人卵泡液中干细胞因子水平及其对卵泡发育的影响

目的 :探讨人卵泡液中是否存在干细胞因子 (SCF)及其与卵泡发育的关系 .方法 :采用夹心ELISA方法检测 3 0例进行体外受精 胚胎移植 (IVF ET)患者超促排卵前、取卵时血清与卵泡液中SCF的水平 .结果 :①取卵时卵泡液中SCF水平 (5 14± 67)ng·L 1,显著高于同期血清水平 (3 95± 4 9)ng·L 1,差别有显著性 (P <0 .0 5 ) ;②取卵时血清中SCF水平与超促排卵前血清中SCF水平相比 ,差别无显著性 [(3 95± 4 9)ng·L 1,(3 74± 3 6)ng·L 1,P >0 .0 5 ];③高、中反应型组卵泡中SCF水平 [(5 64± 64)ng·L 1,(5 3 2± 5 5 )ng·L 1]与低反应型 (3 5 2± 78)ng·L 1相比 ,差别有显著性 (P <0 .0 1) ,且与卵泡发育数目之间呈正相关 (r =0 .4 12 ,P <0 .0 5 ) .结论 :卵泡液中SCF可能来自于卵泡本身 ,而非血浆渗透 .SCF参与人卵泡发育的调控     

卵巢癌细胞多种细胞因子基因表达的研究

本文应用RT-PCR方法,检测5例刚分离的晚期上皮性卵巢癌患者肿瘤细胞和3例卵巢痛患者腹水中肿瘤细胞IL-2、IL-2R、TNF-a,IL-6、TGF-p、IL-10等细胞因子基因的表达,用免疫学方法检测卵巢癌细胞上清液中IL-6活性。结果发现:卵巢癌肿瘤细胞表达IL-6mRNA和抑制性细胞因子TGF-p、IL-10。腹水中存在较多量lL-6可能来自肿瘤细胞。     

Spontaneous ovarian hyperstimulation mimicking an ovarian tumour

Ovarian hyperstimulation syndrome in a spontaneous singletonpregnancy is exceedingly rare. We report a case of ovarian hyperstimulationpresenting as bilateral ovarian masses in association with spontaneouspregnancy, occurring in a woman with disturbed liver function.A possible mechanism is discussed.     

Endocrinology: Two cases of ovarian tumours in women who had undergone multiple ovarian stimulation attempts

Concerns have been raised recently about the possible associationbetween superovulation and ovarian cancer. In order to contributeto the limited literature on this important issue, two casesof ovarian tumours in women who had undergone multiple ovulationinductions are presented. In the first case, the patient hadsecondary anovulatory infertility. She was treated with humanmenopausal gonadotrophin (HMG) alone and in combination withclomiphene citrate or buserelin for six cycles. She then underwentovarian stimulation with buserelin/HMG in the long protocolfor in-vitro fertilization (IVF) and embryo transfer. In preparationfor a new IVF/embryo transfer attempt, 8 months later, the screeningultrasound revealed a cystic formation of the left ovary andan enlargement of the right. During laparotomy, both ovarieswere found to bear large tumours (approximately 6x5x4 cm) whichwere removed. Histological examination showed that they wereepithelial tumours (serous-papillary cystadenomas) of borderlinemalignancy. The patient conceived spontaneously 1.5 years afterthe operation. In the second case, the patient presented withsecondary anovulatory infertility. She underwent ovulation inductionwith clomiphene/HMG and with buserelin/HMG in the long protocol,and intra-uterine insemination with husband's spermatozoa andconceived (singleton pregnancy). She was delivered by Caesareansection, during which a cystic tumour of the left ovary wasremoved. Histological examination revealed a benign mucous cystadenomaof the ovary. In conclusion, the clinical information from thesetwo cases does not support a causal association between ovarianstimulation and ovarian tumours but does potntially supporta facilitating one.     

The significance of coasting duration during ovarian stimulation for conception in assisted fertilization cycles

BACKGROUND: Withholding gonadotrophin administration and postponing HCG injection, termed coasting, has been suggested as a treatment modality in cases of impending ovarian hyperstimulation syndrome (OHSS). It presents an opportunity to reduce the risk of OHSS and salvage the treatment, without apparent compromise to outcome. However, the duration of the coasting period, which would maintain the advantage without reducing conception rate, has not been fully established. In this retrospective study, we attempted to define the optimal interval of coasting in patients at risk of developing OHSS. METHODS: Patients were grouped according to the number of days elapsed between cessation of gonadotrophins and administration of HCG. Overall, out of 207 patients (mean age 30.76 +/- 0.33 years) coasting lasted 1 day in 39 cycles (18.8%), 2 days in 61 cycles (29.4%), 3 days in 49 cycles (23.6%) and > or = 4 days in the remaining 58 cycles (28.5%). RESULTS: There was no difference between the groups in patients' age, serum estradiol concentrations at the time of HCG administration, oocyte maturity, fertilization and embryo cleavage rates. However, patients in whom coasting lasted > or = 4 days had significantly reduced implantation (10.5%) and pregnancy (26.7%) rates compared with patients with a shorter coasting interval (ranges 18.4-27.9 and 41-55.7% respectively; P < 0.05). CONCLUSION: Coasting for >3 days appears to reduce implantation and pregnancy rates while in-vitro oocyte and embryo quality do not appear to be affected. We suggest that in patients who need coasting for >3 days, cryopreservation of embryos should be considered.     

BRCA1 and BRCA2 mutations in Russian familial breast cancer

We have screened index cases from 25 Russian breast/ovarian cancer families for germ‐line mutations in all coding exons of the BRCA1 and BRCA2 genes, using multiplex heteroduplex analysis. In addition we tested 22 patients with breast cancer diagnosed before age 40 without family history and 6 patients with bilateral breast cancer. The frequency of families with germline mutations in BRCA was 16% (4/25). One BRCA1 mutation, 5382insC, was found in three families. The results of present study, and those of a separate study of 19 breast‐ovarian cancer families, suggest that BRCA1 5382insC is a founder mutation in the Russian population. Three BRCA2 mutations were found in patients with breast cancer without family history: two in young patients and one in patients with bilateral breast cancer. Four novel BRCA2 mutations were identified: three frameshift (695insT, 1528del4, 9318del4) and one nonsense (S1099X). © 2002 Wiley‐Liss, Inc.     

Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue

Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.     

Endocrinology: Substrate dependency of C19 conjugates in hirsute hyperandrogenic women and the influence of adrenal androgen

Serum C₁₉ conjugates, specifically 3-androstanediol glucuronide(3G), reflect peripheral androgen action through the actionof 5-reductase activity. The origin of 5-reduced C₁₉ conjugateshas been controversial and it has been suggested that they arederived primarily from adrenal androgens. We examined concentrationsof 3G, 3-androstanediol sulphate (3S), androsterone glucuronide(AoG) and androsterone sulphate (AoS) in 40 hirsute hyperandrogenicwomen. These patients were divided into four groups based uponindividual, combined or normal concentrations of the adrenalandrogens dehydroepiandrosterone (DHEAS) and 11-hydroxy-androstenedione.Testosterone, unbound testosterone and androstenedione weresimilar in these groups. Serum 3G was equally high in all groupsand was correlated significantly with hirsutism, while the otherconjugates were not. Androsterone glucuronide was raised inall groups but was higher in patients with raised DHEAS. Serum3S was raised in all groups and was higher where both adrenalandrogens were raised. Serum AoS was highly correlated withDHEAS. Serum 3G was correlated with unbound testosterone andandrostenedione but not with the adrenal androgens. The glucuronideconjugates were correlated with one another as were the sulphateconjugates but glucuronides and sulphates were not correlated.These data confirm ovarian and adrenal dependency of C₁₉ conjugates.Serum 3G appears to reflect hirsutism most accurately and isleast dependent on adrenal androgens in patients with mixedhyperandrogenism.     

CA 125 concentrations in ovarian 'chocolate' cyst fluid can differentiate an endometriotic cyst from a cystic corpus luteum.

In a prospective study, the concentrations of CA 125, 17 beta-oestradiol and progesterone were assayed in 52 consecutive ovarian cysts, laparoscopically suspected to be endometriomas. Cysts with dark brown 'chocolate' fluid (n = 42) were excised by CO2-laser endoscopy. Cysts with clear fluid were diagnosed by pathology as follicular cysts (n = 5) or pseudoperitoneal cysts (n = 5). Fluids (n = 53) aspirated during echo-guided puncture for in-vitro fertilization (IVF) were assayed simultaneously. Of the 42 women undergoing a cystectomy, the clinical diagnosis of an endometrioma was confirmed by pathology in only 68%, the other cases being corpora lutea (27%) or follicular cysts (5%). Cyst fluids from corpora lutea had lower CA 125 concentrations (< 1000 IU/ml) together with high 17 beta-oestradiol concentrations (> 2000 pg/ml) and/or high progesterone concentrations (> 100 ng/ml). Endometriotic cysts had either very high CA 125 concentrations (> 10,000 IU/ml) as occurred in 78% or lower CA 125 concentrations (< 1000 IU/ml) together with low 17 beta-oestradiol and/or progesterone concentrations. 'Chocolate' fluid-containing cysts aspirated during IVF had similar concentration profiles of CA 125, 17 beta-oestradiol and progesterone and the diagnoses derived from these concentrations were not contradicted in 19/27 women undergoing a laparoscopy within 4 months. In eight women, however, with high CA 125 concentrations in their cyst fluid, no endometriotic cysts were found at laparoscopy. Only 68% of cysts containing 'chocolate' material were endometriotic cysts and CA 125 could be useful in making this diagnosis. This method is recommended when dark brown fluid is aspirated in IVF.     

Relationships between the serum levels of soluble leptin receptor and free and bound leptin in non-pregnant women of reproductive age and women undergoing controlled ovarian hyperstimulation

BACKGROUND: The aim of this study was to investigate the relationships between the serum levels of soluble leptin receptor (SLEPR), and total, free and bound leptin, and the change in the serum SLEPR level during an IVF cycle. METHODS: Serum concentrations of leptin and SLEPR were measured in 50 Japanese women of reproductive age, and 20 patients participating in an IVF programme. The total leptin was fractionated into free and bound portions by gel filtration chromatography. RESULTS: The SLEPR level was negatively correlated with the body mass index (BMI) (r = -0.548, P < 0.0001), total leptin (r = -0.433, P < 0.0001), the percentage of free leptin (r = -0.732, P < 0.0001) and the absolute free leptin concentration (r = -0.506, P < 0.0001). The SLEPR level was positively correlated with the percentage of bound leptin (r = 0.730, P < 0.0001), whereas there was little variation in the absolute bound leptin concentration, regardless of the BMI or SLEPR concentration. During the IVF cycle, total and free leptin elevated during maximal ovarian stimulation, whereas there was no significant difference in the SLEPR concentration. CONCLUSIONS: The results demonstrate a skillful mechanism where a change in the serum SLEPR level regulates, in part, the biological activity of leptin in the circulation.