Sex Hormone Metabolism and Threatened Abortion.

BACKGROUND The aim of this study was to evaluate changes in sex hormone metabolism in patients with threatened miscarriage. MATERIAL AND METHODS We recruited 73 women in early pregnancy (6-8 weeks of gestation) and divided them into the following 2 groups based on whether they had vaginal bleeding: group A (n=34), the threatened abortion group; and group B (n=39), the normal pregnancy group. Human chorionic gonadotrophin (hCG), estradiol (E2), progesterone (P4), and testosterone (T) serum levels were tested and sex hormone metabolites in the urine were detected using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). As the control, data for sex hormones and their metabolites were obtained in normal women of childbearing age without pregnancy (group C: n=23). RESULTS E2 and T serum levels were lower in women with threatened miscarriage (group A). Estrone (E1), E2, estriol (E3), 16α-hydroxyestrone (16α-OHE1), 4-methoxyestrone (4-MeOE1), 2-hydroxyestradiol (2-OHE2), and 4-methoxyestradiol (4-MeOE2) levels were significantly lower in group A (P=0.001, 0.003, 0.009, 0.001, 0.012, 0.032, and 0.047, respectively.). Urine levels of dehydroepiandrosterone (DHEA), androstenedione (A2), and the metabolite of (A2) were also significantly lower in group A (P=0.007, 0.009, and 0.011, respectively). The 2-OHE1/E1, 4-OHE1/E1, 2-MeOE1/E1, and 2-MeOE2/E2 ratios were lower in group B, whereas the 2-OHE2/E2, 4-OHE2/E2, and 4-MeOE2/E2 ratios were dramatically lower in all pregnant women (groups A and B) than in group C. CONCLUSIONS Deficiency in DHEA and abnormal levels of sex hormone metabolites may cause a reduction in the activity of estrogens in women with threatened abortion. These alterations may result in bleeding during the first trimester of pregnancy.

Alterted SLIT2/ROBO1 signalling is linked to impaired placentation of missed and threatened miscarriage in early pregnancy.

AIMS: Two-thirds of early pregnancy failures present with reduced trophoblast invasion, and SLIT2/ROBO1 signalling is considered to play an important role in trophoblast function during pregnancy. We investigated SLIT2/ROBO1 signalling associated with missed and threatened miscarriage during early gestation. METHODS AND RESULTS: Human placenta samples were collected from women with missed miscarriage (n = 25), threatened miscarriage (n = 22) and termination of pregnancy controls (n = 32). Corresponding decreases in beta human chorionic gonadotrophin (ß-hCG) levels and shallow trophoblast invasion were observed in patients with missed and threatened miscarriage, immunohistological staining revealed abnormal Slit2 and Robo1, as well as E-cadherin and activating protein-2 alpha (AP-2α) expression in villi and extravillous trophoblasts, and the expression of these proteins were confirmed in villi and decidua of miscarriage material by Western blotting. Using HTR8/SVneo cells, blocking SLIT2/ROBO1 signalling promoted cell migration, proliferation and suppressed differentiation. Moreover, blocking SLIT2/ROBO1 signalling in HTR8/SVneo cells altered trophoblast differentiation-related and angiogenesis-related gene mRNA expression, which also occurred in the tissues of missed and threatened miscarriage. CONCLUSIONS: SLIT2/ROBO1 signalling may regulate trophoblast differentiation and invasion causing restricting ß-hCG production, shallow trophoblast invasion and inhibiting placental angiogenesis in missed and threatened miscarriage during the first trimester.

Efecto abortive de los anticonceptivos hormonales: una revisión / Abortifacient effect of hormonal contraceptives: a Review

En gran parte de la comunidad científica, así como del ámbito jurídico, al tratar del embrión no nacido, está vigente el criterio según el cual hay que definir el embarazo como el período que comprende sólo desde la implantación hasta el nacimiento natural. Esto lleva consigo otras novedades; por ejemplo, la redefinición de aborto como la eliminación del embrión sólo en ese período, o la extensión de la anticoncepción a cualquier medio que impida la unión entre los gametos como consecuencia de una relación íntima, o también que elimine el producto de la concepción antes de su implantación. De modo que la industria farmacéutica está lanzando al mercado, bajo el nombre de anticonceptivos, productos que actúan también mediante un mecanismo antiimplantatorio. Este hecho tiene grandes repercusiones éticas con relación al respeto del embrión, que obligan a reflexionar acerca de la valoración moral de la prescripción, dispensación y uso de estos medios. Ahora bien, ¿cuáles de los medios contraceptivos actualmente presentes en el mercado incluyen un efecto antiimplantatorio?, ¿qué mecanismos contribuyen a su acción farmacológica y en qué medida lo hacen? Esto es lo que hemos estudiado en este artículo, basándonos en la bibliografía científica disponible. Aunque no ha sido una tarea sencilla, puesto que los resultados aportados por la literatura varían mucho, se ha tratado de ofrecer una conclusión bastante precisa. Básicamente hemos cumplido un doble objetivo: actualizar y completar los estudios -pocos, parciales o lejanos en el tiempo- que tenían este mismo objeto; y ofrecer una valoración ética respecto al respeto de la vida naciente del uso de los anticonceptivos hormonales que pueden tener efecto antiimplantatorio

Most of the scientific community, as well as in a sector of international Law, when referring to the unborn embryo, pregnancy must be defined as the period extending from implantation to natural birth. This implies some novelty, such as the redefinition of abortion as the elimination of the embryo only within this period, and the extension of contraception to any means that impedes the union of the gametes as a consequence of a sexual intercourse, or also that which eliminates the product of conception prior to its implantation. Therefore, the pharmaceutical industry markets, under the name of contraceptives, products that act also by means of an anti-implantation mechanism. This fact has great ethical implications regarding the respect for the embryo which require a reflection on the moral valuation of the prescription, dispensation and use of these means. One may ask: which of the contraceptive means actually present in the market include an anti-implantation effect? What mechanisms contribute to their pharmacological action and in what measure do they do this? This is what we have studied in this article, based on the available scientific bibliography. We have basically fulfilled a double objective: updating and completing the studies -few, partial or distant in time- that had this same subject matter; and offering a moral valuation on the use of hormonal contraceptives that may have an anti-implantation effect, from the point of view of the respect due to the embryonic life

Role of progesterone and progestin therapy in threatened abortion and preterm labour.

Progesterone (P) has been widely used in an attempt to prevent threatened miscarriage, recurrent miscarriage and pre-term labour. Successful pregnancy depends on maternal tolerance of the fetal "semi-allograft". Along with its endocrine effects, P also acts as an "immunosteroid", by controlling the bias towards a pregnancy protective immune milieu. A protein called progesterone-induced blocking factor (PIBF), by inducing a Th2 dominant cytokine production mediates the immunological effects of progesterone. Progesterone plays a role in uterine homing of NK cells and up-regulates HLA-G gene expression, the ligand for various NK inhibitory receptors. At high concentrations, progesterone is a potent inducer of Th2-type cytokines as well as of LIF and M-CSF production by T cells. The possible mechanisms by which progesterone contributes to the maintenance of early and late pregnancy are discussed.

Production of vascular endothelial growth factor and endothelin in the placenta and umbilical cord during normal and complicated pregnancy.

The concentrations of vascular endothelial growth factor and endothelin in the placenta progressively increased during normal pregnancy. Production of vascular endothelial growth factor and endothelin in the placenta exceeded the normal during trimester I miscarriage and trimester III premature birth accompanied by intrauterine hypoxia. The concentration of these vasoactive substances during premature birth also increased in the umbilical cord. The compensatory decrease in the concentrations of vascular endothelial growth factor and endothelin in the placenta and umbilical cord was observed during full-term pregnancy with threatened abortion.

[Expression of leukemia inhibitory factor in chorionic villi of normal early pregnancy, threatened abortion and inevitable abortion].

OBJECTIVE: To examine the expression of leukemia inhibitory factor (LIF) in chorionic villi of normal early pregnancy, threatened abortion and inevitable abortion, and to assess the effects of LIF on threatened abortion and inevitable abortion. METHODS: Expression of LIF in chorionic villi was examined using Western blot. Serum progesterone and human chorionic gonadotropin (hCG) levels were determined using radioimmunoassay. A streptavidin peroxidase conjugated semi-quantitative immunohistochemical assay was used to exam LIF protein expression. RESULTS: The levels of progesterone and hCG in the normal early pregnancy and threatened abortion groups were (95 +/- 26) nmol/L and (75 +/- 14) kU/L, and (90 +/- 26) nmol/L and (68 +/- 13) kU/L, respectively. The differences were not significant (P > 0.05). The levels of progesterone and hCG in the inevitable group were significantly decreased to (36 +/- 17) nmol/L and (13 +/- 3) kU/L, respectively. The differences when compared to the other groups were statistically significant (P < 0.01). LIF protein expression was observed in all cases and located mainly in the cytoplasm of trophoblast cells. The expression of LIF in inevitable abortion group 0.30 +/- 0.02 was lower than that in other groups (P < 0.01). However, there was no significant difference in the expression of LIF between the normal early pregnancy group and threatened abortion group (P > 0.05). CONCLUSION: LIF may play a role in the maintenance of normal pregnancy. Reduction of LIF expression in chorionic villi may induce the decrease of serum progesterone and hCG levels and, ultimately, cause inevitable abortion.

[Expression of leukemia inhibitory factor in the decidua of normal early pregnancy, threatened abortion and inevitable abortion].

OBJECTIVE: To investigate the expression of leukemia inhibitory factor (LIF) in the decidua of normal early pregnancy, threatened abortion and inevitable abortion. METHOD: We examined LIF gene expression in the above-mentioned decidua by a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method, and also examined the serum pregesterone, human chorionic gonadotrapin (hCG) by radioimmunoassay in all cases. RESULTS: (1) Serum levels of pregesterone and hCG are: (91.5 +/- 27.2) nmol/L, (69.9 +/- 14.9) kU/L in normal early pregnancy; (88.4 +/- 24.7) nmol/L, (57.6 +/- 11.2) kU/L in threatened abortion respectively. There was no difference in the levels of pregesterone and hCG between the two groups (P > 0.05). While serum pregesterone, hCG levels in inevitable group were (33.1 +/- 19.6) nmol/L, (10.3 +/- 3.2) kU/L respectively. Compared with normal early pregnancy and threatened abortion group, the levels of serum pregesterone and hCG reduced significantly (P < 0.05). (2) The expression of LIF in three groups: There was no statistically significant difference in the levels of LIF expression between the normal early pregnancy group (2.10 +/- 0.32) and threatened abortion (1.92 +/- 0.20) groups, while the levels of LIF expression in inevitable abortion group (0.7 +/- 0.06) was lower than those in normal early pregnancy group and threatened abortion group (P < 0.05, respectively). CONCLUSION: The reduction of LIFmRNA expression in the decidua of early pregnancy may decrease the serum pregesterone and hCG levels and cause inevitable abortion.

[Calcium-phosphorus-magnesium homeostasis in women with threatened abortion]. / Homeostaza wapniowo-fosforanowo-magnezowa u kobiet z poronieniem zagrazajacym.

One hundred twenty eight women were submitted to research including: 38 healthy not pregnant women, 40 healthy women in the first trimester of uncomplicated pregnancy (6-15 weeks) and 50 pregnant women with symptoms of threatened abortion (6-15 weeks). The following parameters were measured in serum: total Ca, Ca++, ionised inorganic phosphorus (Pi), magnesium (Mg), total protein and albumin and also total alkaline phosphatase activity (APt). Micromethods generally accepted in clinical laboratories were used. The study showed symptoms of threatened abortion are related to decreased concentrations of Pi, Mg, total protein and albumin and reduced activity of APt. Women who did not underwent miscarriage showed significantly higher Pi concentration compared to those who lost pregnancy, what might be of prognostic value. Threatened abortion was not considered to alter calcium homeostasis.

[Tocolytic substituent treatment with Magnerot in threatened abortions and premature labor from the 16th to the 36th gestational week]. / Tokolitichno zamestitelno lechenie s Magnerot pri zaplashvashti aborti i prezhdevremenni razhdaniia ot 16-ta do 36-ta gestatsionna sedmitsa.

The Mg's low level in the sera and the urine correlate with clinical symptoms of uterine contraction in pregnant women from the 16th-36th gestation week. The authors present their experience with the use of removal tocolytic curing with Magnerot tabl. in the cases of 60 pregnant women with uterine pain and contractions from 16th to 36th gestation week and Pelvic Score after Bishop under 4. The effect of the curing is remarkable till from the beginning in the first 4-7 days of it, which is demonstrated with disappearing of the objective and subjective contractions (overviewed in obstetric monitor) and there is normalising of the paraclinical levels of the Mg in the sera and the urine, with normal pregnancy and birth of a healthy and alive child.

Complications of pregnancy in relation to maternal lipid peroxides, glutathione, and exposure to metals.

Lipid peroxides, glutathione, and metals (lead, cadmium, and arsenic) were measured in pregnant women residing in the vicinity of a copper smelter. A diagnosis of pregnancy complications experienced by each woman was made on the basis of interview and clinical record. Patients were assigned to groups of normal or pathologic pregnancies (threatened spontaneous abortion, toxemia, and anemia) according to this diagnosis. Biochemical changes suggestive of increased lipid peroxidation and decreased antioxidant protection (involving the reduced: oxidized glutathione balance) were found in the diagnostic groups of pregnancy complications. These changes were independent of measured maternal variables. Maternal exposure to metals (as indicated by blood lead and cadmium) was associated with a decrease in reduced glutathione in blood. Since increased lipid peroxidation has been implicated in other studies as a pathogenetic factor for maternal toxemia, it is suggested that exposure to metals during gestation could enhance the development of pregnancy complications by increasing lipid peroxidation via depletion of reduced glutathione reserves.

[Changes in the fetoplacental system in threatened abortion]. / Izmenenie feto-platsentarnoi sistemy pri ugroze nedonashivaniia beremennosti.

Comprehensive assessment of the hormonal status of the fetoplacental system in 110 pregnant women, carried out over the course of treatment for threatened abortion, included radioimmunoassays of blood serum estriol, progesterone, and placental lactogen, cardiotocography of the fetus, ultrasonic fetometry and placentography. Trophic, hormonal, and hypoxic disorders of the fetoplacental system were revealed. The therapy resulted in essential improvement of the trophic and hypoxic conditions, though the hormonal function did not normalize as a rule.

Serum levels of steroid and placental protein hormones in ectopic pregnancy.

UNLABELLED: The hormonal profiles of extra-uterine pregnancies (EP) were compared with the normal intra-uterine pregnancies (IUP), and threatened abortions (TA) of good outcome. In 45 cases of EP confirmed histologically, maternal serum human chorionic gonadotropin (hCG), pregnancy specific beta 1-glycoprotein (SP1), 17 beta-estradiol (E2) and progesterone (P) were measured serially before treatment by enzyme immunoassays (EIA). The same hormones were also determined in the control groups, 26 with normal IUP and 24 with TA. All four hormone levels in EP were significantly lower (P less than 0.01-P less than 0.0001) than in normal pregnancies and threatened abortions of matched gestational age except the hCG and E2 in the fifth week of pregnancy. The mean values of E2 and P were found in the normal levels of luteal phase or slightly over them (8th-9th and 9th-10th weeks, respectively). No increase in the hormonal profiles of the above two steroids was noticed between 5 and 10 weeks' gestation in EP. IN CONCLUSION: (a) The significantly lower values of hCG and SP1 in EP were confirmed; (b) the serial and concurrent hormonal measurements assure the verification of EP and the differentiation from normal IUP and TA of good outcome; (c) the ectopic implantation of trophoblast critically reduces its vitability to hCG and SP1 synthesis and it can only partially compensate for the reduction of corpus luteum function.

Relaxin, CA-125, progesterone, estradiol, Schwangerschaft protein, and human chorionic gonadotropin as predictors of outcome in threatened and nonthreatened pregnancies.

Progesterone (P), estradiol (E2), relaxin, CA-125, Schwangerschaft protein, and human chorionic gonadotropin (hCG) were measured in 221 pregnancies (less than or equal to 77 days gestation). The cohort was divided into asymptomatic subjects (group I, n = 117) and those with threatening symptoms (group II, n = 104). Outcome was ascertained as viable (normal at 14 weeks, n = 131), spontaneous abortion (n = 58), or ectopic gestation (n = 32). Statistical analysis revealed no differences in the mean maternal or gestational ages among the viable pregnancies, abortions, and ectopics in group I and group II. In group I, significant differences in the means were noted for P, hCG, relaxin, and CA-125 among those destined to abort, compared with those who were not. In group II, differences were noted in P, hCG, relaxin, and E2 when viable and nonviable pregnancies were compared. Within group II, there were significant differences between the means of E2 and CA-125 when the aborters were contrasted with ectopics. Receiver operating characteristic curve analysis revealed that P was the single most reliable predictor and was most effective in threatened pregnancies. Stepwise logistic regression of the six markers in group II provided an equation of possible clinical utility in differentiating abortion versus ectopic pregnancy in threatened gestations based on CA-125 and E2 levels.

[The pharmacokinetics of magnesium sulfate in pregnant women with threatened abortion and fetal retardation]. / Untersuchungen zur Pharmakokinetik von Magnesiumsulfat bei Schwangeren mit drohender Frühgeburt und fetaler Retardierung.

A contribution concerning distribution and elimination of magnesium sulphate in pregnant women with preterm labour and fetal retardation is given. From the kinetic parameters calculated a dosage regimen is recommended. To describe the physiologic magnesium level in plasma by a two-compartment model a kind of "continuous infusion" was assumed.

Cytotoxic activity and progesterone binding capacity of maternal lymphocytes are not influenced by gestational age and by the number of previous pregnancies.

Cytotoxic activity and progesterone binding capacity of lymphocytes obtained from 135 pregnant women was tested. Cytotoxic activity of healthy pregnant women's lymphocytes was significantly lower (p less than 0.001), while progesterone binding capacity significantly higher (p less than 0.001), than those of lymphocytes obtained from women with threatened abortion or threatened premature labour. Neither cytotoxic activity nor progesterone binding capacity of the lymphocytes was influenced by gestational age. Furthermore, the number of previous pregnancies did not have any effect on either of the two parameters.