【作者】 宋慧玲；

【导师】 郭艺红；

【作者基本信息】 郑州大学 ， 生殖医学， 2011， 硕士

【摘要】 随着社会竞争压力、环境污染、心理压力等因素的影响，妇女生育年龄在推迟,不孕症的发病率逐年升高。尤其由于年龄、手术、免疫、环境理化因子等因素的影响卵巢储备功能低下导致的不孕患者越来越多。在体外授精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)助孕过程中卵巢储备功能低下患者表现为卵巢反应不良和卵子质量下降,从而影响IVF-ET结局。目前卵巢储备功能低下患者发生的卵巢反应不良是困扰辅助生殖临床医生的难题之一。如何有效改善卵巢储备功能低下患者的卵巢反应及IVF-ET结局是目前研究的热点之一。目前国内外多数学者研究认为生长激素(growth hormon,GH)对卵泡的发生、生长起营养作用,有助于改善卵巢功能。GH对卵巢储备功能低下患者的卵巢反应是否有改善,目前探讨很少。目的本研究通过对卵巢储备功能低下患者在IVF-ET助孕治疗中应用GH,来探讨GH对卵巢储备功能低下患者是否有影响,从而为临床应用提供理论依据。方法自2010年1月至2011年2月在郑州大学第一附属医院生殖医学中心就诊行IVF-ET的卵巢储备功能低下(基础内分泌FSH>10.0mIU/ml)的不孕患者240例,按照不同年龄分两部分：年龄<35岁部分171例,年龄≥35岁部分69例；按照是否应用GH分：实验组为应用GH组,对照组为未用GH组。年龄<35岁部分实验组81例,对照组90例；年龄≥35岁部分实验组39例,对照组30例。所有患者均在我中心采用普通长方案降调节,于月经黄体中期采用促性腺激素释放激素激动剂(gonadotrophin releasing hormone agonist, GnRH-a)开始降调节,皮下注射0.1mg/日*14天,降调节达标后,于卵泡晚期开始应用果纳芬(Gn,serono)启动至卵泡成熟,GnRH-a改为0.05mg/日至HCG日,Gn启动日应用GH(注射用重组生长激素,塞增)4.5IU/日*5天为实验组、未用GH为对照组,观察卵巢反应的各项指标。采用SPSS13.0统计学软件对实验数据进行统计学分析。结果1.生长激素(GH)对年轻(年龄<35岁)卵巢储备功能低下患者的卵巢反应及IVF-ET的影响。两组不孕症患者的各项临床基本资料比较包括年龄、不孕年限、bFSH、AFC,结果均无统计学差异(P>0.05)。两组不孕症患者的各项实验室及治疗结局资料比较,结果Gn天数、Gn支数、HCG日E2、获卵数、2PN受精率、优胚率、种植率、妊娠率,这些观察指标,均无统计学差异(P>0.05)。2.生长激素(GH)对高龄(年龄≥35岁)卵巢储备功能低下患者的卵巢反应及IVF-ET的的影响。两组不孕症患者的各项临床基本资料比较包括年龄、不孕年限、bFSH、AFC,结果均无统计学差异(P>0.05)。两组不孕症患者的各项实验室及治疗结局资料比较：Gn用量(Gn支数)实验组显著低于对照组,有统计学差异(P<0.05)；HCG日E2水平、获卵数实验组显著高于对照组,有统计学差异(P<0.05)。用药时间(Gn天数)比较在数值上实验组低于对照组,但无统计学差异(P>0.05)；2PN受精率、优胚率、种植率、妊娠率比较实验组均高于对照组,但是这些观察指标无统计学差异(P>0.05)。结论1.生长激素(GH)对年龄<35岁卵巢储备功能低下患者的卵巢反应及IVF-ET治疗结局无影响。2.生长激素(GH)对年龄≥35岁卵巢储备功能低下患者的卵巢反应及IVF-ET治疗结局有影响,可减少Gn使用量,提高HCG日的E2水平,增加获卵数。3.在辅助生殖技术临床应用中对年龄≥35岁卵巢储备功能低下患者可通过应用生长激素改善卵巢的反应性。更多还原

【Abstract】 Under the increasingly heavy pressure of social competition, more and more women tend to postpone their gestational plan, thus the rate of infertility is gradually elevated. Especially, due to the effect of advanced maternal age, surgery, immune and environmental factors, the number of infertile patients with diminished ovary reserve increases. In the process of in vitro fertilization and embryo transfer, manifestations of declined ovary reserve include low ovarian response and decreased quality of ovum, which are both linked to poor outcome of IVF-ET. Nowadays, poor ovarian responder is one of the issues that bother clinicians most. And how to improve the ovarian response and IVF outcome become one of the focuses in research field. Many scholars stated that growth hormone (GH), to some extent, may improve the ovarian response. So we use the data in our Reproductive Medical Centre to illustrate whether GH functions or not.Objective:To discuss whether GH positively affect the IVF outcome of patients, thus to provide theoretical proof for clinical application.Methods: Two hundred and forty infertile patients with decreased ovarian reserve (basal FSH>10.0mIU/ml), admitted to the Reproductive Medical Centre of the First Affiliated Hospital of Zhengzhou University from January,2011 to February,2011, were enrolled into our study. They were divided in terms of age:171 patients under 35 years old and 69 patients equal to or above 35 years old. And both groups were further divided into two groups by having used GH in their cycles or not. Patients received GH were taken as the experimental group, while those didn’t were taken as the control group. The group less than 35 years old included experimental group with 81 cases and control group with 90 cases. The group equals to or more than 35 years old included experimental group with 39 cases and control group with 30 cases. All the patients in this study had been down regulated according to the conventional long protocol in our centre. Use of GnRHa started from the midluteal phase of the menstrual cycle, with a daily injection of 0.1mg for about 14 days. After achieving the standard of down regulation, GnRHa was continued with a dosage of 0.05mg daily while Gn (Gonal-F, Merck Serono) was given for superovulation, till the day of HCG injection. The experimental group was given GH (Jintropin, Gensci, China) since the beginning of Gn,4.5IU daily for consecutive 5 days. The control group were not given GH. Ovarian response and outcome of IVF were observed in both groups. We use SPSS 13.0 Software to perform statistical analysis.Result:1.Effect of GH on patients under 35 years old with diminished ovarian reserve: No significantly difference was observed between the basic informations of the two groups, such as age, duration of infertility, basal FSH, AFC (all P>0.05). The dosage of Gn was lower, and its duration was shorter in the experimental group than those in the control groups. The level of estradiol, the number of retrieved ovum,2PN fertilization rate, good quality embryo rate, implantation rate and clinical rate were all higher in the control groups. But for all the above items, no significant differences were found (all P>0.05).2. Effect of GH on patients equals to or more than 35 years old with diminished ovarian reserve:No significantly difference was observed between the basic informations of the two groups, such as age, duration of infertility, basal FSH, AFC (all P>0.05). The dosage of Gn was significantly lower(P<0.05), and its duration was shorter in the experimental group than those in the control groups. The level of estradiol and the number of retrieved ovum were significantly higher(P<0.05) in the control groups.2PN fertilization rate, good quality embryo rate, implantation rate and clinical rate were all higher in the control group. But for all the above items, no significant differences were found (all P>0.05).Conclusions1. Growth hormone has no significant effect on the ovarian response and IVF outcome for the patients less than 35 years old with decreased ovarian reserve.2. Growth hormone may diminish the dosage of Gn, elevate the level of estradiol on the day of HCG injection and increase the number of ovum for the patients equal to or more than 35 years old with decreased ovarian reserve.3. In the clinical application of assisted reproductive technologies, the patients who are equal to or more than 35 years old with decreased ovarian reserve improve the ovarian response by having used GH.更多还原