Cecil A. Long

Maternal serum creatine kinase does not predict tubal pregnancy

AbstractPurpose: Our purpose was to validate prospectively the predictive value of maternal serum creatine kinase in the evaluation of ectopic pregnancy.nMethods: Fifty-one consecutive pregnant first-trimester patients who presented for suspected abnormal pregnancy were enrolled. Maternal serum samples were obtained and assayed for creatine kinase. Patients were subsequently evaluated for abnormal pregnancy by serial quantitative hCG levels, transvaginal ultrasonography, and surgery when appropriate. A receiver operating characteristic (ROC) curve was generated comparing intrauterine to extrauterine (ectopic) pregnancy.nResults: Of 51 patients, 18 had an ectopic pregnancy, 16 had a spontaneous abortion, and 17 had an ongoing intrauterine pregnancy. The ROC curve revealed that maternal serum creatine kinase had no ability to predict ectopic pregnancy.nConclusions: Maternal serum creatine kinase is not a reliable predictor of tubal pregnancy.

Serum progesterone predicts abnormal gestations in clomiphene citrate conception cycles as well as in spontaneous conception cycles

OBJECTIVEnTo determine if a discriminatory P concentration could be established that predicted abnormal early pregnancies in clomiphene citrate (CC)-conceived cycles.nnnDESIGNnProgesterone concentrations of gestations between 28 and 49 days from last menstrual period in both spontaneously conceived and CC-stimulated cycles were analyzed using a relative-operating characteristic (ROC) curve.nnnINTERVENTIONSnSerum P concentrations were measured in 222 pregnant patients from the first 49 days of gestation. One hundred sixteen patients conceived in a spontaneous cycle and 106 patients conceived in CC-treated cycles. Two by two contingency tables were used to calculate the true-positive (sensitivity) and false-positive rates at 20 specific P at 20 specific P concentrations. A ROC curve was then generated by plotting the sensitivity of the test against the percent of normal patients incorrectly classified (false positive) at each P level. The best discriminatory value was estimated in each curve at a point of high sensitivity associated with a minimal false-positive value. The areas under the curve and SE were calculated for each group and compared by the critical ratio z-test.nnnRESULTSnThe best discriminatory P concentration was 10 ng/mL (32 nmol/L) for spontaneously conceived pregnancies and 30 ng/mL (95 nmol/L) for CC-treated pregnancies. The area under each ROC curve was significantly predictive. Comparison of the two curves indicated that the ability of P measurements to predict gestational complications was independent of follicular stimulation.nnnCONCLUSIONSnFollicular stimulation with CC increases the discriminatory P value that predicts gestational normalcy but does not alter the clinical utility of the test.

Immunosuppression by conditioned media derived from a cloned choriocarcinoma cell line in serum-supplemented and defined media.

PROBLEM: Immunosuppressive factor(s) of trophoblast origin may contribute to the immunological privilege afforded the fetal allograft. Characterization of these immunoregulators in humans has been impeded by a lack of sufficient quantities of early gestational trophoblast for experimentation.

Immunosuppression by Hydatidiform Mole Trophoblast Is Neutralized by Monoclonal Antibodies to β-Interferon

PROBLEM: In sheep and cattle, trophoblast‐derived interferons serve as signals for the maternal recognition of pregnancy and may regulate the immunologic relationship between the fetus and mother.

Progesterone concentration as a predictor of pregnancy normalcy is the most useful when hCG levels are less than 2000 mIU/mL.

ObjectiveMeasurements of serum progesterone to predict early gestational normalcy have been found to be as predictive as serial hCG titers. Since ultrasound would be the diagnostic tool of choice if hCG was >2000 mIU/ml, the purpose of the present study was to determine the best predictive value of a single progesterone measurement when hCG levels were <2000 mIU/ml.DesignRelative operating characteristic analysis of progesterone level as a predictor of early gestational normalcy when hCG is <2000 mIU/ml.Materials and MethodsNinety-three pregnant patients that conceived spontaneously were evaluated with progesterone measurements when the patients hCG was <2000 mIU/ml. Two-by-two contingency tables were constructed that compared pregnancy outcome with multiple discriminatory serum progesterone concentrations between 0 and 38 ng/mL. From these tables, a relative operating characteristic (ROC) curve was generated to compare the sensitivity and false-positive rates.ResultsOf a total of 93 pregnancies, 27 had a normal outcome and 66 had an abnormal outcome. The ROC curve indicated that a serum progesterone concentration of 12 ng/ml had the highest sensitivity associated with the lowest false-positive rate. The area under the curve was equal to 0.941±0.024. This observation was compared to our previously reported data of progesterone levels that included hCG levels >2000 mIU/ml, yielding an area under the curve of 0.772±0.053. Calculation of the critical ratio z revealed that there is a significant improvement in the predictive value of progesterone when hCG is <2000 mIU/ml (P <0.005).ConclusionA single serum progesterone level has a better predictive value of pregnancy normalcy when hCG measurements are <2000 mIU/ml.

Luteal phase consequences of low-dose gonadotropin-releasing hormone agonist therapy in nonluteal-supported in vitro fertilization cycles

OBJECTIVEnTo determine the follicular and luteal phase impact of low-dose GnRH agonist (GnRH-a) treatment during follicular stimulation for IVF.nnnDESIGNnA randomized prospective study compared patients receiving low-dose GnRH-a and hMG therapy to clomiphene citrate (CC) and hMG cycles.nnnSETTINGnPatients were treated through a university-based IVF-ET program.nnnPATIENTSnThirty-six patients underwent follicular stimulation with low-dose GnRH-a and hMG and were compared with 34 patients undergoing ovulation induction with CC and hMG.nnnRESULTSnSignificantly shorter luteal phase length occurred with GnRH-a and hMG therapy; however, there was no statistically significant difference in luteal P levels. Follicular parameters were the same (peak E2, number of follicles, and number of oocytes), suggesting that folliculogenesis was not altered. There were no statistical differences in pregnancy rates.nnnCONCLUSIONSnSustained low-dose GnRH-a therapy during follicular stimulation does not have a clinical effect on luteal function.

First-trimester rapid semiquantitative assay for urine pregnanediol glucuronide predicts gestational outcome with the same diagnostic accuracy as serial human chorionic gonadotropin measurements

OBJECTIVEnThe purpose of this study was to compare a single urine pregnanediol glucuronide measurement with serial human chorionic gonadotropin titers for the prediction of abnormal early gestations.nnnSTUDY DESIGNnWe analyzed multiple urine pregnanediol glucuronide levels in 19 spontaneously conceived pregnancies during the first 49 days of gestation. A semiquantitative measurement was made by rapid enzyme immunoassay (Phase Check) at different urinary dilutions. To establish the reliability of semiquantitative urine pregnanediol glucuronide assay to detect abnormal gestation, this test was compared with human chorionic gonadotropin doubling times derived from a previously described normal population. A receiver-operator characteristic curve was constructed for each test, and areas under the curve with corresponding SEs were calculated. The critical-ratio z test was used to compare the two assays.nnnRESULTSnThe receiver-operator characteristic curves indicate that both urine pregnanediol glucuronide and human chorionic gonadotropin doubling can predict early gestational complications (p < 0.05). The area under the curve for human chorionic gonadotropin doubling time was 0.809 +/- 0.048, and urine pregnanediol glucuronide had an area of 0.702 +/- 0.072. Comparison of the area under the curve revealed that the ability of urine pregnanediol glucuronide to predict early gestational failure was indistinguishable from that of human chorionic gonadotropin doubling times (p > 0.05). A 1:2 dilution of urine gave the best results in the semiquantitative urine pregnanediol glucuronide test (Phase Check).nnnCONCLUSIONSnOn the basis of receiver-operator analysis, semiquantitative urine pregnanediol glucuronide measurements predict abnormal early gestations as well as serial human chorionic gonadotropin measurements do. The ability of a single urine semiquantitative assay (Phase Check) to predict early gestational complications offers a convenient screening tool that may identify women with abortive or ectopic pregnancies before the onset of symptoms.

Comparison of Immunosuppressive Properties of Hydatidiform Mole Decidua and Trophoblast Extracts

PROBLEM: The immunologic privilege afforded the fetus relies upon immunoregulation within the maternal‐fetal interface. Trophoblast and decidua‐derived immunoregulatory factors enforce this privilege by locally suppressing maternal responses to trophoblast antigens. The relative contribution of trophoblast or decidua immunosuppressive factors to pregnancy immunotolerance are not well characterized. The purpose of this study was to compare the suppressive effects of hydatidiform mole trophoblast and decidua extracts on interleukin‐2‐dependent proliferation.

Regulation of early gestational corpus luteum function in spontaneous and follicular stimulated conceptions

OBJECTIVEnTo determine the regulatory role of hCG on P secretion in normal and abnormal (abortive and ectopic) first trimester pregnancies.nnnSTUDY DESIGNnThe number of doublings of hCG per day (1/DT; reciprocal of hCG doubling time) was correlated with serum P using linear and nonlinear models in normal intrauterine pregnancies, spontaneous abortions, and ectopic pregnancies (EPs) conceived spontaneously or after clomiphene citrate (CC).nnnRESULTSnLinear correlations between P and 1/DTs of hCG were poor. In contrast, nonlinear modeling with a hyperbolic curve fit the data well and allowed all of the data to be included for analysis regardless of the pregnancy type. Furthermore, this model could be used to explain the differential P concentrations seen in normal and abnormal first trimester pregnancies. The nonlinear hyperbolic model demonstrated that follicular events determine the maximal P production during early gestation. Human chorionic gonadotropin 1/DTs approximately equal to 0.5 sustain maximal P production. Progesterone production is then sustained by the rate of change of hCG.nnnCONCLUSIONnNonlinear correlation analysis suggests that P production in early gestations is regulated by prior follicular events and the rate of hCG production.

Gestational Age Correlates With Immunosuppressive Properties of Hydatidiform Mole Pregnancies

PROBLEM: Soluble trophoblast extracts (HME) from some human hydatidiform mole pregnancies suppress IL‐2‐dependent T‐cell proliferation, while others express no immunosuppressive bioactivity. This study was designed to determine if suppression by HME was correlated with gestational age, uterine size, or hCG secretion.