促性腺激素释放激素激动剂在多囊卵巢综合征促排卵高危周期中的应用

目的探讨促性腺激素释放激素激动剂（ＧｎＲＨａ）代替ｈＣＧ在多囊卵巢综合征（ＰＣＯＳ）中诱发排卵治疗的效果及并发症。方法对采用绝经期促性腺激素或卵泡刺激素促排卵治疗的１４例ＰＣＯＳ患者（１８个周期）,于卵泡≥１８ｍｍ时给予ＧｎＲＨａ,观测血清雌二醇（Ｅ２）水平、排卵率、妊娠率、卵巢过度刺激综合征（ＯＨＳＳ）和多胎妊娠发生情况。结果１４例１８个治疗周期给予ＧｎＲＨａ日血清Ｅ２为（８３７９±２９５８）ｐｍｏｌ／Ｌ,周期排卵率和妊娠率分别为８３３％和２２２％。中度ＯＨＳＳ和多胎妊娠各１例。结论在ＰＣＯＳ不孕患者中以ＧｎＲＨａ代替ｈＣＧ具有相似的排卵率和妊娠率,但能明显降低ＯＨＳＳ发生率,减少多胎妊娠。     

体外受精周期中应用长效促性腺激素释放激素激动剂治疗多囊卵…

目的观察长效促性腺激素释放激素激动剂治疗多囊卵巢综合征的疗效。方法：在体外受精－胚胎移植周期中，应用长效及促性腺激素治疗２６例顽固性ＰＣＯＳ患者，并与其中前次常规ＩＶＦ－ＥＴ方案治疗的１９例进行比较。     

体外受精周期中应用长效促性腺激素释放激素激动剂治疗多囊卵巢综合征

目的：观察长效促性腺激素释放激素激动剂（ＧｎＲＨ－ａ）治疗多囊卵巢综合征（ＰＣＯＳ）的疗效。方法：在体外受精－胚胎移植（ＩＶＦ－ＥＴ）周期中，应用长效ＧｎＲＨ－ａ（ｄｅｃａｐｅｐｔｙｌ，Ｆｅｒｉｎｇ）及促性腺激素（Ｇｎ）治疗２６例顽固性ＰＣＯＳ患者（Ｄｅｃａｐｅｐｔｙｌ组），并与其中前次常规ＩＶＦ－ＥＴ方案治疗的１９例（非Ｄｅｃａｐｅｐｔｙｌ组）进行比较。结果：（１）Ｄｅｃａｐｅｐｔｙｌ组受精率和妊娠率分别为７６．２％和３８．５％，明显高于非Ｄｅｃａｐｅｐｔｙｌ组（Ｐ＜０．０５）。（２）Ｄｅｃａｐｅｐｔｙｌ组用药２周后，子宫内膜厚度及卵巢面积明显缩小，用药第４周时，达最小值。（３）Ｄｅｃａｐｅｐｔｙｌ组黄体生成素（ＬＨ）、促卵泡激素、睾酮、雌二醇在用药１周后开始下降，至用药第４周达早卵泡期水平。结论：对在应用常规ＩＶＦ－ＥＴ周期或外源性促性腺激素治疗过程中，发生卵巢过度刺激综合征或过早ＬＨ峰，以及使用外源性Ｇｎ６个周期无受孕的ＰＣＯＳ患者，长效ＧｎＲＨ－ａ联合Ｇｎ超排卵，是较好的方案。     

生长激素在多囊卵巢综合征促排卵中的作用

目的　探讨生长激素(GH)在多囊卵巢综合征(PCOS)患者促排卵中的作用。方法　测定130例PCOS患者(PCOS组)及107例正常妇女(对照组)的血中生殖激素及GH和胰岛素样生长因子Ⅱ(IGF-Ⅱ)的基础水平,并应用GH辅助促排卵方案治疗7例对人绝经期促性腺激素(hMG)反应不良的PCOS患者,观察疗效。结果　PCOS患者血中GH水平明显降低,肥胖者更为明显,非肥胖与肥胖者分别为(2.50±1.33)μg/L及(1.04±0.47)μg/L,而对照组肥胖与非肥胖者分别为(2.95±1.49)μg/L、（5.30±2.26）μg/L（P均<0.05）;PCOS组肥胖者IGF-Ⅱ水平为（136±27）nmol/L,高于非肥胖者的（123±20）nmol/L,两者比较,差异有显著性（P<0.05）。应用GH辅助促排卵治疗,可以明显减少hMG用量1～12支,缩短hMG刺激时间3～12d,增加优势卵泡的数量。结论　PCOS患者存在GH分泌障碍,应用GH辅助促排卵可以提高排卵率。     

促性腺激素释放激素激动剂长、短方案在体外受精-胚胎移植中的比较性研究

目的　探讨促性腺激素释放激素激动剂（GnRH-a）长、短方案控制性超排卵在体外受精-胚胎移植（IVF-ET）中的疗效。方法　将2000年1～5月进行IVF和单精子卵胞浆注射（ICSI）助孕的不孕患者,按病历奇、偶数编号分为GnRH-a长方案组（55例）和短方案组（54例）。长方案组从使用促性腺激素（Gn）治疗周期前的黄体中期开始使用GnRH-a0.9mg/d,至垂体完全降调节后,加用Gn;短方案组从月经第2天开始使用GnRH-a0.45mg/d,同时加用Gn。两组均在优势卵泡达18mm时,肌内注射人绒毛膜促性腺激素（hCG）,36h后取卵行IVF及ICSI。结果　长方案组较短方案组,使用Gn前血清促卵泡激素（FSH）和黄体生成素（LH）水平降低［（4.4±1.2）IU/L比（6.3±1.7）IU/L,（2.7±1.5）IU/L比（4.4±2.8）IU/L,P<0.01］;注射hCG前血清雌二醇（E2）和LH水平降低［（7119±3584）pmol/L比（9523±3587）pmol/L,（1.0±1.0）IU/L比（4.0±3.4）IU/L,P<0.01］;每个卵子E2水平降低［（610±315）pmol/L比（935±450）pmol/L,P<0.01］;Gn用量增多［（28.0±8.6）支比（23.4±8.7）支,P<0.01］,用药时间增长［（11.1±1.2）d比（10.1±1.5）d,P<0.01］;两组平均获卵数、第2次成熟分裂中期卵子数、受精卵数、卵裂数、优质胚胎数及妊娠率无显著差异。结论　在IVF-ET,GnRH-a长、短方案能获得相同的控制性超排卵效果,且GnRH-a短方案能减少Gn用量和缩短治疗时间。     

常规促排卵与GnRHα降调节促排卵后IVF-ET治疗多囊卵巢综合征比较

<正>育龄期女性中多囊卵巢综合征(polycystic ovary syndrome,PCOS)患病率为6%～10%,在无排卵性不孕中占50%～70%。目前临床治疗PCOS不孕症主要用药物促排卵。枸橼酸克罗米酚是促排卵的首     

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。     

多囊卵巢综合征促排卵方案的现状

多囊卵巢综合征(PCOS)患者最常表现闭经或月经稀发,无排卵和不孕。生育年龄有生育要求的治疗以促排卵、调节代谢为主。PCOS促排卵的结局易造成多卵泡发育,卵巢过度刺激综合征(OHSS)、多胎妊娠的发生率较高,或者对促排卵药物不反应或卵泡期过长,提早黄素化等。目前应用于临床的促排卵药物及促排卵方案较多。本文将针对目前PCOS的促排方案加以综述和比较。     

抗苗勒管激素(AMH)在多囊卵巢综合征患者促性腺激素促排卵治疗中的预测意义

目的:探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者高抗苗勒管激素(anti-Müllerian hormone,AMH)水平对人绝经期促性腺激素(h MG)促排卵结局的影响。方法:采用前瞻性研究,分析63例接受h MG促排卵的PCOS患者。比较对h MG有反应与无反应组间的AMH浓度。采用受试者工作特征(receiver operating characteristic,ROC)曲线评估AMH预测卵巢反应性价值。结果:有反应组AMH水平明显低于无反应组(8.43±2.18μg/L vs 11.05±2.85μg/L,P0.001)。多因素逐步回归分析提示AMH是预测卵巢反应性的唯一指标。ROC曲线分析显示AMH是一项潜在有效的预测卵巢反应性的指标。将血AMH界值10.12μg/L作为判断标准,其预测卵巢对h MG反应的敏感性达91.7%,特异性达66.7%。结论:血清AMH可作为有效的预测PCOS患者对h MG反应性的指标。     

Effect of gonadotropin-releasing hormone agonist treatment on growth hormone responses in women with polycystic ovary syndrome

This study supports the importance of regulatory role of the E(2) in growth hormone secretion in women with polycystic ovary syndrome, showing for the first time a different weight-related sensitivity of the growth-hormone axis to hypoestrogenism induced by gonadotropin-releasing hormone agonist.     

Adrenal and ovarian steroid hormone responses to gonadotropin-releasing hormone agonist treatment in polycystic ovary syndrome.

It has been postulated that in polycystic ovary syndrome ovarian steroids can influence adrenal steroidogenesis. To test this hypothesis, basal and dexamethasone-suppressed-corticotropin-stimulated steroid hormone responses were compared among three groups of women before, during, and after gonadotropin-releasing hormone agonist treatment for 3 months. The groups were characterized as follows: (1) women with polycystic ovary syndrome with high dehydroepiandrosterone sulfate levels (greater than 400 micrograms/dl), (2) women with polycystic ovary syndrome with normal dehydroepiandrosterone sulfate levels (less than 300 micrograms/dl), and (3) normal ovulatory women. In response to gonadotropin-releasing hormone agonist, basal serum luteinizing hormone, follicle-stimulating hormone, estradiol, estrone, 17-hydroxyprogesterone, androstenedione, and testosterone in all three groups were suppressed to similar levels. Basal serum dehydroepiandrosterone sulfate levels in the group with high levels declined, but they did not reach the normal, unaltered concentrations in the other two groups. Two subjects with polycystic ovary syndrome in this group with high levels, who showed the greatest declines in basal serum dehydroepiandrosterone sulfate levels (34%, 40%), also had evidence of 3 beta-hydroxysteroid dehydrogenase deficiency before treatment, which was resolved by the end of treatment. In both groups with polycystic ovary syndrome, the increase in maximum incremental rise of dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in response to a pharmacologic dose of corticotropin from a dexamethasone-suppressed baseline (adrenal androgen capacity) remained unaltered during gonadotropin-releasing hormone agonist administration. We conclude that ovarian steroids may promote excessive adrenal androgen secretion in women with polycystic ovary syndrome, may induce 3 beta-hydroxysteroid dehydrogenase deficiency as a mechanism for adrenal involvement in some women with polycystic ovary syndrome, and do not influence adrenal androgen capacity.     

Induction of ovulation in polycystic ovary: human menopausal gonadotropin or human urinary follicle stimulating hormone?

One group of 21 and one group of 22 anovulatory women with polycystic ovaries (PCO) underwent induction of ovulation with human urinary follicle stimulating hormone (HU-FSH)/human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG)/HCG, respectively. No statistically significant differences in ovulation rate were found between patients treated with HU-FSH (95.2%) and those treated with HMG (100%). Eight (38.1%) and 11 (50.0%) patients conceived, six (28.5%) and eight (36.3%) delivered, and two (9.5%) and three (13.6%) aborted with HU-FSH and HMG, respectively. No multiple pregnancies occurred. Serum 17 beta-estradiol (E2) levels and the number of maturing follicles prior to HCG injection were significantly higher with HU-FSH than HMG, while there were no differences in the diameter of the dominant follicle before HCG. Ovarian hyperstimulations were discovered more frequently after HU-FSH/HCG (40%) than HMG/HCG treatments (22.2%). These data do not confirm an effective advantage in the use of HU-FSH in ovulation induction in cases of PCO.     

Hormonal and clinical effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovary syndrome.

The aim of the study was to evaluate the hormonal (focusing on the urinary steroid profile) and clinical effects of chronic gonadotropin-releasing hormone (GnRH) agonist treatment in patients with polycystic ovary syndrome (PCOS) suffering from hirsutism. A long-acting GnRH agonist was administered for 6 months in eight PCOS patients. Hormonal effects were measured by determining serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone and estradiol concentrations, and by profiling urinary steroids using capillary gas chromatography of 24-hour urine samples. To evaluate 5 alpha-reductase enzyme activity, the ratios of androsterone to etiocholanolone and 5 alpha-tetrahydrocortisol to tetrahydrocortisol were calculated in urine samples. The ratio of androgen to cortisol metabolites was also determined before, and 3 and 6 months after therapy. LH and estradiol levels were suppressed significantly after the first injection and testosterone after the second injection of the GnRH agonist. Thus, serum testosterone was normalized. Ratios of urinary steroids reflecting 5 alpha-reductase enzyme activity (androsterone to etiocholanolone and 5 alpha-tetrahydrocortisol to tetrahydrocortisol) and the ratio of androgen to cortisol metabolites decreased significantly after 3 months of treatment. Degree of hirsutism, assessed by Ferriman-Gallwey score, diminished after 6 months, but not significantly. In conclusion, our data show that long-acting GnRH agonist treatment of PCOS patients is effective in reducing serum and urinary androgen levels, but it is not accompanied by an effective reduction in hirsutism during a 6-month treatment period. A longer or a combined treatment would be needed to achieve significant improvement in hirsutism. Gas chromatographic profiling of urinary steroids and the use of specific ratios of the excreted metabolites seems to be a sensitive tool both in the diagnosis of PCOS and in monitoring ovarian suppression.     

Low-dose ovulation induction with urinary gonadotropins or recombinant follicle stimulating hormone in patients with polycystic ovary syndrome.

Patients with polycystic ovary syndrome (PCOS) are highly sensitive to gonadotropins. In recent years a number of publications have shown that chronic low-dose protocols are effective in reducing complications, in particular ovarian hyperstimulation syndrome (OHSS), especially if recombinant human follicle stimulating hormone (rhFSH) is used. The aim of the present study was to compare the efficacy and safety of rhFSH (Gonal-F, Serono) versus urinary human FSH (uhFSH) (Metrodin, Serono) in a low-dose step-up protocol for ovulation induction in clomiphene-resistent infertile PCOS patients. Twenty PCOS patients were recruited in two centers for an open randomized comparative study. A starting dose of a 75-IU ampule of rhFSH or uhFSH was used for 14 days with an increment of 37.5 IU every 7 days. Human chorionic gonadotropin (hCG) (10,000 IU, Profasi, Serono) was administered if one to three follicles achieved a diameter of > or = 16 mm. Sonographic and hormonal (serum estradiol and progesterone) monitoring of the cycles was performed. All the six pregnancies induced were in the rhFSH group, but two of them ended with miscarriage. There were no differences between the two groups concerning the number of ampules used, the stimulation days, the estradiol levels on the day of hCG administration, and the progesterone levels 7 days after hCG administration. Three patients had grade II, and one patient grade III OHSS. In conclusion, our results support the literature data that rhFSH is superior to uhFSH regarding pregnancy rates, not only in in vitro fertilization cycles, but also with a low-dose protocol in patients with PCOS.     

Therapeutic strategies for ovulation induction in infertile women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by hirsutism, obesity, hyperandrogenism and insulin resistance. The syndrome is often accompanied by infertility because of anovulation. Many approaches have been proposed to solve this problem, with the most commonly used therapies being ovarian drilling and pharmacological ovulation induction. Ovarian drilling is a procedure in which a laser fiber or electro-surgical needle punctures the ovary four to ten times. Side-effects are rare and often related to surgery itself. Pharmacological strategies include administration of metformin and insulin-sensitizing agents, clomiphene citrate (CC), gonadotropins and aromatase inhibitors. Metformin appears valuable in increasing ovulation rate, menstrual cyclicity and pregnancy rate. CC is an oral estrogen antagonist that raises circulating concentrations of follicle-stimulating hormone (FSH) and induces follicular growth in most women with PCOS and anovulation. Failure to respond is associated with high body mass index and high androgen levels. Aromatase inhibitors mimic the central reduction of negative feedback through which CC works. Ovulation induction with recombinant FSH has proved successful, but treatment requires skill and experience to avoid multiple pregnancies and ovarian hyperstimulation syndrome. The hypothetical deleterious effects of the high luteinizing hormone concentrations observed in PCOS patients seem to be related to the concomitant hyperinsulinemia (and/or insulin resistance). A thorough understanding of the syndrome and a careful assessment of each patient are the mainstays for choosing an appropriate treatment regimen.     

Prolactin response after gonadotropin-releasing hormone in the polycystic ovary syndrome

The administration of gonadotropin-releasing hormone (GnRH) has been shown to stimulate prolactin (PRL) release under certain conditions. The authors compared PRL responses after GnRH in normoprolactinemic patients with the polycystic ovary syndrome (PCO) with those of normal ovulatory women in the follicular phase. Seven of 15 patients had a significant increase in PRL after GnRH, whereas none of the control subjects had a positive response. After 1 week of oral L-dopa, the responders no longer exhibited this positive response. Baseline PRL levels in responding patients with PCO were similar to levels in control subjects, whereas nonresponding patients with PCO had higher PRL levels. Baseline follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratios were higher in patients with a positive response. The positive PRL response after GnRH was not correlated with baseline serum LH, the LH/FSH ratio, delta maximum LH responses, serum testosterone (T), unbound T, or baseline PRL. The positive response correlated positively with serum levels of unbound estradiol (P less than 0.05) and serum unbound estradiol/unbound T ratios (P less than 0.01). These data suggest that under certain conditions a subgroup of patients with PCO may demonstrate a positive PRL response after GnRH. Dopamine, gonadotropins, and estrogen may play a role in this interaction.