Effects and mechanisms of acupuncture on women related health

Abstract

Globally, public health interventions have resulted in a 30-year increase in women’s life expectancy. However, women’s health has not increased when socioeconomic status is ignored. Women’s health has become a major public health concern, for those women from developing countries are still struggling with infectious and labor-related diseases, and their counterparts in developed countries are suffering from physical and psychological disorders. In recent years, complementary and alternative medicine has attracted wide attentions with regards to maintaining women’s health. Acupuncture, a crucial component of traditional Chinese medicine, has been used to treat many obstetric and gynecological diseases for thousands of years due to its analgesic and anti-inflammatory effects and its effects on stimulating the sympathetic/parasympathetic nervous system. To fully understand the mechanism through which acupuncture exerts its effects in these diseases would significantly extend the list of available interventions and would allow for more reasonable advice to be given to general practitioners. Therefore, by searching PubMed and CNKI regarding the use of acupuncture in treating obstetric and gynecological diseases, we aimed to summarize the proven evidence of using acupuncture in maintaining women’s health by considering both its effectiveness and the underlying mechanisms behind its effects.

Keywords

acupuncture / women health / clinical efficacy / mechanism

1 Introduction

Since 1900, public health interventions have resulted in a 30-year increase in women’s life expectancy. Although women are living longer, they tend to have poorer health outcomes and are predisposed to chronic disease-related disability compared with men [1]. Generally, women’s lifespan can be divided into seven stages, including the fetal period, neonatal period, childhood, adolescence, sexual maturity period, perimenopause, and post-menopause. Of these, the reproductive period lasts about 30 years, and this is the time during which they suffer the greatest diversity of both physical and psychological diseases [2], for example, infertility has become the most common disease among reproductive-age women seeking medical care. When women get pregnant, nausea and vomiting can affect up to 80% of pregnant women [3], resulting in termination of a wanted pregnancy in some severe cases. Meanwhile, some perinatal complications can be life-threatening [4]. When women enter the menopausal transition, due to the loss of steroid hormones they often experience symptoms including hot flashes, resulting in a greater burden of disease and more frequent gynecologic visits [5]. Although many diseases can be ameliorated by surgical or pharmaceutical interventions, such treatments cannot solve these diseases if we pay more attention to the overall state of the patients. Therefore, multiple approaches can be utilized, including physical treatments and complementary and alternative medicine, which has been shown to be effective for many conditions such as chronic pain [6,7]. Acupuncture, which is an important part of traditional Chinese medicine (TCM), has been applied in clinical practice for over 2000 years [8,9]. Written between 476 and 221 BC, the theory related to acupuncture is still used in clinical practice today and accounts for diseases linked to women’s health, including threatened miscarriage, irregular menstruation, and nausea and vomiting of pregnancy (NVP) [7]. Although the use of acupuncture to treat disease has a long history, it only attracted attention and became widespread when it was reported on New York Times as a front-page story in July 1971 [10], and now clinics in over 100 countries are using it for treating and preventing diseases [11]. Based on the theory of meridians and TCM, this technique utilizes fine needles to stimulate specific points on the body surface referred to as acupoints to invoke sensations of soreness, numbness, fullness, or heaviness, which is termed “De Qi” [12,13]. Apart from the traditional form of manual acupuncture, multiple variants of acupuncture have been developed and applied nowadays, including electroacupuncture (EA), laser acupuncture (LA), and transcutaneous electronic acupoint stimulation (TEAS). Proven evidence indicates that acupuncture is effective for many disorders, especially for functional diseases like chronic low back pain [14]. Acupuncture has also been extensively applied to treat obstetric and gynecological diseases to maintain women’s health. In the present work we have conducted a literature review of acupuncture’s application in obstetrics and gynecology and discuss its effectiveness and mechanisms of action.

2 Search strategy and selection criteria

The strategy was developed to search literature in PubMed and tailored in CNKI when necessary. We only included randomized controlled trials (RCTs) and meta-analysis that analyzed the evidence relevant to the acupuncture treating obstetric and gynecological diseases. The literature, published from January 1985 to September 2023, were retrieved from the database. The term was used including “primary dysmenorrhea,” “endometriosis,” “natural vaginal delivery and cesarean delivery,” “polycystic ovary syndrome,” “in-vitro fertilization/embryo transfer,” “nausea and vomiting of pregnancy,” “perinatal complications,” “menopausal transition,” “acupuncture,” “electroacupuncture,” “laser acupuncture,” “transcutaneous electronic acupoint stimulation,” “acupoint injection,” “acupressure,” and “auriculotherapy.”

3 Pain-related conditions affected women’s health

3.1 Overview

Pain, a condition that can be non-cyclic or cyclic, not only adversely influences women’s well-being, but is also a major public health issue. For women, a few physiological conditions and many diseases contribute to or reinforce the pain, including primary dysmenorrhea (PD), endometriosis, and natural vaginal delivery and cesarean delivery [15,16]. It is estimated that up to 95% of menstruating women are affected by PD, and about one fourth of reproductive-age women suffer from severe cases [17]. PD is considered a physical condition that arises due to the excessive release of prostaglandin within the uterus. Thus, non-steroidal anti-inflammatory drugs are recommended as the first-line treatment, yet their use is sometimes limited due to the increased risk of developing ulcers [18]. Acupuncture, as a non-pharmacological treatment, could be effective in pain relief linked to many diseases, including PD, while pain related to the endometriosis can only be improved a small amount until the pathogenic causes are eliminated. Contraceptive drugs is frequently prescribed to alleviate the symptoms including pain, however, the long-term usage increases the risk of venous thrombosis [19] and abnormal menstruation [20]. Labor pain presents a great psychological and physiological challenge for pregnant women, which is regarded as the most severe pain a woman can experience, and therefore painless labor has become an essential part of medical care [21,22] supported by labor analgesia and non-pharmacological treatment, including acupuncture. During the past decades, labor analgesia has been widely accepted by the general population around the world [23], although it raises some concerns including prolonged labor, high costs, and maternal side effects such as intrapartum fever, dural puncture, and postpartum headache [24]. Given the analgesic properties of acupuncture, it might be a promising approach for supporting analgesia during labor.

3.2 Clinical efficacy

It has been shown that both manual acupuncture and EA can, to some extent, alleviate the abdominal pain resulting from PD [25]. A study compared the efficacy for treating PD with multiple acupoints with the single one, namely Shiqizhui (EX-B8). The findings indicated that pain was significantly relieved in the acupuncture groups compared with the no-treatment group [26]. Moreover, scores for measuring the severity of pain were lower during both menstruation and follow-up in those who received acupuncture at multiple acupoint prior menstruation. Even if receiving vitamin K3 injection at the Sanyinjiao (SP6) rather than acupuncture, it yielded analgesic effects [27], indicating a crucial role of acupoint in pain relief of acupuncture.

For pain related to endometriosis, a study conducted by Li and colleagues showed that compared with sham acupuncture the visual analog scale (VAS) score in the acupuncture group was significantly lower (–3.87 vs. −0.98), despite the difference was no longer significant at the end of 24 weeks [28]. Similarly, acupuncture significantly improved all areas of the Endometriosis Health Profile in women with endometriosis based on standard care [29]. Nevertheless, limited evidence is available to support the acupuncture application to treating endometriosis, further studies are needed.

For pain associated with vaginal and cesarean delivery, it has been reported that women receiving EA had significant lower numbers of analgesic pump compressions and pain scores as well as reduced fentanyl consumption at 48 h after surgery [30]. Another trial showed that acupuncture reduced the average intensity of pain and increased the rate of mobilization and removal of the Foley catheter on the first day after operation compared with placebo acupuncture [31]. Recently, Wu et al. investigated the analgesic effect of combined spinal-epidural anesthesia (CSEA) with acupoint injection (AI) on labor pain. The findings indicated that CSEA plus AI significantly reduced VAS scores and the dosage of medication and shortened the duration of labor compared to CSEA alone [32]. Based on the available literature, the most commonly used acupoints included Hegu (LI4), SP6, and Zusanli (ST36) [33]. Tab.1 lists the RCTs mentioned above.

3.3 Mechanism

Excessive prostaglandin release is responsible for the pain related to PD [34], whereas the blood supply, infection, and chronic inflammatory damage are responsible for the pain linked with endometriosis [35]. Acupuncture exerts both anti-inflammatory and analgesic effects by restraining cyclooxygenase synthesis in the local site within the uterus [36]. A study reported that low-intensity EA could invoke the PROKR2^ADV neurons, which subsequently activate the vagal-adrenal axis to inhibit systemic inflammation. Meanwhile, EA with a 0.5-mA current stimulating on ST36 could reduce TNF and IL-6 levels by 50% compared to the control [37]. It has also been demonstrated that the acupoints are surrounding clusters of mast cells [38], and acupuncture can activate TRPV channels on the membrane of mast cells to release bioactive substances that subsequently activate neural receptors to generate the analgesic effects [39]. On the other hand, acupuncture can also disturb the match between the ascending excitatory route and the descending pain control system thus producing analgesic effects [40]. In addition, acupuncture can directly regulate the release of both opioid and non-opioid neurotransmitters, including gamma-aminobutyric acid (GABA), norepinephrine, and 5-hydroxytryptamine (5-HT), they are delivered to a specific spot to reduce pain [41]. EA can also downregulate the biosynthesis of inflammatory cytokines by inhibiting the activation of p38 mitogen-activated protein kinases (MAPK) [42] and accelerate the removal of pain-inducing substances by enhancing uterine artery blood flow [43,44].

Labor pain is caused by the uterine contractions and stretching and dilatation of the cervix, vagina, which are initially linked to the posterior nerve root ganglia at the T10 to L1 levels [45] and then shifted to the S2 to S4 level of the spinal cord as the labor progression [46]. One of the mechanisms through which acupuncture alleviates labor pain may be that it can effectively inhibit the release of endogenous pain-associated substances and inflammatory mediators such as bradykinin, acetylcholine, serotonin, histamine, potassium ions, prostaglandins, leukotrienes, substance P, and lactic acid and thereby effectively relieve the pain by upregulating the pain threshold [12]. Moreover, it has been shown that both pregnancy and labor lead to changes in the helper T cell 1 (Th1)/helper T cell 2 (Th2) balance [47]. A study has shown that spinal epidural anesthesia (CSEA) coupled with AI can successfully alleviate labor pain by rectifying the Th1/Th2 imbalance [32]. Therefore, the capacity of acupuncture to regulate the immune system is another possible mechanism. In addition, by reducing smooth muscle spasms and local ischemia and hypoxia and inhibiting the oxidative stress response of the uterus, acupuncture has unique benefits in improvement of labor pain [48].

The analgesic effect of acupuncture benefits women who are suffering from pain-related conditions, and thus acupuncture might be another option or a useful supplement to standard treatments including painkillers.

4 Polycystic ovary syndrome (PCOS)

4.1 Overview

Globally, PCOS has become the most common endocrinal and metabolic disease, affecting about 10% of reproductive-age women. The typical clinical manifestations are oligo-amenorrhea, hirsutism, overweight or obesity, alongside with or without glucose and lipid metabolic disorder, anxiety and depression [49]. However, the main impetus for women with PCOS to seek medical care is the infertility which make them struggling from physical and mental disorders [50,51]. The treatments of PCOS include lifestyle change, medications, surgery, and complementary and alternative medicine [52]. Numerous evidence has suggested that acupuncture benefits women with PCOS including hyperandrogenism, ovulation disorder, glucose and lipid metabolism dysfunctions, and anxiety and depression.

4.2 Clinical efficacy

4.2.1 Hyperandrogenism and anovulation

Low frequency electroacupuncture (LF-EA) has been shown to be effective in treating anovulation and hyperandrogenism in infertile women with PCOS. After treatment, the level of circulating testosterone decreased by 25%, androsterone glucuronide by 30%, and androstane-3α and 17β-diol-3-glucuronide by 28% in the EA group compared with physical exercise. In addition, menstrual frequency increased to 0.69 from 0.28/month at baseline in the EA group [53]. Another RCT demonstrated that the ovulation rate was higher and the serum levels of estrone, estrone sulfate, E₂, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, free testosterone, dihydrotestosterone, androsterone glucuronic acid, androstane-3α, 17β-diol-3-glucuronic acid, androstane-3α, 17β-diol-17-glucuronic acid in the acupuncture group were lower than those in the control group (P < 0.05) after 10–13 weeks intervention [54]. Moreover, Wu and his colleagues found that the acupuncture, together with clomiphene, significantly improved the live birth to 29.4% [55], as it had been reported that live birth was just 19.1% and 22.5% in women with PCOS treated with clomiphene alone [56,57]. However, the ovulation rate seemed to little change in women receiving active acupuncture. The discrepancy may attribute to sham acupuncture design which are frequently designed as superficial insertion at non-acupoint and non-penetration at acupoint. As the superficial insertion has been demonstrated to produce certain effects invoked by active acupuncture, this would largely narrow the difference between active and sham acupuncture in acupuncture trial, resulting in “negative” results.

4.2.2 Glucose and lipid metabolism

Also, acupuncture has been demonstrated to be effective in improving glucose and lipid metabolism in women with PCOS. In a recent systematic review that compared metformin alone and acupuncture combined with metformin in the treatment of PCOS patients, the pregnancy rate (RR 1.31, 95% CI 1.08–1.60), ovulation rate (RR 1.31, 95% CI 1.07–1.59), and insulin resistance (IR) (MD –0.68, 95% CI –1.01 to 0.35) were improved by acupuncture combined with metformin [58]. An RCT conducted by Dong et al. discovered that the weight, body mass index (BMI), hip circumference, waist-hip ratio (WHR), fasting glucose, insulin sensitivity, visfatin, and HDL-C in the acupuncture group were decreased, while visfatin was also reduced in the sham acupuncture group during the treatment [59].

4.2.3 Anxiety and depression

In addition, acupuncture has a therapeutic effect in improving patients’ anxiety and depression. In 2019, Wang et al. investigated the effects of EA on anxiety and depression in unmarried PCOS patients. They concluded that the Zung-SAS and Zung-SDS scores (P = 0.007, P = 0.027), and the level of 5-HT (P = 0.023) were lower after intervention in the acupuncture group, while the serum norepinephrine (P = 0.028), the SF-36 domain scores for mental health, vitality, social functioning, general health, and health transition, the total score of CHQOL, and the scores of PCOSQOL infertility and body hair dimensions (P < 0.05) were increased. This confirmed that acupuncture has a positive effect on anxiety, depression, and quality of life in PCOS patients [60]. Another RCT demonstrated that acupuncture could improve the scores of depression and anxiety of PCOS women [61]. We have listed some relevant RCTs in Tab.2.

4.3 Mechanism

4.3.1 Hyperandrogenism and anovulation

The pathogenesis of PCOS is complex, involving genetic, epigenetic, and maternal-fetal environmental factors. Androgen excess and IR are considered to be the crucial pathogenesis of this syndrome [62,63]. One underlying mechanism through which acupuncture exerts its effects in the treatment of PCOS might be its capacity to alter the hyperandrogenic environment. Many studies have confirmed this and reached similar conclusions. The possible mechanism for this lies in acupuncture’s ability to activate the nerve growth factor/TrkA-mediated downstream signaling pathway, thereby contributing to the EA-mediated improvement in the circulating and adipose tissue concentrations of androgens [64]. Moreover, EA can break the vicious cycle initiated by excessive androgen secretion by enhancing the expression of ovarian granular cell layer P450 aromatase and decreasing the expression of theca cell layer P450C17α, androgen receptor, and Connexin 43 [65,66]. It is worth noting that a study carried out by Feng et al. not only confirmed that EA treatment of PCOS is mediated by central opioid receptors, but showed that manual acupuncture can also reduce androgen levels by regulating steroid hormone/peptide receptors [67].

4.3.2 Glucose and lipid metabolism

Hyperinsulinemia, another hallmark of PCOS induced by IR, can reduce the hepatic synthesis of sex hormone binding globulin (SHBG) and stimulate the production of androgen by ovarian thecal cells [63]. It was discovered that insulin-mediated glucose disposal was significantly reduced by 35% to 40%, possibly due to a decrease in insulin receptor signaling caused by serine hyperphosphorylation of insulin receptors and IRS-1 [68,69]. LF-EA activates many pathways, including metabolic adaptation and sympathetic nerve activation, in a similar manner to those activated by exercise. Also, the activation of the autonomic nervous system mediates an increase in systemic glucose uptake. These notions were confirmed by the study of Benrick et al., who found that EA can increase systemic glucose uptake in overweight and obese women and can induce various transcriptional and epigenetic changes in adipose tissue [70,71]. Further study found that the decreased levels of MSX1 and SRNX1, which are involved in glucose homeostasis, could be increased by EA treatment in muscle tissue of women with PCOS [72]. Moreover, by downregulating miR-32-3p levels and upregulating the expression of PLA2G4A, which is vital in the pathogenesis of PCOS and diabetes, acupuncture can inhibit the progression of PCOS and diabetes [73]. Another study found that daily administration of EA can regulate metabolic disorders and improve reproductive function in PCOS-like rats via the regulation of visceral fat, brown fat, and the intestinal flora [74].

4.3.3 Anxiety and depression

In addition, neurotransmitter changes are likely to be a major factor in PCOS patients accompanied with anxiety and depression, and numerous studies have shown that acupuncture directly or indirectly regulates neurotransmitters such as β-endorphin, serotonin, acetylcholine, 5-HT, dopamine, and acetylcholine and thus might be of therapeutic benefit [60,75,76].

To summarize, these findings support that acupuncture has a positive effect on the hyperandrogenism, ovulation disorders, glucose and lipid metabolism dysfunctions, and anxiety and depression in PCOS patients.

5 Infertility undergoing in-vitro fertilization/embryo transfer (IVF-ET)

5.1 Overview

The occurrence of assisted reproductive technique brings hope for infertile women who are failure to conventional treatment including pharmacotherapy and/or surgery. Nevertheless, the live birth rates do little increase even if the implantation is up to 90% as the advance of technique [77]. Although many efforts have been inputted, little change is achieved, and how to improve the live birth rate has become a big challenge. In recent years, the complement and alternative medicine are introduced to proving adjuvant therapy, including yoga, herbal medicine, and acupuncture, etc. Among them, herbal medicine and acupuncture are crucial components of TCM. Within the classical book “The Yellow Emperor’s Inner Classic,” infertility is attributed to the “kidney qi deficiency” incorporating the “Seven-Seven Theory.” Based on meridian theory, acupuncture can regulate the function of “kidney qi” to improving reproductive function via stimulating acupoints located on specific meridian. Acupuncture has been demonstrated to have distinct benefits at multiple aspects for patients who are undergoing IVF-ET, including controlled ovarian hyperstimulation (COH), oocyte retrieval, ET, and live birth.

5.2 Clinical efficacy

5.2.1 Controlled ovarian hyperstimulation (COH)

Accumulating evidence supports that acupuncture benefits patients undergoing COH. In a clinical study [78], Hong et al. found that the rate of ovarian hyperstimulation syndrome (OHSS) and transplant cycle cancellation in the EA group were considerably lower than in the control group. In addition, there were significant differences in the days of gonadotropin (Gn) usage (MD = 0.47, 95% CI 0.00–0.94, P = 0.05) between the two groups. However, there was no statistical differences for the clinical pregnancy rate, fertilization rate, or high-quality embryo rate. Further, a meta-analysis [79] showed that compared with COH alone, acupuncture combined with COH could significantly increase the implantation rate (RR = 2.13, 95% CI 1.08–4.21), the number of oocytes retrieved (MD = 1.02, 95% CI 0.72–1.32) and the antral follicle count (MD = 1.52, 95% CI 1.08–1.95), and reduce follicle-stimulating hormone (FSH) levels (MD = −1.52, 95% CI −2.41 to −0.62). Ten studies (including 715 women) were included in a meta-analysis that showed that both acupuncture and acupuncture as an adjunct therapy could significantly improve ovulation [80].

5.2.2 Oocyte retrieval

Up to now, the analgesia of acupuncture is widely accepted and used in clinical practice. In an RCT, Stener-Victorin et al. found that the two treatments of EA and intravenous alfentanil had equivalent effects in terms of pain directly connected with oocyte aspiration, the sufficiency of anesthesia during oocyte aspiration, abdominal pain, and the degree of nausea [81]. A meta-analysis [82] showed that EA without pre-medication can be recommended in paracervical block for pain relief during oocyte retrieval. In addition, the analgesic effect of mixed frequency and fixed frequency EA were comparable when utilized for short-duration EA [83]. Moreover, the use of acupuncture has been shown to increase the rate of live births among women undergoing IVF [84].

5.2.3 ET

5.2.3.1 Reproductive outcomes

A multicenter RCT indicated that clinical pregnancy rate was higher in the TEAS group than in the controls (55.1% vs. 46.7%, P = 0.03) [85]. Moreover, in women older than 35 years, the clinical pregnancy rates (30.8 vs. 13.9%) and embryo implantation rates (48.9% vs. 23.7%) were higher in the TEAS than the control group. There were no significant differences for the live births, biochemical pregnancy, or embryo implantation between the two groups. A meta-analysis [86] showed the significant effects of acupuncture adjuvant to frozen–thawed ET on the outcomes of clinical pregnancy rate (RR = 1.54, 95% CI 1.28–1.85), biochemical pregnancy rate (RR = 1.51, 95% CI 1.21–1.89), endometrial thickness (MD = 0.97, 95% CI 0.43–1.51), and endometrial pattern (RR = 1.41, 95% CI 1.13–1.75; 7 trials), without statistically significant effects for live birth rate (RR = 1.48, 95% CI 0.90–2.43, 4 trials).

5.2.3.2 Anxiety and quality of life associated with ART

It is estimated that over 80% of infertile women, to some extent, experience anxiety [87], and this in turn would have a negative impact on pregnancy outcomes. Therefore, it is crucial to manage the psychosomatic disorders for infertile women during the IVF process. After ET, patients who undergo acupuncture reported considerably less anxiety than the control subjects, enjoyed their treatments more, and felt more relaxed [88,89]. Acupuncture also produced a positive effect on the general health MOS Short Form 36 (SF36) following ET, despite that the benefit was no longer significant (MD 0.1, 95% CI −2.7 to 2.9) at 14 weeks after treatment.

5.2.4 Acupuncture treatment cross several IVF stages

Acupuncture or EA can improve reproductive outcomes among patients undergoing IVF-ET. A single-blind RCT [90] found that the pregnancy rate (31% vs. 23%) and the ongoing pregnancy rate (28% vs. 18%) at 18 weeks were higher in the acupuncture than the control, although the differences were not statistically significant. Similar, TEAS was superior to the control for improving the clinical pregnancy rate, embryo implantation rate, high-quality embryo rate, live birth rate, and biochemical pregnancy rate [91,92]. In addition, no serious adverse events associated with TEAS were reported [92], while high-quality evidence is still required to generalize the usage of acupuncture in these disorders. Tab.3 summarizes the RCTs of the effect of infertility undergoing acupuncture on IVF-ET.

5.3 Mechanism

5.3.1 COH

COH impairs endometrial receptivity during the implantation window, resulting in a lower pregnancy rate and a higher abortion rate. A recent study conclude that high frequency electroacupuncture (HF-EA) could effectively improve endometrial receptivity and blastocyst implantation amount through significantly reducing the protein expression of the E-cadherin, β-catenin, and CLDN1 adhesion molecules and markedly enhancing the LIF/STAT3 signaling pathway in COH rats [93]. In addition, acupuncture may regulate angiogenesis of the endometrium and the number and the activity of uterus dendritic cells (uDCs) in COH rats during the peri-implantation phase [94]. Both VEGF and FGF-2 protein and mRNA levels were significantly lower on day 4 and higher on day 6 and day 8 of pregnancy compared with COH model rats. In vitro, acupuncture regulated the levels of VEGF, IL-15, and IL-18 secreted by uDCs but not the secretion of soluble sFLT-1. EA can also facilitate embryo implantation in COH rats by activating the VEGFR2/PI3K/AKT and VEGFR2/ERK signaling pathways, which have a positive relationship with endometrial angiogenesis [95].

5.3.2 Oocyte retrieval

Acupuncture is recognized as an analgesic technique in the realm of pathological pain, including inflammatory and neuropathic pain. Prior laboratory findings have revealed that acupuncture can mobilize opioid peptides, and electrical stimulation involves the biological activation of endogenous pain-inhibiting systems by releasing endogenous opioids and oxytocin, which appear to be essential for inducing functional changes in various organ systems [96,97]. Furthermore, other studies have proved that signal integrators such as transient receptor potential vanilloid type 1 and purinergic receptor P2X3 are crucial in acupuncture’s analgesic effects [98,99]. Both low- and high-frequency stimulation have been found to produce endorphin-induced analgesia, and the types of endorphins produced depend on the stimulation pattern [100,101]. Moreover, cumulative analgesic effects may be achieved by longer electric stimulation periods [102].

5.3.3 ET

5.3.3.1 Reproductive outcomes

On the embryo implantation day, better developed endometrial pinopodes, elevated endometrial integrin α1β1/αVβ3, elevated leukemia inhibitory factor, and elevated serum progesterone levels were found in the TEAS group compared with controls [85]. Increased ovary and endometrial focal blood flow [103–105] and modulation of chemokines, integrins, and growth factors were found to maintain normal endometrial receptivity [106]. Thus, acupuncture might improve fertility outcomes by enhancing endometrial function during the peri-implantation stage.

5.3.3.2 Anxiety and quality of life

Acupuncture plays a role in increasing the release of β-endorphin, endomorphins, enkephalins, serotonin, and other neurochemical substances to relieve pain and mental stress and reduce anxiety and/or depression of patients [96,107,108].

In summary, acupuncture has multiple benefits in the setting of IVF, including increased oocyte retrieval, optimization of the uterine environment, alleviation of discomfort during and after operations, and stress reduction. However, further evidence-based research is still needed to completely understand the advantages, processes, and optimal usage of acupuncture in IVF.

6 Nausea and vomiting of pregnancy

6.1 Overview

Nausea and vomiting of pregnancy (NVP) affecting up to 80% of pregnant women is often ignored, due to a lack of effective and safe treatment [3]. Hyperemesis gravidarum (HG), an extreme situation of NVP, is the leading cause of termination of a wanted pregnancy in a woman, even if its incidence is less than 1% in pregnant women [109]. In some conditions, NVP/HG can lead to serious maternal and fetal outcomes, including dehydration, electrolyte imbalance, hospitalization, and even termination of a wanted pregnancy [110]. As few drugs is effective and safe, together with the fear of potential teratogenic risks on the fetal, the desire of alleviating symptoms in this population is far from satisfied by practitioners. Recently, strong evidence indicates that acupuncture is effective on symptoms improvement of NVP, providing another option for pregnant women who are unwilling to taking medicine, due to the fear of teratogenic risk.

6.2 Clinical efficacy

Previously, a placebo-controlled, randomized, single-blind, crossover trial was carried out by Carlsson et al. to evaluate the effects of acupuncture on symptoms improvement of women with HG. The results of that study indicated that based on the intravenous fluid, active acupuncture on Neiguan (PC6) could help patients recover more quickly than placebo acupuncture [111]. Later, a multicenter RCT was also carried out by Caroline Smith et al. to evaluate acupuncture effect on NVP-affected women, results indicated that acupuncture was an effective treatment compared with the no acupuncture for women who experience nausea and the dry retching score also decreased in the acupuncture group by the end of the third week (RR 0.72, 95% CI 0.56–0.93, P < 0.01) [112]. Meanwhile, Fatemeh Tara et al. evaluated the efficacy of acupressure on PC6 in women with NVP, they found that four times per day for 15 consecutive days could alleviate the severity of nausea, vomiting, and retching [113]. However, a study showed that in the first trimester of pregnancy, acupressure therapy does not work any better than vitamin B6 at reducing nausea and vomiting in symptomatic women [114]. In addition, a study found that for women with NVP who received auriculotherapy on Shenmen, the score of nausea and vomiting was significantly lower [115]. However, a systematic review found limited benefit with acupressure and no benefit in acupuncture or nerve stimulation in the treatment of NVP [116], as included studies have serious methodological flaws, including small sample sizes, inadequate blinding of participants and investigators, and lack of adequate control conditions [117]. Recently, a randomized, controlled, and 2 × 2 factorial trial was conducted by Wu and colleagues to assess the effect of acupuncture combined with doxylamine-pyridoxine on the moderate and severe NVP. The findings indicated that after treatment, active acupuncture (MD −0.7, 95% CI −1.3 to −0.1), doxylamine-pyridoxine (MD −1.0, 95% CI −1.6 to −0.4) and their combination (MD, −1.6, 95% CI −2.2 to −0.9) produced a greater reduction in Pregnancy-Unique Quantification of Emesis (PUQE) scores compared to their respective control groups and could reduce the amount of antiemetics [118]. This study provided evidence for the establishment of a pregnancy-safe treatment regimen together with an integrative guideline for managing severe NVP and added new evidence for the safety and efficacy of acupuncture as a complementary treatment. In addition, a systematic review and meta-analysis summarized the most frequently used acupoints for the treatment of NVP, including PC6, Waiguan (TE5), ST36, Xinshu (CV17), Zhongwan (CV12), and Gongsun (SP4) [119]. The RCTs described above are listed in Tab.4.

6.3 Mechanism

Nausea and vomiting, a reflex phenomenon, is caused by the contraction of gastric smooth muscles, which forces food out of the stomach and into the esophagus and throat before vomiting out of the mouth. It is well-known that the sensory fibers from sympathetic nerves that innervate the stomach go through the celiac ganglion and superior cervical ganglion to the spinal cord. Approximately 90% of the vagus nerve fibers are afferent, and their signals are processed by the medulla and transmit stimuli from the intestine to the brain. It has been demonstrated that using gastric motility in rats, acupuncture activates somatic A-β fibers, which transmit the stimulus to the spinal cord and modulate visceral and other sensory inputs at the spinal level via somatic visceral reflexes [120], and vagotomy, regional nerve block, local acupoint anesthesia, and brainstem injury can eliminate the effect of acupuncture on gastrointestinal motility [121]. Possible mechanisms for the effect of acupuncture treatment on NVP/HG mainly focus on its antiemetic and gastrointestinal functions [122]. Due to the increased heart rate, respiratory rate, and metabolic demand that occur with NVP, there is a decrease in the parasympathetic capacity needed to organize the neurological regulatory responses. Acupuncture can regulate gastrointestinal motility by stimulating the reflexes of the vagus and sympathetic nerves [123]. The study carried out by Su et al. found that stimulating CV12 could inhibit gastric motility via the efferent sympathetic pathway and the TRPV1 receptor [124]. Therefore, one possible mechanism through which acupuncture might affect the endogenous opioid system and 5-hydroxytryptamine transmission is by activating 5-hydroxytryptamine and noradrenergic fibers, thus affecting the afferent stimulation of the central nervous system on the vomiting center and relieving nausea and vomiting [108,125]. In addition, EA at PC6 could significantly inhibit the frequency of transient lower esophageal sphincter relaxations triggered by gastric distension [126], which could be another mechanism through which acupuncture might relieve NVP by affecting gastric emptying via somatic visceral reflexes.

In summary, acupuncture can alleviate NVP with only mild adverse reactions. In addition, the combination of acupuncture and western medicine has a synergistic effect and may reduce the need for medication. For patients who are unwilling to take medication for treatment, acupuncture may be a suitable option.

7 Perinatal complications

7.1 Overview

The period of pregnancy and labor is a very challenging phase for both mothers and newborns, and the severe case might be life-threatening. The pharmacological treatment of these obstetric complications is often restricted due to prioritizing the safety of fetuses and newborns and breastfeeding and due to the different maternal and perinatal side effects. Numerous evidence has indicated that acupuncture, a non-pharmacologic method, is beneficial for obstetric disorders and complications and can be used in conjunction with pharmacologic agents to reduce medication requirements [125], for example postpartum urinary retention (PUR).

7.2 Clinical efficacy

Acupuncture is an effective option for PUR. A prospective randomized case-controlled trial conducted by Lauterbach et al. suggested that 92% of participants who underwent acupuncture achieved spontaneous micturition within 1 h [128]. Subsequently, Qu et al. assessed whether acupoint hot compress could reduce the incidence of PUR, result indicated that compared with participants who received routine postpartum care, participants who received routine postpartum care together with acupoint hot compress had significantly decreased incidence of PUR (RR 0.58, 95% CI 0.35–0.98); improved postpartum uterine contraction pain at 6.5 h (median score, 1 vs. 2), 28.5 h (1 vs. 1), 52.5 h (1 vs. 1), and 76.5 h (0 vs. 0) after delivery; reduced depressive symptoms (RR 0.73, 95% CI 0.54–0.98); and increased breastfeeding milk volume at 28.5, 52.5, and 76.5 h after delivery [129]. A Chinese scholar compiled a list of acupoints often utilized in the treatment of PUR, including SP6, Zhongji (CV3), Guanyuan (CV4), ST36, Qihai (CV6), Yinlingquan (SP9), Shuidao (ST23), and Weiyang (CV3) [130]. The relevant RCTs are listed in Tab.5.

7.3 Mechanism

The elevated progesterone during pregnancy and immediately postpartum suppresses smooth muscle tone and detrusor contraction, and impaired detrusor muscles together with a relaxed urethra can be a part of the mechanism of PUR [131]. Damage to the pelvic, hypogastric, and pudendal nerves during labor may be another mechanism for PUR. Usually, urinary retention due to sympathetic and parasympathetic nerve injuries is transient and will be restored within 3 months postpartum. In addition, the ischemic nerve injury caused by the extension of the second stage of labor and the direct partial or complete nerve transection caused by spontaneous or surgical delivery trauma can lead to urinary retention. The mechanism of acupuncture in the treatment of PUR may accelerate urination by lowering the bladder urination threshold, improving the excitability of bladder urination muscles and pelvic cavity and perineal nerve muscles, and improving the internal pressure of the bladder, and these effects may be realized by promoting the contraction of urination muscles, relaxing and opening the urethral sphincter, removing the inhibition from the brain on the spinal cord urination center, inducing a urination reflex, and reducing or even eliminating residual urine [132]. The study conducted by Zhang et al. have shown that acupuncture can induce the contraction of bladder detrusor muscles through nerve reflex and parasympathetic efferent impulses, which increase bladder pressure and the relaxation of the internal sphincter, thus regulating the urination function of women with PUR [133].

In conclusion, acupuncture has a significant effect on obstetric diseases such as PUR, with fewer side effects. However, although acupuncture can also treat other obstetric complications, the evidence level is insufficient due to the poor quality of clinical trials and small sample size.

8 Menopausal transition

8.1 Overview

Typically, menopause occurs between the ages of 45 to 56 and is caused by the loss of ovarian activity. During the menopausal transition, approximately 50% to 75% of women experience vasomotor symptoms like hot flashes and night sweats, around 30% have postmenopausal osteoporosis, and nearly 40% suffer from insomnia or mental trouble, resulting in a reduced quality of life [134–136]. Currently, HT is the main protocol for the treatment of menopausal transition, while a systematic review including 22 studies involving 43 637 women suggested that HT might be inappropriate for women at high risk of cardiovascular disease, thromboembolic disease, and some types of cancer [137]. When it comes to high risks of stroke and venous thromboembolism (VTE), HT substantially increases the incidence of dementia and venous thrombosis [138]. The clear efficacy and few adverse effects of acupuncture treatment in menopausal symptom improvement suggests that it could be a viable alternative therapy, particularly for high-risk women [139].

8.2 Clinical evidence

Evidence from recent RCTs supports acupuncture treatment in improving menopausal symptoms and quality of life. In a pragmatic RCT, Avis et al. found that the frequency of vasomotor symptoms declined by 36.7% after 6 months in the acupuncture group but increased by 6.0% in the control group [140]. Another trial indicated that acupuncture was superior to sham acupuncture in reducing hot flash frequency and severity and in decreasing scores on the Menopause Rating Scale (MRS) II [141]. Meanwhile, acupuncture significantly reduce day and night sweats in women with moderate-to-severe menopausal symptoms [142]. Moreover, acupuncture also performed well in improving quality of life for menopausal women, including perimenopausal insomnia (8.03 vs. 1.29, P < 0.05) [143]. A systematic review indicated that the effect of acupuncture treatment on depression relief was equivalent to antidepressants, with no significant difference in the Hamilton Rating Scale of Depression (HRSD) scores between the two groups [144]. In addition, at the week 8 of treatment, the reduction from baseline in the MRS total score was 6.3 in the EA group and 4.5 in the sham EA group, providing a between-group difference of 1.8 (95% CI 0.9–2.8) [145]. Meanwhile, an RCT that evaluated the value of laser acupuncture (LA) on postmenopausal osteoporosis found that LA combined with calcium and vitamin D3 supplements performed better in bone mineral density (BMD) and pain score than drug only [146]. All the RCTs mentioned above are listed in Tab.6.

8.3 Mechanism

The mechanisms through which acupuncture improves menopausal symptoms have been studied for several years. A study found that hot flash status had a positive tendency toward increased levels of circulating IL-6 (P-trend = 0.049), IL-8 (P-trend < 0.001), TNF-α (P-trend = 0.008), and macrophage inflammatory protein-1β (P-trend = 0.04), suggesting that hot flashes might be related to low-grade systemic inflammation [147], and acupuncture can regulate the release of the innate immune cytokines and adaptive immunity cytokines [148]. Li et al. found that acupuncture could modulate the serum levels of E₂, corticotropin releasing hormone, adrenocorticotropic hormone, and corticosterone and improve BMD and bone mineral content in ovariectomized (OVX) rats [149]. EA alleviated osteoporosis secondary to ovariectomy by regulating the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) and Wnt/β-catenin signaling pathways [150]. In the OVX rats, it was demonstrated that EA at CV4 could significantly increase serum alkaline phosphatase (ALP) and bone gla protein (BGP) levels, enhance the maximum and fracture loads, increase BMD, and activate the Wnt-β-catenin signaling pathway, which improved the osteoporotic morphological changes [151]. Another study also showed that EA treatment increased levels of osteocalcin and the BMD of lumbar vertebrae, decreased levels of tartrate-resistant acid phosphatase 5b, and improved bone microstructure in the femur of OVX rats. The ratio of OPG to RANKL and the levels of LRP5, β-catenin, and Runx2 were significantly upregulated after EA, while the expression of phosphorylated (p)-p38 and p-JNK were downregulated in the EA-treated groups compared with the OVX group [152].

The current evidence suggests that acupuncture is beneficial in improving menopause-related symptoms including hot flashes, sleep disturbances, and depression and quality-of-life. Nevertheless, the mechanism of acupuncture treating menopause remains unclear, further studies are needed.

9 Conclusions

Acupuncture, one of the important components of TCM, has been used to maintain women health with a long history in China and now widespread to around the world. Acupuncture provides proven benefit for many obstetric and gynecological diseases, including PD, CGP, PCOS, IVF, NVP, prenatal complication, and perimenopausal syndrome. Until now, effort devoted into both biological and clinical research on acupuncture has a few decades [153], numerous acupuncture studies emerged [154]. However, how acupuncture work and what’s the underlying biochemical mechanism are still myth.

This narrow review analyzes the high-quality clinical trials of acupuncture in the treatment of obstetrical and gynecological diseases, to summarize the current evidence and provides brief review for biological mechanism and clinical effects to articulate a more instructive set of recommendations in the future. For basic experiment, we can explore complex molecular pathways underlying its efficacy including multiomics. For clinician, in view of the rapid growth of evidences, clear, actionable, trustworthy, and patient-centered acupuncture clinical practice guidelines should be formulated by incorporating them into mainstream regiments to improve the quality of women’s health. In the future, women related diseases on which acupuncture have shown great effect in real world but with a low or very low level of evidence are the main priorities for scientific world.

Despite that proven evidence indicated that the acupuncture significantly improves pain relevant disorders, PCOS and NVP, the underlying mechanisms are not fully understood. While due to flaws of methodology and heterogeneity of acupuncture protocol, stronger evidence is still needed to support the usage of acupuncture in IVF-ET, infertility, prenatal complication, and menopausal transition, and the behind mechanisms are also deserved to be elucidated. In fact, therapeutic effects of acupuncture interventions are influenced by many factors including depth of needling, number and locations of acupoints, and De Qi and patients’ expectation, etc. Until recently, an extension of CONSORT was defined for these factors in details by the guidance of Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). With the advantages of being easy to perform, self-controllable, cost effective, and non-invasive, acupuncture will play an important role in maintaining women’ health.

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