Maternal Human Chorionic Gonadotropin Research Articles

This Month in Pediatric Urology

You have accessJournal of UrologyThis Month in Pediatric Urology1 May 2020This Month in Pediatric Urology Julian Wan Julian WanJulian Wan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000784AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail The pediatric articles published in this issue of The Journal represent 2 ends of the pathological spectrum. Peycelon et al focus on the beginning in their report on in utero maternal hormone levels that may predict the risk for hypospadias.1 Aksenov and Granberg evaluate the potential complications of minimally invasive surgery to treat common conditions such as ureteropelvic junction narrowing and vesicoureteral reflux.2 Linking the articles is the acquisition, collection and analysis of large pools of data. The collection, storage, examination and commerce of personal data including medical information has expanded in the last few decades and is likely to continue to grow as greater segments of the population become associated with electronic medical record systems. Despite the many real concerns about privacy and exploitation, there are legitimate scientific applications of these larger data collections. By sampling blood collected as part of general screening, specific disease relationships can be identified and complications may emerge when gathering reports of procedures. Association of Maternal Human Chorionic Gonadotropin and Hypospadias Using a large national registry, Peycelon et al (page 1017) from France examined the association between first trimester maternal serum free beta-human chorionic gonadotropin (HCG) levels and subsequent finding of hypospadias in the newborn. It has been established that tubularization of the urethra occurs early and is usually complete by 16 to 18 weeks of gestation. This process is affected by testosterone activity which, in turn, is affected by the release of HCG from maternal placental syncytiotrophoblasts. The authors suspect that the relationship may depend more on total HCG rather than just the beta subunit. Using a large metropolitan Paris database of maternal blood samples taken as part of routine prenatal screening, they found that proximal hypospadias, but not distal hypospadias or hypospadias overall, was associated with significantly higher levels of beta-HCG. The study was controlled for age and excluded pregnancies that were initiated by artificial reproductive technologies (a known risk for hypospadias), chromosomal anomalies, twins, fetal death and terminations. However, the authors acknowledged the limitations inherent with this type of analysis, most of which relate to potential bias from underreporting of less severe forms and the small number of proximal hypospadias cases (13 of 194 hypospadias cases). Complications of Minimally Invasive Surgery in Children To assess complications in patients treated with minimally invasive surgery, Aksenov et al (page 1010) from North Carolina and Minnesota conducted a review of the existing literature.2 While the Clavien-Dindo (CD) system of classification has been widely used, it was used in only a third of the articles in their review, whereas for the remaining articles complications were adjudicated by the authors and assigned a CD grade. In particular, the authors focused on complications resulting in subsequent surgical, radiological and endoscopic interventions (CD grade IIIa without general anesthesia, CD grade IIIb with general anesthesia). They also noted conversion rates related to open surgery. A significantly lower rate of grade III complications was reported for nephrectomy than for pyeloplasty and ureteral reimplantation. Complex reconstructions, as one would expect intuitively, resulted in the highest grade III complication rate at 12%. Likewise, the complication rate was highest for conversion to open surgery, followed by partial nephrectomy, nephrectomy and ureteral reimplantation. The lowest complication rate occurred after pyeloplasty (1%) which may reflect longer experience with this procedure. The clear separation of open conversion and the need for a complication related subsequent procedure is of practical use when discussing possible risks with families, patients and referring physicians.

Obstetric and perinatal outcomes of pregnancies according to initial maternal serum HCG concentrations after vitrified-warmed single blastocyst transfer.

Do pregnancy, obstetric and perinatal outcomes differ according to initial maternal serum human chorionic gonadotrophin (HCG) level measured on day 11 after single blastocyst transfer? Vitrified-warmed single blastocyst transfer cycles (n = 640) were collected between 1 January 2013 and 30 April 2017 with positive HCG values and retrospectively analysed by receiver operating characteristic curves to predict clinical pregnancy, ongoing pregnancy and delivery. Cycles were divided into a low HCG group (n = 155) and high HCG group (n = 485) based on cut-off value of live birth prediction. Cycles in the HCG group were subdivided into a low-high subgroup (n = 162), medium-high subgroup (n = 162) and high-high subgroup (n = 161) based on tertile points. Pregnancy rates and obstetric and perinatal outcomes were compared. The area under curves for clinical pregnancy, ongoing pregnancy and live birth prediction were 0.95, 0.81 and 0.79, respectively; corresponding cut-off values were 152.2 IU/l, 211.9 IU/l and 211.9 IU/l; HCG less than 211.9 IU/l indicated an extremely low clinical pregnancy rate (34.84%), a high early miscarriage rate (61.11%) and a low live birth rate (12.26%). Rates of gestational diabetes mellitus (GDM) (P = 0.007) and female neonates (P = 0.001) were significantly higher in the LHG group compared with the HHG group; no significant differences were observed in the low versus high HCG group overall. Lower initial maternal serum HCG levels indicated poorer clinical outcomes. Within the high HCG group, a lower initial maternal HCG level was found to be associated with GDM occurrence and proportion of female neonates.

Maternal concentrations of human chorionic gonadotrophin in very early IVF pregnancies and duration of pregnancy: a follow-up study.

Are maternal concentrations of human chorionic gonadotropin (HCG) on a fixed day after embryo transfer associated with duration of pregnancy? A follow-up study of 1917 singleton pregnancies after IVF was performed. Embryos were cultured for 2 days and maternal HCG concentration quantified on day 12 after embryo transfer. Duration of pregnancy was obtained from the Medical Birth Registry of Norway. Association of HCG concentration (log2-transformed) with duration of pregnancy was estimated as hazard ratios (HR) with 95% confidence intervals (CI) by applying Cox regression proportional hazard models, where time to delivery for pregnancies shortened because of planned Caesarean delivery or induction of labour was treated as censored. The estimated median duration of pregnancy from embryo transfer was 266 days (95% CI 266-267 days). Maternal concentration of HCG on day 12 after embryo transfer varied from 1 to 588 IU/l (median 117 IU/l). Duration of pregnancy decreased by increasing HCG concentration, significantly in pregnancies delivered at full term ((257-270 days after embryo transfer; HR 1.127, 95% CI 1.026-1.238, P = 0.012). For each doubling of HCG concentration on day 12 after embryo transfer, duration of pregnancy was shortened by 0.51 days. Adjustment for maternal age, prepregnancy body mass index, being a first-time mother and number of embryos transferred did not change the association. High maternal HCG concentration on a fixed day after embryo transfer is likely to indicate early embryo implantation. After embryo transfer, pregnancies with early implantation are shorter than pregnancies with late implantation.

Is an isolated elevation of maternal human chorionic gonadotropin (hCG) associated with adverse fetal outcomes?

EVIDENCE-BASED ANSWER An isolated elevation in hCG is associated with an increased risk of preterm birth and fetal death (SOR: C, inconsistent case-control studies). Elevated hCG is not associated with increased risk of intrauterine growth restriction (IUGR), small-for-gestational-age (SGA) infants, low Apgar scores, or early preterm birth (SOR: C, consistent case-control studies). Among women with preeclampsia and elevated hCG, there is an increased risk of preterm birth, low birth weight, and newborn intensive care unit (NICU) admission (SOR: C, casecontrol study).

Human chorionic gonadotropin, fetal sex and risk of hypertensive disorders of pregnancy: A nested case-control study.

To assess whether human chorionic gonadotropin (HCG) and fetal sex are two independent risk factors for hypertensive pregnancy in the early second-trimester of pregnancy. This was a retrospective nested case-control study based on a cohort of 2521 singleton pregnancies, among whom we recruited 98 hypertensive pregnancies (subdivided into severe preeclampsia, n=34; mild preeclampsia, n=29 and gestational hypertension, n=35) and 196 normotensive pregnancies. Maternal serum HCG levels were measured at 15-20 weeks of gestation and fetal sex was determined from the neonatal record. Mann-Whitney U and chi-square tests were performed to assess differences of HCG levels and fetal sex between groups. Logistic regressions were performed to evaluate the effect of HCG and fetal sex on hypertensive pregnancy. There were 35 male and 63 female fetuses in the hypertensive group, and 102 male and 94 female fetuses in the normotensive group (p=0.008). HCG (MoM) levels were significantly higher in only severe preeclamptic pregnancies (n=34) (p=0.013). There were no significant differences of the HCG (MoM) levels between male and female fetuses in each sub-group. aOR for increased maternal HCG levels and female fetus were 2.4 (95% CI: 1.434-3.954) and 2.9 (95% CI: 1.227-6.661) respectively in severe preeclamptic pregnancies compared with normotensive pregnancies. There is a female preponderance in hypertensive pregnancies. Increased HCG levels and female fetus are two independent risk factors for severe preeclampsia in the early second-trimester of pregnancy.

Hormonal control of spermatogenesis in men: Therapeutic aspects in hypogonadotropic hypogonadism

During the first two trimesters of intrauterine life, fetal sex steroid production is driven by maternal human chorionic gonadotropin (hCG). The HPG axis is activated around the third trimester and remains active for the first 6-months of neonatal life. This so-called mini-puberty is a developmental window that has profound effects on future potential for fertility. In early puberty, GnRH secretion is reactivated first at night and then night and day. Pulsatile GnRH stimulates both LH and FSH, which induce maturation of the seminiferous tubules and Leydig cells. Congenital hypogonadotropic hypogonadism (CHH) results from GnRH deficiency. Men with CHH lack the mini-pubertal and pubertal periods of Sertoli Cell proliferation and thus present with prepubertal testes (<4mL) and low inhibin serum levels – reflecting diminished SC numbers. To induce full maturation of the testes, GnRH-deficient patients can be treated with either pulsatile GnRH, hCG or combined gonadotropin therapy (FSH+hCG). Fertility outcomes with each of these regimens are highly variable. Recently, a randomized, open label treatment study (n=13) addressed the question of whether a sequential treatment with FSH alone prior to LH and FSH (via GnRH pump) could enhance fertility outcomes. All men receiving the sequential treatment developed sperm in the ejaculate, whereas 2/6 men in the other group remained azoospermic. A large, multicenter clinical trial is needed to definitively prove the optimal treatment approach for severe CHH.

Placental mesenchymal dysplasia, a case of intrauterine sudden death in a normal-sized fetus

placental mesenchymal dysplasia (PMD) is a rare placental anomaly characterized by placentomegaly and grape-like vesicles which resemble molar pregnancy. we report the case of 33-year-old woman (1-gravid) who visited our clinic at 11 weeks of gestation due to a suspected molar pregnancy. Ultrasound examination showed an enlarged placenta with multiple vesicular lesions. Maternal human chorionic gonadotropin level was normal and chorionic villus sampling showed a normal male karyotype (46 XY). The fetus exhibited no specific anomalies and fetal growth was normal during pregnancy with no signs of fetal suffering. At 31 weeks, the pregnancy ended owing to intrauterine fetal death (IUFD). The patient delivered a normal-sized male fetus (1800 g) with no definite anomalies. A pathological examination led to a diagnosis of placental mesenchymal dysplasia. in the presence of placental ultrasound anomalies with no other sign of fetal suffering, the pregnancy should be considered at risk and, therefore, should be monitored carefully including the option of hospitalization.

A test of maternal human chorionic gonadotropin during pregnancy as an adaptive filter of human gestations

The risk of abnormalities and morbidity among live births increases with advanced maternal age. Explanations for this elevated morbidity invoke several maternal mechanisms. The relaxed filter stringency (RFS) hypothesis asserts that mothers, nearing the end of their reproductive lifespan, reduce the stringency of a screen of offspring quality in utero based on life-history traits of parity and interbirth interval (IBI). A separate line of research implicates human chorionic gonadotropin (hCG) during pregnancy as a signal of offspring quality. We test the RFS hypothesis directly by examining whether the difference in gestational hCG across consecutive live births varies positively with the mother's number of previous live births but inversely with her most recent IBI. We applied multivariable regression methods to a unique dataset of gestational hCG for over 500 000 live births from 2002 to 2007. The difference in gestational hCG across mothers' consecutive live births varies positively with both mothers' parity and IBI. These associations remain similar among older mothers (35+ years). Findings support the RFS hypothesis for the parity expectation but not for the IBI expectation. Further evidence for the RFS hypothesis among contemporary human gestations would have to invoke screening mechanisms other than hCG.

Placental mesenchymal dysplasia, a case of intrauterine sudden death of fetus with rupture of cirsoid periumbilical chorionic vessels

We report a 32-year-old woman (1-gravid, 1-para) with a vesicular lesion in her uterus that was pointed out on ultrasound at 8 weeks' gestation. Amniocentesis at 15 weeks' gestation showed a normal female karyotype, 46XX. As the pregnancy advanced, the mole-like lesion became relatively reduced. Throughout gestation, the maternal human chorionic gonadotropin level was normal, but the serum alpha fetoprotein level rose as her pregnancy progressed. Her fetus did not exhibit any remarkable anomalies. The patient visited our hospital complaining of a diminished feeling of fetal movements at 36 weeks 5 days' gestation, and intrauterine fetal death (IUFD) was confirmed. She delivered a 2336-g female without any definite anomalies. A pathological examination led to a diagnosis of placental mesenchymal dysplasia, and androgenetic/biparental mosaicism in the placenta was identified using p57kip2 immunohistochemical staining. And it also revealed that the rupture of the cirsoid chorionic vessels had led to IUFD.

Can sonographic endometrial pattern be an early indicator for tubal ectopic pregnancy and related tubal rupture?

The present study aims to determine whether sonographic endometrial pattern can be addressed as an early indicator for tubal ectopic pregnancy and related tubal rupture in case ultrasonography reveals no adnexal mass and maternal serum beta human chorionic gonadotropin (HCG) level is below the discriminatory zone (<or=1,000 mIU/mL). The study evaluated the endometrial features of 441 naturally conceived and asymptomatic first trimester (99 tubal ectopic, 138 failing and 264 normal intrauterine) with maternal serum beta HCG levels<or=1,000 mIU/mL and indeterminate sonographic findings. Tubal ectopic, failing intrauterine and normal intrauterine pregnancies are statistically similar in aspect of endometrial thickness. However, trilaminar endometrial pattern was significantly less frequent in failing and normal intrauterine pregnancies but significantly more frequent in ruptured tubal pregnancies. Also the relative risk of tubal rupture is significantly higher in case of trilaminar endometrial pattern. Trilaminar endometrial pattern has a sensitivity of 21.2%, specificity of 93.9%, positive predictive value of 50.0% and negative predictive value of 80.5% for distinguishing tubal ectopic pregnancy. Moreover, the sensitivity, specificity, positive and negative predictive values of the same pattern are computed to be 60.0, 95.7, 85.7 and 84.6%, respectively, in the prediction of ruptured tubal pregnancy. Sonographic appearance of endometrium may be used to predict tubal pregnancy when ultrasonography shows no adnexal mass and maternal serum HCG<or=1,000 mIU/mL. That is, trilaminar pattern may indicate tubal pregnancy and warn about a possible related rupture in case of previous ectopic pregnancy or pelvic surgery.

LUTEINIZED CYSTIC OVARIAN HYPERPLASIA ASSOCIATED WITH PLACENTOMEGALY DUE TO CHORANGIOMATOSIS

Luteinized cystic ovarian hyperplasia (LCOH) is a rare benign condition characterized by bilateral ovarian enlargement during pregnancy secondary to high maternal human chorionic gonadotropin serum levels referred to occur under several conditions. We report the case of a 29-year-old obese woman with LCOH incidentally discovered during cesarean section of a single pregnancy at 35 weeks of gestation for fetal intrauterine demise. The fetus showed external ambiguous genitalia, imperforate anus, bilateral dysplastic kidneys, and hydrometrocolpos secondary to atresia of the vagina. The placental weight was 1,450 g (normal for gestational age: 415 g). The placenta showed diffuse chorangiomatosis (CM) characterized by multifocal stem villi enlargement containing increased number of small vessels with alpha-smooth muscle actin positive cells in the walls in a dense reticulin fibers-rich stroma. The combination of LCOH and placentomegaly due to CM appears to be unique.

Maternal serum alpha-fetoprotein and human chorionic gonadotrophin in pregnancies conceived after intracytoplasmic sperm injection and conventional in-vitro fertilization.

Data in the Caucasian population suggest that maternal serum alpha-fetoprotein (AFP) and unconjugated oestriol concentrations are reduced and human chorionic gonadotrophin (HCG) concentrations are elevated in pregnancies conceived after in-vitro fertilization (IVF), leading to a higher than expected Down's syndrome screen-positive rate. There are no previous reports on the serum marker values in pregnancies conceived after intracytoplasmic injection (ICSI). Between 1996 and 1998, we measured maternal serum total HCG and AFP concentrations between 15 and 20 weeks gestation in 42 in-vitro fertilization (IVF) pregnancies and 23 ICSI pregnancies with known normal outcome. The results were compared with that of 2799 naturally occurring singleton pregnancies who were known to have a normal outcome. Median AFP multiple of the median (MOM) in ICSI pregnancies was significantly reduced to 0.76 compared with both that of the controls and that of the IVF pregnancies. For the IVF pregnancies, median HCG MOM was elevated to 1.15, and median AFP MOM was reduced to 0.88 compared with the controls, but these differences were not statistically significant. In both the IVF and ICSI pregnancies the changes might result in a falsely high Down's syndrome risk. In particular, the reduced AFP concentration in ICSI pregnancies was substantial. If this preliminary finding is substantiated by other series, the appropriate adjustment needs to be made to allow for valid interpretation of the screen result and to avoid an unnecessarily high false positive rate.

Early prenatal diagnosis of triploidy

OBJECTIVE: Our purpose was to investigate the role of ultrasonography and maternal serum human chorionic gonadotropin in the early prenatal diagnosis of triploid pregnancies. STUDY DESIGN: A retrospective study on 61,314 consecutive singleton pregnancies examined by ultrasonography at 10 to 14 weeks' gestation was performed to identify the prenatal features of those complicated by triploidy. When available, the serum human chorionic gonadotropin level was measured and ascertained retrospectively. Cases lost to follow-up or for which no karyotype was available were excluded from the final analysis. RESULTS: Overall there were 18 cases of triploidy identified in a population of 58,862 singleton pregnancies, giving a prevalence of 1 in 3270. Fetal defects were observed in 8 (44.4%) of these cases; these included holoprosencephaly ( n = 4), exomphalos ( n = 3), and posterior fossa cyst ( n = 1). In 6 (33.3%) cases the placenta showed molar changes. The fetal crown-rump length was below the 5th percentile in 10 of the 16 (62.5%) cases for which the menstrual age was also available. Fetal nuchal translucency thickness was above the 95th percentile in 12 (66.7%) cases, and the fetal heart rate was below the 5th percentile in 4 of the 13 (30.8%) cases evaluated. The maternal human chorionic gonadotropin level was high in 11 of the 13 (84.6%) cases tested, with similar distribution of the high values in molar and nonmolar triploidies. CONCLUSION: The combination of ultrasonographic examination of the fetoplacental features and measurement of the maternal serum level of human chorionic gonadotropin enables the diagnosis of most cases of triploidy at 10 to 14 weeks' gestation.(Am J Obstet Gynecol 1997;176:550-4.)

HCG used to date pregnancy: Lagrew D, Wilson E, Fried A: Accuracy of serum human chorionic gonadotropin concentrations and ultrasonic fetal measurements in determining gestational age. Am J Obstet Gynecol 149:165, 1984

To assess whether human chorionic gonadotropin (HCG) and fetal sex are two independent risk factors for hypertensive pregnancy in the early second-trimester of pregnancy.This was a retrospective nested case-control study based on a cohort of 2521 singleton pregnancies, among whom we recruited 98 hypertensive pregnancies (subdivided into severe preeclampsia, n = 34; mild preeclampsia, n = 29 and gestational hypertension, n = 35) and 196 normotensive pregnancies. Maternal serum HCG levels were measured at 15–20 weeks of gestation and fetal sex was determined from the neonatal record. Mann–Whitney U and chi-square tests were performed to assess differences of HCG levels and fetal sex between groups. Logistic regressions were performed to evaluate the effect of HCG and fetal sex on hypertensive pregnancy.There were 35 male and 63 female fetuses in the hypertensive group, and 102 male and 94 female fetuses in the normotensive group (p = 0.008). HCG (MoM) levels were significantly higher in only severe preeclamptic pregnancies (n = 34) (p = 0.013). There were no significant differences of the HCG (MoM) levels between male and female fetuses in each sub-group. aOR for increased maternal HCG levels and female fetus were 2.4 (95% CI: 1.434–3.954) and 2.9 (95% CI: 1.227–6.661) respectively in severe preeclamptic pregnancies compared with normotensive pregnancies.There is a female preponderance in hypertensive pregnancies. Increased HCG levels and female fetus are two independent risk factors for severe preeclampsia in the early second-trimester of pregnancy.

Measurement of Human Chorionic Gonadotropin (HCG) Concentrations in Paired Maternal and Cord Sera Using an Assay Specific for the Beta Subunit of HCG

Human chorionic gonadotropin (HCG) concentrations were determined in paired maternal and cord sera using an essay specific for the beta subunit of HCG. The sera of 46 mothers and 46 infants, 24 female and 22 male, were studied. Results were compared to those obtained using a radioimmunoassay for luteinizing-hormone (LH) which cross-reacted with HCG. With either assay system, mean maternal HCG concentrations were lower when the sex of the fetus was male than when the sex of the fetus was female. Mean cord HCG concentrations of male (0.09 +/- 0.02 IU/ml) and female (0.09 +/- 0.04 IU/ml) infants were not different as determined by the beta HCG assay. In contrast, the mean cord serum concentration of HCG was significantly greater (P less than .005) in male infants (0.29 +/- 0.05 IU/ml) than in female infants (0.23 +/- 0.09 IU/ml) as determined by the cross-reacting assay. HCG concentrations were lower in both maternal and cord sera when assayed in the specific HCG system than when assayed in the cross-reacting system. There was a significant correlation (r=.9; P less than .005) between the results obtained with the two assays in both maternal and cord blood. Regardless of the assay system employed, the cord serum concentration of HCG was markedly less than the corresponding maternal serum concentration. There was no correlation between maternal and cord serum HCG concentrations with either assay. These data are in agreement with the results of previous studies employing less specific methodology which indicated that maternal serum HCG concentrations were less when the fetus was male than when it was female. They are also consistent with a placental barrier effect with regard to HCG transfer to the fetus. The difference in results obtained in cord blood with the two assay systems suggests that the newborn male infant secretes more LH and/or alpha LH subunits than the newborn female infant.

Relationship between Concentrations of Human Chorionic Gonadotrophin (HCG) in Maternal Plasma, Amniotic Fluid and Fetal Cerebrospinal Fluid

The cerebrospinal fluid (CSF) of 14 fetuses of 13–24 weeks of gestation has been assayed for the presence of human chorionic gonadotrophin (HCG). The results demonstrated that small amounts of HCG were present in the fetal CSF and showed highest values at 13 weeks, gradually falling to very low values by 19 and 24 weeks of gestation. No correlation appeared to exist between HCG concentration in maternal plasma and HCG concentration in fetal CSF, whereas a significant correlation could be demonstrated between HCG concentration in amniotic fluid and HCG concentration in fetal CSF. It may also be suggested that the blood brain barrier for HCG is incompletely developed in the fetus but this problem requires further investigation.