Pregnancy Diagnosis

The diagnosis of pregnancy requires a multifaceted approach using 3 main diagnostic tools. These are history and physical examination, laboratory evaluation, and ultrasonography. Currently, physicians may use all of these tools to diagnose pregnancy at early gestation and to help rule out other pathologies. The classic presentation of pregnancy is a woman with menses of regular frequency who presents with amenorrhea, nausea, vomiting, generalized malaise, and breast tenderness.

Several hormones can be measured and monitored to aid in the diagnosis of pregnancy. The most commonly used assays are for the beta subunit of hCG. Other hormones that have been used include progesterone and early pregnancy factor. The hCG is a glycoprotein similar in structure to follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyrotropin. It is composed of alpha and beta subunits. The alpha subunit of hCG is similar to the alpha subunit of FSH, LH, and thyrotropin. The free beta subunit of hCG differs from the others in that it has a 30–amino acid tailpiece at the COOH terminus. Free beta subunits are degraded by macrophage enzymes in the kidney to make a beta subunit core fragment, which is primarily detected in urine samples.

Currently, 4 main hCG assays are used: (1) radioimmunoassay, (2) immunoradiometric assay, (3) enzyme-linked immunosorbent assay (ELISA), and (4) fluoroimmunoassay. These assays are highly specific for hCG with antibodies directed against 2 or more isotopes on the intact hCG molecule. Time of detection is related to the sensitivity of the assay being used. Most current pregnancy tests have sensitivity to approximately 25 mIU/mL. Urine devices must be formulated to detect hyperglycosylated hCG, which is the key molecule in early pregnancy.

The beta-hCG subunit is present in the syncytial layer of the blastomere. Hyperglycosylated hCG is a form of hCG produced by invasive cytotrophoblast cells in early pregnancy and implantation. Detection in maternal serum and urine is evident only after implantation and vascular communication has been established with the decidua by the syncytiotrophoblast 8-10 days after conception. hCG is present in the maternal circulation as either an intact dimer, alpha or beta subunit, and degraded form, or beta core fragment. Intact and free beta subunit are initially the predominant forms of hCG, with the beta core fragment emerging as the predominant form in the fifth week after conception.

The cytotrophoblast and syncytiotrophoblast each secrete a variety of hormones that include, but are not limited to, corticotropin-releasing hormone, gonadotropin-releasing hormone, thyrotropin-releasing hormone, somatostatin, corticotropin, human chorionic thyrotropin, human placental lactogen, inhibin/activin, transforming growth factor-beta, insulinlike growth factors 1 and 2, epidermal growth factor, pregnancy-specific beta-1 glycoprotein, placental protein 5, and pregnancy-associated plasma protein-A. To date, no commercially feasible tests that use these hormones have been made available to aid in the diagnosis of pregnancy.

 

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