Discordant and variable production of human chorionic gonadotropin and its free alpha- and beta-subunits in early pregnancy

Abstract

Monoclonal antibodies specific to dimer hCG (alpha beta), free beta-subunit (beta hCG), free alpha-subunit (alpha hCG), and total beta hCG (dimer + free beta hCG) were used to monitor discordant production of hCG and its subunits during the early stages of embryo implantation. Sera collected 3 to 22 days postovum retrieval were assayed from patients participating in an in vitro fertilization program. In the majority of patients with ongoing pregnancies (n = 16), rising levels using the dimer hCG assay were first detected at an average time of 9.2 days post retrieval compared to 8.3 days for the total beta hCG assay and 6.5 days for the free beta hCG assays. Between days 5 to 9 after retrieval, the rises in the total beta hCG assay were due to predominantly free beta hCG subunit production. The proportion of total beta hCG levels due to free beta hCG subunits declined progressively from day 9 to less than 5% by day 22. Free alpha hCG levels remained low with rising levels first detected from day 18. A second group of patients (n = 12) had delayed, slowly rising levels in the total beta hCG assay which were first detected at an average of 12.4 days and associated with mainly biochemical pregnancies (n = 10). In these patients, rising total beta hCG levels were due to predominantly free beta hCG production. The subsequent loss of their pregnancy may be due to poor luteal support associated with delayed rises in dimer hCG levels. In nonconceptual cycles (n = 47) no significant rises were detected in dimer or free hCG subunits. Although the major form of hCG in circulation is dimer hCG, the origin of free beta hCG production in the early stages of implantation may be due to poorly differentiated trophoblastic tissue. Thus falling levels of free beta hCG subunits associated with increasing dimer hCG production may reflect increasing alpha hCG production by the proliferating layer of cytotrophoblastic cells.