Gonadendysgenesie aus gyn?kologischer Sicht

Gonadal dysgenesis (GD) belongs to the group of disorders/differences of sex development (DSD) and is based on an inborn faulty or missing development of the gonads. In complete loss of function or if no testosterone and no testicular anti-mullerian hormone (AMH) is produced, streak gonads and a female phenotype (usually with uterus) arise even in cases of a male karyogram. Leading symptom is primary, hypergonadotropic amenorrhea with normal body height and usually without associated anomalies, with the exception of the Turner syndrome and other rare syndromes. A partial loss of function of the gonads leads to premature ovarian failure (POF) in 46,XX GD and to ambiguous external genitalia in 46,XY GD. In cases with Y in the karyogram, the gonads must be removed due to the risk of up to 30% of malignant development. Associated anomalies, adrenocortical insufficiency and short stature necessitate an interdisciplinary approach, hormone therapy for induction of breast development and prevention of osteoporosis should be initiated by gynecologists.     

Intrauterine blood flow and long-term intellectual, neurologic, and social development

OBJECTIVE: To study the long-term effects of severely abnormal (absent or reversed diastolic) blood flow in the umbilical artery associated with fetal growth restriction on postnatal intellectual, neurologic, and social development. METHODS: Absence or reversal of diastolic blood flow in the umbilical artery was found in 38 consecutive growth-restricted fetuses as determined by biometry and Doppler ultrasound between 1988 and 1992. The 23 infants surviving the prenatal and perinatal period who could be tested were compared at school age with a group of children born at the same gestational age after normal intrauterine growth. They were tested for intellectual, neurologic, and social development by a test battery including the Kaufmann Assessment Battery for Children, Man-Drawing Test, Child Behavior Checklist, Zürich Neuromotor Test, and neuropediatric testing. RESULTS: Intellectual development was significantly better in the control group compared with the study group. In addition, Zürich Neuromotor testing and neuropediatric testing showed significantly better development of control children compared with the study group in 20% of the items tested. There was no detectable difference in social development as measured by the Child Behavior Checklist. CONCLUSION: Severely reduced blood flow to the fetus associated with growth restriction was followed by long-term impairment of intellectual development and partial neurodevelopmental delay.     

Pre-wallerian degeneration in the neonatal brain following perinatal cerebral hypoxia-ischemia demonstrated with MRI

AIM: Pre-Wallerian degeneration was studied in term and near-term neonates with hypoxic-ischemic brain injury, and related to neurodevelopmental outcome. SUBJECTS: Thirty-nine surviving patients with hypoxic-ischemic encephalopathy or seizures and MRI-documented brain abnormalities were included. Patients were grouped according to the MRI findings: group 1 (n = 23), ischemic stroke or watershed infarcts; group 2 (n = 8), lesions of the basal ganglia; group 3 (n = 8), predominantly white matter lesions. METHODS: Cranial MRI, including diffusion-weighted MRI, was performed between 1 and 10 days after birth. ADC maps were created, and presence or absence of pre-Wallerian degeneration in the cerebral peduncles was assessed. RESULTS: Of the 15 neonates with pre-Wallerian degeneration, 14 had permanent abnormalities of motor development, whereas 1 had a transient asymmetry. Six neonates with a poor outcome had no pre-Wallerian degeneration, which may be contributed to the timing of the MRI in 2. Eighteen neonates had no pre-Wallerian degeneration and a normal motor development. CONCLUSION: Pre-Wallerian degeneration of the cerebral peduncles in neonates with hypoxia-ischemia is almost invariably associated with a poor motor development. In neonates with abnormalities of the basal ganglia or white matter and a poor outcome, pre-Wallerian degeneration is less common than in neonates with stroke or watershed infarcts and a poor motor outcome.     

Occurrence of endometrial glandular dysplasia precedes uterine papillary serous carcinoma.

Endometrial glandular dysplasia (EmGD) is a newly defined entity that is commonly and specifically associated with serous endometrial intraepithelial carcinoma and uterine papillary serous carcinoma (UPSC). Endometrial glandular dysplasia has been proposed as a true precancerous lesion of UPSC based on our recent studies showing morphological and molecular linkages between these 2 lesions. The present report is to examine if EmGD occurs before UPSC development and to define the period from the occurrence of EmGD to a full-blown UPSC by studying their clinicopathologic features in a retrospective setting. A total of 250 UPSC and 258 benign cases were used as initial study source. To identify if EmGD existed before the development of UPSC, we blindly reviewed all available endometrial biopsies from a period of 3 months or earlier before hysterectomies. These included an available pool of 27 biopsy specimens from UPSC group and 29 samples from benign control group. Any endometrial abnormalities, which morphologically qualified as EmGD as defined previously in preceding biopsies were recorded. Among all endometrial biopsies before hysterectomies, we morphologically identified a total of 10 EmGD cases; 9 (33%) of 27 were from UPSC group and 1 (3.5%) of 29 were from benign control group. All 10 morphologically diagnosed EmGD cases showed a high p53 staining score (>/=5) except 1 noncontributory from UPSC group and 1 from the benign control group with a score of 0. A high MIB-1 index score was seen in all EmGD cases, whereas low index was found in morphologically benign biopsies. The main purpose of this study is to report these retrospectively identified EmGD cases. The period from identifying EmGD to the presence of either a serous endometrial intraepithelial carcinoma or a full-blown UPSC ranged from 16 to 98 months with an average of 33 months. We conclude that occurrence of EmGD precedes the development of UPSC. The findings support our recently proposed UPSC development model, in which EmGD is likely to be a precursor lesion of UPSC. Further studies are needed to address issues in regard to molecular and cellular mechanisms, reversibility, risk of UPSC development, and clinical management of EmGD.     

邻苯二甲酸二(2-乙基己基)酯致胎鼠隐睾发生过程中胰岛素样因子3的表达分析

目的:探讨环境内分泌干扰物邻苯二甲酸二(2-乙基已基)酯[Di-(2-ethylhexyl)phthalate,DEHP]诱发胎鼠隐睾的分子机制。方法:妊娠昆明小鼠随机分为3组,每组15只:DEHP实验组(A组)、玉米油(溶剂)对照组(B组)和正常对照组(C组)。A组和B组自妊娠12.5￣18.5d分别持续经口每天给予DEHP(500mg/kg)或玉米油,C组不予灌药。结果:B组和C组睾丸组织中胰岛素样因子3(INSL3)mRNA和蛋白质的表达均无差异(P>0.05);A组INSL3mRNA的表达量约为B或C组的1/3,INSL3蛋白质的表达量约为B或C组的1/4,与B或C组比其差异显著(P<0.05)。A组睾丸引带发育不良,睾丸位置异常。结论:环境内分泌干扰物DEHP下调睾丸间质细胞INSL3基因的表达,影响睾丸引带发育,可能是DEHP诱发隐睾的分子机制之一。     

Prognosis of Taiwanese patients with isolated optic neuritis after intravenous methylprednisolone pulse therapy.

BACKGROUND/PURPOSE: To evaluate the clinical manifestations, prognosis, recurrence rate and development of multiple sclerosis between papillitis group and retrobulbar group in Taiwanese patients with isolated acute optic neuritis (AON) after treatment with intravenous methylprednisolone pulse therapy. METHODS: We retrospectively reviewed patients with AON who had received intravenous methylprednisolone pulse therapy. These patients were classified into retrobulbar or papillitis groups. Demographic characteristics, responsiveness to pulse therapy, recurrence rate and incidence of multiple sclerosis were compared between these two groups. RESULTS: Of the 43 patients enrolled in this study, 19 patients (44%) were in the retrobulbar group and 24 patients (56%) were in the papillitis group. Seven cases (16%) showed periventricular plaque on magnetic resonance imaging (MRI). Among these seven patients, five developed definite or probable multiple sclerosis. The incidence of multiple sclerosis in patients with positive brain MRI findings was significantly higher than in patients with negative MRI findings (p = 0.002). There was no statistical difference in final visual acuity between the two group (p = 0.353). Sixteen patients suffered from recurrence of AON (21% in the papillitis group and 58% in the retrobulbar group, p = 0.029). Two patients (8%) in the papillitis group and six patients (32%) in the retrobulbar group developed multiple sclerosis (p = 0.061) with a mean interval of 21.6 +/- 11.2 months. CONCLUSION: AON in Taiwan has a relatively lower percentage of development of multiple sclerosis than in Western countries. The presence of periventricular plaque on MRI is significantly associated with the later development of multiple sclerosis. The retrobulbar group had a stronger association with recurrence and development of multiple sclerosis.     

输卵管积水对人早期胚胎体外发育的影响

目的:探讨人输卵管积水(HSF)对人早期胚胎体外发育的影响。方法:因输卵管积水、阻塞行IVF/ICSI-ET患者取卯时穿刺抽吸HSF30例,送细菌培养及成分分析等。同期收集161例行IVF/ICSI-ET患者受精第1日的261枚异常受精卵(1PN,≥3PN),随机分成3组,分别培养于含不同体积分数的HSF培养液中:A组(50%HSF,n=91)、B组(100%HSF,n=89)和C组(对照组,0%HSF,n=81),观察胚胎发育情况,计算卵裂率、优质胚胎率、囊胚形成及孵出率、优质囊胚率等。结果:4例HSF细菌培养阳性(13.33%);HSF中总蛋白及葡萄糖显著低于该患者同目的血清水平。与C组比,未放入卵子的A、B组培养液平衡后,pH值升高,B组渗透压降低(P<0.05)。3组卵裂率、优质胚胎率无统计学差异(P>0.05);囊胚形成率及优质囊胚率A组(15.38%,21.43%)、B组(11.24%,10%)明显低于C组(28.40%,82.61%)(P<0.05)。结论:HSF影响人囊胚形成及囊胚质量,可能与HSF中低葡萄糖、低蛋白、低渗透压、高pH有关,自然状态下可能还与存在一定比例的细菌有关。     

Long-term and short-term outcome after delayed-interval delivery in multi-fetal pregnancies

OBJECTIVE: To assess a possible difference in the short- and long-term outcome between infants born from a delayed-interval delivery. STUDY DESIGN: We included all neonates that were either born between November 1991 and December 2000 from a delayed-interval delivery in the Isala Clinics, Zwolle, The Netherlands, or admitted to our clinic after birth. Gestational age, time of delay, birth weight, mortality, morbidity, long-term development and adverse outcome were compared between groups. Moreover, the 'delayed infants' group was compared to a reference group. The following statistical tests were used: prevalence ratio, the Wilcoxon test and the t-test. RESULTS: Twenty-nine delivery-delaying procedures were successfully performed in our hospital. We included 17 sets of twins and 3 sets of triplets. The mean delay of 19.6 days accounted for a significant increase in birth weight and neonatal survival as well as a decrease in adverse outcome and presence of a number of disease; a negative effect on long-term development could not be shown. The reference group showed less sepsis than the delayed infants group. No serious maternal complications were observed. CONCLUSION: Delaying the delivery of a second or third infant has a positive effect on short-term outcome. Long-term outcome is comparable to children with the same gestational age.     

有无卵丘细胞对玻璃化冷冻后小鼠卵母细胞细胞骨架及体外发育能力的初步研究

目的:探讨卵丘细胞在玻璃化冷冻中对小鼠卵母细胞发育潜能及细胞骨架的影响。方法:采用玻璃化冷冻技术,保存带卵丘细胞或完全剥除卵丘细胞的小鼠MⅡ期和GV期卵丘复合体/裸卵(COC/DO),复苏且GV卵体外培养成熟后分别作体外受精或免疫荧光标记检查纺锤体和染色体的完整性。结果:MⅡ-COC和GV-COC的复苏率均显著高于MⅡ-DO和GV-DO(分别为86.49%vs60.92%和85.94%vs64.93%,P<0.01)。GV-COC组的受精率、囊胚率均高于GV-DO组,且MⅡ-COC组和GV-COC组的纺锤体和染色体均正常率均分别高于MⅡ-DO组和GV-DO组,但无显著性差异(P>0.05)。结论:卵丘细胞在玻璃化冷冻卵母细胞中能有效减少冷冻对细胞骨架的损伤,并改善卵子复苏及胚胎发育潜能。     

ICSI时不同单精子注入方式对胚胎体外发育的影响

目的:探讨卵母细胞胞浆内单精子注射(ICSI)时回吸与不回吸胞浆对胚胎体外发育的影响。方法:将在本中心接受ICSI治疗的90周期不孕患者的1077枚MII卵子随机分为A组(632枚)和B组(445枚)。A组ICSI时回吸胞浆至卵母细胞直径的1/4-1/2处;B组不回吸胞浆,比较2组的受精率、胚胎可用率和优质胚胎率等。结果:A组和B组的受精率分别为80.85%和82.02%,无统计学差异意义(P>0.05)。A组的胚胎可用率为53.88%,与B组(56.15%)比较无差异(P>0.05);B组的优质胚胎率为20.39%,显著高于A组的13.32%(P<0.05)。结论:ICSI时回吸胞浆和不回吸胞浆对体外受精均是有效的;不回吸胞浆可提高优质胚胎率,对胚胎发育更安全。     

Nucleated red blood cell and platelet counts in asphyxiated neonates sufficient to result in permanent neurologic impairment.

OBJECTIVE: Recent research has suggested that a nucleated red blood cell (NRBC) count >or=26 per 100 white blood cells (%) or the development of a platelet count or=26% was: group 1, 10/21 (47.6%); group 2, 0/14 (0%); group 3, 0/12 (0%). Those with a platelet count or=26% than group 3 (p = 0.0135). A platelet count or=26% and/or a platelet count 相似文献   

人子宫内膜、早孕蜕膜单层细胞及其条件培养液对小鼠早期胚胎发育的作用

为研究人子宫内膜、早孕蜕膜单层细胞及其条件培养液对早期胚胎发育的作用,本文应用酶消化法将人增殖晚期早分泌期子宫内膜及早孕蜕膜消化成单个细胞或细胞团块,分别在体外培养,并冷冻保存。建立单层细胞并制成条件培养液,由于人胚取材较困难,此文采用小鼠早期胚胎共培养,结果显示,人子宫内膜及早孕蜕膜在体外发育良好,并可冷冻保存,复苏率＞ ４０％ 。小鼠胚胎的卵裂率、桑椹胚及囊胚形成率明显高于对照组（Ｐ＜ ０．００１）,早孕蜕膜组较子宫内膜组略高,但无显著性差异。两种细胞的条件培养液均可刺激胚胎发育,但无显著性差异,而胚泡形成率在早孕蜕膜组明显高于对照组（Ｐ＜ ０．０５）。提示：人子宫内膜及早孕蜕膜细胞能释放某些刺激胚胎发育的物质有利于胚胎发育     

The effect of Mycoplasma pulmonis on fertilization and preimplantation development in vitro of mouse eggs

The effect of Mycoplasma pulmonis suspension on mouse on mouse fertilization and preimplantation development in vitro was examined. When sperm were preincubated with M. pulmonis, fertilization of eggs occured less consistently than when untreated sperm were used. There was also a highly significant and consistent reduction in embryonic develoment in the treated group, with relatively few embryos reaching the blastocyst stage. The adverse effects were not seen with M. fermentans or with M. pulmonis organisms inactivated by heating or sonication before incubation with gametes. Likewise, preincubation of M. pulmonis in medium containing tetracycline, an antibiotic which interferes with protein synthesis, resulted in embryonic development similar to that seen in the untreated group. These results suggest that the deleterious effects obtained with viable mycoplasmas are due to some substance produced by their active metabolism. Other results indicate that the egg is susceptible to M. pulmonis for a limited time, since incubation of two-cell embryos with mycoplasmas had no effect on development to the blastocyst stage. The findings are discussed in relation to the possible association between human infertility and mycoplasma infection.     

每周口服米非司酮避孕的临床研究

目的:研究每周一次口服米非司酮25mg或50mg用于常规避孕的可行性。方法:志愿参加避孕研究的健康妇女共33例,随机分为二组,自月经d2-3口服米非司酮,每例观察6个周期。A组(16例)每周口服米非司酮25mg;B组(17例)每周口服50mg。另在A组、B组中各选2例,每例服药前1个周期及服药后2-6个周期间,于黄体中期各取子宫内膜共2次作自身对照,测定子宫内膜形态学改变,应用免疫组化法检测基质金属蛋白酶(MMP)-9和MMP-26的表达。结果:A组共服药50个周期,1例妊娠,4例闭经,1例妇女经量极少;B组共服药81个周期,无1例妊娠,5例闭经,4例经期仅点滴出血。服药后与服药前比较内膜明显变薄,主要表现为基质和腺体发育不同步,大部分腺上皮分泌活动不明显。与对照周期相比,服药后二组MMP-9和MMP-26在子宫内膜腺上皮和基质细胞的表达均显著降低。结论:每周一次口服米非司酮(25mg或50mg)妇女的月经周期改变较大,临床避孕效果理想。每周口服50mg米非司酮可能是比较合适的剂量。但闭经率较高,且闭经的出现不可预测,妇女对其的可接受性较差。     

Chronic Endometritis and Positive Mycoplasma Cultures: Is There a Correlation?

Objective: This study was undertaken to assess the impact of mycoplasma strains (Mycoplasma hominis or Ureaplasma urealyticum) on the development of chronic endometritis.Methods: Fifty-eight patients with acute pelvic infection were enrolled in this prospective cohort study. Endometrial cultures and biopsies were obtained on admission and 5-7 and 21-28 days after completion of treatment.Results: Of 148 samples, 40 were positive for mycoplasma strains (group A) and 58 were positive for mycoplasma with other pathogens (group B). Twenty-seven samples were positive for other pathogens only (group C). Chronic endometritis was seen in 7 (17.5%), 30 (51.7%), and 10 (37%) in group A, B, and C patients, respectively.Conclusions: The presence of mycoplasma strains in the endometrial cavity was not found to be associated with an increased incidence of chronic endometritis.     

Primary Amenorrhoea

Primary amenorrhoea may be defined as the absence of menses and secondary sexual characteristics by age 14, or the absence of menses regardless of the presence of secondary sexual characteristics by age 16. All patients require investigation. Classification of patients with primary amenorrhoea into four groups based on the presence or absence of breasts and the presence or absence of a uterus simplifies the investigations required to make a diagnosis. These four groups are: 1) breasts present, uterus present, 2) breasts absent, uterus present, 3) breasts present, uterus absent and 4) breasts absent, uterus absent. Patients in group one should be investigated and treated in the same manner as secondary amenorrhoea. Patients in group two have hypogonadotrophic hypogonadism or hypergonadotrophic hypogonadism. Patients in group three have either mullerian agenesis or androgen insensitivity syndrome (testicular feminization). Patients in group four are rare and are always 46 XY karyotype. They require further endocrinological testing and treatment. Aft patients with a Y chromosome and the presence of gonads require a gonadectomy because of the risk of malignancy. Aft patients who do not synthesize endogenous estradiol require estrogen replacement therapy, even at this young age, to prevent osteoporosis and, in many cases, to complete their pubertal development.     

Neurodevelopmental outcome of infants resuscitated with air or 100% oxygen: a systematic review and meta-analysis

Background: The use of air for the initial resuscitation of newborn infants has been shown to reduce neonatal mortality. However, a precise estimate of the neurodevelopmental status upon follow-up of infants resuscitated in air is lacking. Objective: To perform a meta-analysis of all studies reporting resuscitation of newborn infants with air or 100% oxygen that included follow-up data. Methods: Bibliographic databases were searched. In addition, we estimated the effect of loss to follow-up on our analysis of abnormal neurodevelopmental outcome. Results: We identified 10 studies in which newborn infants had been randomly or quasi-randomly assigned to resuscitation with air or 100% oxygen. Three of these 10 studies had available follow-up data. A total of 678 infants were enrolled at centers that performed follow-up of these infants. Of these, 113 died, leaving 565 infants potentially eligible for follow-up. A total of 414 children were evaluated (73% of eligible children; 195 resuscitated with air and 219 with 100% oxygen). In the air group, 12.8% of infants had an abnormal neurodevelopmental outcome, compared with 10.5% in the 100% oxygen group [typical relative risk (RR) 1.24, 95% confidence interval 0.73-2.10]. This is consistent with an RR of abnormal development as low as 0.41 or as high as 2.28. Conclusions: Long-term follow-up did not detect any significant differences in these two groups regarding abnormal development. However, the results are imprecise and could be consistent with significant harm or benefit.     

米非司酮对早孕蜕膜肿瘤坏死因子-α及转化生长因子-β表达的影响

目的　探讨米非司酮对胚胎生长及蜕膜肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGF-β）表达的影响。方法　30例不同孕龄的早孕药物流产妇女（药流组）,予口服米非司酮25mg,每日2次共3d,72h后加服米索前列醇600μg。另选取30例正常育龄人工流产妇女（人流组）做对照。采用免疫组化测定两组妇女蜕膜组织中TNF-α和TGF-β的表达程度及量化均值水平。结果　（1）人流组蜕膜组织中TNF-α和TGF-β阳性表达率分别为70.00%（21/30）和86.67%（26/30）;药流组蜕膜组织中TNF-α和TGF-β阳性表达率分别为73.33%（22/30）和86.67%（26/30）;两组间比较,差异无显著性（P>0.05）。（2）药流组蜕膜中TNF-α表达程度（+　+～+　+　+为9例）显著高于人流组（+　+～+　+　+为4例）,两组间比较,差异有显著性(P<0.05);药流组蜕膜中TGF-β量化均值为0.6667,显著低于人流组量化均值0.9167的水平(P<0.05)。结论　口服米非司酮药物流产妇女的蜕膜组织中,出现的TNF-α升高及TGF-β的降低,可能是蜕膜组织因子网络平衡状态紊乱的表现,米非司酮可能通过抑制TGF-β的活性,刺激TNF-α的分泌作用对胚胎发育产生不良影响。     

Mouse embryo toxicity of IL-6 in peritoneal fluids from women with or without endometriosis

BACKGROUND: To determine whether there is a factor (or factors) in the peritoneal fluid of endometriosis patients that impairs embryo growth and embryo implantation. METHODS: Growth and development of two-cell mouse embryos which were cultured in media with peritoneal fluid from women with or without endometriosis and interleukin-1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels in conditioned media were measured. RESULTS: The blastocyst rate in the non-endometriosis group was 46.4 +/- 31.1%, and that of the endometriosis group was 54.6 +/- 28.7%. Logistic regression analysis using the criteria of blastocyst development in 454 embryos, showed that the peritoneal fluid from endometriosis could promote (p=0.015) but IL-6 could arrest embryo growth to blastocyst (p=0.025). IL-1beta and TNF-alpha levels had no significant effect on blastocyst formation. CONCLUSION: Peritoneal fluid from women with endometriosis was not toxic to mouse embryo development. However, IL-6 in the peritoneal fluid deteriorated the growth and development of mouse embryos.     

Sperm antibodies induced by anti-idiotype antibodies: a strategy in development of immunocontraceptive vaccines

The potential of using anti-idiotype antibodies as immunocontraceptive vaccines is evaluated in this study. Two sperm monoclonal antibodies, HS 63 and MS 204, which have significant inhibitory effect on the in vitro and in vivo fertilization of mouse were selected to elicit heterologous anti-idiotype antibodies. Rabbit antisera against HS 63 or MS 204 were collected after the third immunization. After the removal of anti-Fc fragments with an irrelevant mouse IgG immunoadsorbent column, anti-idiotype antibodies (anti-Id HS 63 or anti-Id MS 204) were purified from the antisera with affinity chromatography. HS 63 or MS 204 was used as respective ligand. The purified anti-idiotype antibodies conjugated with hemocyanin were used to immunize female CD-1 mice as the experimental group. Another group of female CD-1 mice were immunized with adjuvant only as the control group. Each group had three mice. The immune responses varied significantly among individual mice. The antisera could stain the acrosomal region of sperm in the indirect immunofluorescent assay in a way which is similar to the original monoclonal antibodies (HS 63 and MS 204). The inhibitory effect of antisera on the sperm fertilization of mouse oocytes in vitro was significant in both cases. In the case of antisera against anti-Id HS 63, the control group showed 81.8% and 49.3% of fertilization rates, whereas the corresponding rates of the experimental group were only 35.7% and 20.5%, respectively. Similarly, for antisera against anti-Id MS 204, the experimental group also revealed lower fertilization rates as compared with those of the controls (50.0% vs. 95.8% and 36.8% and 81.3%). The results of this study suggest that anti-idiotype antibodies against HS 63 and MS 204 contain the internal image of the sperm antigen and they could elicit an immune response with a significant antifertility effect. Therefore, they might not only be contributory to further study and understanding of the original antigens in structure and function but also be used as an alternative in the development of immunocontraceptive vaccines.