The sensitivity and specificity of hyperglycosylated hCG (hhCG) levels to reliably diagnose clinical IVF pregnancies at 6 days following embryo transfer

Abstract

ObjectiveTo determine the sensitivity and specificity of hyperglycosylated hCG (hhCG) measurements for the diagnosis of clinical pregnancies in the IVF setting and how soon post embryo transfer (ET) a pregnancy can be detected using an ultrasensitive (hhCG) assay. To determine if a single, early hhCG measurement can discriminate between biochemical and clinical pregnancies.DesignA 4 center prospective blinded clinical trial was performed with patients undergoing IVF-ET. Patients had blood drawn and submitted for hhCG analysis on the day of ET and at days 4, 6, 8, and 12 thereafter. First morning urines were collected and submitted for hhCG analysis on days 0, 4, 6, 8, 10 and 12.SettingFertility CentersOutcome MeasuresClinical pregnancies were defined as an ultrasound study demonstrating a gestational sac and/or heart beat at appropriate gestational ages.ResultsFifty-six of 58 enrolled patients completed the study. There were 25 clinical and 6 biochemical pregnancies. For blastocyst transfers, a single serum or urine hhCG measurement identified pregnancies (both biochemical and clinical) at 6 days post ET with 100% sensitivity and specificity. There were 6 biochemical pregnancies, all following blastocyst transfers. All of these pregnancies were identified by lower values.

Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor

“…In IVF/ICSI cohort, serum samples taken as early as 9–16 days after oocyte retrieval (around day 4–11 after embryo transfer) could discriminate between an ongoing pregnancy and a pregnancy which would result in a spontaneous abortion . Measurements of hCG‐H can also discriminate between ongoing pregnancies, spontaneous abortions and biochemical pregnancies within 2 weeks following embryo transfer . Measurement of hCG‐H in blastocyst culture media, as a predictor of embryo implantation, and in serum within the first 2 weeks following embryo transfer, as an implantation diagnostic, represents a useful test to reduce distress for couples undergoing assisted reproduction.…”

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization

“…To our knowledge, only three smaller studies to date have examined hhCG in IVF (9, 11, 17). Kovalevskaya, et al measured daily urinary hhCG in 22 donor egg recipients who were not exposed to exogenous hCG injections (11).…”

“…A recent study sought to identify cut-off values for hhCG to predict clinical pregnancy after IVF (9). Strom et al recruited a cohort of 56 patients from four fertility centers and measured serum and urine hhCG levels 4, 6, 8 and 12 days after embryo transfer regardless of embryo stage.…”

“…Because of the high proportion, this finding most likely resulted from residual medication used to induce ovulation and less likely from an early pregnancy that did not progress between days 9 and 16. As well, longitudinal data from the Strom study suggest greater residual hCG drug effect if serum is measured as early as day 5 after egg retrieval (9). Therefore, similar to traditional hCG assays, detectability alone is not predictive of pregnancy outcomes; rather the value of hhCG measurement rests on the identification of a threshold hhCG level which optimize specificity for prediction of pregnancy outcomes.…”

“…HhCG comprises the majority of total hCG produced in the early first trimester, dwindling to less than 1% of total hCG by early second trimester (8). Levels of hhCG are measurable in serum, and several studies have reported that absolute hhCG levels or the ratio of hhCG to total hCG can predict clinical pregnancy after in vitro fertilization (IVF) (9) or discriminate between early pregnancy loss and pregnancies progressing beyond 12 weeks in unassisted conceptions (10-12). However, these studies are limited in sample size, particularly in the peri-implantation time frame.…”