年轻POR女性拮抗剂方案与长方案的新鲜移植周期临床妊娠结局的比较分析

目的:比较分析拮抗剂方案与长方案对年轻卵巢低反应(POR)女性体外受精(IVF)新鲜移植周期临床妊娠结局的影响,以探讨拮抗剂方案的应用价值。方法:回顾性分析2014年1月至2017年6月在广东省妇幼保健院生殖中心行体外受精-胚胎移植(IVF-ET)治疗的204例妇女213个IVF新鲜移植周期的临床资料。按随机数字表法分为拮抗剂组83例(84治疗周期)与长方案组121例(129治疗周期),比较两组一般资料、实验室资料、促排卵资料及妊娠结局的差异。结果:拮抗剂组的窦卵泡计数(AFC)、抗苗勒氏激素(AMH)水平、促性腺激素(Gn)使用天数、Gn总量、HCG日雌二醇(E2)水平、HCG日内膜厚度、移植日内膜厚度、获卵数、成熟卵子数及正常受精数低于长方案组,基础FSH/LH、Gn启动量高于长方案组(P0.05),但两组优质胚胎数、移植胚胎数、移植囊胚比例、冷冻胚胎数、胚胎种植率及早期自然流产率比较均无统计学差异(P0.05)。拮抗剂组和长方案组的临床妊娠率较高,分别为58.14%和63.10%,但是两组临床妊娠率比较无统计学差异(P0.05)。结论:给予年轻POR患者两种方案均可获得较满意的IVF新鲜移植周期临床妊娠结局,拮抗剂方案获卵数较长方案少,但是其优势在于Gn使用量更少,使用时间更短。     

基础卵泡刺激素水平对IVF/ICSI-ET超排卵周期卵巢反应

目的：基础卵泡刺激素(bFSH)可以刺激精子生成和促进卵子成熟,是人体内重要的激素之一。本研究针对体外受精(IVF)周 期bFSH 水平的变化情况,探讨bFSH对卵巢反应的预测价值,为临床研究提供理论基础。方法：回顾性分析2012 年1 月-2012 年 12 月在我院生殖医学中心接受体外受精- 胚胎移植(IVF-ET)治疗的154例患者的临床资料,根据基础卵泡刺激素水平分为A 组 (bFSH≥10 IU/L)、B 组(8≤bFSH≤10 IU/L)和C 组(bFSH<8 IU/L)。对比分析三组对象的年龄、基础窦卵泡数(bAFC)、黄体生成素 (LH)含量、FSH/LH 值、促性腺激素(Gn)的用量、使用时间、受精率及临床妊娠率等。结果：三组患者的年龄、bAFC 及FSH/LH相比 较,差异具有统计学意义(P<0.05);三组的Gn 用量和时间、获卵数及妊娠率比较,差异显著且具有统计学意义(P<0.05);三组基础 LH 值及超排卵周期受精率无显著差异(P>0.05)。结论：基础卵泡刺激素(bFSH)对体外受精女性的卵巢储备功能具有一定的预测 价值,bFSH 水平的高低可作为预测女性不孕患者超排卵周期卵巢反应性的一项重要指标,值得临床推广和应用。     

基础卵泡刺激素水平对IVF/ICSI-ET超排卵周期卵巢反应的预测价值

目的:基础卵泡刺激素(bFSH)可以刺激精子生成和促进卵子成熟,是人体内重要的激素之一。本研究针对体外受精(IVF)周期bFSH水平的变化情况,探讨bFSH对卵巢反应的预测价值,为临床研究提供理论基础。方法:回顾性分析2012年1月-2012年12月在我院生殖医学中心接受体外受精-胚胎移植(IVF-ET)治疗的154例患者的临床资料,根据基础卵泡刺激素水平分为A组(bFSH≥10 IU/L)、B组(8≤bFSH≤10 IU/L)和C组(bFSH8 IU/L)。对比分析三组对象的年龄、基础窦卵泡数(bAFC)、黄体生成素(LH)含量、FSH/LH值、促性腺激素(Gn)的用量、使用时间、受精率及临床妊娠率等。结果:三组患者的年龄、bAFC及FSH/LH相比较,差异具有统计学意义(P0.05);三组的Gn用量和时间、获卵数及妊娠率比较,差异显著且具有统计学意义(P0.05);三组基础LH值及超排卵周期受精率无显著差异(P0.05)。结论:基础卵泡刺激素(bFSH)对体外受精女性的卵巢储备功能具有一定的预测价值,bFSH水平的高低可作为预测女性不孕患者超排卵周期卵巢反应性的一项重要指标,值得临床推广和应用。     

药学角度探讨和分析不同来源卵泡刺激素对体外受精-胚胎移植结局的影响

目的:比较基因重组卵泡刺激素(r-FSH)及高纯度尿源性卵泡刺激素(HP-u FSH)对体外受精-胚胎移植(IVF-ET)妊娠结局的影响,结合临床表现从药学角度探讨和分析。方法:回顾分析具IVF/单精子卵细胞浆内显微注射授精(ICSI)指诊并首次接受IVF/ICSI助孕的不孕症患者235例,以给予的FSH药物种类不同分为2组:HP-u FSH组(n=135)和r-FSH组(n=100)。主要研究指标为出生率,次要研究指标为临床妊娠率,流产率及着床率。结果:HP-u FSH组外源性促性腺激素(Gn)总量和FSH量均多于r-FSH组(P0.01),获卵数和可移植胚胎数较r-FSH组少(P0.01),受精率较r-FSH组低(P0.05)。两组平均Gn刺激天数,妊娠结局及中重度卵巢过度刺激综合征(OHSS)发生率均无统计学差异(P0.05)。对患者年龄35岁和≥35岁分别进行分组发现,年龄35岁患者中的HP-u FSH组较r-FSH组平均年龄更大,不孕年限更长,基础窦卵泡数(AFC)更少(P0.01),≥35岁患者中的HP-u FSH组与r-FSH组的基本特征(年龄,不孕年限,AFC)无统计学差异(P0.05);无论年龄35岁或年龄≥35岁,HP-u FSH组的Gn量和FSH量较r-FSH组均更大,获卵数及可移植胚胎数更少(P0.01)。结论:在IVF/ICSI周期治疗中,国产HP-u FSH与r-FSH进行COS具有等同的IVF临床妊娠率及出生率。     

基础卵泡刺激素水平对IVF／ICSI—ET超排卵周期卵巢反应的预测价值

目的：基础卵泡刺激素（bFsH）可以刺激精子生成和促进卵子成熟,是人体内重要的激素之一。本研究针对体外受精（IVF）周期bFSH水平的变化情况,探讨bFSH对卵巢反应的预测价值,为临床研究提供理论基础。方法：回顾性分析2012年1月-2012年12月在我院生殖医学中心接受体外受精．胚胎移植（IVF—ET）治疗的154例患者的临床资料,根据基础卵泡刺激素水平分为A组CoFSH≥10IU／L）、B组（8≤bFsH≤10IU／L）和c组（bFSH〈8IU／L）。对比分析三组对象的年龄、基础窦卵泡数（bAFC）、黄体生成素（LH）含量、FSH／LH值、促性腺激素（Gn）的用量、使用时间、受精率及临床妊娠率等。结果：三组患者的年龄、bAFC及FSH／LH相比较,差异具有统计学意义（P〈0．05）;三组的Gn用量和时间、获卵数及妊娠率比较,差异显著且具有统计学意义（P〈0．05）;三组基础LH值及超排卵周期受精率无显著差异（P〉0．05）。结论：基础卵泡刺激素（bFSH）对体外受精女性的卵巢储备功能具有一定的预测价值,bFSH水平的高低可作为预测女性不孕患者超排卵周期卵巢反应性的一项重要指标,值得临床推广和应用。     

ART患者早期流产组织染色体异常及相关因素分析

目的:分析ART患者早期流产组织染色体异常及其相关影响因素。方法:回顾性分析2013-2017年ART患者行早期流产组织染色体检查的409例样本,分析胚胎染色体非整倍性发生及其与女方年龄、不孕年限、不孕因素、促排卵指标之间的关系。结果:ART流产患者中,流产组织染色体非整倍性发生率为57.46%,发生频次以16三体占比最高(23.95%),其次是22三体(13.45%)及Turner(9.24%)。流产组织染色体非整倍性患者平均年龄高于染色体整倍性患者(P0.001)。16三体组患者年龄低于22三体(P0.01)及Turner组(P0.05)。16三体组患者平均Gn使用量低于22三体组(P0.05)。16三体组患者移植15天血HCG值低于22三体(P0.05)及Turner组(P0.01)。结论:ART患者流产组织染色体非整倍性与女方年龄正相关,但16三体及Turner的发生与女方年龄相关性不大,且16三体更容易引发早期流产。     

促排卵过程中添加重组人生长激素对卵巢储备功能低下患者IVF-ET结局的影响及妊娠结局的影响因素探讨

摘要 目的：探讨促排卵过程中添加重组人生长激素（r-hGH）对卵巢储备功能低下（DOR）患者体外授精-胚胎移植（IVF-ET）结局的影响,并分析妊娠结局的影响因素。方法：选择2021年1月至2022年1月徐州市中心医院拟接受IVF-ET治疗的DOR患者60例、徐州医科大学附属沭阳医院拟接受IVF-ET治疗的DOR患者36例,共计96例,采用随机数字表法分为两组,每组48例,对照组予以常规促排卵治疗,观察组促排卵过程中添加r-hGH治疗,比较两组促排卵、体外受精、胚胎移植以及妊娠相关指标。此外,根据妊娠结局将所有患者分成妊娠成功组和妊娠失败组,采用多因素Logistic回归分析IVF-ET结局的影响因素。结果：观察组胚胎种植率、临床妊娠率高于对照组（P＜0.05）;观察组与对照组注射重组人促卵泡激素（Gn）天数、Gn用量、人绒毛膜促性腺激素（HCG）日雌二醇（E2）水平、HCG日黄体生成素（LH）水平、HCG日子宫内膜厚度、获卵数、成熟卵数、受精率、卵裂率、可移植胚胎数、优质胚胎数、移植胚胎数、早期流产率比较差异无统计学意义（P＞0.05）。单因素分析结果显示：妊娠失败组女方平均年龄大于妊娠成功组,基础卵泡刺激素（FSH）水平、IVF周期≥2个的患者比例高于妊娠成功组,促排卵应用了r-hGH的患者比例低于妊娠成功组,HCG日子宫内膜厚度小于妊娠成功组,基础窦卵泡数（AFC）个数、成熟卵数、优质胚胎数少于妊娠成功组,差异均有统计学意义（P＜0.05）。多因素Logistic回归分析结果显示：女方年龄≥35岁、基础FSH≥14.40 IU/L、HCG日子宫内膜厚度＜10 mm、基础AFC＜5.5个是DOR患者IVF-ET妊娠失败的危险因素,而促排卵应用r-hGH治疗是保护因素（P＜0.05）。结论：促排卵过程中增加r-hGH治疗可提高DOR患者IVF-ET胚胎种植率、临床妊娠率。女方年龄、基础FSH和AFC、HCG日子宫内膜厚度、r-hGH治疗均与IVF-ET妊娠结局有关。     

LHRH激发试验LH峰值对性早熟女童GnRHa疗效的诊断价值

为了探讨促黄体生成素释放激素(LHRH)激发试验中LH峰值对中枢性性早熟(CPP)女童促性腺激素释放激素类似物(Gn RHa)疗效的评估价值。选取2014年1月~2016年1月我院收治的中枢性性早熟(CPP)女童40例,给予Gn RHa(曲普瑞林)50~100μg/kg肌肉注射,1次/28 d。治疗3个月及以后的每6个月进行LHRH激发试验,分别取LH峰值1 IU/L、2 IU/L、3 IU/L作为LH受抑的界限值,与临床发育受抑情况进行比对,计算3个LH峰值诊断发育受抑的灵敏度、特异度及准确度。40例患儿治疗疗程为6~24个月,共完成了119次LHRH激发试验。治疗后6个月的基础LH值较治疗前明显降低((0.46±0.17)IU/L vs(0.81±0.26)IU/L),差异具有统计学意义(t=1.273,p0.05);Pearson相关性分析:基础LH值与LH峰值之间呈线性正相关(r=0.712,p0.05)。LH峰值2 IU/L诊断临床发育受抑的灵敏度、特异度和准确度分别为88.9%、100.0%、99.2%。LHRH激发试验中LH峰值2 IU/L可以作为判断CPP女童Gn RHa治疗效果的有效指标。     

基础窦卵泡数对IVF/ICSI-ET超排卵周期卵巢反应的预测价值*

摘要目的：窦卵是女性宫腔内的泡状细胞,与女性卵巢的发育及功能密切相关。本研究针对体外受精(IVF)周期中基础窦卵泡数 (antral follicle count, AFC)的变化情况,探讨AFC 对卵巢反应的预测价值,为临床研究提供理论基础。方法：回顾性分析2012 年1 月至2012 年12 月在我院生殖医学中心接受体外受精- 胚胎移植的157 例患者的临床资料,根据基础窦卵泡数将所选病例分为 A 组(bAFC逸10)和B组(bAFC＜10)。对比并分析两组研究对象的促性腺激素(Gn)的用量及使用时间、获卵数、人绒毛膜促性腺激 素(HCG)注射日的血清中雌激素(E2)水平、受精率、临床妊娠率等。结果：A 组患者的Gn 用量、HCG日E2 值、获卵数及临床妊娠 率均显著高于B 组,差异具有统计学意义(P<0.05);两组患者的年龄和基础卵泡刺激素水平差异显著且具有统计学意义(P<0.05); 两组患者的不孕原因、不孕年限及助孕方式无明显差异(P>0.05)。结论：基础窦卵泡对体外受精女性促排卵周期的卵巢反应及助 孕结局具有一定的预测价值,其数量的多少可作为促排卵过程中评价卵巢反应性的参考指标,应在临床进一步推广。     

冷冻胚胎移植周期中内膜形态及内膜厚度对妊娠结局的预测价值分析

目的:评价内膜厚度及内膜形态对于体外受精-胚胎移植中冷冻胚胎解冻复苏移植的临床妊娠结局的预测价值。方法:回顾性分析1521个冷冻胚胎解冻复苏移植周期,将患者按子宫内膜厚度分为4组,子宫内膜≤6 mm、6.1-8.0 mm、8.0-12 mm、12.0 mm,根据子宫内膜形态分为A型内膜、B型内膜、C型内膜。分别比较不同内膜厚度分组及不同内膜形态分组患者的年龄,移植胚胎数目、内膜准备方案构成比、移植胚胎类型(卵裂期胚胎、囊胚)构成比及各组间的临床妊娠率和活产率。采用ROC曲线分析子宫内膜厚度、形态对临床妊娠结局的预测价值。使用逐步回归分析内膜厚度、形态、年龄及移植胚胎类型与妊娠结局的相关性。结果:纳入1521个解冻复苏周期中按内膜厚度分为4组,各组周期数分别为96周期、454周期、893周期、78周期,各组间平均年龄分别为34.1±5.5岁、33.3±5.4岁、32.5±5.2岁、33.7±6.0岁(P0.05)。内膜厚度≤6 mm组临床妊娠率为31.3%,子宫内膜≤6mm、6.1-8.0 mm、8.0-12 mm、12.0 mm组临床妊娠率分别为48.5%、51.8%、47.4%(P0.05)。子宫内膜≤6 mm、6.1-8.0 mm、8.0-12 mm、12.0 mm组间活产率分别为18.8%、37.7%、44.6%、39.7%(P0.05)。A型、B型及C型内膜组周期数分别为920周期、189周期及412周期,三组间平均年龄分别为32.3±5.1、33.0±5.7、34.2±5.5岁(P0.05)。A型/B型及C型内膜组临床妊娠率分别为51.2%、46.6%及46.4%,三组间活产率分别为42.1%、36.0%及37.1%,三组间差异无统计学意义(P0.05)。子宫内膜厚度ROC曲线下面积为0.534(95%可信区间0.505-0.564),子宫内膜形态ROC曲线下面积为0.526(0.476-0.955)。逐步回归分析纳入内膜厚度、内膜形态、年龄、胚胎类型4个可变量,女方年龄(OR=0.929,P0.001),移植胚胎中囊胚比例(OR=1.595,P0.001)与临床妊娠率明显相关,内膜厚度(OR=1.054,P=0.05)及内膜形态(OR=0.864)与临床妊娠率无相关性。结论:虽然子宫内膜薄临床妊娠率下降,但是子宫内膜厚度与内膜形态不能够预测体外受精-胚胎移植解冻复苏周期临床妊娠率,患者年龄以及移植胚胎的发育潜能才是预测临床妊娠率的参考指标。     

Early pregnancy assessment with transvaginal ultrasound scanning.

OBJECTIVE: To establish normal parameters in early pregnancy through transvaginal ultrasonography so that gestational age can be determined and to correlate the sonographic findings with serum human chorionic gonadotropin (hCG) levels calibrated against the first international reference preparation standard. SETTING: Infertility clinic. PATIENTS: Thirty-five women with normal intrauterine pregnancy. INTERVENTIONS: Serial measurement of the serum hCG level and the diameter of the gestational sac through transvaginal ultrasonography. MAIN RESULTS: The gestational sac could not be visualized when the hCG level was less than 1100 IU/L. The average growth rate of the sac was 0.9 mm/d. The threshold values for sac diameter, serum hCG level and gestational age below which the yolk sac was not visible were 3.7 mm, 1900 IU/L and 36 days respectively; the corresponding values above which the yolk sac was always visible were 6.7 mm, 5800 IU/L and 40 days. The threshold values below which cardiac activity was not visible were 8.3 mm, 9200 IU/L and 41 days respectively, and the corresponding values above which cardiac activity was always visible were 14.0 mm, 24,000 IU/L and 46 days. The mean gestational ages and the 95% confidence and prediction intervals were tabulated so that measurement of the gestational sac diameter could be used to estimate gestational age early in normal pregnancy. CONCLUSIONS: Transvaginal ultrasonography enables detection of an intrauterine sac and reliable estimation of gestational age on the basis of sac dimensions before an embryo can be seen.     

Involvement of gonadotropins in induction of luteolysis in pigs

In our previous study we have demonstrated that treatment of endometrial explants with LH increased 13,14-dihydro-15-ketoprostaglandin F(2alpha) (PGFM) accumulation in pigs. This was particularly visible on Days 14-16 of the estrous cycle. Action of gonadotropin in porcine endometrium appears to be mediated by LH/hCG receptors whose number is dependent on the day of the estrous cycle. In the current study i.v. infusion (1 hour) of hCG (200 IU) performed on Days 10 (n=4) and 12-14 (n=4) of the porcine estrous cycle did not affect plasma PGFM (ng/ml+/-SEM) concentrations. In contrast, administration of hCG on Days 15-17 produced, depending on plasma PGFM level before the infusion period, three different types of response: I. plasma PGFM surge of amplitude 0.62+/-0.15 was observed when the mean basal pre-infusion PGFM plasma level was 0.23+/-0.05 (n=6 gilts); II. the delayed PGFM surge of amplitude 0.62+/-0.15 was determined when basal pre-infusion PGFM level was 0.80+/-0.20 (n=6); and III. lack of PGFM response to hCG was found when basal pre-infusion PGFM level was 1.09+/-0.61 (n=6). Concentrations of plasma PGFM before and after saline infusion did not differ on Days 12-14 and 16 of the estrous cycle. In the next experiment blood samples were collected every 1 hour on Days 12-19 of the estrous cycle to determine concentrations of LH, PGFM and progesterone in four gilts. In particular gilts, plasma peaks of LH closely preceded surges of PGFM in 72.7, 84.6, 75.0 and 66.6 percent, respectively. The highest PGFM surges followed a decline in plasma progesterone concentration. We conclude that the increased PGF(2alpha) metabolite production after hCG infusion during the late luteal phase of the estrous cycle as well as the relationship between plasma LH and PGFM peaks suggest the LH involvement in the elevation of endometrial PGF(2alpha) secretion in pigs, and, in consequence, induction of luteolysis.     

Ovarian steroid secretion changes after hCG stimulation in early pregnant pigs

Administration of human chorionic gonadotropin (hCG) to promote ovarian steroid secretion near the time of recognition of pregnancy was evaluated. Neither 500 or 1000 IU of hCG caused a significant increase in luteal function as determined by progesterone (P(4)) concentrations in peripheral blood following treatment on Day 12. Estradiol concentrations were elevated (P<0.01) for the 500 IU hCG group on Days 13, 14, 15 and 16 versus the control group. The 1000 IU of hCG group had three-to five-fold greater (P<0.01) estradiol concentrations than controls on Days 14, 15 and 16 post mating. Treatment with hCG also reduced (P<0.05) the number of resorbed embryos. The results suggest that hCG treatment on Day 12 of pregnancy reduced embryo loss and influenced peripheral estradiol secretion patterns.     

The application of single beta-human chorionic gonadotropin (β-hCG) level measurement in women undergoing single blastocyst transfer

We previously explored the associations between β-hCG on the 14th day post–embryo transfer (ET) and reproductive outcomes and established a series of cutoff values to predict different outcomes. The aim of this study was to explore the parameters associated with β-hCG levels and establish β-hCG cutoff values in women undergoing single blastocyst transfer. The patients were transferred with either fresh or frozen-thawed blastocysts. Serum β-hCG levels were compared among different groups. Cutoff values of β-hCG were established and applied to divide the patients into different groups, among which the β-hCG groups were compared. Develop day negatively affected β-HCG levels in those who were pregnant or gave live birth (P < 0.001, 0.008). Inner cell mass significantly affected β-hCG levels in women who were pregnant or gave live birth (P = 0.013, 0.044). Trophectoderm significantly affected β-hCG levels in women with most reproductive outcomes, except biochemical pregnancy (BP) (P = 0.184). The cutoff values of β-hCG for predicting positive outcomes were 194.1, 503.0, 1048.0, and 2590.5 mIU/L. BP rates and adverse pregnancy outcome rates were significantly lower in the higher β-hCG groups (P < 0.001). Shorter gestational age and lower birth weight and length (P = 0.005, 0.041, 0.003) were observed in the lowest-concentration β-hCG group. The application of a single β-hCG measurement was sufficient to predict reproductive outcome in women undergoing blastocyst transfer, under the full consideration of blastocyst parameters. However, the association between β-hCG and obstetric outcomes remains to be investigated and fully explained.     

Assessment of luteal rescue and desensitization of macaque corpus luteum brought about by human chorionic gonadotrophin and deglycosylated human chorionic gonadotrophin treatment

The objective of the current study was to investigate the mechanism by which the corpus luteum (CL) of the monkey undergoes desensitization to luteinizing hormone following exposure to increasing concentration of human chorionic gonadotrophin (hCG) as it occurs in pregnancy. Female bonnet monkeys were injected (im) increasing doses of hCG or dghCG beginning from day 6 or 12 of the luteal phase for either 10 or 4 or 2 days. The day of oestrogen surge was considered as day ‘0’ of luteal phase. Luteal cells obtained from CL of these animals were incubated with hCG (2 and 200 pg/ml) or dbcAMP (2.5,25 and 100 M) for 3h at 37°C and progesterone secreted was estimated. Corpora lutea of normal cycling monkeys on day 10/16/22 of the luteal phase were used as controls. In addition thein vivo response to CG and deglycosylated hCG (dghCG) was assessed by determining serum steroid profiles following their administration. hCG (from 15–90 IU) but not dghCG (15-90 IU) treatment in vivo significantly (P < 0.05) elevated serum progesterone and oestradiol levels. Serum progesterone, however, could not be maintained at a elevated level by continuous treatment with hCG (from day 6–15), the progesterone level declining beyond day 13 of luteal phase. Administering low doses of hCG (15-90 IU/day) from day 6–9 or high doses (600 IU/day) on days 8 and 9 of the luteal phase resulted in significant increase (about 10-fold over corresponding control P < 0.005) in the ability of luteal cells to synthesize progesterone (incubated controls) in vitro. The luteal cells of the treated animals responded to dbcAMP (P < 0.05) but not to hCC added in vitro. The in vitro response of luteal cells to added hCG was inhibited by 0,50 and 100% if the animals were injected with low (15-90 IU) or medium (100 IU) between day 6–9 of luteal phase and high (600 IU on day 8 and 9 of luteal phase) doses of dghCG respectively; such treatment had no effect on responsivity of the cells to dbcAMP. The luteal cell responsiveness to dbcAMP in vitro was also blocked if hCG was administered for 10 days beginning day 6 of the luteal phase. Though short term hCG treatment during late luteal phase (from days 12—15) had no effect on luteal function, 10 day treatment beginning day 12 of luteal phase resulted in regain ofin vitro responsiveness to both hCG (P < 0.05) and dbcAMP (P < 0.05) suggesting that luteal rescue can occur even at this late stage. In conclusion, desensitization of the CL to hCG appears to be governed by the dose/period for which it is exposed to hCG/dghCG. That desensitization is due to receptor occupancy is brought out by the fact that (i) this can be achieved by giving a larger dose of hCG over a 2 day period instead of a lower dose of the hormone for a longer (4 to 10 days) period and (ii) the effect can largely be reproduced by using dghCG instead of hCG to block the receptor sites. It appears that to achieve desensitization to dbcAMP also it is necessary to expose the luteal cell to relatively high dose of hCG for more than 4 days     

Improvement of pregnancy rate in Japanese Black cows by administration of hCG to recipients of transferred frozen-thawed embryos

Japanese Black primiparous and multiparous beef cows (n = 120) were selected as recipients and randomly divided into three groups (A, B, and C) of 40 recipients each. Group A received an intramuscular (i.m.) treatment of 1500 IU human chorionic gonadotropin (hCG) on day 1 (day 0 = onset of estrus), while Group B received an i.m. treatment of hCG on day 6. Group C received an i.m. treatment of 5 ml saline on day 6 as a control. On day 7, frozen-thawed embryo transfer was conducted in all groups, and pregnancy was diagnosed by palpated per rectum 40-50 days after the transfer. Twelve recipients were randomly selected from each group. Plasma progesterone (P) and estradiol-17beta (E2) concentrations were determined in these recipients on days 6, 7 and 14, and at the time of pregnancy diagnosis, and their ovaries were examined for a corpus luteum and follicles by palpated per rectum. The pregnancy rate in Group B was higher (67.5%. P < 0.05) than the rate in Group C (45.0%) and in Group A (42.5%). The plasma P concentration on day 14 tended to be higher although not significantly in Group B than in Groups C and A. At the time of pregnancy diagnosis, the blood P concentration of pregnant recipients in Group B was higher (P < 0.05) than that of those in Groups C and A. The plasma E2 concentrations on days 7 and 14 were lower (P < 0.05) in Group B than in Groups C and A. These results showed that administration of hCG 6 days after estrus improved the pregnancy rate for non-surgical frozen embryo transfer 7 days after estrus by enhancing luteal function and depressing E2 secretion.     

Human chorionic gonadotropin and luteinizing hormone-releasing hormone reverse the blockade of ovulation in pregnant mare's serum gonadotropin-primed immature rats by the anti-androgenic drug, hydroxyflutamide

The present study was designed to examine mechanism(s) of the anti-ovulatory action of the anti-androgen, hydroxyflutamide (OH-F). Prepubertal rats were treated with 4 IU pregnant mare's serum gonadotropin (PMSG) (day -2) to induce first estrus and ovulation. They received OH-F in sesame oil or oil alone at 08:00 and 20:00 h on day 0 (the day of proestrus) and ovulations were assessed on the morning of day 1. Eighty-three percent of control animals ovulated with a mean of 7.7 +/- 1.1 corpora lutea per rat. Hydroxyflutamide blocked ovulation in all but 2 of the 12 rats receiving this drug alone. All of OH-F treated rats that received 5 and 25 IU human chorionic gonadotropin (hCG) ovulated with means +/- SEM of 9.1 +/- 0.1 and 7.3 +/- 1.4 corpora lutea per rat, respectively. The dose of 0.2 IU hCG was essentially ineffective, while the effect of 1.0 IU hCG was intermediate. At the dose of 20 ng and above (100 and 500 ng) luteining hormone-releasing hormone (LHRH) completely overcame the ovulation blockade in the OH-F treated animals, while a 4-ng dose was ineffective. At 18:00 h on the day of proestrus, serum LH levels in control animals were 17.56 +/- 2.60 ng/mL, which were 920% above basal levels (1.90 +/- 0.13) indicating a spontaneous LH surge. This surge was suppressed in OH-F treated rats. Injection of LHRH, at the dose of 20 ng and above, reinstated the LH release in OH-F treated animals. Thus, the anti-androgen, OH-F, inhibits ovulation in PMSG-treated immature rats through its interference with the preovulatory LH surge; the inhibition can be reversed by hCG or LHRH. Hydroxyflutamide does not appear to interfere at the level of the pituitary, but may have direct action at the hypothalamic and (or) extrahypothalamic sites involved in the generation of positive feedback signals that control LH release.     

Initiation of follicular maturation during mid-pregnancy by the administration of LH in the rat

Pregnant rats were injected twice daily for 1-3 days (Days 13-16 of pregnancy) with various doses of ovine LH. Follicular maturation was determined by the ability of the follicles to ovulate in response to 10 i.u. hCG as well as by endogenous production of oestradiol-17 beta and inhibin. In control animals, no ovulation was induced by hCG given on Day 16 of pregnancy. An injection of hCG on Day 16 of pregnancy, however, induced ovulation in LH-treated animals (6.25-50.0 micrograms LH per injection, s.c. at 12-h intervals from Days 13 to 16). Concentrations of oestradiol-17 beta and inhibin activity in ovarian venous plasma increased after the administration of LH, indicating that development of ovulatory follicles had been induced. Abolishing the decline in plasma LH values therefore induced maturation of a new set of follicles or prevented the atresia of large antral follicles usually seen at this time of pregnancy. Plasma and pituitary concentrations of FSH decreased in LH-treated animals compared with those in control animals. Concentrations of progesterone, testosterone and oestradiol-17 beta in the peripheral plasma were not significantly different between the two groups. These results suggest that the increase in inhibin secretion from the ovary containing maturing follicles after LH treatment may suppress the secretion of FSH from the pituitary gland. These findings indicate that (1) the development of ovulatory follicles can be induced by the administration of exogenous LH during mid-pregnancy in the rat and (2) basal concentrations of FSH are enough to initiate follicular maturation even in the presence of active corpora lutea of pregnancy, when appropriate amounts of plasma LH are present.     

Risk Factors and Early Predictors for Heterotopic Pregnancy after In Vitro Fertilization

This study investigated the risk factors and early predictors for heterotopic pregnancy (HP) after in vitro fertilization and embryo transfer (IVF-ET). From January 2008 to January 2013, 41 cases of HP and 72 cases of intrauterine twin pregnancy after IVF-ET were recruited and retrospectively analyzed. Compared with intrauterine twin pregnancy group, the HP group had a lower basal luteinizing hormone (LH) level (P = 0.005) and more cases had a history of hydrosalpinx (P = 0.008). After 14 days of IVF-ET, the serum β-HCG (β-human chorionic gonadotropin), E2 (Estradiol) and P (Progesterone) levels were lower in HP group (P<0.001, respectively). Moreover, vaginal bleeding and abdominal pain were the significant features of HP before diagnosis (P<0.001, respectively). Further by logistic regression, serum β-hCG, P levels on the 14th day after ET, and vaginal bleeding were identified as the independent factors of HP. These results indicate that when two or more embryos transferred in IVF procedure, β-hCG, P levels on the 14th day after ET, and vaginal bleeding could be taken as predictors for HP.     

Pharmacokinetics of eCG and induction of fertile estrus in bitches using eCG followed by hCG

The aim was to design a protocol combining eCG followed by hCG for estrus induction in the bitch. In Experiment 1, three ovariohysterectomized bitches received 10 000 IU of eCG iv, and 15 days later 10 000 IU of eCG im. Blood samples were taken up to 144 h after each injection to measure eCG concentrations. In Experiment 2, 25 healthy, intact late anestrous bitches were assigned to one of five doses of eCG (5, 10, 15, 20, 44, or 50 IU/kg eCG im; [TRT5-TRT50]). Sexual behavior (SB), clinical signs of estrus (CSE) and vaginal cytology (VC) samples were obtained and scored before eCG administration and every other day until onset of estrus, or for 14 days. In Experiment 3, intact late anestrous bitches were assigned to a treatment group (TRT; n = 16) and received eCG (50 IU/kg im) followed by hCG (500 IU im) 7 days later; or to a placebo group (PLA; n = 8) where they received 1 mL saline solution im. All bitches that were induced in estrus were mated or AI with fresh semen. In Experiment 1, maximum observed concentration (C_max) eCG were similar between im and iv routes (6.1 ± 0.9 vs. 8.6 ± 0.5 IU/mL, P > 0.08), whereas time for maximum observed concentration (T_max.) was longer for im compared to iv routes (17.5 ± 0.5 vs. 11.6 ± 0.3 h, P < 0.01). The area under the curve (AUC) was similar for im and iv routes (P > 0.48), and eCG was detectable in serum for at least 144 h for both routes. In Experiment 2, 3 days or 3 to 5 days after treatment, all bitches in TRT50 had higher scores compared to TRT5-44 animals (P < 0.01). In TRT50, the mean interval from treatment to estrus was 4.0 ± 0.4 days. In Experiment 3, the mean interval from treatment to estrus was shorter in the TRT group compared to the PLA group (4.1 ± 3.3 vs. 68.5 ± 4.4 days, P < 0.01). The previous interestrus interval was similar for TRT and PLA groups (199.6 ± 7.2 vs. 197.5 ± 10.2 days), but the new interestrus interval was shorter for the TRT compared to the PLA group (164.0 ± 7.2 vs. 212.2 ± 10.2 days; treatment by interval interaction, P < 0.007). Serum P₄ concentrations increased on the first day of cytologic diestrus after treatment in bitches in TRT (0.7 ± 0.3 vs. 22.8 ± 4.2 ng/mL; P < 0.01); but did not change in PLA (P > 0.84). Ninety-four percent of animals were bred (15/16; AI, n = 7; natural mating, n = 8), and 80% (12/15) became pregnant. None of the bitches had any side effects from the eCG and hCG therapy. We concluded that 50 IU/kg of eCG combined 7 days later with 500 IU of hCG was effective to induce normal and fertile estrus in bitches at 164 days post estrus, with an 80% pregnancy rate, with no side effects, and with a reduction of 48 days of the interestrus interval.