In this study, we searched all the data about acupuncture combined with Chinese medicine for infertility caused by tubal obstructive and retrieved 33 relevant studies. Eighteen randomized controlled trials were included, involving 1623 patients. The results indicated that:(1) Compared with hydrotubation, acupuncture combined with CHM for tubal obstructive infertility was associated with a higher pregnancy rate, better tubal recanalization, and better relief of signs and symptoms. (2) The incidence of ectopic pregnancy was lower using acupuncture combined with CHM than with hydrotubation for infertility caused by tubal obstruction. This study suggests that there is a prospect for acupuncture combined with CHM in the treatment of infertility caused by tubal obstruction. Slight abdominal pain was observed during and after the operation, and recovery from the pain was achieved in a week without special treatment. No noticeable side effects were detected after drinking decoction, applying Chinese medicine externally, or by enema. Slight allergies in local areas were alleviated without any treatment. No abnormal changes were seen on lab test indexes (blood and urine routine examination) or type-B ultrasonic probe with pelvic cavity before and after the administration.
Mechanisms of acupuncture and CHM
Although the Acupuncture points and CHM selected in these 18 articles are not the same, we can still find more commonly used herbs and acupoints in them. The following twelve acupoints have been used in more than five (including five) studies, including Zigong(EX-CA1), Zhongji(RN3), Qihai(RN6), Sanyinjiao(SP6), Guanyuan(RN4), Shenshu(BL23), Zusanli(ST36), Xuehai(SP10), Taichong(LR3), Ganshu(BL18), Ciliao(BL32), Mingmen(DU4). The following eight herbs had been most frequently used in more than five (including five) studies, including Danggui(Angelica Sinensis), Chishao(Radix Paeoniae Rubra), Baizhu(Atractylodes macrocephala), Dangshen(Codonopsis pilosula), Gancao(liquorice), Danshen(Salvia miltiorrhiza), Lulutong(Fructus liquidambaris), Baijiangcao(Herbal patriniae).
The evidence of Acupuncture and CHM for TOI includes the following aspects: (1)Improving the hemodynamics of the ovary and uterus. A study showed that Chinese herbal medicine treating salpingitis obstructive infertility could effectively improve the hemodynamic rheological indicators of the uterus and ovary. In this study, the hemorheological indexes of the rats in the tubal obstructive infertility model in the experimental group were significantly lower than those in the western medicine group treated with cefuroxime and metronidazole. Another study showed that acupuncture combined with traditional Chinese medicine in treating salpingitis obstructive infertility could inhibit the expression of sICAM-1 protein, effectively improve hemorheological indicators, and promote the absorption and dissipation of inflammation. [27][28](2)Regulating immunity. A study confirmed that acupuncture could effectively increase the levels of β-endorphins in rats' peripheral blood and hypothalamus[29]. In regulating the female gonadal axis, β-endorphin, an endogenous opioid peptide, is a universal messenger of the nervous, endocrine, and immune systems and plays a crucial role in neuromodulation and maintaining the stability of the body's internal environment[30]. Domestic studies have also shown that acupuncture can regulate the endocrine system, stimulate ovarian function, and acupuncture can promote the absorption of inflammation. It has incomparable advantages for dredging the fallopian tubes, promoting the combination of sperm and egg, and improving the pregnancy rate[31]. (3)Regulates the hypothalamic-pituitary-ovarian axis. It has been reported at home and abroad that traditional Chinese medicine treatment can effectively improve women's ovarian function and increase the natural conception rate[32] [33]. A meta-analysis showed that treatment with CHM significantly reduced FSH levels in women[34], and another study showed that Danggui Buxue decoction had estradiol activity in vitro[35].
The limitations of the included studies in this meta-analysis are as follows: Firstly, the methodological quality was low due to the lack of description of blinding in most of the included studies. Blinding is necessary to prevent study results from being influenced by placebo effects or observer bias[36]. However, in the related research on acupuncture, it is difficult to apply the blind method to the patient because acupuncture needs to be implemented on the patient. In addition, traditional Chinese medicine formulations are mainly decoctions, which can be better differentiated from clinical drug capsules or placebos. In conclusion, it is challenging to achieve double-blindness in the clinical application of acupuncture combined with traditional Chinese medicine. Secondly, pregnancy and live birth rates are clinical trials' most reliable efficacy indicators for infertility. These two indicators are closely related to patients and have tremendous clinical significance. However, the live birth rate requires long-term follow-up of all patients. Unfortunately, none of these articles have data on live birth rates. Thirdly, most of the studies included in this meta-analysis used inconsistent acupuncture points and herbal decoctions. In traditional Chinese medicine, combining different acupoints and herbs will lead to other effects, and factors such as the preparation of the herbs and the method of decoction will affect the therapeutic effect. Therefore, we did not select specific acupoints or traditional Chinese medicines, and we believe that the review's conclusions are general. Finally, there are irregularities in the evaluation criteria for symptom relief, and the results largely depend on the patient's subjective evaluation. Therefore, a larger, high-quality, multicenter RCT should be performed.
The data included are published reports, excluding any grey literature (workshop proceedings, unpublished reports, presentations, and evidence from unconventional sources) and ongoing research. We only analyzed published studies, so unpublished studies with negative results may be missed. Therefore, the efficacy indicators may not reflect the actual situation. All included RCTs were conducted in China, which may lead to publication bias and affect the validity and reliability of this systematic review.
Implications for research
JAMA recommends that HSG (Hysterosalpingography) be used in diagnosing TOI to identify the site of obstruction, followed by surgical repair (e.g., hysteroscopy with tubal cannulation for proximal tubal obstruction, tubal re-anastomosis, or fimbrioplasty for distal obstruction) or IVF. Although surgical treatment can restore tubal patency in the short term and increase the odds of pregnancy in women with TOI, it also increases the risk of infection and lumen adhesions postoperatively[37].
In some Asian countries, acupuncture and CHM are commonly used in TOI as a complementary and alternative therapy. Although acupuncture and traditional Chinese medicine can increase the pregnancy rate and improve the degree of tubal blockage, there is a lack of high-level evidence-based medical research. Therefore, further studies on the efficacy and safety of acupuncture and CHM in treating TOI are encouraging and promising. However, doctors tend to choose acupoints and herbs based on the syndrome differentiation theory (a key concept in TCM), which leads to subjectivity in selecting acupoints and herbs. At the same time, the non-uniform diagnosis and treatment standards will also affect the objective evaluation of the curative effect. Therefore, in the future, it is necessary to urge standardized diagnosis and treatment, explore more appropriate treatment methods, and establish a standardized TOI treatment system in traditional Chinese medicine.