Discordant and Variable Production of Human Chorionic Gonadotropin and Its Free α- and β-Subunits in Early Pregnancy

Abstract

Monoclonal antibodies specific to dimer hCG (αβ), free 0-subunit (βhCG), free a-subunit (αhCG), and total βhCG (dimer + free αhCG) 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 βhCG assay and 6.5 days for the free βhCG assays. Between days 5 to 9 after retrieval, the rises in the total βhCG assay were due to predominantly free βhCG subunit production. The proportion of total βhCG levels due to free βhCG subunits declined progressively from day 9 to less than 5% by day 22. Free αhCG 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 βhCG 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 βhCG levels were due to predominantly free βhCG 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 βhCG production in the early stages of implantation may be due to poorly differentiated trophoblastic tissue. Thus falling levels of free βhCG subunits associated with increasing dimer hCG production may reflect increasing αhCG production by the proliferating layer of cytotrophoblastic cells.