子宫肌瘤患者及接受UAE治疗后血清性激素水平分析

目的：探讨性激素在子宫肌瘤发病中的意义。方法：采用化学发光技术检测正常对照61例(对照组)、子宫肌瘤患6l例(患组)以及44例子宫肌瘤接受子宫动脉栓塞治疗(UAE)后的患，血清促卯泡成熟激素(FSH)、促黄体生成激素(LH)、雌激素(E2)、垂体泌乳素(PRL)、睾酮(T)水平。结果：子宫肌瘤患组的血清FSH、LH、PRL、T水平均明显高于对照组；血清E2水平与对照组无显差异。其中44例接受UAE治疗的子宫肌瘤患术后血清LH、E2、PRL、T水平均比术前明显降低，FSH与术前无显差异；术后血清FSH、PRL、T水平均明显高于对照组，LH、E2水平明显低于对照组。结论：PRL、T是子宫肌瘤的发病因素。     

隐睾或去垂体大鼠血清中抑制素与FSH的关系

本研究观察了实验性隐睾与去垂体大鼠的血清、睾丸与间质液中抑制素水平与血清中FSH的水平。发现隐睾大鼠术后1～2周末,血清中抑制素水平下降到对照组的20～40％左右,FSH水平可增加到对照组水平的200％,二者之间有一个明显的负相关(r=-0.38,P=0.013)。去垂体大鼠的FSH水平下降到不能探测水平时,抑制素水平也明显下降。本实验认为抑制素调节着FSH的分泌,而FSH也部分地控制了抑制素的产生。     

克罗米芬兴奋试验预测卵巢储备功能的价值

目的探讨克罗米芬兴奋试验（CCT）在不孕妇女中预测卵巢储备功能的作用。方法对2001年1月至2005年2月就诊于广东省妇幼保健院的666例不孕症患者作为研究对象，分为A组（≥35岁）461例为高龄组，B组（〈35岁）205例为低龄组，另取156例年龄〈35岁、非女方不孕原因者作为对照组，对三组受试者进行CCT。结果CCT异常发生率A组、B组及对照组分别为27．76％、34．14％、2．56％，A组及B组与对照组比较差异均有非常显著性意义（P〈0．01）。基础卵泡刺激素（FSH）〈10IU／L、雌二醇（E2）〈180pmot／L的不孕患者CCT异常发生率分剐为17．46％、24．19％，均明显低于FSH≥10IU／L、E2≥180pmol／L患者的64．19％及39．4％（P〈0．01）。结论CCT预测卵巢储备功能较基础FSH更敏感，CCT可作为常规了解卵巢储备功能的一项检测方法。     

DEVELOPMENT OF NEW LHRH ANTAGONISTS

An ideal antagonist of LHRH is one which can act on the pitutary to inhibit LHRH-stimulatod LH / FSH secretion by competitive occupying the LHRH receptor in the pitutary gland. Its action should be very specific, fast and highly effective, the durations     

Synthesis of gonadotrophins and its regulation in the pituitary gland

Regulation of the synthesis of pituitary gonadotrophins LH andFSH has been studied in the rat using either cell-free translationof pituitary mRNAs, or hybridization techniques with syntheticoligodeoxynucleotides or cloned complementary DNAs. Gonadectomygreatly increases and supplementing gonadectomized rats withgonadal steroids diminishes the rate of synthesis of the gonadotrophinsubunits. Hybridization experiments suggest that gonadal steroidsregulate the expression of the genes coding for pituitary gonadotrophinsubunit precursors. Using the incorporation of labelled methionineby pituitary cells in culture, followed by specific immunoprecipitationof LH-related subunits and SDS-poly-acrylamide gel analysisof immunoprecipitated peptides, there was evidence that gonadotrophinreleasing hormone (GnRH) significantly enhances the radioactivityincorporated into both - and LH-subunits. This effect is specific,it is not a secondary effect due to the release of LH. A cyclicAMP (cAMP) analogue, 8-Br-cAMP, as well as forskolin and choleragen,which are cAMP generators and a diacylglycerol analogue, tetradecanoylphorbolacetate (TPA), mimic the stimulatory action of GnRH on the synthesisof the polypeptide chains of LH. However, no evidence has beenobtained that either cAMP or diacylglycerols mediate this GnRHeffect. These results suggest that the synthesis of pituitarygonadotrophins is under a double control of gonadal steroidsand GnRH which exert opposite effects, inhibitory for steroidsand stimulatory for GnRH. The negative control by steroids occursat the genomic level, while the positive effect of GnRH proceedsvia different mechanisms which remain to be elucidated.     

Hypergonadotrophinaemia with reduced uterine and ovarian size in women born small-for-gestational-age

BACKGROUND: Fetal growth restraint has been associated with FSH hypersecretion in early infancy and in early post-menarche, and with reduced uterine and ovarian size in adolescence. It is unknown whether these reproductive anomalies persist, respectively, into late infancy and into the reproductive age range. METHODS: We report follow-up findings in two age groups of girls. A cohort of infants [n=26; n=10 born appropriate-for-gestational-age (AGA) and n=16 born small-for-gestational-age (SGA)], who had been studied at the age of approximately 4 months, was assessed again at the age of 12 months. A cohort of teenagers (n=28), who had been studied at the age of approximately 14 years, was assessed again at the age of approximately 18 years; this group was complemented by a transversal cohort of similar age (n=19) for a total of 47 young women (n=27 AGA; n=20 SGA). In infants, only serum FSH was measured; adolescents underwent endocrine-metabolic screening, ultrasound assessment of uterine-ovarian size, and evaluation of body composition by dual X-ray absorptiometry. RESULTS: Serum FSH levels were higher in SGA than AGA infant girls at 4 and 12 months, and higher in SGA than AGA adolescents at 14 and 18 years (all P<0.01). Longitudinal ultrasound assessments disclosed a late-adolescent increment of uterine size that was less obvious in SGA than AGA girls. In contrast, ovarian volume remained stable in both subgroups. Compilation of longitudinal and transversal results at 18 years of age corroborated the persistent reduction in the uterine size of SGA girls (by approximately 20%; P<0.005) and in their ovarian volume (by approximately 40%; P<0.0001); moreover, SGA girls displayed not only a persistent elevation of FSH (by approximately 50%; P<0.001), but also a rise of LH and fasting insulin, as well as an excess of abdominal fat (all P<0.01). CONCLUSIONS: The gynaecology of young women born SGA was found to be characterized by hypergonadotrophinaemia and by a reduced uterine and ovarian size.     

IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.     

The effects of anterior hypothalamic deafferentation on FSH-releasing activity in the intact female hamster

Summary To study the role of the anterior hypothalamic area (AHA) in the control of the estrous (E) rise of follicle stimulating hormone (FSH), female hamsters were subjected to anterior hypothalamic deafferentation (D) or sham deafferentation (S) on 1500 h of proestrus (P). Serum levels of FSH and luteinizing hormone (LH) were measured by radioimmunoassay and FSH and LH releasing activities measured by bioassay in the anterior (AH) and medial basal hypothalamus (MBH) at several time periods during P and E. D did not affect serum levels of LH, whereas there was an attenuation of FSH levels during P and E. D caused an increase in FSH releasing activity in the AH within 1 h, while LH releasing activity was elevated 8 h after D. In animals with D, LH releasing activity in the MBH was elevated during P and was similar to controls during E. FSH releasing activity in the MBH increased during early E and dropped precipitously by 1400 h of E. Collectively, these data demonstrate dichotomous changes in FSH and LH releasing activities and provide further evidence for dual control mechanisms for these two gonadotropins.Supported in part by NIH grant RR-5417     

An open,randomized single-centre study to compare the efficacy and convenience of follitropin beta administered by a pen device with follitropin alpha administered by a conventional syringe in women undergoing ovarian stimulation for IVF/ICSI

BACKGROUND: A pen device, similar to an insulin pen, has been recently marketed for the administration of follitropin beta in cartridges. A randomized controlled trial was performed to compare the efficacy and convenience of this pen device delivering follitropin beta with a conventional syringe delivering follitropin alpha. METHODS: A total of 200 patients needing IVF/ICSI treatment and willing to self-inject were enrolled in the study. All subjects had ovarian stimulation according to a long protocol and were randomized to the pen or the conventional syringe group during down-regulation by means of a computer-generated randomization list using random numbers. Patients were asked to fill in a daily local tolerance book after each injection. On the day of hCG the patients scored a Visual Analogue Scale (VAS) for pain and convenience. RESULTS: The average duration, total dose of recombinant FSH and number of cumulus oocyte complexes retrieved were 10.8/12.0 days (P = 0.001), 1880/2226 IU (P < 0.001) and 15.2/13.1 respectively in the pen device and conventional syringe groups; the presence of pain after the daily injection was significantly higher in the conventional syringe group (P = 0.027); the visual analogue scale score was similar for pain but significantly more convenient for the pen device (P < 0.001). The live birth rate per embryo transfer was 32.9 and 34.4% respectively in the pen device and conventional syringe groups. CONCLUSIONS: Self-injection with the pen device is safe and easy, more convenient and less painful for the patient, requires less FSH and shortens the treatment duration.     

Follicle stimulating hormone measured in unextracted urine throughout the menstrual cycle correlates with age and ovarian reserve

BACKGROUND: A method was previously described to measure FSH reliably in unextracted urine. The aim of the current study was to establish the course of FSH measured in urine throughout the cycle. METHOD: Daily urinary FSH (uFSH) concentrations were determined in 14 regularly menstruating volunteers aged 23-39 years during one complete menstrual cycle. RESULTS: In each subject, mean daily uFSH measured in urine, as gold standard for FSH tone, correlated significantly with FSH in early follicular phase fixed to menstruation on cycle day 3 (r = 0.75, P = 0.002), or fixed to ovulation 9 days before the pre-ovulatory FSH surge (r = 0.87, P = 0.0001), or when selected as being the highest follicular phase value (r = 0.91, P = 0.0001). Age correlated significantly with mean daily uFSH (r = 0.67, P = 0.009), highest follicular phase uFSH (r = 0.60, P = 0.024), uFSH on cycle day 3 (r = 0.80, P = 0.0006), and uFSH 9 days before FSH surge (r = 0.65, P = 0.0016). The uFSH was also measured on cycle day 3 in 104 IVF patients in a cycle prior to pituitary down-regulation. The uFSH correlated significantly with numbers of follicles (P = 0.02) and oocytes (P = 0.024). CONCLUSION: It is concluded that cycle day 3 uFSH is a good reflection of the mean uFSH of the complete cycle, and there is a highly significant correlation between uFSH and age and ovarian reserve. Measurement of FSH in urine on cycle day 3 seems to be a reliable and non-invasive tool for determining ovarian reserve in IVF.