[Validity of the oncological cytodiagnostics and colposcopy examination versus biopsy in cervical carcinoma prevention]. / Validita onkologické cytodiagnostiky a kolposkopie versus biopsie v prevenci rakoviny cervixu.

THE AIM OF THE STUDY: The basic praebioptic methods detecting the precancerous lesions of the uterine cervix are oncologic cytology (PAP smears) and colposcopy. However in the Czech Republic the incidence of the invasive carcinomas during the last 10 years did not considerably decrease. Therefore the goal of our study is to estimate the validity of the prebioptic methods and compare the results of praebioptic methods (procedures) versus biopsy. TYPE OF THE STUDY: Analysis of the results of the oncologic cervical cytology comparing with the results of cervical biopsies performed during the years 2002-2003 were compared to those of the year 2009. THE SUBJECT AND METHODS OF THE STUDY: evaluation of the prebioptic methods (cytology, colposcopy) versus biopsy prior and during the start of the National Screening in the Czech Republic. SETTING: 1. Centre for Gynaecological Oncological prevention, 1st Faculty of Medicine, Charles University Prague, Department of Gynaecology and Obstetrics. 2. Institute of Physiology, Department of cybernetics, 1st Faculty of Medicine, Charles University, Prague. 3. Institute of Pathology, University of Ostrava. 4. Institue for Mother and Child Care, Prague. SUMMARY: We screened the documentation related to the treatment of 423 women with cervical lesions, examined at the Oncological prevention centre of the Obstetrical and Gynaecological Department of the 1st Faculty of Medicine Charles University Prague and the General Teaching Hospital in Prague 2. Results of the oncologic cytology, colposcopy and biopsy were compared. The comparison revealed differences related to the time of examinations. During the years 2002 and 2003 the agreement between cytologic diagnosis and biopsies in the group of HSIL was 40 %. In the year 2009 the agreement between HSIL and CIN was 68% the colposcopic diagnosis of precancerous lesions with those of bioptic specimens, during the years 2002 and 2003 was 90% while in the year 2009, during the National Screening, the agreement reached 98%.

Reduced progesterone metabolites in human late pregnancy.

In this review, we focused on the intersection between steroid metabolomics, obstetrics and steroid neurophysiology to give a comprehensive insight into the role of sex hormones and neuroactive steroids (NAS) in the mechanism controlling pregnancy sustaining. The data in the literature including our studies show that there is a complex mechanism providing synthesis of either pregnancy sustaining or parturition provoking steroids. This mechanism includes the boosting placental synthesis of CRH with approaching parturition inducing the excessive synthesis of 3beta-hydroxy-5-ene steroid sulfates serving primarily as precursors for placental synthesis of progestogens, estrogens and NAS. The distribution and changing activities of placental oxidoreductases are responsible for the activation or inactivation of the aforementioned steroids, which is compartment-specific (maternal and fetal compartments) and dependent on gestational age, with a tendency to shift the production from the pregnancy-sustaining steroids to the parturition provoking ones with an increasing gestational age. The fetal and maternal livers catabolize part of the bioactive steroids and also convert some precursors to bioactive steroids. Besides the progesterone, a variety of its 5alpha/beta-reduced metabolites may significantly influence the maintenance of human pregnancy, provide protection against excitotoxicity following acute hypoxic stress, and might also affect the pain perception in mother and fetus.

[Detection of placenta-specific microRNAs in maternal circulation]. / Detekce placentárne specifických mikroRNA v materské cirkulaci.

OBJECTIVE: We focused on the detection of microRNAs in maternal circulation during the course of physiological pregnancy. We tested initially microRNAs (mir-135b and miR-517a) which presence in maternal circulation had been previously demonstrated and those microRNAs (miR-518b and miR-517a) with up-regulated expression profile in placentas derived from pregnancies during the onset of preeclampsia. Further we selected those microRNAs, which were reported to be placenta specific according to the miRNAMap database (these microRNAs were significantly expressed in the placenta and simultaneously showed no or minimal expression in other tissues). SETTING: Division of Molecular Biology and Cell Pathology, Department of Gynaecology and Obstetrics, Third Faculty of Medicine, Charles University, Prague. METHODS: RNA enriched for small RNAs (including microRNAs) was isolated from 1 ml of maternal plasma during the 12th, 16th and 36th week of gestation and 200 microl of peripheral blood derived from healthy non-pregnant women. Consequently relevant microRNA was transcribed into cDNA using specific stem-loop primer and detected by specific real-time PCR assay. RESULTS: From the cohort of tested microRNAs we excluded those ones, which were not detectable in maternal circulation during pregnancy (miR-136 and miR-519a) and/or were demonstrated in peripheral blood of healthy non-pregnant women (miR-34c, miR-224, miR-512-5p, miR-515-5p, miR-516-5p, miR-518f*, miR-519d, miR-519e). CONCLUSION: On the base of the current study results we finally selected 6 most suitable microRNAs (miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) for subsequent studies concerning the follow-up of placenta specific microRNAs in maternal circulation during pregnancy and the differentiation between normal and pathologic pregnancies (preeclampsia, IUGR) within the same gestational age.

[Doc. MUDr. Antonín Cernoch and his original technical surgery modifications]. / Vzpomínky na docenta MUDr. Antonína Cernocha v jeho originálních operacních postupech.

Antonin Cernoch an outstanding gynaecologic surgeon, was head of the Czech institute for postgraduate medical education in the years 1960 - 1970. His important surgical work exhibited many stimulating ideas for contemporary gynaecology and obstetrics. The Cernoch's original modifications of surgical repairs of uterine cervix are presented in this article and are very important ideas for surgical practice. The original procedures repair damaged uterine cervix together with adjoining tissue as well as surgical removing advanced malignant ovarian tissue are documented in pictures. The effective treatment was used in more than 400 causes. Both, excellent surgery strategy and experience of doc. MUDr. A. Cernoch is of practical importance for gynaecologic surgeons.

Is maternal progesterone actually independent of the fetal steroids?

Progesterone and estradiol are the foremost steroid hormones in human pregnancy. However, the origin of maternal progesterone has still not been satisfactorily explained, despite the generally accepted opinion that maternal LDL-cholesterol is a single substrate for placental synthesis of maternal progesterone. The question remains why the levels of progesterone are substantially higher in fetal as opposed to maternal blood. Hence, the role of the fetal zone of fetal adrenal (FZFA) in the synthesis of progesterone precursors was addressed. The FZFA may be directly regulated by placental CRH inducing an excessive production of sulfated 3beta-hydroxy-5-ene steroids such as sulfates of dehydroepiandrosterone (DHEAS) and pregnenolone (PregS). Due to their excellent solubility in plasma these conjugates are easily transported in excessive amounts to the placenta for further conversion to the sex hormones. While the significance of C19 3beta-hydroxy-5-ene steroid sulfates originating in FZFA for placental estrogen formation is mostly recognized, the question "Which maternal and/or fetal functions may be served by excessive production of PregS in the FZFA?" - still remains open. Our hypothesis is that, besides the necessity to synthesize de novo all the maternal progesterone from cholesterol, it may be more convenient to utilize the fetal PregS. The activities of sulfatase and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) are substantially higher than the activity of cytochrome P450scc, which is rate-limiting for the placental progesterone synthesis from LDL-cholesterol. However, as in the case of progesterone synthesis from maternal LDL-cholesterol, the relative independence of progesterone levels on FZFA activity may be a consequence of substrate saturation of enzymes converting PregS to progesterone. Some of the literature along with our current data (showing no correlation between fetal and maternal progesterone but significant partial correlations between fetal and maternal 20alpha-dihydroprogesterone (Prog20alpha) and between Prog20alpha and progesterone within the maternal blood) indicate that the localization of individual types of 17beta-hydroxysteroid dehydrogenase is responsible for a higher proportion of estrone and progesterone in the fetus, but also a higher proportion of estradiol and Prog20alpha in maternal blood. Type 2 17beta-hydroxysteroid dehydrogenase (17HSD2), which oxidizes estradiol to estrone and Prog20alpha to progesterone, is highly expressed in placental endothelial cells lining the fetal compartment. Alternatively, syncytium, which is directly in contact with maternal blood, produces high amounts of estradiol and Prog20alpha due to the effects of type 1, 5 and 7 17?-hydroxysteroid dehydrogenases (17HSD1, 17HSD5, and 17HSD7, respectively). The proposed mechanisms may serve the following functions: 1) providing substances which may influence the placental production of progesterone and synthesis of neuroprotective steroids in the fetus; and 2) creating hormonal milieu enabling control of the onset of labor.

[Prevention of the invasion of malignant cells of gynecologic tumors during surgery]. / Prevence invaze maligních bunek pri gynekologických operacích nádoru.

OBJECTIVE: In experiments performed on Vistar rats with Walker tumors, F. Luksch observed transfer of malignant cells during different manipulations into the blood circulation of the animals. During gynecologic surgery of a choriocarcinoma and of an ovarian carcinoma Luksch and Cernoch prooved trace of malignant cells within the blood circulation related to the manipulation of tumors during surgery. Therefore, as prevention of the metastazing of tumor cells, they proposed to ligate ampular portions of oviducts and hypogastric vessels as the first step of the radical surgeries. METHODS: Our observation is based on radical surgeries of 42 patients with cervical uterine carcinomas at the stage II.a (T2, N0, M0). In the first group 13 cases the ligature of oviducts and hypogastric vessels was performed at the start of the surgery. In the second group of 29 patients were operated without ligatures. RESULTS: After five years in the group of 13 ligated patients 10 patients (77%) survived. In the group of 29 unligated patients only 7 (24%) were alive. The results proove substantial differences. CONCLUSION: Although the members are small, there is doubt, that the ligation of oviducts and hypogastric vessels prior radical surgeries in patients affected by malignant gynecologic tumors substantially reduces metastazing of malignant cells nad improve the five years survival of surgically treated patients with gynecologic malignant tumors.

[Classification of twins and their ultrasonographic diagnosis]. / Klasifikace dvojcat a základy jejich ultrazvukové diagnostiky.

OBJECTIVE: Systematic classification of all forms of twins and mechanisms of twinning. DESIGN: Review of published cases. Morphogenesis based on personal experience related to human blastogenesis including observation of anterior twinning in two early human embryos. SETTING: Institute for the Care of Mother and Child, Prague, Department of Gynecology and Obstetrics, 1st Medical Faculty, Charles University, Prague, Department of Medical Genetics, Medical Faculty, Palacký University Olomouc, Institut Unica, Brno. METHODS: Analysis of cases described in literature completed by observed cases. RESULTS: Classification of twins. A) Separated twins: 1. dichorial a) monozygotic (very rare), b) dizygotic (most frequent); 2. monochorial (always monozygotic) a) diamnial, b) monoamnial. B) Conjoined twins (always monozygotic) 1. isopagi (equal conjoined twins) a) originating from peripheral fusions of two germ discs, b) originating from duplications of axial structures; 2. heteropagi (unequal conjoined twins): autosit (main twin), heterosit (parasitic twin). CONCLUSION: The developmental mechanisms of twinning are discussed, special attention is paid to equal conjoined twins and to the possibilities of their early prenatal ultrasonographic diagnostics.

[Immunopathological and histopathological aspects of ectopic implantation with possible effect on fertility disorders]. / Imunopatologické a histopatologické aspekty ektopické nidace s mozným ovlivnením plodnosti.

OBJECTIVE: To evaluate leucocytic infiltration of fetomaternal interface in ectopic pregnancy and to evaluate the changes in cell immunity against trophoblast (AT-CMI) in women with extrauterine pregnancy (GEU) in their medical history. To assess the effect of these factors on possible fertility disorders in a woman. DESIGN: A retrospective study. SETTING: Mother and Child Care Institute, Prague. METHODS: In most of the patients, we addressed GEU through laparoscopy. The tube was extirpated in toto and immediately fixed in Baker's solution. Thereafter, it was prepared in a dissection microscope and then processed in a standard way. In order to identify the intensity of AT-CMI, we used the leucocyte migration inhibition test. The cytotrophoblastic cell line JAR was used as an antigen. The degree of inhibition of the migration was monitored by means of a computer image analyser. Inhibition of migration below 75% was rated as favourable. RESULTS: We monitored the presence of inflammatory infiltrate in the place of implantation and correlated the findings with the hCG levels and the presence of the foetal ovum or its part in the tube. In 28 patients (23.5%) of the total number of 119 patients in the group, we observed an inflammatory infiltrate in the place of implantation. In these patients, the hCG levels were lower and in 17 of them (60.7%) we did not prove the presence of a foetal ovum or its parts. In women with GEU in their medical history, the AT-CMI positivity was established in 61.1% of the women 1 year after surgery, in 56.8% of the women 1-3 years after surgery and in 41.2% of the women 3 years after surgery. CONCLUSION: Ectopic pregnancy involves a pathological fetomaternal interface. The leucocytic infiltrate in the area of implantation may be of secondary character and may cause gradual destruction of the ectopically positioned product of conception. The results of our study indicate a possible participation of the increased AT-CMI in the destruction of the ectopically located trophoblast. Persisting anti-trophoblast immunity may influence the occurrence and course of further gravidities.

[Ventral prolapse of the embryo: case report]. / Ventrální prolaps embrya: kazuistika.

OBJECTIVE: A pathologic human embryo 3 mm long affected by a "ventral prolaps" was present in a product of conception implanted within the Fallopian tube. The gestational age was 7 weeks. The malformation was characterized by a deep protrusion of the embryonal body (containing the medullary tube and the notochord adherent to the ceiling of the yolk sac) through the umbilical ring of the germ disc delineated by ectoderm covered mesenchymal streaks with primordia of the umbilical veins. Similar two affected embryos were depicted by Kollmann in his Handatlas in 1907, but were considered normal. DESIGN: Case report. SETTING: Institute for the Care of Mother and Child, Prague, Institute for Postgraduate Medical Education, Prague. RESULTS: Implanted product of conception found within the Fallopian tube exhibited a characteristic embryonic defect described as the "ventral prolaps". CONCLUSION: Ventral prolaps of the embryo represents a characteristic embryonal malformation of unknown developmental significance.

[Ectopic omental pregnancy--laparoscopic diagnosis and therapy]. / Ektopická omentální gravidita--laparoskopická diagnostika a lécba.

OBJECTIVE: Description of a very rare case of primary omental pregnancy. DESIGN: Case report. SETTING: Institute for the Care of Mother and Child, Prenatal Diagnostic Centre, Prague, Institute for Postgraduate Medical Education, Prague. SUBJECT AND METHOD: Implanted product of spontaneous conception was found in the omentum. The gestational sac on omentum had the appearance of a haemorrhagic tumor 2 cm in diameter. CONCLUSION: After dissection, an intact embryo of 7 mm with a 4 mm yolk sac was discovered.

[Ovarian implantation of the embryo in IVF and ET--early mole with proliferative trophoblast]. / Ovariální implantace embrya po IVF a ET--casná mola s proliferujícím trofoblastem.

OBJECTIVE: Case report of a very rare case of ovarian implantation after IVF and ET treated by laparoscopy. DESIGN: Case report. SETTING: Institute for the Care of Mother and Child, Prenatal Diagnostic Centre and Trophoblastic Disease Centre, Prague, Institute for Postgraduate Medical Education, Prague. RESULTS: We observed implanted product of conception found within the ovarian stroma 35 days after ET. At laparoscopy, the genital sac appeared as an inconspicious haemorrhagic cyst, 2 cm in diameter. After dissection, in the intact sac appeared amorphous 2 mm embryo and 3 mm yolk sac. The trophoblast of the anchoring chorionic villi exhibited marked hyperproliferation and was classified as a proliferating mole. CONCLUSION: The intact early product of conception exhibited trophoblastic hyperplasia.

Massive fetomaternal transplacental hemorrhage as a perinatology problem, role of ABO fetomaternal compatibility--case studies.

BACKGROUND: Massive fetomaternal transplacental hemorrhage is not simply a problem of possible alloimunization in Rh incompatibility but also endangers the fetus (newborn) by massive anemization. Bleeding from placental vessels can occur after small trauma to the gravid uterus with mild or no clinical signs (bleeding or spotting, pain, hypertonus). The rupture of anchoring villi related to early uterine contractions is also possible. In the case of slow blood loss, the fetus reacts by adequate or inadequate compensatory reactions (hydrops fetus). Rapid and massive blood loss is followed by perinatal hypoxic damage and finally death. Our goal was to map out the diagnostic and therapeutic possibilities in regard to specific neonatal care. CASE REPORT: We evaluated four cases of fetomaternal transfusion during a 2-year period with special regard to postpartum adaptation of the newborn and the perinatal outcome. The incidence of adverse outcomes following massive fetomaternal transplacental hemorrhage was 50% (2 of 4). There was one perinatal death and one infant was affected by spastic quadriplegia. CONCLUSIONS: For diagnosis, it is possible to use cardiotocography (decreased variability, sinusoid pattern), ultrasound (biophysical profile) and special hematological tests for quantitative determination of fetal erythrocytes in the maternal blood. For the treatment of such cases one should consider premature termination of pregnancy or intraumbilical transfusion.

[Chorioamnionitis and early-onset neonatal sepsis do not significantly affect levels of interleukin-6 in very low birth weight neonates]. / Chorioamniitis a casná novorozenecká sepse neovlivnují významne hladinu interleukinu-6 u novorozencu velmi nízké porodní hmotnosti.

OBJECTIVE: To determine the influence of maternal chorioamnionitis and neonatal sepsis on interleukin-6 (IL-6) levels in cord blood and in blood obtained from very low birth weight (VLBW) infants within the first two hours of life. DESIGN: Prospective clinical study. SETTING: Institute for the Care of Mother and Child, Prague. METHODS: We measured the serum levels of IL-6 in 30 consecutive VLBW infants born in our institute. IL-6 levels were evaluated in cord blood and in neonatal blood within 2 hours after delivery. Maternal chorioamnionitis and neonatal sepsis within the first 72 hours of life were monitored. RESULTS: Maternal chorioamnionitis was detected in 7 of 30 patients (23.3%). There was no significant increase in IL-6 level in cord blood of newborns with maternal chorioamnionitis (p = 0.42). Serum level of IL-6 in this group did not differ from the level in newborns of mothers without signs of intraamniotic infection (p = 0.39). Neonatal early-onset sepsis was diagnosed in 7 of 30 patients (23.3%). There was no influence of neonatal sepsis on IL-6 level in cord blood (p = 0.98) and IL-6 level in neonatal blood (p = 0.19). We did not find any correlation between the group "chorioamnionitis positive" and "sepsis positive" (p = 0.31). CONCLUSION: IL-6 in cord blood or in neonatal blood within 2 hours of life was not enough sensitive and specific marker of maternal chorioamnionitis as well as for early-onset neonatal sepsis in the group of very low birth weight infants.

Periovarian peritoneal adhesions in women with endometriosis. Structural patterns.

OBJECTIVE: To draw attention to the structural features of adhesions associated with pelvic endometriosis since they are less well studied than endometriosis proper. STUDY DESIGN: Sixty-two samples of periovarian adhesions were laparoscopically obtained from 24 infertile women 26-38 years of age and were prepared for detailed histologic analyses. RESULTS: Macroscopically, the adhesions were either velamentous or cordlike and grossly were free of endometriosis. Most adhesions were attached to the connective tissue of the ovarian tunica albuginea; in two cases they were attached to the corpus luteum. Upon microscopic analysis, velamentous adhesions consisted of fibrous sheets of collagen connective tissue, with the surface lined with single-layered coelomic epithelium. The cord-like adhesions consisted of "hyalinized" fibrous tissue and were either avascular or vascularized. Irregular cystic or tubular structures that could be regarded as endometriosis were found in four patients. Hyaline cartilage within the tissue of the adhesion was an unexpected finding in one patient. CONCLUSION: Microscopic analysis permitted grouping of the adhesions in the following way: (1) Connective tissue adhesions (23 patients) with the following subcategories: (A) fibrous, either avascular or encompassing degenerating blood vessels (6 patients); (B) vascularized, containing granulomatous tissue (12 patients); (C) vascularized with stromoglandular endometrioid cysts or tubules (4 patients); (D) rare types, such as that encompassing hyaline cartilage (1 patient). (2) Fibrin adhesions (1 patient). From the clinical point of view, the presence of endometrial tissue within adhesions raises the question of whether there is a need for removal, rather than just lysis, of adhesions to avoid persistent pain.

[Early intra-amniotic bleeding and its results: dangers of chorionic villi sampling and early amniocentesis]. / Casné intraamniální krvácení (EIAB) a jeho následky: nebezpeccí odberu choriových klku a casné amniocentézy.

Four human fetuses are described exhibiting malformations related to EIAB. Two of these fetuses were aborted as a result of early prenatal diagnostic procedures: one after transcervical CVS, one after early amniocentesis. In three of these fetuses intraamniotic bleeding originating from the umbilical vein near the umbilical insertion produced cords of clotted blood and blood clots adhering to the surface of the fetus. Subsequently, the clots were organized by invading mesenchymal fibroblasts from fetal skin. The cords bent around extremities produced amputations (TLD) and constricted the umbilical vessels, if bent around the umbilical cord. The organizing surface blood clots located predominantly in the folds of the embryo, or fetus, influenced the growth of underlying tissues, producing oblique facial clefts, microphthalmia or micrognathia. EIAB represents a serious complication of invasive procedures related to prenatal diagnosis and must be regarded as the cause of malformations, such as TLD, or ADAM sequence. To avoid EIAB, CVS and amniocentesis should not be done before the end of the 11th gestational week.