Cut-off value of initial serum ß-hCG level predicting a successful MTX therapy in tubal ectopic pregnancy: a retrospective cohort study.

OBJECTIVE: To determine the optimal serum ß-hCG cut-off level to predict MTX treatment success in tubal ectopic pregnancy (EP). STUDY DESIGN: Data of 240 women, who presented between 2003 and 2011 at the Department of Gynecology and Obstetrics, Medical University of Vienna, with tubal EP and who received MTX as primary treatment, were retrieved from the hospital information system (KIS). 198 patients could be included for final evaluation. Statistical analysis included area under the ROC curve, maximal Euclidean and Youden index, chi-squared and a five-fold cross validation. RESULTS: The serum ß-hCG level cut-off value was calculated at 2121mlU/ml with a specificity of 76.54% and sensitivity of 80.56% (AUC 0.789; p<0.001). Patients with an initial serum ß-hCG level below 2121mlU/ml (n=131) experienced MTX treatment failure in 5.3% (n=7), compared to 43.3% (n=29) of patients with an initial serum ß-hCG level equal to or above 2121mlU/ml (n=67). There was no statistically significant correlation between clinical symptoms and the MTX therapy outcome (p=0.580; likelihood quotient p=0.716). CONCLUSION: The correct decision of therapy in patients with tubal ectopic pregnancy still represents a challenge. In this study we can conclude that, according to our results there is no endpoint of initial serum ß-hCG levels, which can be clearly used as cut-off value for the optimal management of tubal EP. However, an initial serum ß-hCG level of less than 2121mlU/ml seems to be a good value to expect a successful MTX treatment. Limitations are the retrospective study design and the inability of classifying clinical symptoms like pain as an objective parameter. Wider implications of the findings may include more detailed patient information and more accurate selection of suitable patients for MTX therapy.

Genetic disorders in premature ovarian failure.

This review presents the genetic disorders associated with premature ovarian failure (POF), obtained by Medline, the Cochrane Library and hand searches of pertinent references of English literature on POF and genetic determinants cited between the year 1966 and February 2002. X monosomy or X deletions and translocations are known to be responsible for POF. Turner's syndrome, as a phenotype associated with complete or partial monosomy X, is linked to ovarian failure. Among heterozygous carriers of the fragile X mutation, POF was noted as an unexpected phenotype in the early 1990s. Autosomal disorders such as mutations of the phosphomannomutase 2 (PMM2) gene, the galactose-1-phosphate uridyltransferase (GALT) gene, the FSH receptor (FSHR) gene, chromosome 3q containing the Blepharophimosis gene and the autoimmune regulator (AIRE) gene, responsible for polyendocrinopathy-candidiasis-ectodermal dystrophy, have been identified in patients with POF. In conclusion, the relationship between genetic disorders and POF is clearly demonstrated in this review. Therefore, in the case of families affected by POF a thorough screening, including cytogenetic analysis, should be performed.

Umbilical venous leptin concentration and gender in newborns.

OBJECTIVE: To investigate the relationship between umbilical venous leptin concentration and gender in 20 pairs of newborns matched 1:1 for birth weight and gestational age at sampling. MATERIALS: Blood samples were obtained from 40 women at delivery, identified as having an uncomplicated pregnancy. Umbilical venous blood samples were obtained from their newborns (20 males and 20 females) at birth. Specimens were analyzed using a human leptin 125-I radioimmunoassay. RESULTS: Fetal leptin correlated positively with birth weight (rs = 0.541; P < .001). Umbilical venous leptin concentrations in female newborns (median: 10.7 ng/mL, range: 3.5-34.4 ng/mL) were significantly higher (P = .028) than in male newborns (median: 7.7 ng/mL, range: 2.0-19.3 ng/mL). There was no significant correlation between maternal and fetal leptin concentrations. Multiple logistic regression analysis revealed birth weight and gender to be independent factors influencing fetal cord leptin. CONCLUSION: Our results suggest that in the fetus, as in children and adults, gender and weight are the major determinants of circulating leptin levels.

Decreased maternal serum leptin in pregnancies complicated by preeclampsia.

OBJECTIVE: To determine whether circulating levels of leptin differed between women with preeclampsia and women who had an uncomplicated pregnancy. METHODS: Maternal and umbilical venous plasma leptin concentrations obtained at delivery were compared in 36 pairs of women with either preeclampsia or normal pregnancy, matched 1:1 for prepregnancy body mass index and fetal gestational age at delivery. RESULTS: Prepregnancy body mass index was 21.1 +/- 2.1 kg/m2 in either study group (range 17.6-25.3 kg/m2 and 17.7-25.3 kg/m2 in the normal and preeclamptic group, respectively). Mean fetal gestational age at delivery was 40.1 +/- 1.3 weeks and 40.1 +/- 1.2 weeks in the normal and preeclamptic group, respectively. Median leptin concentrations were significantly lower (P <.0001) in women with preeclampsia (8.3 ng/mL, range 3.5-20.0 ng/mL) than in normal pregnant women (20.2 ng/mL, range 6.0-63.7 ng/mL). Median umbilical venous leptin was not significantly different between groups (preeclampsia 11.8 ng/mL, range 2.0-37.2 ng/mL; normal 7.6 ng/mL, range 1.6-24.3 ng/mL; P = .377). Umbilical venous leptin levels correlated positively with birth weight in both groups (preeclampsia rho = 0.501, P = .002; normal rho = 0.517, P = .001), whereas no correlations were found between maternal and fetal hormone concentrations. Maternal leptin concentrations did not correlate with birth weight. CONCLUSION: Our data suggest that the correlation between umbilical venous leptin concentration and birth weight is independent of the presence of preeclampsia. Given the inconsistency in literature concerning circulating leptin levels in preeclampsia, further studies should investigate the regulatory systems of leptin in preeclampsia.

Maternal serum leptin concentrations do not correlate with cord blood leptin concentrations in normal pregnancy.

OBJECTIVE: To determine whether there is a difference in maternal leptin concentration and cord blood concentration, consistent with the hypothesis of a noncommunicating, two-compartement model of fetoplacental leptin regulation. METHODS: Blood samples were collected from 139 women, identified as having an uncomplicated pregnancy, from an antecubital vein at delivery. Cord blood samples were taken from the umbilical vein. Leptin was measured by radioimmunoassay, and its relationship to fetal and maternal anthropometrics was assessed by Spearman correlation. Differences in maternal and cord blood leptin levels between male and female infants were tested with the Mann-Whitney Utest. Maternal and cord blood leptin were compared by the Wilcoxon signed rank test. The outcome measures were maternal and cord blood leptin at delivery, fetal birth weight, length, weight/length ratio, and ponderal index, maternal prepregnancy body mass index, pregnancy weight gain, relative weight gain, and body mass index at delivery. RESULTS: No correlations were found between maternal and cord blood leptin concentrations. Fetal leptin level correlated with birth weight (rho = 0.665; P <.0001), length (rho = 0.490; P <.0001), ponderal index (rho = 0.260; P =.002), and weight/length ratio (rho = 0.625; P <.0001). Median leptin concentrations were higher in female (9.3 ng/mL, range 1.5-34.4 ng/mL) than in male (8.2 ng/mL, range 1.6-38.3 ng/mL) neonates, but this difference was statistically not significant. Logistic regression analysis showed a significant influence on umbilical venous leptin concentration for birth weight (P <.0001) but not for gender. Maternal leptin concentrations were significantly higher than cord leptin concentrations (P <.0005 for the male and female neonates and the entire group). CONCLUSION: There was no correlation between maternal and cord leptin, which supports the hypothesis of a noncommunicating, two-compartment model of fetoplacental leptin regulation.

Impact of maternal anthropometry and smoking on neonatal birth weight.

The purpose of this study was to determine the effect of maternal pre-pregnancy body mass index (BMI) and maternal smoking habits on neonatal birth weight. We reviewed 10,240 normal singleton term pregnancies between 1985 and 1995 at the University Department of Obstetrics and Gynecology, Vienna. Birth weights of infants of overweight smokers were greater than those of smokers in general and similar to birth weights of nonsmokers, but smoking did have a fetal growth-retarding effect in overweight smoking mothers. Infants of underweight mothers who increased their daily cigarette consumption during pregnancy had significantly lowest birth weight. Our results suggest that the negative effects of smoking during pregnancy cannot be mitigated by a higher pre-pregnancy BMI and/or an improved weight gain during pregnancy. Especially the infants of underweight mothers benefit from their mothers' decision to cease smoking.

Premature ovarian failure: etiology and prospects.

A search of past and current articles on ovarian physiology and premature ovarian failure (POF) using MEDLINE was performed in order to present an overview of clinical manifestations, necessary laboratory investigations, possible etiologies and treatments for POF. POF is defined as gonadal failure before the age of 40 years. Initially, POF was thought to be permanent, but it is now believed that spontaneous remissions and even pregnancies are possible in affected women. In most cases, the etiology of POF remains elusive, but several rare specific causes have been identified. Although the etiology of POF is heterogenic, the treatment principles are the same. Hormone replacement therapy (HRT) is still the cornerstone of treatment. The only proven method of obtaining a pregnancy in patients with POF is fertilization of a donor oocyte. Cryopreservation of oocytes has worked well in animals but awaits refinement before it can be applied routinely to humans with prodromal POF, or to patients before chemotherapy or irradiation in order to save their oocytes for future fertilization. New alternatives to traditional HRT and methods of fertility preservation are under development, but understanding of the basic pathophysiology of POF is necessary for the development and use of innovative treatments.

Serum leptin concentration in cord blood: relationship to birth weight and gender in pregnancies complicated by pre-eclampsia.

The aim of the study was to investigate cord blood leptin concentrations and their relationship to birth weight and gender in term pregnancies complicated by pre-eclampsia. Cord blood samples were obtained from 52 women, identified as having pre-eclampsia, and their newborns (31 males and 21 females) immediately after birth. Specimens were analyzed using a human leptin 125I radioimmunoassay. The relationship between leptin and anthropometrics was assessed by Spearman correlation. Differences in cord blood leptin levels between male and female infants were tested with the Mann-Whitney U test. The correlation between leptin and gender was computed using the product-moment-biseral correlation analysis for continuous and dichotomous variables. The multiple logistic regression analysis examined influences of sex, birth length, birth weight, birth weight/birth length ratio, ponderal index and maternal leptin as covariates on the fetal cord leptin level. Fetal leptin correlated positively with birth weight, length and weight/length ratio, in the total group and in the male subgroup and additionally with ponderal index in the female subgroup. Cord blood leptin concentrations in female newborns were significantly higher than in male newborns (p = 0.015), and concentrations correlated with gender (r = -0.315; p = 0.023). Multiple logistic regression analysis revealed four potential independent factors influencing fetal cord leptin: gender, birth weight, birth weight/birth length ratio and maternal leptin. In conclusion, cord leptin concentrations in pregnancies complicated by pre-eclampsia correlate positively with birth weight and gender. Leptin concentrations in female newborns are higher compared to male newborns.

Unexpected pregnancy during hormone-replacement therapy in a woman with elevated follicle-stimulating hormone levels and amenorrhea.

Pregnancy in patients with hypergonadotropic amenorrhea, although previously reported, remains quite rare. Women may conceive spontaneously or following different regimens of ovulation induction, thus indicating that ovarian failure is not always permanent. The case of an 18-year-old woman with premature ovarian failure, who conceived during hormone-replacement therapy, is reported. During hormone-replacement therapy, elevated gonadotropin levels returned to the physiologically normal range. It is suggested that this restored the receptors to luteinizing hormone and to follicle-stimulating hormone, which might have been downregulated. This hypothesis is supported by previous results from clinical trials and experimental work on a rat model.

Recombinant luteinizing hormone in ovarian hyperstimulation after stimulation failure in normogonadotropic women.

The aim of this study was to examine the effect of an additional administration of recombinant luteinizing hormone (r-LH) to a gonadotropin-releasing hormone agonist (GnRHa) long protocol using recombinant follicle-stimulating hormone (r-FSH). In particular we determined whether such a stimulation protocol would be more effective in women (1) who respond poorly to stimulation with GnRHa long protocol using r-FSH only, and (2) whose LH concentrations after down-regulation in the cancelled cycle were low but above the values reported in the literature to be sufficient for folliculogenesis. After GnRHa desensitization 150 IU r-FSH and 75 IU r-LH were administered subcutaneously daily to six normogonadotropic women with low response to ovarian hyperstimulation using a GnRHa long protocol with r-FSH and low LH concentrations after down-regulation in the cancelled cycle. All six women had an oocyte retrieval and an embryo transfer after follicular stimulation. One women conceived but had a miscarriage in the eleventh week of gestation. Our results suggest that women with low response to a GnRHa long protocol with r-FSH, and whose LH concentration after down-regulation in the cancelled cycles were low, benefit from the additional administration of r-LH in a GnRHa long protocol using r-FSH. It seems that due to the additional administration of r-LH the LH concentration in the follicular phase is sufficient to support folliculogenesis.

Hormonal breast augmentation: prognostic relevance of insulin-like growth factor-I.

Many women would like to after their breasts but are deterred by the risks involved. Silicone breast implants have been linked to a variety of illnesses, the most controversial of which are connective-tissue diseases. These circumstances urged us to perform this pilot study using a non-invasive method that involved the application of 17 beta-estradiol as it is known that estradiol enhances expression of insulin-like growth factor-I (IGF-I) which can promote growth in breast tissue. Forty-five women were included in the study. Their breast volume, IGF-I, prolactin (PRL) and estradiol levels were measured before treatment and between each application of 80 mg estradiol polyphosphate. The women's satisfaction with the results obtained was also subsequently evaluated. In 21 women (46.7%), breast size increased from 824.3 +/- 13.7 mm to 898.5 +/- 12.5 mm after 6 months. In these women a significant increase in IGF-I values was noted after 4 weeks of treatment. The increase in IGF-I values was not statistically significant in the remaining women. In addition, treatment was not successful in these women. IGF-I concentration seems to be of prognostic value as far as the response of breast tissue to estrogen stimulation is concerned. If IGF-I levels do not increase within 1 month, treatment should be discontinued. If IGF-I values do increase, this indicates that treatment is likely to be successful and can therefore be continued.

Effects of estradiol valerate on growth hormone and prolactin response to growth hormone-releasing hormone stimulation in pre- and postmenopausal women.

We investigated the relationship between the growth hormone and prolactin response to stimulation of growth hormone-releasing hormone (GHRH) and changes in body weight in pre- and postmenopausal women before and after 4 and 20 weeks of oral hormone replacement therapy (HRT). Ten postmenopausal women (with levels of follicle-stimulating hormone (FSH) of > 30 mIU/ml) were compared to ten premenopausal women suffering from post-pill amenorrhea (FSH < 10 mIU/ml). Both patient groups reported anamnestic body weight increases in the course of the former use of sex hormones. Additionally, ten postmenopausal women without anamnestic weight changes were studied. A significant reduction in the growth hormone response to GHRH was observed during the first month of HRT in women gaining weight, which was restored to pre-therapeutic levels after 6 months of HRT. A small but statistically significant increase in insulin-like growth factor (IGF)-I levels occurred in the course of HRT in all patients studied. These changes in growth hormone stimulation testing and IGF-I levels were accompanied by distinct changes in body weight. No reduction in the GHRH response was observed in those patients who did not gain body weight. Although GHRH stimulation induces a significant rise of prolactin concentrations in all patients before therapy no influence on prolactin levels could be demonstrated during HRT.

Androgen serum levels in women with premature ovarian failure compared to fertile and menopausal controls.

OBJECTIVE: The purpose of our study was to examine androgen serum levels and bone density in women with premature ovarian failure (POF) compared to healthy normal controls. STUDY DESIGN: Thirty-three women 19-35 years of age with idiopathic POF were compared to 33 well-matched women with normal ovarian function and 32 healthy postmenopausal (PMP) women concerning 17-hydroxyprogesterone (17-OHP), androstendione (A), testosterone (T), dehydroepiandrosterone-sulfate (DHEAS), insulin-like growth factor 1 (IGF-1), as well as bone density (BD). RESULTS: Women with POF showed statistically significantly lower concentrations of 17-OHP, A, T (p < 0.001) and a reduced bone density (p < 0.001) compared to fertile controls. No differences were found between POF and PMP women concerning estradiol (E2), T, A and 17-OHP. Regarding DHEAS, no statistically significant differences were found between women with POF and fertile controls whereas PMP women proved to have significantly lower DHEAS concentrations than fertile controls. Women with POF had the highest IGF-1 serum concentrations and PMP women the lowest. CONCLUSION: An important decrement of ovarian steroids and bone density was noticed in women with POF, while the time since menopause had no influence on androgen concentrations. The hormone concentrations in women with POF are similar to those observed in normal PMP women with the exception of DHEAS and IGF-1 levels.

[6-sulfatoxymelatonin in women with secondary amenorrhea]. / 6-Sulfatoxymelatonin bei Frauen mit sekundärer Amenorrhoe.

We evaluated the overnight urinary excretion of 6-sulfatoxymelatonin in a group of 347 women (range: 18-69 years). 26 women (range 20-29 years) with normogonadotrophic, hypoestrogenemic amenorrhoea (WHO II) were selected and compared with a group of 26 women menstruating normally (range: 19-30 years) with respect to urinary 6-sulfatoxymelatonin excretion, serum 17 beta-estradiol levels and response to the thyroid releasing hormone (TRH) test. Patients with hyperprolactinemia, hyperandrogenemia, thyroid dysfunction and weight problems were excluded. 6-sulfatoxymelatonin was found to be significantly higher in the amenorrhoeic women than in the controls (p < 0.000001). In the amenorrhoeic patients a statistically significant inverse correlation was found between serum 17 beta-estradiol levels and urinary 6-sulfatoxymelatonin excretion. A positive correlation was obtained between the thyroid stimulation hormone (TSH) value measured at 20 minutes after stimulation and 6-sulfatoxymelatonin excretion. Further clinical research in this field is required to evaluate its clinical impact, especially in patients with secondary amenorrhea.

Effects of hormone replacement therapy on growth hormone secretion patterns in correlation to somatometric parameters in healthy postmenopausal women.

OBJECTIVES: The aim of the present study was to investigate the influence of a continuous estrogen, cyclic progesterone replacement therapy on the secretion of growth hormone (GH) and IGF I as well as of somatometric-GH correlation patterns. METHODS: The study included 23 healthy postmenopausal women. Of the proband group 13 randomly selected women were treated with orally applicated 2 mg estradiol-valerat (E2V) and 10 mg dydrogesterone for 10 months. Ten women did not receive any hormonal treatment during this time. After 10 months all probands were reexamined and their GH and IGF I secretion, as well as their somatometric-hormonal correlation patterns, compared with those of a fertile control group. RESULTS: It could be shown, that in postmenopausal women a 10-month oral hormone replacement therapy led to a significant increase of GH- and IGF I levels, however, the treated postmenopausal women did not reach the levels of the fertile controls. Those women who did not receive any hormonal treatment and the postmenopausal women before HRT showed nearly identical GH- and IGF I levels as well as somatometric-GH correlation patterns. CONCLUSIONS: The results of the present paper indicate a marked influence of estrogens on GH and IGF I secretion. Furthermore, hormonal replacement therapy (HRT) may influence somatometric GH correlation patterns too.