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LH/hCG receptor ELISA: Diagnostic tests for fertility treatment (IVF) and early detection of pregnancy disorders

Origin Biomarkers has developed three novel diagnostics. These tests measure the blood concentration of the soluble (circulating) form of LHCGR and its complex with hormones LH and hCG by ELISA.

Test 1: sLHCGR alone
Test 2: LH-sLHCGR (Hormone-receptor complex)
Test 3: hCG-sLHCGR (Hormone-receptor complex)
Under Development & Validation: TSH-LHCGR

Discovery

Secretion of sLHCGR from tissues followed by detection of sLHCGR in blood and follicular fluid.

Technology

Based on unique biomarkers for EARLY detection of preeclampsia and other pregnancy diseases/infertility

Thyroid Stimulating Hormone (TSH) levels during pregnancy can affect fetal brain development. Because of receptor similarities, TSH can bind to LHCGR, its non-cognate receptor, particularly during early pregnancy when hCG levels are high. This binding can be monitored using our TSH-sLHCGR assay. The clinical significance of this assay is currently being evaluated.

IVF applications: Human Infertility Treatment

There are three major clinical applications of pre-treatment sLHCGR based on the data presented here. SLHCGr concentration is an indicator of

a) embryo implantation/clinical pregnancy,

b) early miscarriage,

c) multiple and premature births.

Increase the chance of clinical pregnancy and reduce early miscarriage

First, high pre-treatment serum sLHCGR indicates a likely poor implantation rate (stimulation cycle) and increased early pregnancy loss (EPL) rate on embryo transfer with and without prior ovarian stimulation. This allows clinicians to identify a set of patients with potentially poor outcomes well before the treatment begins. Data from pre-treatment sLHCGR concentrations provides access to an additional stratum of information which can be used to tune treatment regimes more finely. In light of this, failed implantation and early miscarriage rates could be reduced without impacting the number of successful treatments.

The clinical pregnancy in fresh and frozen embryo transfer could be similar

The second clinical application is the potential advantage to patients undergoing fresh embryo transfer with very low pre-treatment sLHCGR. These women tend to have a higher than average clinical pregnancy rate (38%), not significantly different from that of frozen embryo transfer (43.9%). Therefore, clinical success rate for this group of patients could be rendered independent of the mode of embryo transfer.

Reduce multiple births without compromising with the success rate

Blood tests showing very low sLHCGR prior to embryo transfer can help to estimate the likelihood of multiple births following  transfer of 2 or more embryos and premature (≤ 34 wks) births following single embryo transfer.

 

Applications in Prenatal Diagnosis

First trimester tests for Down’s, premature birth and preeclampsia

Down’s Syndrome

The sLHCGR and hCG-LHCGR together with PAPP-A , free beta hCG and NT (combined screen markers) increase the detection rate and reduce the false positive rates dramatically.

The LHCGR-R (ratio of sLHCGR:hCG-LHCGR) is an independent marker for Downs.

Preeclampsia & Premature birth

The free sLHCGR or LHCGR-D (total sLHCGR minus hCG-sLHCGR) is a more effective marker for predicting preeclampsia at early pregnancy than PLGF/sFlt-1 system

Our Publications on LH/hCG receptor

Banerjee S, Smallwood A, Chambers AE, Papageorghiou A, Loosfelt H, Spencer K, Campbell S, Nicolaides K: A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies. Reprod Biol Endocrinol2005, 3:25
Abstract | HTML | PDF

Chambers AE, Stanley PF, Randeva H, Banerjee S. Microvesicle-mediated release of soluble LH/hCG receptor (LHCGR) from transfected cells and placenta explants. Reprod Biol Endocrinol. 2011 May 15;9:64. doi: 10.1186/1477-7827-9-64.
Abstract | HTML | PDF

Chambers AE, Nayini KP, Mills WE, Lockwood GM, Banerjee S. Circulating LH/hCG receptor (LHCGR) may identify pre-treatment IVF patients at risk of OHSS and poor implantation. Reprod Biol Endocrinol. 2011 Dec 23;9:161. doi: 10.1186/1477-7827-9-161.
Abstract | HTML | PDF

Chambers AE, Griffin C, Naif SA, Mills I, Mills WE, Syngelaki A, Nicolaides KH, Banerjee S. Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down's syndrome, preterm delivery and preeclampsia. Reprod Biol Endocrinol. 2012 Dec 17;10:113. doi: 10.1186/1477-7827-10-113.
Abstract | HTML | PDF

Chambers AE, Mills WE, Mercadé I, Crovetto F, Crispi F, Bodi LR, Pugia M, Mira A, Lasalvia L, Banerjee S, Casals E, Gratacos E. The utility of circulating LHCGR as a predictor of Down's syndrome in early pregnancy. BMC Pregnancy Childbirth. 2014 Jun 6;14:197. doi: 10.1186/1471-2393-14-197.
Abstract | HTML | PDF

Crovetto F, Figueras F, Crispi F, Triunfo S, Pugia M, Lasalvia L, Chambers AE, Mills WE, Banerjee S, Mercadé I, Casals E, Mira A, Rodriguez-Revenga Bodi L, Gratacós E.
Forms of Circulating Luteinizing Hormone Human Chorionic Gonadotropin Receptor for the Prediction of Early and Late Preeclampsia in the First Trimester of Pregnancy.
Fetal Diagn Ther. 2015 Feb 11. [Epub ahead of print]
Abstract