The feto-placental unit stimulates the pregnancy-associated increase in maternal bone metabolism

The aim of the study was to investigate role of the feto-placental unit in the pregnancy-induced increase in maternal bone metabolism. To achieve this, circulating concentrations of carboxy terminal pro-peptide of type I pro-collagen (PICP, a marker of bone formation) and cross-linked carboxy terminal telopeptide of type I collagen (ICTP, a marker of bone resorption) were measured in three groups of pregnant women. Group 1 comprised 12 women with singleton pregnancies; group 2, nine women with twin pregnancies; and group 3, 19 women with multifetal pregnancies (> or =3 fetuses) before and after selective fetal reduction to twin pregnancies. Blood samples were obtained at 10-12 weeks gestation (groups 1-3, pre-fetal reduction in group 3) and 4 weeks and 8 weeks later (groups 2 and 3). Before fetal reduction there was a significant correlation between the number of fetuses and the concentrations of both PICP and ICTP (r = 0.503 and P = 0.001 and r = 0.573 and P < 0.001 respectively). The circulating concentrations of PICP and ICTP were significantly higher in the pre-reduction multifetal pregnancies than in the twin pregnancies (P < 0.001 and P = 0.0013 respectively). The circulating concentrations of ICTP in multifetal pregnancies fell by 4 weeks after fetal reduction to those observed in control twins. Concentrations of PICP were unaltered after fetal reduction. Higher order multiple pregnancies had the greatest decline in ICTP concentrations. These data suggest that the increased bone turnover observed in the multifetal pregnancies is due to a factor derived from the feto-placental unit and that this factor acts primarily to stimulate bone resorption.     

Pregnancy: Corpus luteum failure in ectopic pregnancy

The endocrinology of ectopic pregnancy was studied in orderto investigate the origin of the discordance in the circulatingamounts of human chorionic gonadotrophin (HCG) and those ofoestradiol and progesterone. Serial maternal blood samples wereobtained at 4–9 weeks gestation from 93 patients who becamepregnant following in-vitro fertilization and embryo transferincluding 10 ectopic, 21 anembryonic and 62 normal singletonpregnancies. The samples were analysed for HCG, Schwangerschaftprotein-1 (SP-1), pregnancy-associated plasma protein-A (PAPP-A),progesterone and oestradiol. In ectopic pregnancies, concentrationsof all substances analysed were significantly reduced comparedto singleton pregnancies from 5 weeks gestation (P < 0.05–0.001)but they were not significantly different from those of anembryonicpregnancies. In ectopic pregnancies, associations were foundbetween the concentration of both HCG and SP-1 and those ofprogesterone and oestradiol. No associations were found betweenPAPP-A and any other substances analysed. This may be due toinsensitivity of the PAPP-A assay; alternatively PAPP-A concentrationsmay be differentially reduced in ectopic pregnancy. These findingssuggest that progesterone and oestradiol are derived from thecorpus luteum in early ectopic pregnancy but that the corpusluteum fails rapidly and the dominant source of both hormonesbecomes the trophoblast as early as 5 weeks.     

Maternal plasma concentrations of insulin-like growth factor binding protein-1 and placental protein 14 in multifetal pregnancies before and after fetal reduction

The aim of this study was to investigate the changes in maternalplasma insulin-like growth factor binding protein-1 (IGFBP-1)and placental protein 14 (PP14) in multifetal pregnancies beforeand after embryo reduction. Maternal plasma IGFBP-1 and PP14were measured serially in three groups of pregnant women at8–21 weeks gestation. Groups 1 and 2 were 12 singletonand 12 twin pregnancies achieved after in-vitro fertilization(IVF). Group 3 comprised 26 women with multifetal pregnanciesundergoing embryo reduction to twins. In the IVF pregnanciesmaternal plasma IGFBP-1 and PP14 increased with gestation toreach a peak at 20 and 10 weeks respectively; the mean concentrationsin twin pregnancies were significantly higher than in singletons.In multifetal pregnancies the mean plasma concentration of bothproteins was similar to that of IVF twin pregnancies beforereduction; after reduction, the values fell to less than thoseof twins. These findings suggest that the maximum secretorycapacity of the endometrium is achieved with twin pregnancies.In multifetal pregnancies undergoing iatrogenic reduction totwins, total residual endometrial function was less than intwin conceptions.     

Endocrinology of in-vitro fertilization pregnancies during the first trimester

The endocrine function of the corpus luteum and placenta andthe inter-relationships between ovarian steroids and the placentalproteins in pregnancies achieved following ovarian stimulation,in-vitro fertilization and embryo transfer (IVF-ET) have beeninvestigated. The serum concentrations of human chorionic gonadotrophin(HCG), Schwangerschaft protein-1 (SP-1), pregnancy-associatedplasma protein A (PAPP-A), progesterone and oestradiol weremeasured at weekly intervals between the 4th (ET plus 2 weeks)and 14th week of gestation in 86 pregnancies. The mean concentrationsof the placental proteins and oestradiol were significantlyhigher in twin than in singleton pregnancies from as early as5 weeks gestation, but the mean concentrations of progesteronewere significantly higher only at the end of the first trimester.Ranking, as demonstrated by the presence of statistically significantcorrelations between serum levels of each substance analysedin week 13 with those of preceding weeks, was established forprogesterone and SP-1 from the 5th week, for oestradiol andPAPP-A from the 7th week and for HCG from the 8th week of gestation.The presence of statistically significant correlations betweeneach substance analysed suggests that the placenta becomes thedominant source of oestradiol from 8 weeks gestation and ofprogesterone not until 12 weeks gestation, and that the placentalsynthesis of HCG, SP-1, PAPP-A, oestradiol and progesteroneappear to be linked. There were no statistically significantcorrelations between the serum concentrations of HCG and eitherprogesterone or oestradiol until the production of each hadbecome predominantly placental.     

The contribution of maternal serum markers in the early prenatal diagnosis of molar pregnancies

The aim of this study was to evaluate the usefulness of maternal serum markers in the early prenatal diagnosis of molar pregnancies. The ultrasound features, cytogenetic and histopathological findings of 10 cases of molar pregnancy diagnosed at 11-13 weeks of gestation were compared retrospectively with the maternal serum concentrations of human chorionic gonadotrophin (HCG), alpha fetoprotein (AFP), pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta1-glycoprotein (SP1). Free beta-HCG and intact HCG concentrations were very high [> or = 2.5 multiples of the median (MoM)] in all cases. AFP concentrations were extremely low in all cases of singleton complete moles (< or = 0.5 MoM) and were high in one case of twin complete mole, in one case of triploid partial mole and two cases of euploid partial mole (> or = 2.5 MoM). Serum PAPP-A and SP1 were high in complete moles. The combined use of ultrasound features, maternal serum proteins and fetal cytogenetic findings should enable the early differential diagnosis in utero and perinatal management of those molar pregnancies presenting with an anatomically normal fetus.     

Pregnancy: Differential increase in the maternal serum concentrations of the placental proteins human chorionic gonadotrophin, pregnancy-specific {beta}1-glycoprotein, human placental lactogen and pregnancy-associated plasma protein-A during the first half of normal pregnancy, elucidated by means of a mathematical model

The present study was performed to compare the increase in maternalserum concentrations of four placental proteins during the firsthalf of 240 normal pregnancies. The proteins were pregnancy-associatedplasma protein-A (PAPP-A), human chorionic gonadotrophin (HCG),human placental lactogen (HPL) hormone, and pregnancy-specific1-glyco-protein (PSG), all produced by trophoblast cells. Themedian increases were observed to be very close to exponentialgrowth curves. Based on simple assumptions, these growth curvescould be explained as being solely dependent on the growth ofthe placenta. The assumptions were that the proteins were producedin the placenta at a constant rate per gram of placental cellmass and secreted into the circulation shortly after synthesis.Our investigations showed that for two of the proteins, PSGand HPL, the rate constants were, in fact, close to the reportedgrowth rate of the placenta, whereas the PAPP-A production rateconstant was significantly higher than those of the others.The production curve for HCG was very different from that ofthe other proteins. PAPP-A and HCG must therefore have morecomplicated mechanisms for regulating the production. An equationwas constructed that permitted estimation of the molar productionof the placental proteins per gram of placental cell mass perday during the first half of normal pregnancy. The value washighest for HPL and lowest for PAPP-A.     

The role of a single free {beta}-human chorionic gonadotrophin measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability

This prospective controlled study investigated the concentrationsof free -human chorionic gonadotrophin (HCG) subunit in 554women with a singleton intrauterine or tubal pregnancy. Theypresented with vaginal bleeding and/or abdominal pain in thefirst 18 weeks of pregnancy. The control group comprised 156women with musculo-skeletal pain and no vaginal bleeding. Theirpregnancies continued to term. The study group comprised 398women (141 threatened-continuing pregnancies, 37 threatened-miscarriages,185 non-continuing pregnancies and 35 tubal pregnancies). Free-HCG concentrations were significantly lower in the non-continuing,threatened-miscarriage and tubal pregnancy groups [mean 4.62,6.50 and 4.27 ng/ml respectively; 95% confidence interval (CI)3.75–-5.69, 4.46–9.48 and 2.92–6.2 respectively]than in the control and threatened-continuing groups (mean 41.61and 48.22 ng/ml respectively; 95% CI 34.53–50.13 and 42.03–55.32respectively) (P < 0.001 in all cases). A cut-off value at20 ng/ml was found to differentiate between the ‘viable’(control and threatened-continuing) and the ‘abnormal’(non-continuing, threatened-miscarriage and tubal) pregnancies,with 88.3% sensitivity and 82.6% positive predictive value.An excellent diagnostic and prognostic usability of free HCGwas confirmed by a receiver operating characteristic curve plotIn conclusion, a single serum free -HCG measurement taken inearly pregnancy is valuable in the immediate diagnosis of earlypregnancy failure and the long-term prognosis of viability.     

Distribution of fetal erythroblasts enriched from maternal blood in multifetal pregnancies

BACKGROUND: The aim of this study was to establish the frequency of fetal cells in the maternal blood of multifetal pregnancies and compare this figure with singleton pregnancies. METHODS: We obtained maternal blood from 31 pregnancies with 2-6 fetuses at 11-16 weeks gestation and from 50 normal singleton controls (11-14 weeks gestation). Fetal erythroblasts were isolated from maternal blood using triple density gradient separation and anti-CD71 magnetic cell-sorting techniques. The enriched erythroblasts were stained with Kleihauer-Giemsa and with fluorescent antibodies for the zeta (zeta), epsilon (epsilon) and gamma (gamma) globin chains. The percentage of fetal cells positive for each stain was calculated. Fluorescence in-situ hybridization (FISH) for X and Y chromosomes was also performed. RESULTS: The percentage of erythroblasts enriched from maternal blood that stained positive for zeta, epsilon and gamma globin chains and with Kleihauer-Giemsa was significantly higher in the multifetal compared with singleton pregnancies. The median enriched percentage of positively stained erythroblasts was about three times higher in the twin than in singleton pregnancies (P < 0.0001), nearly twice as high in the triplet than in twin pregnancies (P < 0.01) and five times higher in the triplet than singleton pregnancies (P < 0.0001). FISH for Y chromosome confirmed the increase in fetal cell proportion in the multifetal pregnancies. CONCLUSIONS: These findings suggest that there is an increase in the physiological feto-maternal cell trafficking in multifetal pregnancies compared with singleton pregnancies, which is likely to be due to the increased placental surface area and vasculature.     

Pregnancy: Ectopic pregnancy after in-vitro fertilization is characterized by delayed implantation but a normal increase of serum human chorionic gonadotrophin and its subunits

We studied the dynamics of serum human chorionic gonadotrophin(HCG) and its free (HCG) and (HCGP) subunits in 49 early pregnanciesachieved by in-vitro fertilization (IVF) and embryo transfer.Of the 49 early pregnancies, nine were normal singleton pregnancies,11 were twin pregnancies, 11 were ectopic, eight ended in aclinical (spontaneous) abortion and 10 ended in a preclinicalabortion. The HCG, HCGa and HCGP concentrations in serum weremeasured on days 12, 19 and 26 after embryo transfer. Most ectopicpregnancies could be distinguished from singleton (and twin)pregnancies on the basis of low HCG concentrations by 12 daysafter embryo transfer, but clinical abortions could not be distinguishedfrom singleton pregnancies. In general, the measurement of HCGaand HCG and the molar ratios of the various forms provided onlymarginal additional value to that obtained from HCG, but ondays 19 and 26 after embryo transfer HCGa was the most sensitiveindicator of a normal pregnancy after IVF and embryo transfer.We conclude that in ectopic pregnancies the concentrations ofHCG, HCGa and HCGP increase as expected but 1.5 days later thanin normal pregnancies. This appears to be the result of a delayin implantation.     

Maternal serum inhibin A concentrations in early pregnancy after IVF and embryo transfer reflect the corpus luteum contribution and pregnancy outcome

To compare maternal serum inhibin A concentrations in early pregnancy with pregnancy outcomes and treatment protocols, serum samples were collected from 237 women undergoing in-vitro fertilization (IVF) and embryo transfer cycles. Samples were collected on day 16 after oocyte retrieval for beta human chorionic gonadotrophin (HCG) pregnancy testing and inhibin A measurement. The samples were divided into non-pregnant (n = 128) and pregnant (n = 109) groups, the pregnancies were followed and outcomes determined. Inhibin A concentrations were significantly lower in non-pregnant women than in women with ongoing pregnancies (P: < 0.001) and those resulting in spontaneous abortions (P: < 0.001). In ongoing pregnancies, inhibin A concentrations were significantly lower in the absence of functioning ovaries (donor oocyte/embryo) (P: < 0.01) and in natural cycles (frozen-thawed embryo transfer) (P: < 0.01) compared with concentrations after ovarian stimulation. Further, since inhibin A concentrations were not significantly different between singleton and multiple pregnancies in the ovarian stimulation protocol, the size of the early trophoblast does not appear to influence the secretion of inhibin A. These data strongly support the concept that the corpus luteum is a major source of circulating inhibin A in early pregnancy. Additionally, low concentrations of serum inhibin A may be useful in predicting betaHCG-positive preclinical 'biochemical' pregnancies.     

Correlation between first trimester fetal bone length and maternal serum pregnancy-associated plasma protein-A (PAPP-A)

BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is produced by the embryo and placenta during pregnancy, and its maternal serum concentrations are related to subsequent fetal growth. Evidence from animal models and in vitro experiments suggests that PAPP-A is particularly involved in the regulation of bone development. The aim of this study was to assess the correlation between late first trimester fetal bone length and maternal serum levels of PAPP-A. METHODS: In a cross-sectional observational study, ultrasound measurements of fetal long bones and fluorimetric immunoassays for maternal serum PAPP-A were performed in 514 singleton pregnancies at 10-14 weeks of gestation. RESULTS: There were 501 uncomplicated pregnancies. There were significant correlations between PAPP-A values and length of humerus, femur and tibia [r values 0.12 (P = 0.01), 0.11 (P = 0.01) and 0.10 (P = 0.03), respectively]. The association with the length of ulna and foot did not reach statistical significance (r values 0.08 and -0.03, respectively). CONCLUSIONS: Maternal serum PAPP-A levels at 10-14 weeks of gestation are significantly associated with the length of fetal long bones such as humerus, femur and tibia. This provides further evidence that PAPP-A may be involved in the regulation of bone development.     

Placental and ovarian hormones in anembryonic pregnancy

The circulating levels of human chorionic gonadotrophin (HCG),pregnancy-associated plasma protein-A (PAPP-A), Schwangerschaftprotein 1 (SP-1), oestradiol and progesterone were measuredin 81 pregnant patients between 4 and 11 weeks gestation, followingin-vitro fertilization and embryo transfer. The patients weredivided as follows: singleton anembryonic pregnancies, n = 22;singleton pregnancies which spontaneously aborted followingthe demonstration of fetal heart activity, n = 7; and normalsingleton pregnancies, n = 52. The levels of all substancesmeasured were significantly reduced in women with anembryoniccompared to those with singleton pregnancies which proceededto term. The serum levels of SP-1, weeks 6–8 (P < 0.01);HCG, weeks 6–8 (P < 0.05); oestradiol, weeks 5–8(P < 0.05) and progesterone, weeks 6–8 (P < 0.05),were lower in anembryonic pregnancies than in those of pregnancieswhich spontaneously aborted. These differences may be a reflectionof the fact that miscarriage, after the demonstration of fetalheart activity, represents fetal demise at a later stage inpregnancy. In anembryonic pregnancies, significant associationswere found between HCG and both oestradiol and progesteronelevels from weeks 6 and 8, suggesting that in the absence ofan embryo, HCG is the prime determinant of steroid synthesisby the corpus luteum.     

Factors determining early pregnancy loss in singleton and multiple implantations

BACKGROUND: The incidence of first trimester pregnancy loss is much lower in IVF twin pregnancies than in IVF singleton pregnancies. The objective of this study was to determine which embryonic and maternal factors contribute to this finding. METHODS: Retrospective data analysis of the outcome of 1593 pregnancies after day 3 double-embryo transfer (DET) after IVF or ICSI treatment. RESULTS: Of 1148 single implantations at 6 weeks, 936 (81.5%) were ongoing pregnancies. Of 445 multiple implantations at 6 weeks, 354 (79.6%) were ongoing multiple pregnancies, 80 (17.9%) were ongoing singleton pregnancies and 11 (2.5%) ended in a spontaneous abortion. Total pregnancy loss was 18.5 and 2.5% (P < 0.001) in singleton and twin gestations, respectively. Loss per gestational sac was 18.5 and 11.46% (P < 0.001), respectively. Determinants contributing to the continuation of gestation beyond 6 weeks were young maternal age, possibility to cryopreserve embryos and short GnRH agonist flare-up stimulation protocol. Whereas factors promoting multiple implantation at 6 weeks of gestation were young maternal age, high cumulative embryo score (CES), male infertility, long stimulation protocol and thick endometrium. CONCLUSIONS: Although multiple implantation at 6 weeks is predominantly determined by (morphological) embryo quality, the continuation of pregnancy beyond 6 weeks becomes more dependent on the combination of genetic and developmental potential of the embryo(s) and an optimal uterine milieu.     

Transfusion-dependent homozygous {beta}-thalassaemia major: successful twin pregnancy following in-vitro fertilization and tubal embryo transfer

Homozygous -thalassaemia (thalassaemia major) is a severe, transfusion-dependentanaemia that also causes infertility due to endocrine impairment.Very few pregnancies are reported among such patients and thereis only one report in the literature referring to a pregnancyachieved with ovulation induction and intra-uterine insemination.We report here the first successful twin pregnancy followingin-vitro fertilization and tubal embryo transfer in a transfusion-dependenthomozygous -thalassaemic woman with an oligoastheno-zoospermicpartner. Prior to ovarian stimulation, desferrioxamine was discontinueddue to potential fetotoxicity. Pre-gestational transfusionaland chelating therapies were resumed after delivery. In suchpatients, ovulation induction and assisted reproductive techniquesappear crucial in achieving pregnancy with concurrent haematologicalbalance without desferrioxamine administration.     

Coelomic fluid chorionic gonadotrophin and protein concentrations in normal and complicated first trimester human pregnancies

Coelomic fluid and maternal serum samples were collected from43 normal pregnancies and 18 missed abortions between 7 and12 weeks of gestation. The samples were analysed for the concentrationsof intact human chorionic gonadotrophin (HCG), free HCG, freeHCG and total protein. The relationships between the biologicalfindings and the ultrasound and pathological features were assessedby regression analysis. In normal pregnancies, intact HCG, freeHCG and free HCG concentrations were respectively 1.3, 185 and33 times higher in coelomic fluid than in maternal serum. Thecoelomic concentrations of intact HCG and free HCG decreasedsignificantly with advancing gestation. No relationship wasfound between coelomic fluid and maternal serum concentrationsof the different variables. These findings suggest that in normalpregnancies, the concentration of HCG in the coelomic fluid,as in maternal serum, is mainly influenced by cytotrophoblasticdifferentiation and that the metabolic clearance of HCG moleculesis slower in the coelomic cavity than in maternal serum. Inmissed abortions, the serum concentrations of intact HCG, HCGand free HCG and the coelomic concentration of total proteinwere significantly lower than in normal pregnancies. In threeout of nine anembryonic pregnancies diagnosed by ultrasound,embryonic remnants were present at histological examination.The coelomic concentration of total protein was extremely lowin all missed abortions with advanced trophoblastic necrosis,whereas the HCG concentration was low when embryonic remnantswere absent. These findings support the concept that embryonicand placental development are closely related in the first trimesterof human pregnancy, placental biological functions persistingonly for a limited period of time after embryonic demise.     

Are pregnancy-associated plasma protein-A (PAPP-A) and CA 125 measurements after IVF-ET possible predictors of early pregnancy wastage?

Pregnancy-associated plasma protein-A (PAPP-A), a macromolecular glycoprotein of placental origin, was reported to be depressed in established ectopic pregnancies. CA 125 is a known marker for ovarian cancer found to be elevated during the first trimester of pregnancy and in women with pelvic inflammatory disease. The present study investigated the usefulness of these parameters to predict the outcome of pregnancy in asymptomatic patients with a positive pregnancy test after in-vitro fertilization and embryo transfer (IVF-ET). Blood samples (n = 159) were obtained at different periods of time post-ET from 39 women, 21 of whom experienced a normal pregnancy, 12 had an intrauterine abortion and six had an ectopic pregnancy. PAPP-A and CA 125 were measured by radioimmunoassays. From day 30 onwards in normal pregnancies, PAPP-A was significantly increased over non-pregnant controls. In the spontaneous abortion group, the levels of PAPP-A were significantly lower than in normal pregnancy but higher than in non-pregnant controls. In ectopic pregnancy, PAPP-A remained at the level of non-pregnant controls throughout the entire observation period. CA 125 was significantly increased in all types of pregnancy. However, in two cases of hyperstimulation followed by a normal pregnancy and in four cases of ectopic pregnancy with signs of peritoneal irritation (hydrosalpinx, ruptured ectopic or salpingitis) the levels of CA 125 were 15-50 times higher than in normal pregnancies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Second trimester maternal serum pregnancy specific beta-1 glycoprotein (SP-1) levels in normal and Down syndrome pregnancies

Maternal serum pregnancy specific beta-1 glycoprotein (SP-1) levels in the second trimester may be predictive of Down syndrome (DS). An enzyme immunoassay was used to measure SP-1 sera from 46 DS pregnancies and 117 normal control women matched for maternal age, gestational age, and length of storage. In the normal control samples, there were slight correlations between the SP-1 concentration and maternal age. The maternal serum SP-1 levels increased with each week of gestation from 15 to 20 weeks. All but one of the DS sera had SP-1 levels greater than the normal median. Using a cutoff of 2.8 multiples of the median (MoM), 15.2% of the DS pregnancies were detected with a false-positive rate of 4.3%. A combinational logistic regression analysis of maternal age and pregnancy related serum proteins will detect additional DS pregnancies and decrease the false-positive rate. The combination of maternal age and SP-1 detected 33 (71.7%) of Down syndrome pregnancies. The addition of maternal serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels allowed for the detection of 36 (78.3%) of the DS pregnancies with a decrease in the false-positive rate to 3.4%. The measurement of other serum constituents in conjunction with AFP appears to be a valuable addition to current screening programs, as this can increase the proportion of DS cases detected prenatally.     

Predictive value of a single serum pregnancy associated plasma protein-A or progesterone in the diagnosis of abnormal pregnancy

The value of a single measurement of serum levels of pregnancy associated plasma protein-A (PAPP-A) or progesterone (P4) in predicting abnormal gestations was assessed in 65 patients. P4 was greater than 20 ng/ml (mean +/- SEM 61.2 +/- 6.6 ng/ml, range 22.4-100.0 ng/ml) in all patients with normal intrauterine pregnancies (n = 21), and greater than 20 ng/ml (mean +/- SEM 8.5 +/- 3.9 ng/ml, range 0.1-68.8 ng/ml) in 16 out of 17 patients destined to abort spontaneously. Patients with ectopic gestations (n = 27) exhibited P4 values less than 20 ng/ml (mean +/- SEM 6.4 +/- 1.2 ng/ml, range 0.1-17.2 ng/ml). P4 levels in normal pregnancies were significantly higher (P = 0.001) than those of abnormal gestations. PAPP-A levels ranged from undetectable to 6448 mIU/ml in normal gestations. In 42 out of 44 abnormal pregnancies levels of PAPP-A were less than 100 mIU/ml, as were 7 out of 14 normal intrauterine pregnancies of less than 7 weeks gestational age. No ectopic demonstrated a value of PAPP-A greater than 50 mIU/ml and in 23 out of 27 ectopics, levels were undetectable. However, PAPP-A was less specific than P4 in correctly discriminating normal from abnormal gestations and exhibited lower positive and negative predictive values. It can be concluded therefore that a single PAPP-A measurement is of limited value in discerning normal from abnormal pregnancy prior to 8 weeks gestation. However, a single serum P4 is highly accurate and specific in detecting abnormal pregnancy, regardless of gestational age.     

Pregnancy: Reduced circulating placental protein concentrations during the first trimester are associated with preterm labour and low birth weight

Serum concentrations of human chorionic gonadotrophin (HCG),Schwangerschaftsprotein 1 (SP-1), pregnancy-associated plasmaprotein A (PAPP-A), progesterone and oestradiol were measuredat weekly intervals between the fifth (embryo transfer plus3 weeks) and 13th week of gestation during the first trimesterof pregnancies achieved following in-vitro fertilization (IVF)and embryo transfer in a group of women who delivered before(n = 8) or at term (n = 52). Those women who had a preterm deliveryhad significantly lower concentrations of PAPP-A (weeks 7–13;P = 0.0001–0.028) and SP-1 (weeks 6–8 and 10–12;P = 0.004–0.04). After correction of birth weight forsex and gestational age at delivery, preterm delivery was foundnot to be associated with growth retardation. However, comparisonof the circulating concentrations of the substances analysedin mothers who delivered babies of < 85% of the 50th centileof the normal range of birth weight for a given gestationalage and sex, with those who delivered babies of >85% revealedthat the concentrations of HCG (P = 0.012–0.04 on weeks6–9) and SP-1 (P = 0.003–0.03 on weeks 7, 9–13)were significantly lower in the former group. Weak, inconsistentassociations were found between the circulating concentrationsof HCG, SP-1 and PAPP-A and both corrected birth weight andgestational age at delivery. Thus, both the gestational ageat delivery and low birth weight may be related to impairedplacental development/function during the first trimester.     

A longitudinal study of maternal serum vascular endothelial growth factor in early pregnancy

Using a competitive radioimmunoassay to measure total immunoreactive vascular endothelial growth factor (VEGF), we describe for the first time longitudinal changes in serum VEGF in early pregnancy. The measurements were obtained from 26 women following the transfer of cryopreserved embryos; 18 singleton and eight twin pregnancies were identified by ultrasound at 6 weeks gestation and subsequently delivered as live births. Subjects did not have corpora lutea and exogenous hormone support was provided for the first 70 days of pregnancy. Serum VEGF increased approximately 30 days after embryo transfer and thereafter continued to rise in both singleton and twin pregnancies over a period of 20-40 days after which concentrations remained elevated. The longitudinal profile of serum VEGF concentrations was characterized by a logistic curve for singleton and twin pregnancies; the profile of VEGF concentrations in the twin pregnancies was significantly higher than in the singleton pregnancies (P < 0.0001). Profiles of the longitudinal concentrations of serum human chorionic gonadotrophin (HCG), oestradiol and progesterone were created by polynomial regression for singleton and twin pregnancies. The VEGF profiles were positively correlated with the profiles of HCG (r = 0.44, P = 0.02) and oestradiol (r = 0.36, P = 0.07) but not progesterone (r = 0.16, P = 0.42). Serum VEGF concentrations in the singleton thawed embryo pregnancies were compared with gestation- matched normal singleton pregnancies with corpora lutea. Concentrations of VEGF were significantly (P = 0.004) greater in the pregnancies with corpora lutea although this difference became less marked with advancing gestation. In addition to its important role in angiogenesis, we speculate that VEGF is involved in mechanisms which control the maternal cardiovascular adaptation to pregnancy.