title: Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT.
abstract: Does embryo culture medium influence pregnancy and perinatal outcome in IVF?
  
  
  
  Embryo culture media used in IVF affect treatment efficacy and the birthweight of newborns.
  
  
  
  A wide variety of culture media for human preimplantation embryos in IVF/ICSI treatments currently exists. It is unknown which medium is best in terms of clinical outcomes. Furthermore, it has been suggested that the culture medium used for the in vitro culture of embryos affects birthweight, but this has never been demonstrated by large randomized trials.
  
  
  
  We conducted a multicenter, double-blind RCT comparing the use of HTF and G5 embryo culture media in IVF. Between July 2010 and May 2012, 836 couples (419 in the HTF group and 417 in the G5 group) were included. The allocated medium (1:1 allocation) was used in all treatment cycles a couple received within 1 year after randomization, including possible transfers with frozen-thawed embryos. The primary outcome was live birth rate.
  
  
  
  Couples that were scheduled for an IVF or an ICSI treatment at one of the six participating centers in the Netherlands or their affiliated clinics.
  
  
  
  The live birth rate was higher, albeit nonsignificantly, in couples assigned to G5 than in couples assigned to HTF (44.1% (184/417) versus 37.9% (159/419); RR: 1.2; 95% confidence interval (CI): 0.99-1.37; P = 0.08). Number of utilizable embryos per cycle (2.8 ± 2.3 versus 2.3 ± 1.8; P < 0.001), implantation rate after fresh embryo transfer (20.2 versus 15.3%; P < 0.001) and clinical pregnancy rate (47.7 versus 40.1%; RR: 1.2; 95% CI: 1.02-1.39; P = 0.03) were significantly higher for couples assigned to G5 compared with those assigned to HTF. Of the 383 live born children in this trial, birthweight data from 380 children (300 singletons (G5: 163, HTF: 137) and 80 twin children (G5: 38, HTF: 42)) were retrieved. Birthweight was significantly lower in the G5 group compared with the HTF group, with a mean difference of 158 g (95% CI: 42-275 g; P = 0.008). More singletons were born preterm in the G5 group (8.6% (14/163) versus 2.2% (3/137), but singleton birthweight adjusted for gestational age and gender (z-score) was also lower in the G5 than in the HTF group (-0.13 ± 0.08 versus 0.17 ± 0.08; P = 0.008).
  
  
  
  This study was powered to detect a 10% difference in live births while a smaller difference could still be clinically relevant. The effect of other culture media on perinatal outcome remains to be determined.
  
  
  
  Embryo culture media used in IVF affect not only treatment efficacy but also perinatal outcome. This suggests that the millions of human embryos that are cultured in vitro each year are sensitive to their environment. These findings should lead to increased awareness, mechanistic studies and legislative adaptations to protect IVF offspring during the first few days of their existence.
  
  
  
  This project was partly funded by The NutsOhra foundation (Grant 1203-061) and March of Dimes (Grant 6-FY13-153). The authors declare no conflict of interest.
  
  
  
  NTR1979 (Netherlands Trial Registry).
  
  
  
  1 September 2009.
  
  
  
  18 July 2010.
authors.affiliation: Department of Obstetrics & Gynaecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Sander H M
authors.initials: SH
authors.lastname: Kleijkers
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eleni
authors.initials: E
authors.lastname: Mantikou
authors.affiliation: IVF Department, Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: Slappendel
authors.affiliation: Center for Reproductive Medicine, St. Elisabeth Hospital, Tilburg, The Netherlands.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Consten
authors.affiliation: Section of Reproductive Medicine, Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jannie
authors.initials: J
authors.lastname: van Echten-Arends
authors.affiliation: Department of Obstetrics and Gynaecology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Wetzels
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Madelon
authors.initials: M
authors.lastname: van Wely
authors.affiliation: Department of Obstetrics & Gynaecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Luc J M
authors.initials: LJ
authors.lastname: Smits
authors.affiliation: Department of Obstetrics & Gynaecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Aafke P A
authors.initials: AP
authors.lastname: van Montfoort
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Repping
authors.affiliation: Department of Obstetrics & Gynaecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands john.dumoulin@mumc.nl S.mastenbroek@amc.uva.nl.
authors.forename: John C M
authors.initials: JC
authors.lastname: Dumoulin
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands john.dumoulin@mumc.nl S.mastenbroek@amc.uva.nl.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Mastenbroek
mesh_terms: D001724:Birth Weight / Q000502:physiology*; D003470:Culture Media; D004311:Double-Blind Method; D046149:Embryo Culture Techniques / Q000379:methods*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D050498:Live Birth; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome
chemical_list: D003470:Culture Media
keywords: IVF/ICSI; birthweight; culture medium; human preimplantation embryos; live birth