Li Yang (李阳), Ji Jun (纪军), Xu Jia (徐佳)

1 Yueyang Hospital of Integrative Chinese & Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China

2 Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China

Literature Review

Review on studies of acupuncture treatment for luteinized unruptured follicle syndrome

Li Yang (李阳)1, Ji Jun (纪军)2, Xu Jia (徐佳)1

1 Yueyang Hospital of Integrative Chinese & Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China

2 Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China

Luteinized unruptured follicle syndrome (LUFS), a specific type of ovulation disorder, is for a cause of female infertility. Acupuncture therapy has a good effect for LUFS. In order to understand the clinical effects and research situation of acupuncture therapy for LUFS, the author analyzed and reviewed the relevant literature. It was indicated by the findings that acupuncture therapy and integrative therapy of acupuncture and Chinese herbs have good therapeutic effect for this disease. Acupuncture therapy has the effect to promote ovulation. By the therapeutic principle to tonify the kidney and circulate blood, acupuncture therapy mostly was adopted in the period of ovulation. The acupoints are mostly selected from the lower abdomen and lower limbs, possibly based upon syndrome differentiation at the same time. The needling techniques are of certain characteristics. But, the issues of low quality, un-standardized inclusive, exclusive criteria and effective criteria still exist in the current clinical study.

Acupuncture-moxibustion Therapy; Acupuncture Therapy; Acupuncture Medication Combined; Moxibustion Therapy; Ovulation Disorder; Infertility, Female; Review

Luteinized unruptured follicle syndrome (LUFS) refers to that before or after immature, the follicles are not ruptured but the granule cells start luteinization and secrete progestin, causing a series of changes similar to ovulatory cycle in the effector organ, such as normal menstrual cycle, biphasic change in the basal body temperature, change in the secretory phase of the endometrium before and during menstruation[1]. Because there is no follicle discharge, LUFS belongs to a specific type of ovulation disorder and is one of the reasons causing female infertility[2]. It has been indicated in the studies that its incidence rate was 5%-10% in normal women of childbearing age and was 25%-43% in women with infertility[3]. The pathogenesis of this disease is still in the study. Currently, it is believed that its occurrence may be related to central hormone secretion disorder (such as insufficiency of luteinizing hormone secretion caused by dysfunction of the reproductive axis), ovarian local disorder (such as changes in the hemodynamics, the peripheral steroid hormones and cytokines), local mechanical factor (such as ovarian local ‘embedding’ caused by pelvic inflammation), iatrogenic factor (such as luteinization caused by Clomiphene), mental and psychological factors[4-5]. For patients expecting pregnancy, the expectant treatment, ovulation promotion by medications and ovulation by puncture under ultrasonic wave are used in the modern medicine[4]. But, the expectant treatment is low in pregnancy rate, and the ovulation inducing medications would induce LUFS or ovarian hyperstimulation syndrome. It has been indicated in the studies that during the ovulation promotion by Clomiphene, the luteinization rate of thefollicles approach 41.2%[6]. The ovulation promotion by puncture is at risk of infection. Acupuncture therapy can regulate Zang-fu organs, unblock the Thoroughfare Vessel and Conception Vessel, tonify the kidney, and circulate blood. Since the ancient times, there were many reports about acupuncture treatment for infertility. It has been frequently indicated by the findings of the studies that acupuncture has the effect to promote ovulation. In order to understand the clinical effects and research situation of acupuncture treatment for LUFS, we searched the relevant documents and reviewed the research progress about acupuncture treatment for LUFS.

1 Document Screening

1.1 Searching strategy

By Chinese characters meaning acupuncturemoxibustion, acupuncture, electroacupuncture (EA), moxibustion, catgut-embedding, acupoint injection, hydro-acupuncture, plum blossom needle, ear points, acupoints and acupoint therapy as one group of the key words, and by luteinization, LUFS, and luteinized unruptured follicle as another group of the key words, the two groups of key words were respectively combined in pairs to search in PubMed, China National Knowledge Internet (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), SinoMed and Springer Database, with the publishing years restricted from January 1979 to July 2015.

1.2 Inclusion and exclusion criteria of documents

Inclusion criteria: Publicly published in the international and domestic journals and databases; in languages of Chinese or English; in the contents about acupuncture treatment for LUFS; clinical observation or research.

Exclusion criteria: Repeatedly published documents; reviews and theoretical researches.

1.3 Document screening process and results

Based upon the searching strategy and collecting methods, totally 155 articles on acupuncture treatment for LUFS were searched out. A total of 126 articles of repetition or incompatibility with the inclusion criteria were excluded, including 86 articles of repeatedly searched, 19 articles of unmatched contents, 12 articles of general reviews, 6 articles of theoretic discussion, 1 article of animal experiment, and 2 articles of similar sources of the cases. Finally, 29 domestic articles were taken, including 22 articles of clinical study[7-28], and 7 articles of case observation[29-35]. Please see Figure 1 for document screening process.

2 General Situation of Treatment

2.1 Control study

In 22 articles, the control groups were established with human chorionic gonadotropin (HCG) in predominance, partially with Clomiphene Citrate (CC) plus HCG, CC, human menopausal gonadotropin (HMG) plus HCG, or blank control, or with Chinese herbs . Please see Table 1 for details. For the intervention modes and number of the articles in the treatment group, please see Table 2 for details. It has been indicated by the findings from the included articles: no matter by simple acupuncture therapy or integration of acupuncture and Chinese herbs , they were better than the control groups for improving the ovulation rate and pregnancy rate of LUFS patients, with statistical significant differences.

Figure 1. Document screening process

Table 1. Interventions in the control group and article number

Table 2. Interventions in the treatment group and article number

2.2 Case observation

In 7 articles of case observation, there was 1 article of simple acupuncture treatment[29]. Another 4 articles about acupuncture, moxibustion plus Chinese herbs , including 2 articles about acupuncture plus Chinese herbs , 1 article about EA plus Chinese herbs[32]and 1 article about acupoint injection plus Chinese herbs[33]. There were two articles about acupuncture plus Chinese herbs and Western medications, including 1 article about acupuncture plus Western medications[34]and 1 article about EA plus Western medications[35]. The observation showed that no matter simple acupuncture or acupuncture plus medications, they could enhance the ovulation rate and pregnancy rate of LUFS patient.

Generally, acupuncture therapies for LUFS patient, no matter simple acupuncture, integrated acupuncture and Chinese herbs, or integrated therapy by acupuncture and Chinese herbs and medications, could enhance the ovulation rate and pregnancy rate of the patient, better than the routine treatment by medications in the therapeutic effect. It has been indicated by the study in 1 article that the therapeutic effect was better in acupuncture plus Chinese herbs than simple Chinese herbs . Besides, it has been found out from the above control studies that after simple acupuncture, or acupuncture plus Chinese herbs , pulse index (PI) of blood flow in the ovarian artery[8-10,13,15,17,28], and resistance index (RI) in the ovarian artery[8-10,13,15,17,25,28]were decreased than before the treatment, and luteinizing hormone (LH) and estradiol (E2)[7,9,13,17,28]were elevated than before the treatment, better than HCG or CC plus HCG treatment groups, indicating that acupuncture therapy and acupuncture plus Chinese herbs could improve the patient’s endocrine, induce LH peak, improve the blood perforation of the ovarian artery, so as to induce ovulation, better than medications. It has found out in 1 article[35]of case observation that herbal decoction for promoting ovulation could promote the follicles to develop continuously to the dominant follicles, and then the following acupuncture and Chinese herbs could promote ovulation. Acupuncture is obviously effective for stranded type and large follicular type.

3 Therapeutic Ideas

3.1 Therapeutic principles

This disorder belongs to the scope of ‘infertility’ in traditional Chinese medicine (TCM). It is mostly believed that kidney deficiency is a pathogenic reason and the dysfunctions in the liver, spleen, kidney, Thoroughfare Vessel and Conception Vessel, disharmony of the uterine collaterals, and obstruction of stagnant blood are the key for disorder of follicle discharge. Most medical practitioners regard the methods to tonify the kidney and circulate blood as the basic therapeutic principle, for instance; to tonify the kidney and circulate blood[8-9,12-13,16,20,25-26,31]; to benefit the kidney, circulate qi and circulate blood[32]; to warm and tonify the kidney yang, circulate blood and dredge the collaterals, and regulate the Thoroughfare Vessel and Conception Vessel[18]; to warm and tonify the kidney yang, promote transformation of yin and yang, circulate blood and dredge the collaterals[7,27]; to tonify the kidney, soothe the liver and circulate blood[11,14-15,19]; to tonify and benefit the liver and kidney, and circulate qi and blood[30,32-33]. Some medical practitioners also make the therapeutic principles in accordance with decrease, increase and conversion of yin and yang in the kidney during the menstrual cycle, i.e. to tonify the kidney and nourish yin at the later stage of menstruation; to tonify the kidney and dredge the collaterals during menstruation; to warm the kidney, assist yang, benefit qi and nourish blood in the early stage of menstruation; to circulate qi and blood and regulate menstruation during menstruation[21], or in accordance with the principle for combination of syndrome differentiation and disease identification, to benefit the kidney and circulate blood during the follicular phase; and to regulate qi and remove stagnation during ovulation[17].

3.2 Intervention time of acupuncture

The moment for acupuncture intervention is mainly based upon ovulation in predominance. The treatment is mostly given every day, in order to promote follicle discharge and is also given during the follicular phase, in order to promote the development of the follicles (Table 3).

Table 3. Intervention moment and time of acupuncture

3.3 Acupoint selection

There were 27 articles using body acupoints for treatment, mainly the acupoints at the lower abdomen and lower limbs. The commonly used acupoints in the lower abdomen were Guanyuan (CV 4) (26 articles), Zhongji (CV 3) (18 articles), Zigong (EX-CA 1) (18 articles), Qihai (CV 6) (9 articles), Dahe (KI 12) (5 articles), Guilai (ST 29) (5 articles), Qixue (KI 13) (4 articles), Luanchao (Extra) (4 articles). The commonly used acupoints in the lower limbs were Sanyinjiao (SP 6) (24 articles), Zusanli (ST 36) (11 articles), Xuehai (SP 10) (11 articles), Taichong (LR 3) (7 articles), Taixi (KI 3) (5 articles), Fenglong (ST 40). There were also Neiguan (PC 6) and Hegu (LI 4) (3 articles) in the upper limbs. Besides, 19 acupoints in the upper abdomen, lumbosacral and naval region were used. Except the selection of Shenshu (BL 23), Zhongwan (CV 12) and Xiawan (CV 10) in 4 articles, the other acupoints were used less than 3 articles.

In acupuncture, the plan to select 2-5 acupoints in the abdomen and 4-6 acupoints in the limbs were often adopted, indicating the therapeutic idea to promote ovulation by acupuncture. Some medical practitioners considered to select the acupoints by syndrome differentiation in combination of the acupoints. For instance, Neiguan (PC 6)[10,16,22]and Taichong (LR 3)[20,23]were added for blood stasis and qi stagnation. Fenglong (ST 40)[10,20,22]was added for obvious phlegm and dampness and Xuehai (SP 10) was added for blood deficiency. Taixi (KI 3) was added for kidney deficiency and Yinlingquan (SP 9)[20,23]was added for spleen deficiency.

There were totally 2 articles about ear pointembedding method, with Subcortex (AT4), Kidney (CO10), Liver (CO12), Spleen (CO13), Ear Centre (HX1), Central Rim (AT2,3,4i) and Endocrine (CO18)[11-12].

3.4 Needling techniques

There were 10 articles talking about the application of the needling techniques, arrival of the needling sensation and the needling sensation reaching the diseased areas. For instance, in puncturing Guanyuan (CV 4) and Zhongji (CV 3), the needle tips were inserted toward the perineum, for producing sore, numb and distending sensation in the perineum. Zigong (EX-CA 1) and Luanchao (Extra) were manipulated with strong stimulation, for inducing downbearing sensation in the lower abdomen[10,22-23,26]. In puncturing the acupoints in the abdomen, the needle tips were inserted obliquely downward, for producing sore, numb, distending and heavy sensation in the local areas[21], or the needles were repeatedly lifted, thrust and twisted till sore, numb, distending and heavy sensation appeared[25]. The reinforcing-reducing manipulations were also used. For instance, Qihai (CV 6), Guanyuan (CV 4), Zhongwan (CV 12), Xiawan (CV 10) and Zhongji (CV 3) were punctured with reinforcing manipulation. Bilateral Huaroumen (ST 24), Wailing (ST 26), Sanyinjiao (SP 6) and Zigong (EX-CA 1) were punctured with reducing manipulation[16]. Or Guanyuan (CV 4) and Qihai (CV 6) were punctured with reinforcing manipulation and Zhongji (CV 3), Xuehai (SP 10) and Sanyinjiao (SP 6) were punctured with reducing manipulation[18]. Or Zigong (EX-CA 1), Guanyuan (CV 4), Zhongji (CV 3) and Sanyinjiao (SP 6) were all punctured with reducing manipulation[17]. Or Guanyuan (CV 4), Zigong (EX-CA 1)[15]and Sanyinjiao (SP 6) were punctured with reinforcing manipulation and Taichong (LR 3)[19]and Xingjian (LR 2) were punctured with reducing manipulation[15].

The documents of electroacupuncture apparatus accounted for 27.5%. Guanyuan (CV 4), Zhongji (CV 3), Sanyinjiao (SP 6), Zigong (EX-CA 1) and Luanchao (Extra)on the side of dominant follicle were linked with electroacupuncture apparatus, and also Qihai (CV 6) and Xuehai (SP 10) were linked with electroacupuncture apparatus. The parameters of electroacupuncture apparatus included sparse-dense wave, current intensity ＜ 5 mA or within the patient’s tolerance[10,22-23], or continuous wave[20,26], frequency of 2 Hz[20], intensity within the patient’s tolerance[26]. The acupoints selected for tapping technique of plum blossom needle were similar to those for acupuncture, mainly the acupoints in the abdomen and lower limbs, and were tapped till local skin became red and congested[13].

4 Evaluation

4.1 Quality control

In the included 29 articles, 18 articles were designed with randomized controlled study, accounting for 62.1%. Among them, only 8 articles discussed the random grouping method[8,13,10,12,22,24-26], and 18 articles described the sampling number of singular group of 20-45 cases, without large samples. The majority of the articles were not published with the descriptions related to the inclusion criteria, exclusion criteria, dropped-off cases, safety assessment and research quality. As for the therapeutic courses, the natural months of 1-6 months were described in some articles and also the menstrual cycles of 1-6 months were described in some articles. We believe that the menstrual cycle of 21-35 d was in the normal scope, and the menstrual cycle of the patients should be taken as the observation unit in clinical study and it was not reasonable to set up the courses with the natural months. Besides, the diagnostic criteria for LUFS should be stipulated upon continuous appearance of follicular luteinization in the two menstrual cycles, together with the time that sinus follicles develop to the mature follicles. Therefore, we believe the clinical observation should not be less than three cycles. It has also been shown in the studies that with the increase of the therapeutic cycles, the ovulation rate could be elevated, and the pregnancy rate could be enhanced somewhat in the three therapeutic cycles than in one therapeutic cycle[31].

4.2 Criteria of therapeutic effect, inclusion and exclusion

The goal of acupuncture treatment for LUFS was supposed to promote ovulation. Therefore, ovulation was an important item to assess the therapeutic effect. In the included documents, there were two methods to calculate the ovulation rates: (total cases of ovulation ÷ total observed cases) × 100% and (total number of ovulatory cycles ÷ total number of the observed cycles) × 100%. We believe that the ovulation does not occur in the treatment of every cycle during the treatment. Therefore, the latter calculating method is more objective. Infertility can be caused by many factors. The ovulation rate and pregnancy rate are not parallel. The pregnancy rate could be impacted by many factors, such as organic (genital malformation, fallopian tube adhesion, and uterine fibroids), inflammatory, immunological, other endocrine factors, and even male factors. We do not think the pregnancy rate could be used as an item to evaluate the therapeutic effect of acupuncture treatment for LUFS. Besides, despite acupuncture therapy or combining acupuncture with medications, the improvement of the patients’symptoms should be brought into the judging criteria of the therapeutic effect. But, only 5 articles[12,15,19-20,26]mentioned the improvement of TCM syndromes in the patients, better than the control groups by medications. Luteinized follicle can be divided into the three types by B-ultrasonic diagnosis, i.e. small follicle luteinized type, stranded type and constant-enlarging type[36]. The pathogenesis is different in three types and the therapeutic methods should be different. Small follicle luteinized type is mainly treated by promoting the development of the follicles. The stranded type and constant-enlarging types are mainly treated by promoting ovulation. In the included documents, only 2 articles[30,32]designed different kinds of therapeutic plans for three different types of luteinized follicles. Most documents did not report the type classification by B-ultrasonic diagnosis. We believe that the intervention time and treatment by acupuncture should be focused to promote ovulation and the latter two types should be taken as the observed targets.

5 Discussion

The clinical observation and study of acupuncture treatment for LUFS have attracted attention among medical practitioners. In summary, it can be seen that the treatment of LUFS by acupuncture and integrated acupuncture and Chinese herbs can produce good therapeutic effect. Acupuncture has the effects to promote ovulation. In the future study, it is necessary to develop multiple-centered and large-sample randomized controlled studies, strengthen the mechanical study of modern medicine, and positively explore the new therapeutic methods and ideas, based upon the principles to follow quality control, unify the criteria of the therapeutic effects, and standardize the inclusion and exclusion criteria, in order to form a more effective and standard therapeutic plan for helping more LUFS patients.

Conflict of Interest

There was no potential conflict of interest in this article.

Acknowledgments

This work was supported by the 3-year Action Plan for Shanghai Development of Traditional Chinese Medicine (上海市中医药事业发展三年行动计划, No. ZYSNXDCC-HPGC-FC-009, No. ZYSNXD-CC-MZY006); the 3-year Action Plan for Shanghai Further Accelerating Development of Traditional Chinese Medicine [上海市进一步加快中医药事业发展三年行动计划(2014-2016), No. ZY3-CCCX-1-2001].

Received: 18 May 2015/Accepted: 23 June 2015

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以人为本是“科学发展观”的核心，也是我们管理工作的核心，企业和员工是一个利益共同体，这就需要以实现和谐发展为落脚点，着力营造和谐融洽、充满友爱、精诚团结、蓬勃向上的氛围，要想处理好与各方面的关系，就要打好“三张牌”，让每一名干部员工都能感受到企业的和谐温暖，得到价值回报，实现和谐共融，为可持续发展营造有利的氛围。

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Translator: Huang Guo-qi (黄国琪)

针灸治疗未破裂卵泡黄素化综合征的研究述评

未破裂卵泡黄素化综合征(luteinized unruptured follicle syndrome, LUFS)是排卵障碍的特殊类型, 是导致女性不孕的原因之一。针灸治疗LUFS有较好的疗效, 为了解针灸治疗LUFS的临床疗效及研究现状, 笔者对相关文献进行整理、分析与评论, 结果表明针灸及针药结合治疗本病有较好的疗效, 针刺具有促排卵作用。针灸治疗以补肾活血为主要治则, 多作用于排卵期; 取穴多位于下腹部及下肢, 同时可配合辨证取穴; 针刺手法有一定特色。但目前临床研究尚存在研究质量不高, 纳入、排除及疗效标准不规范等问题。

针灸疗法; 针刺疗法; 针药并用; 灸法; 排卵障碍; 不育,女性; 综述

R246.3 【

】A

Author: Li Yang, master degree candidate

Xu Jia, chief physician.

E-mail: maiyixu@163.com