Heparin-binding epidermal growth factor significantly improves human blastocyst development and hatching in serum-free medium.
The purpose of this study was to determine the effect of heparin-binding epidermal growth factor (HB-EGF) on human embryo development in vitro from days 2 to 14 post-insemination. Embryos were cultured in a complex serum-free medium (CSFM3) in the absence and presence of 1 nM and 100 nM HB-EGF. Development to the blastocyst stage of A-C-grade embryos (A grade = highest quality) was improved in the presence of 1 nM HB-EGF from 40.7% to 65.4% and significantly increased to 71.0% in the presence of 100 nM HB-EGF (P < 0.05). Moreover, the percentage of blastocysts hatching was improved in the presence of 1 nM HB-EGF from 45.5% to 70.5% and almost doubled to 81.8% (P < 0.05) in the presence of 100 nM HB-EGF. HB-EGF promoted the development of high-grade (classed as BG1) and medium-grade (BG2) blastocysts. There was no difference in blastocyst quality between the control and HB-EGF-treated embryos as assessed by blastocyst cell number and consumption of the major energy substrates, pyruvate and glucose, measured on day 6 of culture. Further development was assessed by culturing the blastocysts on growth factor-reduced Matrigel (GFR-Matrigel). Adherence and outgrowth were observed, with these embryos producing significantly more human chorionic gonadotrophin over days 7-14 compared with those cultured on plastic (47.8 +/- 8.0 mU versus 23.0 +/- 8.6 mU). The addition of recombinant human growth factors to clinical in-vitro fertilization medium may be useful in promoting embryo development with a view to carrying out blastocyst transfers.
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, UK.
K L
KL
Martin
D H
DH
Barlow
I L
IL
Sargent
D001757:Blastomeres / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004624:Embryo Transfer; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D011247:Pregnancy
D016895:Culture Media, Serum-Free; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor