Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization Sandy Chuan, M.D.,a Michael Homer, M.D.,b Raj Pandian, Ph.D.,c Deirdre Conway, M.D.,d Gabriel Garzo, M.D.,e Lisa Yeo, C.L.S., S/E.L.D.,e and H. Irene Su, M.D., M.S.C.E.b a San Diego Fertility Center, San Diego, California; b Division of Reproductive Endocrinology and Infertility, University of California, San Diego, San Diego, California; c Pan Laboratories, Irvine, California; d Utah Fertility Center, Pleasant Grove, Utah; and e Reproductive Partners Medical Group, La Jolla, California
Objective: To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Design: Cohort Setting: Academic assisted reproduction center. Patient(s): Consecutive patients undergoing IVF-ET Intervention(s): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Main Outcome Measure(s): Ongoing pregnancy beyond 9 weeks of gestation. Result(s): Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. Conclusion(s): In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing Use your smartphone pregnancies. (Fertil SterilÒ 2014;101:392–8. Ó2014 by American Society for Reproductive to scan this QR code Medicine.) and connect to the Key Words: Early pregnancy, hCG, hyperglycosylated hCG, in vitro fertilization Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/chuans-hyperglycosylated-hcg-ivf-outcomes/
H
yperglycosylated human chorionic gonadotropin (hhCG) is a variant of human chorionic gonadotropin (hCG), which is a molecule produced by placental trophoblast cells in pregnancy, in gestational
trophoblastic disease, and by other tumors (1–3). The hCG glycoprotein consists of an alpha subunit, a beta subunit, and variable carbohydrate content. Heterogeneity in either the protein or carbohydrate components
Received May 30, 2013; revised and accepted November 5, 2013; published online December 17, 2013. S.C. has nothing to disclose. M.H. has nothing to disclose. R.P. has nothing to disclose. D.C. has nothing to disclose. G.G. has nothing to disclose. L.Y. has nothing to disclose. H.I.S. has served on the advisory board for Ferring Pharmaceuticals. Supported by HD058799 (IS), American Cancer Society MRSG-08–110–01-CCE (IS). The laboratory with the patent on the particular test used in this study paid for the samples that were run. Reprint requests: H. Irene Su, M.D., M.S.C.E., Moores Cancer Center, UCSD, 3855 Health Sciences Drive, #0901, La Jolla, CA 92093–0901 (E-mail: [email protected]). Fertility and Sterility® Vol. 101, No. 2, February 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2013.11.003 392
discussion forum for this article now.*
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distinguishes one form of hCG from another. The hyperglycosylated variant of hCG is structurally distinct because of four double-size O-linked oligosaccharides and four larger Nlinked sugar side chains (4). A monoclonal antibody highly specific for hhCG has been purified and has
Objective: To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Design: Cohort Setting: Academic assisted reproduction center. Patient(s): Consecutive patients undergoing IVF-ET Intervention(s): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Main Outcome Measure(s): Ongoing pregnancy beyond 9 weeks of gestation. Result(s): Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. Conclusion(s): In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing Use your smartphone pregnancies. (Fertil SterilÒ 2014;101:392–8. Ó2014 by American Society for Reproductive to scan this QR code Medicine.) and connect to the Key Words: Early pregnancy, hCG, hyperglycosylated hCG, in vitro fertilization Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/chuans-hyperglycosylated-hcg-ivf-outcomes/
H
yperglycosylated human chorionic gonadotropin (hhCG) is a variant of human chorionic gonadotropin (hCG), which is a molecule produced by placental trophoblast cells in pregnancy, in gestational
trophoblastic disease, and by other tumors (1–3). The hCG glycoprotein consists of an alpha subunit, a beta subunit, and variable carbohydrate content. Heterogeneity in either the protein or carbohydrate components
Received May 30, 2013; revised and accepted November 5, 2013; published online December 17, 2013. S.C. has nothing to disclose. M.H. has nothing to disclose. R.P. has nothing to disclose. D.C. has nothing to disclose. G.G. has nothing to disclose. L.Y. has nothing to disclose. H.I.S. has served on the advisory board for Ferring Pharmaceuticals. Supported by HD058799 (IS), American Cancer Society MRSG-08–110–01-CCE (IS). The laboratory with the patent on the particular test used in this study paid for the samples that were run. Reprint requests: H. Irene Su, M.D., M.S.C.E., Moores Cancer Center, UCSD, 3855 Health Sciences Drive, #0901, La Jolla, CA 92093–0901 (E-mail: [email protected]). Fertility and Sterility® Vol. 101, No. 2, February 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2013.11.003 392
discussion forum for this article now.*
* Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
distinguishes one form of hCG from another. The hyperglycosylated variant of hCG is structurally distinct because of four double-size O-linked oligosaccharides and four larger Nlinked sugar side chains (4). A monoclonal antibody highly specific for hhCG has been purified and has
