本文選題：卵巢儲備功能下降 + 針灸�。� 參考：《中國中醫(yī)科學(xué)院》2017年碩士論文

【摘要】：研究背景卵巢儲備功能下降(Diminished ovarian reserve,DOR),是指卵巢內(nèi)存留的可募集卵泡數(shù)量減少和(或)卵泡細(xì)胞質(zhì)量下降,導(dǎo)致女性生育能力下降及性激素缺乏的疾病,臨床表現(xiàn)為女性在月經(jīng)初潮后到40歲之前出現(xiàn)的月經(jīng)異常,如月經(jīng)量少、月經(jīng)稀發(fā)、閉經(jīng)、不孕等,并伴有一系列的更年期癥狀,嚴(yán)重影響了女性的健康。研究證實,DOR患者很難獲得和維持正常的妊娠,這也是其帶來不孕癥的重要原因。據(jù)統(tǒng)計,在女性不孕的發(fā)生人群中,10%是由于卵巢儲備功能下降引起的。隨著經(jīng)濟(jì)社會生活壓力的增大、環(huán)境污染的惡化及婦女生育年齡的推遲等變化,DOR的發(fā)病率逐年增加,并越來越有呈年輕化的趨勢,尤其是其導(dǎo)致的不孕,給個人與家庭帶來沉重的負(fù)擔(dān)。并且,卵巢功能的衰退是一個逐漸發(fā)展的過程,如果沒有及時有效的干預(yù)措施,DOR患者的卵巢可在1-6年逐漸萎縮,最終發(fā)展為卵巢早衰(Premature ovarian failure,POF)。隨著現(xiàn)在我國二孩政策的全面放開,有生育意愿的女性多集中在70后和80后,據(jù)統(tǒng)計,符合二胎政策的女性有60%在35歲以上,她們趨于生育的最后時機(jī),卵巢儲備功能的降低及生育潛能的下降不可避免,因此,DOR的有效治療極為重要。目前,現(xiàn)代醫(yī)學(xué)對DOR的病因及致病機(jī)制尚不明了,一般認(rèn)為年齡是導(dǎo)致卵巢儲備功能下降的最主要因素,另與遺傳、免疫、環(huán)境、手術(shù)、放化療、個人孕產(chǎn)史、感染、血型等因素有關(guān)。臨床中DOR的治療方案的選擇主要與患者病因、年齡、生育狀況、生育要求、卵巢內(nèi)有無發(fā)育中卵泡及經(jīng)濟(jì)情況等確定。常用的治療方法為激素替代療法、促排卵、免疫抑制、輔助生殖技術(shù)等。激素替代療法大多用于無生育要求的患者,能明顯改善低雌激素癥狀,并見效快。但這一療法停用后復(fù)發(fā)率高,并不能特異性地改善卵巢功能,并且有禁忌癥和明顯的副作用。比如激素替代療法的禁忌癥包括子宮內(nèi)膜增生、子宮肌瘤、乳腺癌、子宮內(nèi)膜癌及血栓性疾病。對于有生育要求的患者,臨床上常采用促排卵治療和輔助生殖技術(shù)幫助受孕,但成功率低,經(jīng)濟(jì)負(fù)擔(dān)重,遠(yuǎn)期療效差,且存在著多種禁忌證,如促排卵治療常常會引發(fā)卵巢過度刺激,從而進(jìn)一步損害卵巢功能。免疫調(diào)節(jié)劑在理論上對自身免疫性DOR治療有效,但長期應(yīng)用不良反應(yīng)大,療效不確切。中醫(yī)沒有“卵巢儲備功能下降”病名,但“閉經(jīng)”、“年未老經(jīng)水?dāng)唷�、“血枯�?“不孕”等疾病癥狀表現(xiàn)與其相似,可以認(rèn)為是古代醫(yī)學(xué)對DOR的認(rèn)識。從古至今,中醫(yī)藥一直在治療此類疾病上發(fā)揮著很大的作用。并且,中醫(yī)學(xué)不同時代不同醫(yī)家對此類疾病也有著獨特的認(rèn)識,并應(yīng)用了多種治療思路和手段。目前,很多臨床及實驗研究也已經(jīng)證實:針灸療法廣泛應(yīng)用于卵巢早衰、多囊卵巢綜合癥等多種排卵障礙性疾病。針刺療法在治療DOR方面,因其效果好、副作用少、價格低、便于接受等越來越得到臨床的肯定。臨床試驗研究顯示,針刺治療可以改善女性血清激素水平,改善月經(jīng)情況,改善患者更年期癥狀,提高試管嬰兒成功率等�？梢�,針灸治療有確切的療效。但是,針灸治療卵巢儲備功能下降的研究文獻(xiàn)較少,大多是針?biāo)幗Y(jié)合或其它綜合療法,并且治療思路、治療方法、療效判定標(biāo)準(zhǔn)各異。目前中醫(yī)對該領(lǐng)域的病因病機(jī),辨證與治療還未形成完備的理論體系,相關(guān)文獻(xiàn)、報告相對缺乏,而且對針灸治療該病并沒有顯示出針灸的特色,辨證分型和治療配伍等多于內(nèi)科疾病的思路相似,并且,針灸治療起效的作用機(jī)制、臨床療效都缺乏廣泛并深入的研究和質(zhì)量較高的文獻(xiàn)。導(dǎo)師多年來從事針刺治療卵巢儲備功能下降患者的工作,擁有較為豐富的臨床經(jīng)驗,認(rèn)為卵巢儲備功能下降是一個“經(jīng)水漸消”的過程,腎精虧虛是根本原因,沖任失調(diào)為疾病關(guān)鍵,情志失暢與疾病發(fā)生互為因果,使用調(diào)經(jīng)促孕針刺法,以補(bǔ)腎精,調(diào)沖任,暢情志,使腎精充足,沖任條暢,神志安定,以此來治療卵巢儲備功能下降,具有較好的療效。故本人跟師學(xué)習(xí),記錄卵巢儲備功能下降患者的臨床病例并加以整理,進(jìn)一步觀察臨床療效,分析總結(jié)導(dǎo)師使用調(diào)經(jīng)促孕針刺法治療卵巢儲備功能下降的診療經(jīng)驗,重視沖任、腎精、情志對卵巢儲備功能的影響,以經(jīng)絡(luò)理論為基礎(chǔ),突出針灸特色和穴位雙向調(diào)節(jié),局部與遠(yuǎn)端相配合,對針灸治療卵巢儲備功能下降提供思路和方法。并且,卵巢儲備功能減退是卵巢早衰的第一個階段,選擇卵巢儲備功能減退期開展針灸臨床療效的研究,符合中醫(yī)“未病先防”的“治未病”思想,對改善卵巢儲備功能,預(yù)防卵巢早衰具有十分重要的意義。研究目的總結(jié)導(dǎo)師調(diào)經(jīng)促孕針刺法治療卵巢儲備功能下降的診療經(jīng)驗,通過觀察調(diào)經(jīng)促孕針刺法對卵巢儲備功能的影響,對調(diào)經(jīng)促孕針刺法治療卵巢儲備功能減退的臨床療效進(jìn)行初步評價研究,為今后開展多中心,大樣本臨床研究奠定基礎(chǔ)。研究方法本研究所有病例資料來源于2016年1月到2017年4月中國中醫(yī)科學(xué)院針灸醫(yī)院卵巢早衰專病門診的患者,符合DOR診斷標(biāo)準(zhǔn),均簽署知情同意書。采用中央隨機(jī)系統(tǒng)隨機(jī)分為針刺組和空白等待組。測定兩組患者治療前后的血清激素水平(卵泡刺激素(Follicle-stimulating hormone,FSH)、黃體生成素(Luteinizing hormone,LH)、FSH/LH、雌二醇(Estradiol,E2)、抗繆勒管激素(Anti Mueller hormone,AMH)、竇卵泡計數(shù)(Antral follicle count,AFC)及月經(jīng)癥狀評分和焦慮自評量表(Self-RatingAnxietyScale,SAS),進(jìn)行療效評價。研究結(jié)果(1)本試驗共隨機(jī)分組46例患者,其中納入分析的患者40例,針刺組和空白等待組各20例,6例患者中途停止治療或改變治療方案。總脫失率為13.4%,整個試驗過程未出現(xiàn)嚴(yán)重不良事件。(2)與治療前比較,針刺組治療后FSH值具有下降趨勢,具有統(tǒng)計學(xué)差異(P=0.000.05);空白等待組無明顯變化,無統(tǒng)計學(xué)差異(P=0.170.05)。針刺組和空白等待組治療后FSH差值比較顯示,針刺組的FSH差值變化更明顯,差異具有統(tǒng)計學(xué)意義(P=0.0020.05)。(3)治療后,針刺組的FSH/LH正常率提高,空白等待組FSH/LH正常率降低,兩組具有統(tǒng)計學(xué)差異(P=0.0470.05)。(4)與治療前比較,針刺組治療后E2水平治療后具有上升趨勢,具有統(tǒng)計學(xué)差異(P=0.0080.05);空白等待組E2無明顯變化,無統(tǒng)計學(xué)差異(P=0.90.05)。治療后,針刺組的E2差值變化更明顯,兩組比較差異具有統(tǒng)計學(xué)意義(P=0.0060.05)。(5)與治療前比較,針刺組治療后AMH有不同程度變化,無統(tǒng)計學(xué)差異(P=0.860.05);空白等待組無明顯變化,無統(tǒng)計學(xué)差異(P=0.650.05)。針刺組和空白等待組治療后AMH差值比較,雖有不同程度的變化,差異無統(tǒng)計學(xué)意義(P=0.890.05)。(6)與治療前比較,針刺組治療后AFC具有上升趨勢,差異具有統(tǒng)計學(xué)意義(P=0.0010.05);空白等待組無明顯變化,無統(tǒng)計學(xué)差異(P=0.440.05)。針刺組和空白等待組治療后AFC差值比較,針刺組變化更明顯,差異具有統(tǒng)計學(xué)意義(P=0.0080.05)。(7)與治療前比較,針刺組治療后月經(jīng)癥狀評分具有降低趨勢,差異具有統(tǒng)計學(xué)意義(P=0.0050.05);空白等待組無明顯變化,無統(tǒng)計學(xué)差異(P=1.000.05)。針刺組和空白等待組治療后月經(jīng)癥狀評分差值比較,針刺組變化更明顯,差異具有統(tǒng)計學(xué)意義(P=0.0110.05)。(8)與治療前比較,針刺組治療后SAS評分具有降低趨勢,差異具有統(tǒng)計學(xué)意義(P=0.010.05);空白等待組無明顯變化,無統(tǒng)計學(xué)差異(P=0.310.05)。針刺組和空白等待組治療后SAS評分差值比較,針刺組變化更明顯,差異具有統(tǒng)計學(xué)意義(P=0.0060.05)。(9)安全性分析:針灸組有2例受試者因體位變動出現(xiàn)了滯針,6例受試者出現(xiàn)皮下瘀血,均立即采取有效措施干預(yù),所有患者未出現(xiàn)嚴(yán)重不良反應(yīng)。研究結(jié)論調(diào)經(jīng)促孕針刺法可以改善卵巢儲備功能下降患者血清激素水平,降低FSH值,縮小FSH/LH值,升高E2,增加患者竇卵泡計數(shù),改善月經(jīng)情況及焦慮情緒,對AMH有一定的改善趨勢,但未有統(tǒng)計學(xué)意義。針刺治療后,針刺組效果明顯高于空白等待組,并且患者無明顯的不良反應(yīng),證明調(diào)經(jīng)促孕針刺法作為一種較為安全的治療手段,對卵巢儲備功能下降有較好的治療效果。
[Abstract]:The decline in ovarian reserve function (Diminished ovarian reserve, DOR) refers to the decrease in the number of follicles in the ovarian memory and (or) the decline in the mass of follicle cells, the decline of female fertility and the lack of sex hormones, the clinical manifestations of menstrual abnormalities, such as the amount of menstruation, before the menarche to 40 years of age. Fewer, dilute menstruation, amenorrhea, infertility, and a series of menopause symptoms, which seriously affect the health of women. Studies have proved that DOR patients are difficult to obtain and maintain normal pregnancy, which is also an important cause of infertility. According to statistics, 10% of the women who are infertile are caused by a decline in ovarian reserve function. With the increase of the pressure of economic and social life, the deterioration of environmental pollution and the delay of the age of women's birth, the incidence of DOR has increased year by year, and it is becoming more and more young, especially the infertility caused by it, which brings a heavy burden to individuals and families. And the decline of egg nest function is a gradual process of development, if not. With timely and effective intervention, DOR patients' ovaries can gradually shrink in 1-6 years and eventually develop into premature ovarian failure (Premature ovarian failure, POF). With the comprehensive release of the two child policy in China, women with childbearing will concentrate more than 70 and after 80. According to statistics, 60% women who meet the second child policy are over 35 years old, and they tend to be more than 35 years old. At the last time of birth, the decrease of ovarian reserve function and the decline of fertility potential are inevitable. Therefore, effective treatment of DOR is very important. At present, the etiology and pathogenesis of DOR are still unknown in modern medicine. It is generally considered that age is the most important factor leading to the decline of ovarian reserve function, and it is also associated with heredity, immunity, environment, surgery, chemotherapy and chemotherapy. It is related to the history of pregnancy, infection, blood type and other factors. The selection of DOR is mainly determined by the etiology, age, reproductive status, reproductive requirements, ovarian follicles and economic conditions in the ovary. The commonly used treatment methods are hormone replacement therapy, ovulation promotion, immunosuppression, assisted reproductive technology and so on. Hormone replacement therapy Most of the patients who have no fertility requirements can significantly improve the symptoms of low estrogen and have a rapid effect. However, the relapse rate is high after discontinuation of this treatment, and the ovarian function can not be improved specifically, with contraindications and obvious side effects. For example, the contraindications of hormone replacement therapy include endometriosis, myoma of uterus, breast cancer, and endometrium. Cancer and thrombotic diseases. For the patients with fertility requirements, ovulation induction and assisted reproductive technology are often used to help pregnant, but the success rate is low, the economic burden is heavy, the long-term effect is poor, and there are many taboos, for example, ovulation stimulation often leads to ovarian hyperstimulation, which further damages ovarian function. Immunomodulator In theory, it is effective for the treatment of autoimmune DOR, but the long-term application of adverse reactions is large and the curative effect is not accurate. There is no "ovarian reserve function decline" in traditional Chinese medicine, but the symptoms of "amenorrhea", "no old classics of the year", "blood withered" and "infertility" are similar. It can be considered to be the understanding of the ancient medicine to the DOR. From ancient times to the present, Traditional Chinese medicine has been playing a great role in the treatment of such diseases. Moreover, different doctors in different times of traditional Chinese medicine have a unique understanding of this kind of disease, and have applied a variety of treatment ideas and means. At present, many clinical and experimental studies have also confirmed that acupuncture and moxibustion therapy is widely used in premature ovarian failure, polycystic ovary syndrome, and so on. A variety of ovulatory disorders. Acupuncture therapy in the treatment of DOR, because of its good effect, less side effects, low price, easy to accept and so on more and more clinical affirmation. Clinical trial study shows that acupuncture treatment can improve the level of serum hormone in women, improve menstruation, improve patients' menopause symptoms, improve the success rate of test tube infants, etc. See, acupuncture and moxibustion have definite curative effect. However, there are few studies on acupuncture and moxibustion treatment of ovarian reserve function, most of which are combination of acupuncture and medicine or other comprehensive therapy, and the treatment ideas, treatment methods and the standard of curative effect are different. At present, Chinese medicine has not formed a complete theoretical system for the pathogenesis, syndrome differentiation and treatment in this field, Xiang Guanwen. The report is relatively lack, and it does not show the characteristics of acupuncture and moxibustion for the treatment of the disease. Syndrome differentiation and treatment of compatibility are similar to those of internal medical diseases. Moreover, the mechanism of action of acupuncture and moxibustion treatment and the clinical efficacy are lack of extensive and in-depth study and high quality literature. The decline in the reserve function of the patients has a relatively rich clinical experience. It is considered that the decline of the ovarian reserve function is a process of "fading through water". The deficiency of the kidney is the fundamental cause. The key to the disease is the maladjustment of the disease. In order to treat the decline of ovarian reserve function, it has a good effect to treat the decline of ovarian reserve function. Therefore, I learn from the teacher, record the clinical cases of ovarian reserve function, further observe the clinical curative effect, analyze and summarize the diagnosis and treatment of the decrease of ovarian reserve function using the acupuncture method of regulating menstruation and promoting pregnancy. Experience, attach importance to the influence of Chong and Ren, kidney essence and emotion on ovarian reserve function. Based on the theory of meridians and collaterals, highlight the characteristics of acupuncture and moxibustion and the two-way regulation of acupoints, and cooperate with the distal part to provide ideas and methods for the reduction of ovarian reserve function by Acupuncture and moxibustion. The study on the clinical effect of acupuncture and moxibustion in the period of hypofunction is in line with the idea of "treating the disease without disease first" in Chinese medicine. It is of great significance to improve the ovarian reserve function and prevent premature ovarian failure. The effect of the method on ovarian reserve function was preliminarily evaluated and studied in the treatment of ovarian reserve dysfunction by regulating menstruation and acupuncture. It laid the foundation for the development of multi center and large sample clinical study in the future. All the data of this study were derived from the ovary of the acupuncture Hospital of Chinese Academy of traditional Chinese medicine from January 2016 to April 2017. The patients in the outpatient department of premature senility were in accordance with the DOR diagnostic criteria and signed the informed consent. The central random system was randomly divided into the acupuncture group and the blank waiting group. The serum hormone levels (Follicle-stimulating hormone, FSH), luteinizing hormone (Luteinizing hormone, LH), FSH/LH, and estradiol (E) were measured before and after the treatment of two groups. Stradiol, E2), anti Mueller tube hormone (Anti Mueller hormone, AMH), sinus ovum count (Antral follicle count, AFC), menstrual symptom score and anxiety scale (Self-RatingAnxietyScale, SAS) were evaluated. The results of the study were evaluated (1) 46 patients were divided into 40 cases, acupuncture group and blank waiting group. The total loss rate was 13.4%, the total loss rate was 13.4%, and the whole test process had no serious adverse events. (2) compared with the treatment before treatment, the FSH value of the acupuncture group had a downward trend, with statistical difference (P=0.000.05); there was no significant change in the blank wait group and no statistical difference (P=0.170.05). (P=0.170.05). Compared with the blank waiting group after treatment, the difference of FSH showed that the difference of FSH difference was more obvious in the acupuncture group, and the difference was significant (P=0.0020.05). (3) after treatment, the normal rate of FSH/LH in the acupuncture group increased, the normal rate of FSH/LH in the blank waiting group decreased, and the two groups had statistical difference (P=0.0470.05). (4) compared with the treatment before treatment, the acupuncture group was treated with E2 water. After the treatment, there was a rising trend, with statistical difference (P=0.0080.05); there was no significant difference in E2 in blank waiting group (P=0.90.05). After treatment, the difference of E2 in the acupuncture group was more obvious, and the difference between the two groups was statistically significant (P=0.0060.05). (5) compared with the treatment before treatment, there were different degrees of change in the acupuncture group after treatment, and no unification. There was no significant difference (P=0.860.05) in the blank waiting group (P=0.650.05). The difference of AMH difference between the acupuncture group and the blank waiting group was not statistically significant (P=0.890.05). (6) compared with the treatment before treatment, AFC had a rising trend after the acupuncture group, and the difference was statistically significant (P=0.0 10.05); there was no significant difference in the blank waiting group (P=0.440.05). The difference of AFC in the acupuncture group and the blank waiting group was more obvious, and the difference was significant (P=0.0080.05). (7) compared with the treatment before treatment, the symptom score of the acupuncture group was reduced, and the difference was statistically significant (P=0.00 50.05); there was no significant difference in the blank waiting group (P=1.000.05). The difference between the acupuncture group and the blank waiting group was more obvious than the acupuncture group, and the difference was statistically significant (P=0.0110.05). (8) compared with the treatment before treatment, the SAS score of the acupuncture group had a decreasing trend, and the difference was statistically significant (P =0.010.05); there was no significant difference in the blank waiting group (P=0.310.05). The difference of the SAS score between the acupuncture group and the blank waiting group was compared, and the change of the acupuncture group was more obvious (P=0.0060.05). (9) the safety analysis: there were 2 cases in the acupuncture group and 6 cases of the subjects appeared subcutaneous. Blood stasis, effective measures were taken immediately, all patients had no serious adverse reactions. Conclusion acupuncture can improve serum hormone level, decrease FSH value, reduce FSH/LH value, increase E2, increase the number of sinus ovum, improve menstrual situation and anxiety, and improve the AMH. There was no statistical significance. After acupuncture treatment, the effect of acupuncture group was obviously higher than that of the blank waiting group, and there was no obvious adverse reaction in the patients. It was proved that the acupuncture method of regulating menstruation and pregnancy was a more safe treatment method, and had better therapeutic effect on the decline of ovarian reserve function.
【學(xué)位授予單位】：中國中醫(yī)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R246.3

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