调经促孕针刺法对卵巢储备功能下降影响的临床探索性研究

发布时间：2018-07-07 20:28

本文选题：卵巢储备功能下降 + 针灸　；参考：《中国中医科学院》2017年硕士论文

【摘要】：研究背景卵巢储备功能下降(Diminished ovarian reserve,DOR),是指卵巢内存留的可募集卵泡数量减少和(或)卵泡细胞质量下降,导致女性生育能力下降及性激素缺乏的疾病,临床表现为女性在月经初潮后到40岁之前出现的月经异常,如月经量少、月经稀发、闭经、不孕等,并伴有一系列的更年期症状,严重影响了女性的健康。研究证实,DOR患者很难获得和维持正常的妊娠,这也是其带来不孕症的重要原因。据统计,在女性不孕的发生人群中,10%是由于卵巢储备功能下降引起的。随着经济社会生活压力的增大、环境污染的恶化及妇女生育年龄的推迟等变化,DOR的发病率逐年增加,并越来越有呈年轻化的趋势,尤其是其导致的不孕,给个人与家庭带来沉重的负担。并且,卵巢功能的衰退是一个逐渐发展的过程,如果没有及时有效的干预措施,DOR患者的卵巢可在1-6年逐渐萎缩,最终发展为卵巢早衰(Premature ovarian failure,POF)。随着现在我国二孩政策的全面放开,有生育意愿的女性多集中在70后和80后,据统计,符合二胎政策的女性有60%在35岁以上,她们趋于生育的最后时机,卵巢储备功能的降低及生育潜能的下降不可避免,因此,DOR的有效治疗极为重要。目前,现代医学对DOR的病因及致病机制尚不明了,一般认为年龄是导致卵巢储备功能下降的最主要因素,另与遗传、免疫、环境、手术、放化疗、个人孕产史、感染、血型等因素有关。临床中DOR的治疗方案的选择主要与患者病因、年龄、生育状况、生育要求、卵巢内有无发育中卵泡及经济情况等确定。常用的治疗方法为激素替代疗法、促排卵、免疫抑制、辅助生殖技术等。激素替代疗法大多用于无生育要求的患者,能明显改善低雌激素症状,并见效快。但这一疗法停用后复发率高,并不能特异性地改善卵巢功能,并且有禁忌症和明显的副作用。比如激素替代疗法的禁忌症包括子宫内膜增生、子宫肌瘤、乳腺癌、子宫内膜癌及血栓性疾病。对于有生育要求的患者,临床上常采用促排卵治疗和辅助生殖技术帮助受孕,但成功率低,经济负担重,远期疗效差,且存在着多种禁忌证,如促排卵治疗常常会引发卵巢过度刺激,从而进一步损害卵巢功能。免疫调节剂在理论上对自身免疫性DOR治疗有效,但长期应用不良反应大,疗效不确切。中医没有“卵巢储备功能下降”病名,但“闭经”、“年未老经水断”、“血枯”,“不孕”等疾病症状表现与其相似,可以认为是古代医学对DOR的认识。从古至今,中医药一直在治疗此类疾病上发挥着很大的作用。并且,中医学不同时代不同医家对此类疾病也有着独特的认识,并应用了多种治疗思路和手段。目前,很多临床及实验研究也已经证实:针灸疗法广泛应用于卵巢早衰、多囊卵巢综合症等多种排卵障碍性疾病。针刺疗法在治疗DOR方面,因其效果好、副作用少、价格低、便于接受等越来越得到临床的肯定。临床试验研究显示,针刺治疗可以改善女性血清激素水平,改善月经情况,改善患者更年期症状,提高试管婴儿成功率等。可见,针灸治疗有确切的疗效。但是,针灸治疗卵巢储备功能下降的研究文献较少,大多是针药结合或其它综合疗法,并且治疗思路、治疗方法、疗效判定标准各异。目前中医对该领域的病因病机,辨证与治疗还未形成完备的理论体系,相关文献、报告相对缺乏,而且对针灸治疗该病并没有显示出针灸的特色,辨证分型和治疗配伍等多于内科疾病的思路相似,并且,针灸治疗起效的作用机制、临床疗效都缺乏广泛并深入的研究和质量较高的文献。导师多年来从事针刺治疗卵巢储备功能下降患者的工作,拥有较为丰富的临床经验,认为卵巢储备功能下降是一个“经水渐消”的过程,肾精亏虚是根本原因,冲任失调为疾病关键,情志失畅与疾病发生互为因果,使用调经促孕针刺法,以补肾精,调冲任,畅情志,使肾精充足,冲任条畅,神志安定,以此来治疗卵巢储备功能下降,具有较好的疗效。故本人跟师学习,记录卵巢储备功能下降患者的临床病例并加以整理,进一步观察临床疗效,分析总结导师使用调经促孕针刺法治疗卵巢储备功能下降的诊疗经验,重视冲任、肾精、情志对卵巢储备功能的影响,以经络理论为基础,突出针灸特色和穴位双向调节,局部与远端相配合,对针灸治疗卵巢储备功能下降提供思路和方法。并且,卵巢储备功能减退是卵巢早衰的第一个阶段,选择卵巢储备功能减退期开展针灸临床疗效的研究,符合中医“未病先防”的“治未病”思想,对改善卵巢储备功能,预防卵巢早衰具有十分重要的意义。研究目的总结导师调经促孕针刺法治疗卵巢储备功能下降的诊疗经验,通过观察调经促孕针刺法对卵巢储备功能的影响,对调经促孕针刺法治疗卵巢储备功能减退的临床疗效进行初步评价研究,为今后开展多中心,大样本临床研究奠定基础。研究方法本研究所有病例资料来源于2016年1月到2017年4月中国中医科学院针灸医院卵巢早衰专病门诊的患者,符合DOR诊断标准,均签署知情同意书。采用中央随机系统随机分为针刺组和空白等待组。测定两组患者治疗前后的血清激素水平(卵泡刺激素(Follicle-stimulating hormone,FSH)、黄体生成素(Luteinizing hormone,LH)、FSH/LH、雌二醇(Estradiol,E2)、抗缪勒管激素(Anti Mueller hormone,AMH)、窦卵泡计数(Antral follicle count,AFC)及月经症状评分和焦虑自评量表(Self-RatingAnxietyScale,SAS),进行疗效评价。研究结果(1)本试验共随机分组46例患者,其中纳入分析的患者40例,针刺组和空白等待组各20例,6例患者中途停止治疗或改变治疗方案。总脱失率为13.4%,整个试验过程未出现严重不良事件。(2)与治疗前比较,针刺组治疗后FSH值具有下降趋势,具有统计学差异(P=0.000.05);空白等待组无明显变化,无统计学差异(P=0.170.05)。针刺组和空白等待组治疗后FSH差值比较显示,针刺组的FSH差值变化更明显,差异具有统计学意义(P=0.0020.05)。(3)治疗后,针刺组的FSH/LH正常率提高,空白等待组FSH/LH正常率降低,两组具有统计学差异(P=0.0470.05)。(4)与治疗前比较,针刺组治疗后E2水平治疗后具有上升趋势,具有统计学差异(P=0.0080.05);空白等待组E2无明显变化,无统计学差异(P=0.90.05)。治疗后,针刺组的E2差值变化更明显,两组比较差异具有统计学意义(P=0.0060.05)。(5)与治疗前比较,针刺组治疗后AMH有不同程度变化,无统计学差异(P=0.860.05);空白等待组无明显变化,无统计学差异(P=0.650.05)。针刺组和空白等待组治疗后AMH差值比较,虽有不同程度的变化,差异无统计学意义(P=0.890.05)。(6)与治疗前比较,针刺组治疗后AFC具有上升趋势,差异具有统计学意义(P=0.0010.05);空白等待组无明显变化,无统计学差异(P=0.440.05)。针刺组和空白等待组治疗后AFC差值比较,针刺组变化更明显,差异具有统计学意义(P=0.0080.05)。(7)与治疗前比较,针刺组治疗后月经症状评分具有降低趋势,差异具有统计学意义(P=0.0050.05);空白等待组无明显变化,无统计学差异(P=1.000.05)。针刺组和空白等待组治疗后月经症状评分差值比较,针刺组变化更明显,差异具有统计学意义(P=0.0110.05)。(8)与治疗前比较,针刺组治疗后SAS评分具有降低趋势,差异具有统计学意义(P=0.010.05);空白等待组无明显变化,无统计学差异(P=0.310.05)。针刺组和空白等待组治疗后SAS评分差值比较,针刺组变化更明显,差异具有统计学意义(P=0.0060.05)。(9)安全性分析:针灸组有2例受试者因体位变动出现了滞针,6例受试者出现皮下瘀血,均立即采取有效措施干预,所有患者未出现严重不良反应。研究结论调经促孕针刺法可以改善卵巢储备功能下降患者血清激素水平,降低FSH值,缩小FSH/LH值,升高E2,增加患者窦卵泡计数,改善月经情况及焦虑情绪,对AMH有一定的改善趋势,但未有统计学意义。针刺治疗后,针刺组效果明显高于空白等待组,并且患者无明显的不良反应,证明调经促孕针刺法作为一种较为安全的治疗手段,对卵巢储备功能下降有较好的治疗效果。
[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.
【学位授予单位】：中国中医科学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R246.3

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