ABSTRACT
OBJECTIVES: Tubal rupture as a result of an ectopic pregnancy is the leading cause of first trimester maternal mortality. Currently, the diagnosis of ectopic pregnancy depends on transvaginal ultrasound and serial serum measurements of human chorionic gonadotrophin (hCG), which requires follow up. The objective of this study was to examine whether single point measurements at presentation could distinguish between women with ectopic pregnancy, viable pregnancy, and spontaneous miscarriage. DESIGN AND METHODS: Serum total hCG (hCGt), hyperglycosylated hCG (hCGh), free beta subunit of hCG (hCGß), progesterone (P), and CA-125 were measured by chemiluminescence immunoassay over a 3 month period in 441 women presenting at the emergency room with abdominal pain and a positive pregnancy test. Patient outcomes were followed and confirmed by histology. 65 samples were excluded due to poor sample storage, or lost to follow up. RESULTS: The pregnancy outcomes were 175 viable pregnancies, 175 spontaneous miscarriages, and 26 ectopic pregnancies. A serum hCGt <3736 mIU/mL cut off was 100% sensitive, with 76% specificity, for distinguishing ectopic pregnancy from viable pregnancy; but did not differentiate spontaneous miscarriage. Serum CA125 <41.98 U/mL produced 100% sensitivity and 43% specificity in distinguishing ectopic pregnancy from spontaneous miscarriage. Sequential application of hCGt and CA-125 cut off followed by ultrasound could detect 100% of ectopic pregnancies with 87% specificity for all intrauterine pregnancies. CONCLUSION: The combination of serum hCGt <3736 mIU/mL, followed by CA125 <41.98 U/mL is a promising algorithm for detecting all ectopic pregnancy at initial presentation.
Subject(s)
Abortion, Spontaneous/diagnosis , CA-125 Antigen/blood , Chorionic Gonadotropin, beta Subunit, Human/blood , Pregnancy, Ectopic/diagnosis , Abortion, Spontaneous/blood , Adult , Algorithms , Early Diagnosis , Female , Humans , Pregnancy , Pregnancy Trimester, First , Pregnancy, Ectopic/blood , ProgesteroneABSTRACT
Human chorionic gonadotropin (hCG) is produced by trophoblast cells throughout pregnancy, and gene expression studies have indicated that hCG-beta subunit (hCGß) expression is active at the 2 blastomere stage. Here, we investigated the qualitative hCG output of developing embryos in culture and hCG isoforms expressed in the secretome as a novel sensitive method for detecting hCG. Culture media was collected from the culture plates of 118 embryos in culture (including controls and embryos at different stages of culture) from 16 patients undergoing routine fertility treatment. The hCGß was detectable in media from 2 pronuclear (2PN) stage embryos through to the blastocyst stage. The hCGß was absent in 1PN and arrested embryos as well as all media controls. Prior to hatching, hyperglycosylated hCG (hCGh) was observed selectively in 3PN embryos, but after hatching, along with hCG, became the dominant hCG molecule observed. We have reported at the 2PN stage the earliest evidence of hCGß expression in embryos. There is a suggestion this may be indicative of quality in early embryos, and hCGh seen at the pronuclear stage may suggest triploid abnormality. The dominance of hCG, and hCGh expression, seen after blastocyst hatching may be indicative of potential implantation success. Thus, hCG isoforms have potential roles as biomarkers of embryo viability for embryo/blastocyst transfer.
Subject(s)
Blastocyst/metabolism , Chorionic Gonadotropin, beta Subunit, Human/metabolism , Chorionic Gonadotropin/metabolism , Infertility/metabolism , Biomarkers/metabolism , Culture Media, Conditioned/metabolism , Embryo Culture Techniques , Embryo Implantation , Embryo Transfer , Female , Fertilization in Vitro , Glycosylation , Humans , Infertility/physiopathology , Infertility/therapy , Pregnancy , Prognosis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
BACKGROUND: Early diagnosis of ectopic pregnancy uses ultrasound with serial measurements of total human chorionic gonadotropin (hCG). The objective of this study was to explore the possibility that an isolated measurement of hCG isoforms/subunits rather than total hCG could be used as a single test for ectopic pregnancy. METHODS: Total and intact hCG, free hCG beta- and alpha-subunits (hCGbeta and -alpha), and hCG beta-core fragment were measured by RIA and IRMA in the serum and urine of 76 women presenting at outpatient emergency departments with a positive pregnancy test, lower abdominal pain, and/or vaginal bleeding. Final diagnoses were based on outcomes of pregnancies and tissue histology. RESULTS: Twenty-seven of the 76 women were subsequently diagnosed with viable pregnancies, 37 with spontaneous miscarriage, and 12 with ectopic pregnancy. Concentrations of all forms of hCG were lower in cases of ectopic pregnancy and spontaneous miscarriage than in viable pregnancies. Serum samples gave better results than urine samples. The free hCGbeta isoform (P <0.0001) had 100% sensitivity at a specificity of 79% at a 281 pmol/L (6.5 micro g/L) cutoff. Total hCG (P = 0.005) had comparable ROC characteristics with a 100% sensitivity and 68% specificity at a cutoff value of 1053 pmol/L (375 IU/L). Neither hCGbeta (P = 0.7) nor total hCG (P = 0.4) could distinguish ectopic pregnancies from spontaneous miscarriage. CONCLUSION: Measurement of serum free hCGbeta at the time of presentation can identify women with a high probability of ectopic pregnancy who may benefit from closer surveillance, reducing the risk of tubal rupture.
