of acupuncture for live birth during FET was reported.

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3. Mechanism of acupuncture treatment of female infertility

The etiology of female infertility is complex, including ovulation dysfunction, tubal pelvic factors, immune factors, and unexplained infertility. Recently, researches on the mechanism of infertility are mainly divided into the general influence of HPO axis, the influence of the ovary (ovarian micro-environment, oocyte quality, ovarian blood vessel, etc.), fallopian tube (inflammation, fallopian tube adhesion), or uterine cavity (anatomic anomaly, endometrium adhesion, imbalance of maternal-fetal interface, etc.). Acupuncture is an alternative auxiliary therapy for infertility, especially for COH during ovulation. Its mechanism of improving pregnancy outcomes has also attracted the attention of scientific researchers.

3.1 Influence of the HPO axis

The HPO axis plays an important role in female estrous cycle and reproduction, and its normal positive and negative feedback is the basis for ensuring normal reproductive function and promoting egg maturation, and triggering ovulation. The secretion and release of gonadotropin-releasing hormone (GnRH) released by the hypothalamus to the pituitary portal system can be induced and controlled by the stimulation of other mediators in different brain regions [33, 34]. Various mediators such as central neurotransmitters and neuropeptides are integrated into the hypothalamus to regulate the reproductive system. The neurotransmitters norepinephrine and prostaglandin E2 regulate the activity of hypothalamic neurons and are potential stimulators affecting the release of GnRH in the hypothalamus [35]. Zhu et al. found that electroacupuncture (EA) stimulated bilateral Sanyinjiao and bilateral Zusanli, three times a week, five sessions in total. It was found that GnRH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), as well as 17 β-estradiol, progesterone (P), and norepinephrine were changed in the EA group compared with the blank or placebo group. Studies have shown that EA can regulate the homeostasis of the HPO axis in physiological rats [36].

The most common abnormalities of the HPO axis are ovulation disorders. Such as PCOS, POI, POF, etc. Stener-Victorin reported that repeated EA stimulation significantly promoted beta-endorphin release from the hypothalamus in polycystic ovary (PCO) rats and decreased nerve growth factor (NGF), corticotropin-releasing factor, and endothelin-1 in the PCO rats [37, 38]. Further studies showed that low-frequency EA with PCOS for a total of 25 sessions improved impaired endorphin dysfunction and regulated the immune system in steroid-induced PCO rats [39]. In another study, EA improved disturbed estrus cycles in adolescent PCO rats, upregulated lutein level and ovarian volume [40], and EA elevated LH, and restored reduced estradiol and GnRH.

3.2 Influence of the ovary

Ovarian tissue facilitates the maturation of ovum. Ovarian dysfunction will lead to poor development of ovum, resulting in embryo fertilization failure, which may eventually lead to poor pregnancy outcomes. Current studies have shown that ovarian dysfunction was caused by ovarian inflammation, excessive oxidative stress of ovarian interstitial cells, abnormal intestinal flora, epigenetic changes, abnormal ovarian immunity, etc. The effects of acupuncture on ovarian function through physical stimulation have been reported as follows:

During follicular development, granulosa cells are responsible for providing nutrients required maturation of the ovum. Follicular atresia and apoptosis are closely related to granulosa cell apoptosis. Acupuncture can increase the expression of B-cell lymphoma-2 (BCL-2) and reduce the expression of BCL-2 protein to reduce the apoptosis of granulosa cells, hence serving as an escort for follicular development. EA has been shown to effectively improve oocyte quality and embryo development potential in PCOS infertility patients [41]. EA has been shown to improve follicular dysplasia in PCOS patients by inhibiting overexpression of anti-Mullerian hormone (AMH) and increasing the expression of P450arom [42]. Acupuncture can improve ovulation disorder by down-regulating lnccmeg3 expression, inhibiting phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and reducing granulocyte autophagy [43].

Fat and environmental factors are strongly associated with the development of POF, and diets high in fat and sugar (HFHS) can impair ovarian function and ovum quality [44]. Recent studies have shown that acupuncture can improve ovarian damage induced by HFHS. Promote follicular maturation by inhibiting ovarian fibrosis and follicular atresia [45]. Moreover, the study found that it was mainly related to inhibiting ovarian oxidative stress and Fe2+ accumulation in modeled rats, and further exploration found that it may be related to affecting intestinal flora changes.

3.3 Influence of the endometrium

Endometrium is the soil for successful embryo implantation. At present, ART technology has obtained relatively good-quality embryos, nevertheless, the implantation rate remains low. Among them, the poor implantation environment of embryos caused by abnormal endometrium is the focus of attention. Among them, an abnormal intimal environment, including abnormal intimal blood flow, leads to low receptivity and decreased ability to accept embryos, leading to recurrent implantation failure (RIF). Or the imbalanced intimal immunity may lead to the disturbance of the maternal-fetal immune interface and affect the embryo implantation window (WOI). The research showed that acupuncture treatment significantly repaired endometrium dysfunction, especially caused by COH.

3.3.1 Balance between the window of implantation and embryo after ovarian hyperstimulation

Studies have demonstrated that COH-induced hyper-physiological levels of estrogen and progesterone, high progesterone ratio, unbalance of glycosyl coupling, or imbalance of human chorionic gonadotropin (HCG) administrated rats. COH procedure may lead to endometrial dysplasia, endometrial and embryonic dysplasia, and affect angiogenesis, leading to implantation failure [46]. Many cytokines are involved in the regulation of angiogenesis in the endometrium, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and the angiopoietin family [47, 48]. Dong et al. Established a rat model of COH by injecting serum gonadotropin (PMSG) and HCG into pregnant mares. The rats were treated with EA from the day of PMSG injection to the third day of gestation. The results showed that the endometrial VEGF content and endometrial dendritic cells (DCs) were affected while the patient was in the peri-implantation phase. It was found that acupuncture combined with progesterone could improve endometrial VEGF and regulate DCs to promote implantation [49]. The team further found that EA promoted the implantation of COH rat embryos by activating the VEGFR2/PI3K/AKT and VEGFR2/ERK signaling pathways, which are positively correlated with endometrial angiogenesis [50]. A recent study conducted by the team, a scanning electron microscope on the rat endometrium after COH. The pinopodes of the endometrium tissues were observed after ovarian retrieval, after four days, five days, and six days by a microscope, respectively, and found that the pinopodes were distributed in advance after COH. atrophy and subside in advance, and the acupuncture treatment group can significantly pull back the forward movement of pinopodes. Thus, EA can synchronize embryo implantation and endometrial acceptance, and restore timely WOI. [21].

You et al. also found that acupuncture could improve endometrial acceptance after COH, and low-frequency acupuncture (2 Hz, 1 mA, 20 min) and high-frequency acupuncture (50 Hz, 1 mA, 20 min) were administrated in Guanyuan and Zusanli, respectively. High-frequency EA significantly decreased the protein expression levels of E-cadherin, β-catenin, and CLDN1 adhesion molecules after the COH procedure, and significantly enhanced the LIF/ STAT3 signaling pathway [51], LIF promoted cell transplantation, differentiation, and regulated endometrial receptivity. Moreover, LIF regulates phosphorylation of STAT3 and affects embryo implantation in the endometrium [52]. The team further found that EA promoted the expression of LIF/STAT3 signals by inhibiting miR-223-3p, thereby enhancing the expression of endometrial adhesion proteins (E-cadherin, β-catenin, and CLDN1 adhesion molecules) to successful embryo implantation [53].

In conclusion, COH increases the content of serum estrogen and progesterone, regulates the hormone receptors on the endometrium, and thus affects WOI, resulting in the failure of embryo implantation. However, acupuncture/EA during COH can synchronize WOI with embryonic development and improve the rate of embryo implantation while improving the quantity and quality of embryos. And high-frequency EA has more advantages than low-frequency EA.

3.3.2 Improvement of the endometrium morphology

Normal endometrial morphology is the key factor of embryo implantation, including endometrial thickness, endometrial typing, sub-endometrial blood flow, etc. Excessive curettage, endocrine disruption, and endometrial tuberculosis would lead to thinning of the endometrial and limited growth. Thin endometrium may also be caused by dysplasia of the basal vessels of the endometrium. Thin endometrium has an impact on female fertility, resulting in low implantation rates and high miscarriage rates [54]. It has been shown that EA combined with bone marrow mesenchymal stem cells (BMSC) can improve the thickness of thin endometrial rats molded with 95% ethanol, and EA promotes migration of transplanted BMSCs to the damaged uterus by activating the stromal cell-derived faction-1/C-X-C chemokine receptor 4 (SDF-1/CXCR4) axis. It was also found that the secretion of VEGF and basic fibroblast growth factor (bFGF) in endometrial lesions increased, and the implantation rate of embryos increased. Therefore, it is suggested that EA plays an important role in supporting BMSCs to repair thin endometrium, possibly by promoting the migration of BMSCs and enhancing the paracrine effect of bone marrow mesenchymal stem cells [55].

3.3.3 Equilibrium of the maternal-fetal immune interface

Immune cells located at the interface between the placenta and uterus are thought to play an important role in successful pregnancy. Recent studies have shown that the composition and function of these cells are locally controlled by the uterine mesenchymal cell peri-implantation. Key immune cell types include: natural killer (NK) cells, macrophages, dendritic cells and T cells, and the balance of these cells determines the success of embryo implantation to varying degrees [56].

Huang et al. found that acupuncture could regulate the endometrial immune microenvironment of pregnant rats. Acupuncture in the Zusanli and Sanyinjiao rats detected that it could improve the poor reception status of the endometrium by promoting the secretion of LIF and interleukin-12 (IL-12) in the endometrium [57]. Further research found that significantly reduced implanted embryos after mifepristone modeling, while acupuncture and progesterone treatment could significantly improve the implantation. Mifepristone significantly decreased the expression of CCL2 and CXCL8 protein and mRNA, and acupuncture or progesterone significantly reversed the expression of CCL2 and CXCL8 protein and mRNA. Acupuncture with progesterone significantly increased uterine natural killer (uNK) cell subsets in rats with failed implantation [58]. Further studies showed that acupuncture promoted implantation and placenta formation in embryonic rats by improving the expression of CXCR1 and CXCR2 at the maternal-fetal boundary [59].

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4. Mechanism of acupuncture treatment of male infertility

Male infertility is one of the most common diseases in andrology, which accounts for about half of the incidence of infertility in couples. Some male diseases such as oligospermia, asthenospermia, azoospermia, and others may be some of the common factors leading to male infertility. IVF-ET, ICSI, and intrauterine insemination (IUI) are important methods for male infertility in ART. However, the success rate of ART remained unsatisfactory due to various factors, and the evaluation of the male was often neglected. By optimizing male fertility, couples are able to choose less invasive ART techniques and/or enhance ART outcomes. In recent years, acupuncture, as the non-pharmacological therapy of traditional Chinese medicine with the advantages of significant efficacy and few adverse effects, has been increasingly accepted in the treatment of male infertility. The efficacy and possible mechanisms of acupuncture for male infertility are described below to provide a basis for the treatment of male infertility with acupuncture.

4.1 Acupuncture improves sperm parameters

The male sperm factor is an important aspect of pregnancy failure. Impaired sperm parameters such as semen volume, sperm concentration, sperm motility, and total sperm count are closely associated with conception and embryo quality [6061]. A retrospective, real-world study demonstrated that progressive sperm motility was the main ART outcomes predictor for the frozen cycle, which need to be improved for ART success [62]. Recently, a Bayesian network meta-analysis found that EA can effectively improve sperm motility [63]. In addition, spermatozoa morphology is also an important indicator of male sperm quality. A decline in normal spermatozoa morphology may reduce pregnancy rates and affect the outcome of ART [64]. Gurfinkel et al. found that the ratio of normal-form sperm in patients with semen abnormalities was significantly increased after acupuncture and moxibustion treatments [65].

Acupuncture could increase the blood flow of the testis and provide a suitable internal environment for spermatogenesis. A prospective, randomized study [66] found that 10 Hz EA stimulation resulted in a significant increase in testicular artery parameters in volume flow, end-diastolic velocity, PSV, diameter, and area. The mechanism may be related to the testicular sympathetic reflex response controlled by the supraspinal pathway. Siterman et al. [67] found an increase in sperm concentration and a reduction in local testicular temperature to normal levels after acupuncture treatment in oligozoospermia caused by inflammation of the reproductive tract. Immune factors are another important cause of male infertility, which may be caused by antisperm antibodies (AsAb), that is immune infertility [68]. A clinical report pointed out that the positive rate of AsAb decreased significantly after the treatment of acupuncture combined with herbal drugs, and the curative effect was better than that of oral prednisone [69].

4.2 Regulation mechanism of sperm quality by acupuncture

Sperm quality is an important aspect of pregnancy failure. The sperm parameters, such as semen volume, sperm concentration, sperm motility, and total sperm count, are closely associated with conception and embryo quality, and impaired sperm parameters may reduce pregnancy rates and affect the outcome of ART. With the increasing acceptance of acupuncture in ART procedures, several studies have demonstrated the effect of acupuncture in improving sperm quality, and research on the related mechanisms has been gradually conducted. In recent years, oxidative stress which affects semen parameters has gradually attracted attention in the pathogenesis of male infertility [70]. And the sperm CatSper channel was essential for male fertility [71] and the endocrine system plays an important role in the regulation of male sperm parameters [72]. Accumulated evidence showed the potential of acupuncture in the improvement of sperm quality by regulating oxidative stress [71], sperm CatSper channels, and the hypothalamic–pituitary-gonadal axis which may be the related mechanism of acupuncture for male infertility.

4.2.1 Acupuncture regulates sperm anti-oxidative stress pathway

Particularly, EA combines the benefits of electrical stimulation and traditional acupuncture therapy, which could regulate the oxidative stress pathway and reduce oxidative stress injury. In order to observe the effect of EA on the antioxidant function of Leydig cells in aged rats with low T levels, the study found that the levels of serum total testosterone (TT) and free testosterone (FT) and the expressions of phosphorylated extracellular signal-regulated protein kinase (p-ERK), ERK, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxy-genase-1 (HO-1) proteins in the testis were significantly increased after EA treatment, which may be related to the regulation of the anti-oxidative stress pathway of ERK/Nrf2/HO-1 and the reduction of oxidative stress injury by EA to improve the reproductive function Figure 2 [73].

Figure 2.

EA regulates the anti-oxidative stress pathway of ERK/Nrf2/HO-1 [73]. Abbreviation: TT, total testosterone; FT, free testosterone; p-ERK, phosphorylated extracellular signal-regulated protein kinase; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1, heme oxy-genase-1; EA, electroacupuncture.

4.2.2 Acupuncture regulates sperm CatSper channels

CatSper channel, a sperm-specific calcium channel including four pore-forming α subunits (CatSper1-CatSper4), was essential for the regulation of sperm motility, hyperactivity, and male fertility [71, 74]. The abundance of CatSper protein was significantly decreased in sperm of idiopathic asthenozoospermia (iAZS) patients. The result of animal experiment showed that the sperm motility of idiopathic asthenozoospermia rats was improved after EA treatment. In particular, 2 Hz-EA treatment can reverse the decreased protein tyrosine phosphorylation, over-activation, acrosome reaction, and other sperm dysfunction and fertility impairment in AZS rats. The possible mechanism may be associated with that 2 Hz TEAS or EA treatment enhanced the functional expression of CatSper channels in the sperm [11]. In addition, an RCT demonstrated that the sperm count and motility in patients with abnormal semen parameters were improved after 2 months of treatment of TEAS, which may be related to the increase of zinc, Neutral α-glucosidase and fructose levels in seminal plasma and the regulation of calcium-and integrin-binding protein-1 (CIB1) and cyclin-dependent kinase 1 (CDK1) (Figure 3) [75].

Figure 3.

Mechanism of EA in the treatment of asthenospermia through the CatSper pathway [11]. Abbreviation: EA, electroacupuncture; iAZS, idiopathic asthenozoospermia.

4.2.3 Acupuncture regulates the hypothalamic: Pituitary-gonadal axis

The endocrine system plays an important role in maintaining normal reproductive function. The spermatogenesis was regulated by the hypothalamic–pituitary-gonadal axis [72]. The hypothalamus synthesizes and secretes GnRH to stimulate the pituitary, which produces FSH and LH to act on testes and regulate the endocrine and spermatogenic processes [76]. Abnormal FSH and LH levels decreased testosterone synthesis, which is required for the spermatogenic cycle and plays an integral role in spermatogenesis, sperm maturation, and sperm release, resulting in decreased fertility and even infertility. A systematic review and meta-analysis demonstrated that 2 Hz transcutaneous electrical acupoint stimulation (TEAS) and EA were effective in improving the reproductive hormones FSH, LH, and testosterone in Oligoasthenospermia patients [63]. Cao et al. conducted an animal experiment and found that acupuncture reduced the LH level and increased the testosterone level and sperm density and motility in rats with oligoasthenospermia [77].

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5. Summary and outlook

Over the past two decades, acupuncture has played a significant and increasingly recognized role in supporting and enhancing various assisted reproductive techniques. Acupuncture holds promising prospects as a complementary therapy in the field of assisted reproductive technology, offering potential improvements in reproductive outcomes, emotional well-being, and overall patient experiences. By incorporating acupuncture into routine practice, individuals undergoing assisted reproductive treatments have the opportunity to enhance their chances of success and overall satisfaction.

Acupuncture serves as a valuable aid in reproductive technology by targeting specific acupuncture points and meridians that are closely associated with reproductive function. Skilled acupuncturists utilize techniques such as needling, moxibustion, and acupressure to stimulate these points, restoring the body’s energy balance. This holistic approach aims to optimize the reproductive system, improve the quality of eggs and sperm, regulate menstrual cycles, enhance uterine receptivity, and support the implantation process.

The development of acupuncture-assisted reproductive technology has been a gradual process, with research studies and clinical trials providing evidence of its potential benefits. However, it is important to note that further high-quality research is needed to consolidate these findings and provide stronger support. Continued exploration of acupuncture’s mechanisms of action, refinement of treatment protocols, and larger-scale clinical trials will contribute to a better understanding of its efficacy and enable its optimal integration into standard assisted reproductive technology protocols.

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Conflict of interest

The authors declare no conflict of interest.

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Abbreviations

IVFIn vitro fertilization
ARTassisted reproductive technology
AIartificial insemination
IVF-ETin vitro fertilization-embryo transfer
CPRclinical pregnancy rate
LBRlive birth rate
EAelectroacupuncture
HPOhypothalamic–pituitary-ovarian
COHcontrolled ovarian hyperstimulation
OHSSovarian hyperstimulation syndrome
PORpoor ovarian response
UBFuterine blood flow
PCOSpolycystic ovary syndrome
POIpoor ovarian insufficient
POFpremature ovarian failure
DORdiminished ovarian reserve
OBFovary blood flow
PSVpeak systolic velocity
ICSIintracytoplasmic sperm injection
OPRongoing pregnancy rate
FETfrozen embryo transfer
GnRHgonadotropin-releasing hormone
FSHfollicle-stimulating hormone
LHluteinizing hormone
PCOhypothalamus in polycystic ovary
NGFnerve growth factor
BCL-2B-cell lymphoma-2
AMHanti-Mullerian hormone
PI3Kphosphatidylinositol 3-kinase
mTORmammalian target of rapamycin
HFHShigh in fat and sugar
RIFrecurrent implantation failure
WOIembryo implantation window
HCGhuman chorionic gonadotropin
VEGFvascular endothelial growth factor
FGFfibroblast growth factor
PMSGserum gonadotropin
DCsdendritic cells
BMSCbone marrow mesenchymal stem cells
SDF-1stromal cell derived faction-1
CXCR4C-X-C chemokine receptor 4
bFGFbasic fibroblast growth factor
NKnatural killer
IL-12interleukin-12
uNKuterine natural killer
AsAbantisperm antibodies
TTtotal testosterone
FTfree testosterone
p-ERKphosphorylated extracellular signal-regulated protein kinase
Nrf2nuclear factor erythroid 2-related factor 2
HO-1heme oxy-genase-1
iAZSidiopathic asthenozoospermia
CIB1calcium-and integrin-binding protein-1
CDK1cyclin-dependent kinase 1
TEAStranscutaneous electrical acupoint stimulation

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Written By

Jie Yang, Liying Liu, Xiaoyan Zheng, Jingwen Zhang and Yuanyuan Lai

Submitted: 31 May 2023 Reviewed: 01 June 2023 Published: 27 June 2023