Jia-Xuan Wang,Guo-Hua Lin

1Guangzhou University of Chinese Medicine,Guangzhou,China.2Department of Acupuncture and Moxibustion,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,China.

Introduction

Polycystic ovary syndrome(PCOS)is one of the most common complications in gynecology,with a female incidence rate of 5%to 10%worldwide.It has serious reproductive effects,such as anovulatory infertility,menorrhagia,amenorrhea,high androgens,pregnancy complications,etc.[1].Its pathogenesis is complex and its symptoms are numerous,mainly affecting women in puberty and childbearing age.Related research reports that the current incidence of infertility in women of childbearing age(15 to 49 years old)is 50%to 74%[2-3].At present,modern medical treatment about PCOS mostly uses drugs to improve symptoms,correct endocrine and metabolic disorders,ovulationinduction,orsurgery.Amongthem,clomiphene is the first-line drug used in medical treatment,but approximately 20%of patients do not respond to this drug,and this drug produces a series of adverse effects,such as ovarian enlargement,headache,blurred vision,very few cases of hepatitis,hair loss,and even ovarian hyperstimulation syndrome[4].

InthefieldoftraditionalChinesemedicine,acupuncture therapy occupies an irreplaceable position.InHuangdineijing(B.C.220~211,Han Dynasty),the tools of acupuncture needles are divided into nine kinds,called"nine needles",which treat different types of disease.Currently,it has developed into electro-acupuncture,water needle,and small needle knife.However,through long-term clinical research,doctorshavefoundthattheeffectofsimple acupuncture on chronic diseases is difficult to sustain;thus,it is necessary to"retain needles"to enhance and consolidate their curative effect.Leaving needles in acupuncture points is called"retaining the needle".It is first published inSuwen(B.C.220~211,Han Dynasty):a person who has been sick for a long time is considered to contain evil deep within them;therefore,an acupuncturist treats them by putting needles deep inside them and leaving the needles there foralongtime.Inthemid-1960s,Chinese acupuncturists explored a new method of needle retention to treat poliomyelitis in children:they embedded catgut sutures in the acupuncture points of children and found that their effects lasted for one month after being embedded once;thus,the number of treatment was greatly reduced.This is the prototype of modern acupoint embedding technology[5].

Acupointembeddingisanacupuncture-based combinationoftraditionalChineseandwestern medicines.It has the advantages of long curative effect,low number of treatments,low side effects,and an ability to treat both the symptoms and root causes of diseases.It has been accepted by more patients[6].Acupointembeddingtreatmentofgynecological diseases is also very common in clinical practice.The acupuncture points Diji(SP8),Xuehai(SP10),Tianshu(ST25),Guanyuan(RN4),Qugu(CV2),Ciliao(BL32)and Pishu(BL20)have a total effective rate of 95%for acupoint embedding treatment of uterine dysfunctional bleeding[7].Catgut sutures presoaked in compound angelica injection were applied to the points Zhongji(RN3),Xuehai(SP10),Ciliao(BL32),and Tianshu(ST25)to treat dysmenorrhea with a total effective rate of 98.70%[8].Recent studies have shown that in patients with PCOS and kidney deficiency,acupoint embeddingcombinedwithtraditionalChinese medicine and Daying-35 can downregulate luteinizing hormone(LH),LH/follicle stimulating hormone(FSH)ratio,and improve ovulation rate to a greater extent than single medicine[9].However,there is also an international multicenter randomized controlled trialshowingthatacupunctureisineffectivein increasing the live birth rate of patients with PCOS[10].This clinical study was designed to compare the efficacyofacupointembeddingcombinedwith clomiphene with clomiphene alone in the treatment of PCOS.We compared body mass index(BMI),number of menstrual cycles,and serological levels of LH,FSH,LH/FSH ratio,and testosterone before and after treatment.

Materials and methods

Case selection

Diagnostic criteria:Refer to the diagnostic criteria revised by the Rotterdam Working Group of the American Society for Reproductive Medicine[11].There are 2 items in the following 3 items:(1)rare ovulation or no ovulation;(2)hyperandrogenism or clinical manifestations of hyperandrogenism(such as hairy,hemorrhoids,etc.);(3)ultrasound examination showing one or both sides of the ovary with a diameter of 2~9 mm,follicles≥12,and/or ovarian volume≥10 ml3.

Inclusion criteria

Patients who(1)met the diagnostic criteria for PCOS and had pregnancy requirements;(2)were aged 20 to 35 years old;(3)did not use exogenous hormones within 3 months before the test.

Exclusion criteria

Patients who(1)did not meet the inclusion criteria;(2)had high blood pressure,heart disease,diabetes,and other serious diseases of their organs or systems;(3)had depression,anxiety,and other mental disorders,or were difficult to communicate;(4)were pregnant within 6 weeks or had a history of breastfeeding in the past 6 months,acupuncture,acupoint embedding,or hormone therapy in the past 3 months.

General information

Sixty cases were outpatients of the department of acupuncture and gynecology from September 2016 to June 2018.According to the order of treatment and random number table method,patients were randomly divided into the acupuncture-medicine combination and single medicine groups,with 30 cases in each group.

Treatment

Patients in the single medicine groups was treated with clomiphene alone at an oral dose of 50 mg daily,on the 3rd to 7th day of menstruation for 5 days for 4 menstrualcycle.Andpatientsinthe acupuncture-medicine combination group were treated with acupoint embedding combined with clomiphene.Prepared#4-0catgut sutures and#7 disposable injection needles.Passed a catgut suture thread from thetipofaninjectionneedle,disinfectedthe acupuncture points[Guanyuan(RN4),Zhongji(RN3),Zigong(EX-CA1),Zusanli(bilateral)(ST36),Fenglong(bilateral)(ST40)]with an iodophor cotton swab,and punctured the needle through the catgut suture into the acupuncture point approximately 1.5 cm deep.Pushed the whole catgut suture into the acupuncture point,pulled out the injection needle and then covered disposable infusion stickers.Continue to disinfect the acupuncture point and punctured the next acupuncture point.Once a month,a total of 4 menstrual cycles was treated.

Observation items and methods BMI

Number of menstrual cycles

Record the number of menstrual cycles before the start of the trial and after 2 months of discontinuation of treatment.

Serum sex hormone test

Serum levels of LH,FSH,LH/FSH ratio,and testosterone were measured before the first treatment.After the end of treatment,patients who were on the 3rd to 5th day of their menstrual cycles or had amenorrheastillneededtoundergofurther examination when the dominant follicle was still detected in the B-ultrasound examination.The venous blood of the patients in the fasting state was collected.Next,the levels of testosterone,FSH,and LH in the blood were measured,and LH/FSH ratio was calculated.

Efficacy criteria

According to the criteria of the"Diagnostic and EfficacyStandardsforClinicalDiagnosisof Traditional Chinese Medicine",the following efficacy criteria were formulated in combination with the content of this study[12].Significant effect:menstrual cycleandmenstrualflowreturnedtonormal,endocrine system returned to normal,and the level of androgen secretion was normal.Effective:menstrual cycle and menstrual flow were close to normal,and endocrinesystemwasbasicallynormal.Invalid:menstrual cycle and menstrual volume did not change,and endocrine system still could not return to normal.

Statistical methods

In this study,all collected data were statistically analyzed using the SPSS 19.0 statistical software.The statistical methods used were as follows.All research data were first tested for normality by the K-S normality test.If an approximate normal distribution was met,the measurement data before and after treatment in the group were then analyzed by the paired t-test,and differences in the measurement data between groups were determined by the independent sample t-test.The paired rank sum test was used for the comparison of the measurement data that did not conformtonormaldistribution,andthetwo independent sample rank sum test was used for comparison between groups.The rank and clinical efficacy between the two groups were compared using the rank sum test,and all test results were evaluated withP<0.05 as a criterion for determining whether there was a significant difference.

Results

Comparison of baseline data

The patients in the acupuncture-medicine combination group ranged in age from 20 to 33 years,with an average of 23.55±1.68 years;the course of disease was 1 to 6 years,with an average of 2.65±1.06 years.The patients in the single medicine group were 20 to 34 years old,with an average of 23.49±1.50 years old;the course of disease was 1 to 6 years,with an average of 2.98±1.01 years.There were no significant differences in the general data between the two groups(P>0.05)(Table 1).

BMI and number of menstrual cycles

Thereweresignificantdifferencesbetweenthe acupuncture-medicine combination and the single medicine groups before and after treatment(P=0.034,P=0.024).Comparison between the two groups showedthataftertreatment,theBMIofthe acupuncture-medicine combination group was lower than that of the single medicine group(24.3±1.6 vs 26.1±1.8),and the number of menstrual cycles was higher(3.6±1.5 vs 2.8±1.2).The difference was statistically significant(P=0.018,P=0.025)(Table 2).

Serum sex hormone levels

There was a statistically significant difference in the decrease of LH and LH/FSH ratio between the acupuncture-medicine combination and the single medicine groups before and after treatment(P=0.007,P=0.005).There was a statistically significant difference in the decrease of testosterone(P=0.009).Comparison between the two groups showed that LH(9.53±5.46 vs 12.29±5.67)and LH/FSH ratio(1.02±0.57 vs 1.45±0.23)were lower after treatment,and the difference was statistically significant(P=0.041,P=0.039)(Table 3).

Clinical efficacy

The total effective rate of these two groups were 76.67%and 70%,respectively.Clinical efficacy in the acupuncture-medicine combination group was higher than that in the single medicine group,and the difference was statistically significant(P=0.043),as shown in Table 4.

Table 1 Comparison of the general conditions

Table 2 BMI index and the number of menstrual cycle

Table 3 Comparison of LH,FSH,LH/FSH and testosterone

Table 4 Comparison of clinical effects

Discussion

Modern medicine believes that PCOS is a common metabolic disorder in clinical practice,and its special symptoms are hyperandrogenism,ovulation disorders,and ovarian polycystic changes[13].Among the clinical indicators of PCOS,elevated androgen level is one of the most typical manifestations.Excessive androgen levels will affect the maturation of follicles in women.In severe cases,it will lead to ovulation disorders;moreover,itwillalsoaffectthe decidualization of endometrium,leading to infertility[14].Atpresent,theovulation-promotingdrug clomiphene is a commonly used modern medicine.Related research reports showed that single use of clomiphene has low simple pregnancy rate and causes certain adverse reactions,and the disease was easy to repeat after stopping the drug[15].

Ancient Chinese literature had not record the disease name of PCOS.Its symptoms can be attributed to the syndromes of amenorrhea,late menstruation,menstrual disorders,and infertility in Chinese medicine[16].Chinese medicine believes that the normal operation of women's menstrual events depends on the coordination of their physiological functions.If affected by internal andexternalpathogenicfactors,thewoman's reproductive function will be abnormal,resulting in untimely menstrual cycle.Wanshinüke(A.D.1549,Ming Dynasty)recorded that women might be unable to get pregnant because of menstrual cycle disorder.Furengui(A.D.1368~1644,Ming Dynasty)said that the cause of menstrual disorder was the deficiency of Shenjing(an essencial biologically active substance of kidney).These recordation on ancient literature suggest the close relationship between kidney and menstruation.The blood and Qi filling of the Chong meridian and Ren meridian is very important in achieving pregnancy.The essence of PCOS is of deficiency in origin and excess in superficiality.The disease is located in the Chong meridian and Ren meridian and related to the kidney,spleen,and liver.Therefore,the Ren meridian acupoint Guanyuan(RN4)and Zhongji(RN3)were selected.Zigong(EX-CA1),one of the acupoints beyond meridians,can treat embryonic developmental diseases.Most women with PCOS are fat;thus,we selectedZusanli(bilateral)(ST36)andFenglong(bilateral)(ST40),acupuncture points of the stomach meridian that can strengthen the spleen,and regulate the Chong meridian and Ren meridian.

At present,Liu Xiaoqing reported that acupoint catgut treatment can regulate endocrine hormones in thebodyandthehypothalamicsputumpituitary-ovarian axis,which can regulate the normal secretion of reproductive endocrine hormones,further improving the ovulation function and tending to normalize and reduce weight[17].Crosignani PGet al.showed that 5%to 10%loss of body weight can reduce testosterone,therebygraduallynormalizingthe menstrualcycleandmenstrualflow,andalso increasing the pregnancy rate of PCOS patients[18].He Yingpiaoet al.used acupoint embedding therapy to treatobesityinpatientswithPCOS,usingthe acupoints Zhongji(RN3),Diji(SP8),Hegu(LI4),Sanyinjiao(SP6),Taichong(LR3)and Fenglong(ST40)[19].During the treatment,13 cases of amenorrhea had 10 cases of menstrual cramps,and 19 of 23 cases of menstrual disorders returned to normal menstrual cycle,with a total effective rate of 80.6%.Among them,23 cases had different degrees of weight loss(2~10kg),and the effective rate was 63.9%.Acupoint embedding can further stimulate acupuncture points through the catgut suture for a long time,so as to dredge the channel and regulate yin and yang.It also can reduce the number of outpatients,save the patient's time and cost,and enhance patient compliance.

In this study,acupoint embedding combined with clomiphene was used to treat PCOS and showed satisfactory results.The total effective rates of the treatment and control groups were 76.67%and 70%,respectively.Thedifferenceinclinicalefficacy between the groups was statistically significant.In addition,the combination of acupuncture and medicine can effectively decrease BMI,LH level,and LH/FSH ratio,as well as increase the number of menstrual cycles.In view of the limited ability and time,this study has not yet investigated fetal live birth rate in patients with PCOS,which is the most powerful indicator of the ultimate efficacy.Therefore,we should continue to study this in the next work.

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