生长激素对不同年龄卵巢储备功能趋于低下患者IVF-ET治疗结局的影响

目的:探讨生长激素(GH)对不同年龄卵巢储备功能趋于低下患者在IVF-ET中是否有影响。方法:行IVF-ET的卵巢储备功能趋于低下的不孕患者240例,均采用普通长方案降调节。观察不同年龄患者加用GH后的卵巢反应,并以不加用GH者为对照组。结果:年龄<35岁GH组81例,对照组90例;年龄≥35岁GH组39例,对照组30例。年龄<35岁的不孕症患者Gn使用天数、Gn使用支数、hCG注射日E2水平、获卵数、2PN受精率、优质胚胎率、种植率、妊娠率等观察指标,对照组和GH组间均无统计学差异(P>0.05)。年龄≥35岁的不孕症患者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注射日E2水平、获卵数实验组显著高于对照组,差异有统计学意义(P<0.05)。结论: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;而对年龄≥35岁则有一定影响,可减少Gn使用量,提高hCG注射日的E2水平,增加获卵数。     

卵巢低反应专家共识

卵巢低反应(POR)是卵巢对促性腺激素(Gn)刺激反应不良的病理状态。POR诊断标准满足以下3条中的2条即可:1高龄(≥40岁)或存在卵巢反应不良的其它危险因素;2前次IVF周期卵巢低反应,常规方案获卵数≤3个;3卵巢储备下降[窦卵泡数(AFC)5~7个或抗苗勒管激素(AMH)0.5~1.1μg/L]。其病因主要与年龄、遗传和免疫因素、环境因素等有关。在IVF助孕中建议采用常规的Gn RHa长方案、Gn RHa短方案和Gn RHA方案进行促排卵,也可采用非传统的微刺激方案、自然周期方案等方法。另外,使用生长激素(GH)、雄激素(A)、雌激素、口服避孕药(OC)等及中医中药来预处理有利于患者治疗结局的改善。     

黄体期使用生长激素在高龄卵巢储备功能减退患者中的临床应用

目的探讨黄体期使用生长激素(GH)对高龄卵巢储备功能减退(DOR)患者超促排卵治疗的影响。方法选择接受体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)且高龄(年龄≥35岁)DOR不孕患者156例为研究对象,均采用拮抗剂方案,分为研究组(加用GH)和对照组(不加用GH)。分析GH对促性腺激素(G n)使用总量、G n使用时间、获卵数、移植前内膜厚度、双原核(2 P N)率、优质胚胎率、着床率的影响。结果 Gn使用时间、Gn使用总量、移植前内膜厚度组间有统计学差异(P0.05)。h CG注射日E 2水平、获卵数、2 P N受精率、优质胚胎率、着床率、临床妊娠率及累积妊娠率组间无统计学差异(P0.05)。研究组临床妊娠率为28.0%、对照组为19.4%,研究组累积妊娠率为33.3%、对照组为20.0%,组间均无统计学差异(P0.05),但研究组临床妊娠率及累积妊娠率有上升趋势。结论 GH对年龄≥35岁DOR患者可明显降低Gn的使用总量及使用时间,增加子宫内膜的厚度,临床妊娠率及累积妊娠率有提高的趋势。     

生长激素释放激素(GHRH)使对促性腺激素(Gn)不敏感妇女卵巢的反应性改善

粒层细胞的增殖与分化主要依赖于促卵泡素(FSH)及雌二醇(E_2)。某些旁分泌因子如胰岛素样生长因子(IGFs)与FSH有协同作用。生长激素(GH)可通过促使卵泡合成IGF-Ⅰ或直接作用于卵巢引起粒层细胞分化。GH能使持续无排卵妇女卵巢对人绝经期促性腺激素(hMG)治疗的反应性改善。本研究目的是了解GHRH是否也能使体外受精(IVF)超排卵治疗时对hMG反应差的患者卵巢的反应性改善。作者根据hMG效能指数(注射hCG前血浆E_2峰值与注射hMG总安瓿数之比值)将1988年3～7月按方案Ⅰ超排卵的67例IVF患者分为反应正常及     

IVF-ET中卵巢低反应患者拮抗剂方案中应用生长激素的研究

目的:研究卵巢低反应(POR)患者采用拮抗剂方案加用生长激素(GH)对子宫内膜容受性及妊娠结局的影响。方法:对采用拮抗剂方案促排卵行体外受精-胚胎移植(IVF-ET)助孕的188例POR患者的资料进行回顾性分析。以加用GH者为研究组(n=98),其余不加用GH者为对照组(n=90),比较组间的临床资料、实验室数据及妊娠结局,以评估GH治疗对POR患者的临床疗效。结果:研究组的Gn使用时间、Gn RH-A使用时间及总Gn使用量显著少于对照组,而获卵数、MII卵子数、受精卵数、优质胚胎数、h CG注射日血E2水平均显著高于对照组,差异均有统计学意义(P0.05);h CG注射日子宫内膜厚度组间比较差异无统计学意义(P0.05),但研究组子宫内膜血流改善显著,差异有统计学意义(P0.05);研究组生化妊娠率、临床妊娠率、种植率、活产率略高于对照组,但差异无统计学意义(P0.05)。结论:对于POR患者,GH改善了子宫内膜血流,可能提高了子宫内膜容受性,但对妊娠结局没有改善。     

垂体前叶功能减退症诊治

<正>垂体分为垂体前叶和垂体后叶,垂体前叶即腺垂体,主要分泌6种激素,分别为生长激素(growth hor-mone,GH)、卵泡刺激素(follicle stimulating hormone,FSH)、黄体生成激素(luteinizing hormone,LH)、促肾上腺皮质激素(adrenocorticotrophic hormone,ACTH)、促甲状腺激素(thyroid stimulating hormone,TSH)及催乳激素(prolactin,PRL)。垂体或下丘脑的多种病损可累及腺垂体内分泌功能,当垂体全部或绝大部分受     

人类卵巢胰岛素样生长因子系统与多囊卵巢综合征

多囊卵巢综合征 (PCOS)的发病机制涉及下丘脑、垂体、肾上腺、胰岛、脂代谢异常等 ,卵巢局部调节失衡也起一定的作用。PCOS患者卵巢泡膜细胞生成雄激素过多 ,与高黄体生成激素、高胰岛素有关。卵巢颗粒细胞不能继续增殖及合成雌二醇 ,导致优势卵泡选择受阻。但PCOS患者卵泡液中促卵泡激素、胰岛素样生长因子 (IGF) Ⅰ水平正常。颗粒细胞在体外对促卵泡激素、IGF Ⅰ反应不低 ,说明芳香化酶功能良好。因此提出 ,“PCOS患者卵泡局部存在促卵泡激素抑制物 ,阻断芳香化酶激活”的假说。本文拟介绍妇女生长激素 IGF Ⅰ轴、卵巢IGF系…     

抗苗勒管激素与女性生育功能关系研究进展

抗苗勒管激素(anti-Müllerian hormone,AMH)是女性生殖生理调节因子之一。AMH可在胚胎期参与生殖系统发育调节。生育期女性的AMH主要由次级卵泡、窦前和窦状卵泡颗粒细胞表达,调节卵泡的生长发育,不受促性腺激素的调节,可早期准确评估卵巢储备功能。AMH可抑制卵泡的募集、选择,对生殖内分泌疾病如多囊卵巢综合征(PCOS)和卵巢早衰(POF)的发病机制及诊断有重要价值。     

早期营养摄入对早产儿瘦素、胰岛素样生长因子-1及生长激素的影响

瘦素（leptin）、胰岛素样生长因子-1（insulin-like growth factor-1，IGF-1）和生长激素（growth hormone，GH）是生长发育的主要调节因子，在胎儿期及生后的生长发育过程中发挥着一定的调控作用。为了探讨早期营养摄入对早产儿leptin、IGF-1、GH的影响，本研究以不同营养方式下leptin、IGF-1、GH水平的变化来反映早产儿的营养状况，从而寻求更适合于早产儿生长的营养方式及客观评价指标。     

IGF—I对卵巢的自分泌调节及其临床应用

IGF-I 又名生长介质 C,是一种单链多肽物质,在 GH 刺激下由肝脏合成,为 GH 作用于骨组织的中间物质。近年研究表明,卵巢粒层细胞也能自行分泌 IGF-I,并受 GH、Gn 及 E_2的调控,它作用于局部参与调节粒层细胞的增殖与分化,对启动始基卵泡的发育及优势卵泡的选择均起重要作用。GH 可直接或间接提高卵巢内 IGF-I 水平,从而提高卵巢对 Gn 的敏感性,应用于临床治疗 hMG 不敏感的无排卵妇女能显著减少 hMG 用量,可乐宁试验有预测卵巢对 hMG 敏感性的价值。GH 对人体无明显副作用,具有广阔的应用前景。     

Adverse effects of luteinizing hormone on fertility: fact or fantasy

High tonic serum concentrations of luteinizing hormone (LH) in the follicular phase, frequently witnessed in polycystic ovary syndrome, have been associated with decreased reproductive function. Impaired rates of fertilization, conception and miscarriage are obtained when LH levels are high before oocytes are collected, during ovulation induction or in women with regular cycles. Conversely, treatment that decreases LH concentrations, such as gonadotrophin-releasing hormone analogue or laparoscopic ovarian puncture, eases induction of ovulation and pregnancy and improves miscarriage rates. Tonic hypersecretion of LH appears to induce premature oocyte maturation, causing the problems with fertilization and miscarriage.     

戈那瑞林(GnRH)在多囊卵巢综合征患者中的促排卵作用

目的:探讨国产戈那瑞林(GnRH)预防多囊卵巢综合征(PCOS)不孕患者中促排卵后卵巢过度刺激综合征(OHSS)发生的临床价值。方法:PCOS不孕患者14例,常规使用氯米氛和hMG/FSH促进卵泡发育,当卵泡直径≥18mm时给予戈那瑞林100μg(皮下注射)诱发排卵,指导当天同房;阴道超声证实排卵后给予黄体酮20mg/d肌注,16d后复诊。观察排卵率、妊娠率、OHSS和多胎妊娠的发生率。结果:排卵率85.7%,妊娠率50%,其中1例多胎妊娠出现中度OHSS,但无重度OHSS的发生。结论:戈那瑞林(GnRH)可降低PCOS患者诱发排卵时中、重度OHSS的发生。     

Interest of growth hormone-releasing hormone administration for improvement of ovarian responsiveness to gonadotropins in poor responder women.

OBJECTIVE: We have investigated the beneficial effect of a somatotroph axis stimulation on ovarian response to gonadotropin. DESIGN: Growth hormone-releasing hormone (GH-RH) was administered in a prospective study in women undergoing an in vitro fertilization protocol. PATIENTS: Twelve patients were selected for their poor ovarian response to previous stimulations using gonadotropin-releasing hormone analog (GnRH-a) and human menopausal gonadotropins (hMG). INTERVENTIONS: Five hundred micrograms of GH-RH1-29 were administered two times daily concomitantly with GnRH-a and hMG from day 2 of the cycle to the time of ovulation. MAIN OUTCOME MEASURES: Stimulation of somatotroph axis was appreciated by measuring over-night urinary growth hormone (GH) output, plasma GH, and insulin-like growth factor I (IGF-I) and follicular fluid (FF) IGF-I. The effects of GH-RH administration on ovarian function were determined by plasma estradiol levels and follicular data. RESULTS: Administration of GH-RH was associated with a significant improvement of urinary (P less than 0.025) and plasma (P less than 0.001) GH concentrations and of the hormonal response to hMG (P less than 0.01). Levels of IGF-I followed a biphasic plasma variation, and a slight increase in recruited follicles, retrieved oocytes, and FF IGF-I content was also observed. CONCLUSIONS: Activation of the somatotroph axis by GH-RH enhances the hormonal ovarian response to hMG and may be an adjunctive therapy to improve follicular maturation.     

Ovulation induction in a poor responder with panhypopituitarism: a case report and review of the literature.

BACKGROUND: Most women with panhypopituitarism will undergo successful ovulation induction with gonadotropin therapy. Few proven treatment options exist for those who respond poorly to such therapy. A poor response may indicate diminished ovarian reserve, or reflect a deficiency of other key components for ovarian function. CASE: A 31-year-old female with panhypopituitarism and a poor response to gonadotropin therapy took growth hormone (GH) replacement for 4 months prior to restarting gonadotropins. When the serum level of insulin-like growth factor-I normalized, she began ovulation induction with gonadotropins with transdermal estradiol. After 63 days of gonadotropin therapy, she had a leading follicle of 18 mm, followed by follicles of 16.5 mm and 15.5 mm. The serum estradiol was 796 pg/ml, and human chorionic gonadotropin was administered. The patient conceived with timed intercourse. A prior attempt at ovulation induction with gonadotropins alone failed to produce follicular development. CONCLUSION: Prolonged gonadotropin treatment may be necessary to achieve ovulation and avoid the misdiagnosis of ovarian failure. Co-treatment with GH and estrogen may improve the follicular response in a poor responder with panhypopituitarism.     

Role of nerve growth factor and FSH receptor in epithelial ovarian cancer

The neurotrophins (NT) including nerve growth factor (NGF) are a family of related growth factors that are of major importance in the regulation of neuronal survival and differentiation. In the ovary, they can help in follicular maturation and ovulation by inducing the FSH receptor (FSHR). Current literature shows that perimenopausal ovarian surface epithelium (OSE) can also express FSHR. By G protein link, this FSHR is capable of precipitating neoplasia of OSE, which is the commonest in the ovary. NT are implicated as the cause of this aberrant expression of FSHR in OSE. By central action NT can lower serum FSH, as is found in ovarian cancer. Thus, NGF deregulates expression of FSHR in OSE and secretion of FSH from the pituitary. This phenomenon may hold the key to the hitherto unexplained carcinogenic process of sporadic epithelial ovarian cancer.     

顺铂腹腔注射对小鼠卵巢功能损伤机制的研究

目的 探讨顺铂（CDDP）对卵巢功能损伤的机制。方法 小鼠腹腔注射CDDP后,检测血清生殖激素水平、卵巢排卵计数、卵巢组织中丙二醛（MDA）的含量及总抗氧化能力（T-AOC）,观察卵巢形态。结果 CDDP给药后小鼠血清FSH和LH均升高,而E2和P均降低。卵巢组织MDA增高,T-AOC降低,卵泡计数减少,卵泡闭锁增加,细胞间质增生明显,卵巢呈现“纤维化”改变。结论 CDDP可通过氧化损伤作用,使细胞外基质的形成与降解的失衡,从而抑制卵泡和颗粒细胞功能状态,使卵巢功能早衰。     

Can growth hormone increase, after clonidine administration, predict the dose of human menopausal hormone needed for induction of ovulation?

Recent observations claimed that growth hormone (GH) administration increased the sensitivity of the ovary to gonadotropin stimulation. These findings prompted us to assess whether ovarian response to human menopausal gonadotropin (hMG) is correlated to GH reserve. Before hMG administration, 25 patients were tested for GH reserve by administration of clonidine. Of the 25 patients, 8 showed a significant increase in GH (9.2 +/- 4.5 ng/mL) and needed a significantly lower dose of hMG/human chorionic gonadotropin to elicit a good ovarian response than the 17 patients who did not respond to clonidine administration may help to estimate the initial dose range of hMG necessary for induction of ovulation.     

Growth hormone: a reproductive endocrine-paracrine regulator?

Growth hormone (GH) is not classically considered as a reproductive hormone, although a vast literature indicates that it has roles in reproductive function. It is required for sexual differentiation and pubertal maturation and it participates in gonadal steroidogenesis, gametogenesis and ovulation. GH is also required for fetal nutrition and growth during pregnancy and for mammary development and lactation. Although some of these roles reflect the action of GH on the secretion and action of LH and FSH (Chandrashekar and Bartke, 1998), they also reflect direct actions of GH and indirect actions mediated through the local production of insulin-like growth factor I. Moreover, as GH is produced in gonadal and mammary tissues, these actions may reflect local autocrine or paracrine actions of extrapituitary GH, as well as the endocrine actions of pituitary GH. The roles of GH in reproductive function are considered in this review.     

Effect of tubal sterilization on ovarian follicular reserve and function

OBJECTIVE: Tubal ligation may reduce the ovarian blood flow and lead to tissue damage to the ovary. If so, this may also result in a significant decrease of the total follicular pool. We performed a long-term evaluation of ovarian reserve and function after tubal sterilization in a longitudinal prospective comparison cohort. STUDY DESIGN: In an university tertiary-care center, 26 women undergoing laparoscopic tubal sterilization with the use of bipolar coagulation, and 26 matched control subjects underwent measurement of follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, and inhibin on menstrual cycle day 3 before (baseline) and at 6, 12, 18, 24, and 60 months after the sterilization for ovarian reserve evaluation. At baseline and 12 and 24 months after tubal ligation, women who underwent sterilization were sampled every other day across an entire menstrual cycle for follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, inhibin, and progesterone determination to evaluate ovarian function. RESULTS: No significant changes were observed either within or between groups for any parameter, despite the fact that a 45% and 30% increase in follicle-stimulating hormone concentration from baseline to the 60-month control was detected in tubal sterilization and control groups of women, respectively. No significant changes were observed in the mean area under the curve of follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin, and progesterone per menstrual cycle at baseline and 12 and 24 months after sterilization. CONCLUSION: This 5-year follow-up study suggests that there is neither an accelerated decline of ovarian follicular reserve nor ovarian dysfunction after tubal sterilization by electrocoagulation.