在中期LH峰后连续两次鼻内注入某种LHRH的高活性类似物对促性腺细胞和黄体的影响

作者曾报道在正常妇女黄体期中期,给予鼻内注入一种LHRH的高活性类似物——Buserelin(HOE-766,D-丝〔丁叔〕~6-去甘~(10)-LHRH乙基酰胺),或单次用1,000μg或连用两次500μg,可使孕酮及雌二醇水平降低,黄体期缩短1～4天。若在黄体期第六至九天用药,该类似物的溶黄体作用最强。本文观察了在正常妇女的中期LH峰以后每天(第一至十天)注射该类似物对于促性腺激素分泌和黄体机能的影响。选33例19～40岁的正常妇女为志愿者。月经周期规律,无内分泌及妇科疾患。在开始试验前至少6个月未用口服避孕药及激素制剂。整个研究包括     

醋炔诺酮肟的抗着床作用原理的研究

醋炔诺酮肟(2.5～5.0毫克/公斤/日)于妊娠第2天单次或第2、3天连续二次灌胃,可使小鼠卵子在输卵管(42.6～67.8%)运行提前一天进入子宫;但在妊娠第1天给予2.5毫克/公斤,则有76.6%卵子滞留于输卵管内,其中17.2%孕卵出现滞育现象(2细胞期)或异常。卵子移植实验表明,该药主要是抑制内膜分化,直接损伤胚泡作用较小。以醋炔诺酮肟1毫克/公斤/日给予妊娠第2和3天大鼠,第4天血清雌二醇峰、孕酮和子宫胞浆雌二醇受体水平均显著地受到抑制。提示醋炔诺酮肟可能通过加速小鼠卵子转运、干扰大鼠着床的激素平衡和抑制内膜分化,导致孕卵与内膜发育不同步,从而达到抗着床作用。     

d1-18甲基炔诺酮和炔雌醇合用做为事后节育片的作用机理

11名健康有排卵女性,在预计排卵期前后口服事后片ovral 1片(内含炔雌醇0.1毫克+d1-18甲基炔诺酮1.0毫克),12小时后重复1次。在对照及用药周期从周期第八天起到月经来潮第一天止,每天用特异的放射免疫法测定血清黄体生成素(LH)、催乳激素(PRL)、孕酮(P)、17α-羟孕酮及雌二醇(E_2)水平,结果表明Ovral对血浆激素水平及周期长短的影响有明显的个体差异。9例于LH高峰时或其前服药,其中3例用药前后个体配对t试验表明,用药后LH峰显著降低(P<0.001),平均黄体期缩短为2天(对照周期平均为11天),此3例中2例在排卵前E_2峰之后用药,对照及用药周期的E_2水平相似,另1例于LH峰前3天用     

孕酶缩短大鼠输卵管雌激素受体的核保留时间和拮抗雌激素对卵的运输作用

本文研究目的为:(1)确定孕酮是否能拮抗雌激素引起的加速卵的运输作用。(2)检查雌激素刺激和加速卵运输之间输卵管受体水平的变化。(3)确定应用孕酮能否改变由输卵管雌激素诱导的雌激素受体水平的变化。(4)证实孕酮对卵的运输和对输卵管雌激素受体的动力学影响系经孕酮受体介导。当评价此点用 RU486阻断孕酮受体。实验采用成年雌性 Spraque-Dawley 大鼠,通过阴道细胞涂片确定动情周期变化。在动情前期与有生育力的雄鼠合笼,次日如在阴道发现精子定为妊娠第一天。一组在妊娠第一天注射雌二醇(E_2)。二组注射雌二醇和孕酮(E_2·P)。三组同上,但为阻断孕酮受体,于皮下埋置 RU486渗透泵对照组     

正常孕酮水平的妇女子宫内膜延迟成熟(黄体期失调综合征)

黄体期缺欠是妇女不育的重要原因,故对黄体期功能的正确评价是不孕症评价的重要部分,除基础体温(BBT)图外,分宫内膜活检及孕酮水平测定的时间是评价黄体期的主要方法。子宫内膜不足,即孕酮水平正常而子宫内膜成熟延缓或子宫内膜对孕酮反应不良,有人认为“很罕见”,但近来资料显示血浆孕酮水平和子宫内膜活检不符的发生率很高,并证明有反应不良宫内膜的妇女缺乏孕酮胞浆受体。作者对称为黄体期失调单纯内膜不足的发生率和预后进行研究。总结了1978～1982年间不孕症门诊的121名育龄妇女,均有完整的 BBT 图,黄体期10天或多于10天的有127个周期。在月经前的11天到4天之间做3次血浆孕酮放免测定,正常血浆孕酮水平规定为在月经前11天和4天之间取血,三次孕酮水平的总合≥15ng/ml,当两次的总合或仅1次孕酮化验是等≥15ng/ml 时也认为正常。最后一次采血同时做宫内膜活检,用 HE 和希夫氏染色,     

黄体期缺损周期中血清雌二醇与孕酮间的关系

一般认为黄体期缺损(LPD)是黄体产生孕酮不足的结果,而雌激素分泌并无影响。不少学者持有异议:黄体中期雌二醇水平与下个周期的卵泡发育密切相关,雌二醇比孕酮更能影响早孕的预后;在月经生理中,雌二醇可为颗粒细胞增生创造良好的环境,使促卵泡激素(FSH)及促黄体生成素(LH)能作用于相应的受体上,诱导芳香化活力,合成卵泡液中之成份,最后使LH释放,作用于黄体中之LH受体,这些都是正常黄体功能所必需的,一定量的黄体中期雌二醇(750pg/ml)及孕酮(8.0ng/ml)又是怀孕及维持早孕所不可缺少的,因此,排卵前的雌二醇水平与黄体功能及孕酮     

子宫内膜延迟分泌或不完全分泌改变的孕激素受体变化

有3.5%的不孕症患者由于黄体期功能不全,发生黄体期短,在黄体期时血清中孕酮水平低以及子宫内膜生长延迟等现象。但是在正常子宫内膜及生长延迟的内膜之间孕酮的值常有交错重叠现象。也有研究提示尽管血清中孕酮水平正常,可仍有子宫内膜不完全成熟。由于对黄体功能不全患者子宫内膜孕酮受体的研究较少,本文着重探讨正常子宫内膜及子宫内膜延迟分泌或分泌不全的孕酮受体水平与血清中孕酮水平的关系。 36例因不孕而求诊者被纳入本研究,检查项目包括基础体温,在月经的晚滤泡期、黄体中期及晚期分别采血测孕酮及雌二醇。在预期的月经前2～4天嘱患者复诊并在此时取子宫内膜活检。从子宫     

人工黄体期促排卵在卵巢储备功能低下患者中的应用

目的:比较微刺激方案与人工黄体期促排卵方案在卵巢储备功能低下患者体外受精-胚胎移植(l VF-ET)周期中的应用效果,探讨人工黄体期促排卵在卵巢储备功能低下患者中的价值。方法:回顾分析2014年4月至2015年3月在焦作市妇幼保健院生殖中心行IVF助孕的210周期,比较氯米芬微刺激方案组和人工黄体期促排卵方案组的一般资料、促排卵情况、获卵数、取消周期率、2PN率、可利用胚胎率及冷冻胚胎移植妊娠结局等。结果:两组患者的年龄、基础FSH水平及窦卵泡数等比较,差异无统计学意义(P0.05)。与微刺激组比较,人工黄体期促排卵组的Gn天数及Gn总量较多,差异有统计学意义(P0.05)。人工黄体期促排卵组的HCG日E2及P水平均明显高于微刺激组,而LH水平明显低于微刺激组,差异均有统计学意义(P0.05)。人工黄体期促排卵组的获卵数及优胚数较微刺激组多,差异有统计学意义(P0.05)。两组胚胎解冻后妊娠率无明显差异(P0.05)。结论:对于卵巢储备功能低下的患者,人工黄体期促排卵方案可取得较高的获卵数及可利用胚胎数,解冻移植后可获得较满意的临床妊娠结局,提示人工黄体期促排卵方案可为卵巢储备功能低下的患者争取更多的妊娠时机。     

控制性卵巢刺激治疗中血清催乳素水平的变化特点

目的 探讨控制性卵巢刺激(COS)治疗中血清催乳素水平的变化特点.方法 收集接收体外受精-胚胎移植的患者72例,共115个周期,采用促性腺激素释放激素激动剂结合促性腺激素(Gn)长、短方案促排卵治疗,定时经阴道B超监测卵泡发育情况及子宫内膜厚度,并采用酶联免疫发光法检测不同时间点血清雌二醇、黄体生成素(LH)、孕酮和催乳素的水平,分析患者雌二醇、LH、孕酮水平与催乳素水平之间的相关性.结果 对催乳素与雌二醇水平进行相关和回归分析发现,随着雌二醇水平的上升,催乳素水平有显著上升的趋势,两者呈显著正相关关系(r=0.5897,P＜0.01).对催乳素与孕酮水平进行相关和回归分析发现,孕酮水平随催乳素水平的升高而升高,两者呈显著正相关关系(r=0.1412,P＜0.01).但是LH水平与催乳素水平之间未见明显关联.结论 在控制性卵巢刺激治疗中,催乳素的分泌不受Gn的影响,而雌二醇水平的升高可能刺激催乳素的分泌,且催乳素与孕酮水平呈正相关关系.     

应用抗孕激素甾体研究孕酮对小鼠胚泡转运的影响

早在1942年Alden就发现大鼠排卵后切除卵巢,并不影响卵的运输,从而提出大鼠卵运输是不受排卵后卵巢激素分泌的影响。然而,至今在小鼠身上并无类似报导。有人设想,输卵管肌肉活动促进卵子的运输,是受排卵前卵巢分泌的孕酮所控制,而不受排卵后卵巢分泌的激素所影响。本文试图在小鼠身上用抗孕酮甾体证明这种假设。于小鼠妊娠的第1天切除卵巢,并不影响卵的运输,如于动情前期的当天给予孕酮,胚泡转运明显加快。如在妊娠的第1,2,3天给予抗孕激素的甾体-RMI_(12936),胚泡在生殖道内的位置和对照组相比明显延迟,说明该激素阻止胚泡的转运。作者     

Lower levels of inhibin A and pro-alphaC during the luteal phase after triggering oocyte maturation with a gonadotropin-releasing hormone agonist versus human chorionic gonadotropin

OBJECTIVE: To investigate the effect of triggering oocyte maturation with GnRH agonist on corpus luteum function by measuring luteal phase levels of inhibin A and pro-alphaC. DESIGN: Prospective randomized trial. SETTING: In vitro fertilization (IVF) program at a university hospital. PATIENT(S): Infertile women undergoing IVF-ET treatment. INTERVENTION(S): Controlled ovarian hyperstimulation with FSH and GnRH antagonist, triggering of final oocyte maturation with either hCG (n = 8) or GnRH agonist (n = 8), IVF-ET, and collection of blood samples every 2-3 days during the luteal phase. MEASUREMENTS AND MAIN RESULTS: Luteal phase serum levels of inhibin A and pro-alphaC, P, and E(2). RESULT(S): Levels of inhibin A, pro-alphaC, estrogen, and P were significantly lower from day 4 to day 14 after triggering final oocyte maturation by GnRH agonist compared with hCG. Maximal luteal serum inhibin A and pro-alphaC levels were 91.5 +/- 23.6 and 184.1 +/- 23.5 pg/mL in the GnRH agonist-treated women compared with 464.7 +/- 209.1 and 7,351.6 +/- 934.3 pg/mL in women treated with hCG. CONCLUSION(S): Triggering final oocyte maturation with GnRH agonist instead of hCG in IVF cycles dramatically decreases luteal levels of inhibins, reflecting significant inhibition of the corpus luteum function. This effect may explain, at least in part, the mechanism of ovarian hyperstimulation syndrome prevention by the use of GnRH agonist.     

血清性激素含量与体外受精-胚胎移植结局的关系分析

目的 探讨在控制性超排卵中血清性激素变化与妊娠结局的关系。方法 随机选择兰州大学第一医院辅助生殖医学中心2003—2004已接受试管婴儿技术治疗，采用黄体期长方案进行控制性超排卵临床妊娠病例147例，未妊娠140例，分析比较组间各项观察指标。结果 两组间患者降调节时间、促性腺激素（Gn）总量、募集卵泡数、获卵数、MII卵数差异均有显著性（P〈0．05），HCG注射日血清孕酮（P）值、血清雌二醇／孕酮（E2／P）比值差异有显著性（P〈0．05）；促性腺激素释放激素激动剂（GnRH—a，达菲林）用量、Gn天数差异无显著性（P〉0．05），降调节后血清黄体生成素（LH）、HCG注射日血清E2、取卵日血清E2、胚胎移植日血清催乳激素（PRL）水平差异无显著性（P〉0、05）。结论 在控制性超排卵治疗中，观察调控血清性激素含量至关重要。HCG注射日血清P值、E2／P比值是预测助孕结局的重要指标，血清E2／P值在1．32—6．11，血清P值在0．637—1.645μg/L时，临床妊娠率增加。     

来曲唑/FSH促排卵中GnRHa与hCG诱发卵泡成熟效果的比较

目的:比较曲普瑞林和hCG在来曲唑(LE)/FSH促排卵行IVF-ET治疗中诱发卵泡成熟的效果。方法:391个IVF-ET治疗周期随机分成促性腺激素激动剂(GnRHa)组(n=267)和hCG组(n=124),所有患者均采用LE/FSH促排卵方案,当主导卵泡平均直径达18～20mm时,GnRHa组患者采用达菲林0.1mg诱导卵泡成熟,hCG组采用hCG10000IU诱导卵泡成熟,比较组间的获卵数、MII卵率、受精率、卵裂率、优胚率、临床妊娠率和中-重度卵巢过度刺激综合症(OHSS)发生率。同时比较两组患者诱导日(d0)、取卵日(d2)、胚胎移植前日(d4)和胚胎移植后第4日(d9)的血清E2、P、LH水平。结果:hCG组Gn使用总量、MII卵率、卵裂率、中-重度OHSS发生率显著高于GnRHa组(P<0.05)。Gn使用天数、获卵数、受精率、种植率、临床妊娠率、流产率组间无统计学差异(P>0.05)。GnRHa组d0LH、d2LH、d9LH水平显著高于hCG组(P<0.05),而d2P、d4E2、d4P、d4LH、d9E2、d9P水平显著低于hCG组(P<0.05)。结论:在LE/FSH促排卵方案中可以用GnRHa替代hCG诱导卵泡成熟,而不影响IVF结局,并显著降低OHSS发生率。GnRHa诱导卵泡成熟的IVF周期其黄体期存在黄体功能不全,需适当补充外源性hCG加强黄体支持。     

Relationships between in vitro progesterone production by granulosa-luteal cells and certain characteristics of human stimulated cycles

OBJECTIVE: To explore the conditions of a suitable luteal phase in human stimulated cycles, progesterone (P) production by cultured granulosa cells from preovulatory follicles was related to preovulatory serum estradiol (E2) and number of oocytes. DESIGN: Progesterone production was measured in the presence or absence of human chorionic gonadotropin (hCG) using radioimmunoassay; data were compared using Student's t-test; correlations used linear regression. SETTING: In vitro fertilization and embryo transfer (IVF-ET) for infertility treatment at hospital Antoine Beclère, Clamart, France; scientific studies at Institut National de la Santé et de la Recherche Médicale, Unit 187, Clamart, France. PATIENTS, PARTICIPANTS: Nineteen women, 33 +/- 4 years old, undergoing IVF-ET for nonovarian causes. MAIN OUTCOME MEASURES: High preovulatory E2 usually correlates with high luteal P level. Atretic follicle has reduced follicular E2 production combined with a loss of responsiveness to gonadotropins. RESULTS: Granulosa-luteal cell P production correlated with E2 level (P less than 0.0002). Six cycles, with 14 oocytes recovered per cycle on average, showed reduced plasma E2 per oocyte (P less than 0.001) combined with reduced responsiveness to hCG by granulosa-luteal cells (P less than 0.02). CONCLUSION: Recovery of numerous oocytes might be associated with follicular atresia and deficient luteal phase.     

胚胎移植日血清P/E_2与IVF结局的相关性研究

目的探讨体外受精-胚胎移植(invitrofertilization-embryotransfer,IVF-ET)过程中移植日血清孕激素(progesterone,P)/雌激素(estradiol,E2)与IVF-ET结局的关系。方法选年龄24~39岁,移植胚胎累积评分均无差异的输卵管因素患者244例作为研究对象,根据移植结局分为妊娠组和非妊娠组,检测接受体外受精-胚胎移植助孕技术的不孕妇女移植日雌孕激素的血清浓度,比较两组P/E2差异,并根据P/E2将总体研究对象分组,分析胚胎移植日P/E2与IVF结局的相关关系。结果妊娠组与非妊娠组胚胎移植日平均P/E2无差异(P>0.05),P/E2130~175范围内,临床妊娠率最高,为46.88%,与P/E2<130和>175范围的妊娠率差异有显著性(P<0.05),P/E2<130和>175两组人群妊娠率无差异(P>0.05单侧)。结论P/E2在130~175时,子宫内膜容受性最佳,临床妊娠率最高。     

IVF-ET后补充小剂量雌激素不改善妊娠率

目的:探讨体外受精-胚胎移植(IVF-ET)黄体支持中补充小剂量雌激素(E2)对妊娠率的影响。方法:①回顾性分析912个IVF-ET周期,根据黄体支持方案将其分为A组(511个周期),给予黄体酮80mg/d;B组(401个周期),给予黄体酮80mg/d+补佳乐2mg/d,比较组间妊娠率;②按照hCG日与ET日E2比值,分为<4.0组(291个周期)和≥4.0组(220个周期),比较二组妊娠率,了解E2下降程度与妊娠的关系;③另选择IVF超排卵妇女因某种因素未行移植(24个周期)和自然周期排卵妇女(32个周期)比较黄体中期E2水平,以了解超促排卵对黄体中期E2的影响。结果:黄体期补充与不补充E2组间种植率和妊娠率均无差异(P>0.05);E2下降程度不同的二组间种植率和妊娠率也无差异(P>0.05)。IVF超排妇女黄体中期E2水平明显高于自然周期妇女(P<0.01)。结论:取卵后E2水平下降不影响IVF结局,补充E2进行黄体支持不能改善IVF妊娠率。     

Serum progesterone levels in women treated with human menopausal gonadotropin and human chorionic gonadotropin for in vitro fertilization

For evaluation of the adequacy of luteal function after in vitro fertilization-embryo transfer (IVF-ET), serum progesterone (P) levels were measured on days 3, 7, and 10 after laparoscopic follicle aspiration. Fifty-six infertile patients were treated during 86 cycles with human menopausal gonadotropin-human chorionic gonadotropin (hMG-hCG) for stimulation of follicular development. Serum estradiol (E2) levels were measured daily during hMG-hCG treatment. P levels were determined in 67 cycles. The mean (+/- standard deviation [SD]) of the sums of 3 P levels was 55.63 +/- 24.13 ng/ml. There were 11 pregnancies. The mean of the sums of 3 P levels of pregnant patients was 64.45 +/- 26.23 ng/ml and of 56 nonpregnant cycles was 53.90 +/- 23.35 ng/ml. The duration of luteal phase varied from 9 days to 15 days. The mean of the sums of 3 P values of patients with different luteal phase lengths ranged from 28.8 ng/ml to 60.51 +/- 25.68 ng/ml. The mean of the sums of 3 P levels of women with normal luteal phase and that of women with luteal phase defect by endometrial biopsy study were used as controls for comparison. There was poor correlation (r = 0.3441) between E2 peak levels and P levels; the sum of 3 P levels did not indicate luteal phase inadequacy in IVF-ET patients; and the majority of the nonpregnant cycles (32/56) showed a luteal phase of 11 days or less, in spite of adequate P levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

GnRH-agonist triggering for final oocyte maturation in GnRH-antagonist IVF cycles induces decreased LH pulse rate and amplitude in early luteal phase: a possible luteolysis mechanism

The use of GnRH agonist to trigger final oocyte maturation in GnRH-antagonist in vitro fertilization (IVF) cycles has been shown to significantly reduce or even eliminate the risk of ovarian hyperstimulation syndrome (OHSS) by inducing rapid luteolysis early in the luteal phase. The exact mechanism of this early luteolysis is still widely unknown. Since luteinizing hormone (LH) has a major role in corpus luteum support, we sought to explore the pattern of LH secretion early in the luteal phase. Ten high risk patients for developing OHSS and triggered with GnRH agonist were included. Frequent blood sampling (every 20?min for 6?h) to measure LH, estradiol and progesterone was done on the day of oocyte collection (n?=?5, Group 1) and on the day of embryo transfer, 48?h after oocyte collection (n?=?5, Group 2). We found that the mean LH concentration and its secretion rate decreased significantly in Group 2 compared to Group 1. Both groups had similar number of LH pulses characterized by very small amplitude. In Group 2, there was a steady significant decrease in estradiol and progesterone over time. The results of this study show that LH secretion deviates significantly from normal physiologic pattern, which can explain, at least in part, the post-GnRH-agonist trigger early luteolysis mechanism.     

不同剂量黄体酮在体外受精-胚胎移植中黄体支持的效果

目的:探讨不同剂量黄体支持对IVF-ET周期黄体期雌、孕激素水平及临床结局的影响。方法:回顾分析长方案超促排卵IVF-ET305周期,根据hCG日雌激素水平采取4种不同黄体支持方案;对照组53例,hCG日血清E2值≤8000pmol/L,胚胎移植日开始肌注黄体酮60mg/d到验孕日。实验组:A组43例,hCG日血清E2值≤4000pmol/L,在取卵第2天开始肌注黄体酮20mg/d联合2000IU hCG q3d×4次到验孕日;B组115例,hCG日E24000pmol/L～8000pmol/L,取卵后第2天开始肌注40mg/d黄体酮到验孕日;C组94例,hCG日血清E2值≥8000pmol/L,取卵后第2天开始肌注60mg/d黄体酮到验孕日。结果:4组患者年龄、不孕年限、不孕因素、Gn用药天数、用药量、移植胚胎数均无明显差异(P0.05);4组hCG日雌激素水平、获卵数、ET日和种植窗期雌激素水平均有显著差异(P0.05),但4组ET日及种植窗期的E2/P值无显著差异;4组的种植率和妊娠率分别为27.68%、32.18%、32.54%、29.33%和41.51%、46.51%、50.43%、42.55%,无统计学差异。结论:不同剂量黄体支持有助于维持黄体期雌、孕激素平衡,有利于减少黄体酮剂量而不影响妊娠结局。     

A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization.

OBJECTIVE: To compare the effects of gonadotropin-releasing hormone agonist (GnRH-a) initiation either preceding or concurrent with controlled ovarian hyperstimulation (COH) in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Fifty-five patients were prospectively randomized to receive either GnRH-a on cycle day 21 before COH until ovarian suppression was achieved (group I) or GnRH-a concurrently with COH commencing on cycle day 3 (group II). MAIN OUTCOME MEASURES: Serum gonadotropin and ovarian steroid hormone levels, as well as fertilization, spontaneous abortion, and live birth rates. RESULTS: Twenty-six patients in group I and 29 patients in group II underwent COH for IVF-ET. Patients in group II had significantly higher serum luteinizing hormone, progesterone, and testosterone levels during stimulation with human menopausal gonadotropins (hMG) before oocyte retrieval (P < 0.05). Despite similar fertilization, biochemical, and clinical pregnancy rates, the spontaneous abortion rate was higher in group II (5/6) compared with group I (1/7) (P < 0.05). Thus, the live birth rate/retrieval for group I was 6 of 24 (25%) as compared with that of group II, which was 1 of 26 (3.8%) (P < 0.05). CONCLUSIONS: The initiation of GnRH-a in the follicular phase concurrently with hMG is associated with evidence of premature luteinization, hyperandrogenemia, and poorer pregnancy outcome compared with luteal phase administration of GnRH-a before hMG for IVF-ET.