title: Birthweight distribution in ART singletons resulting from embryo culture in two different culture media compared with the national population.
abstract: OBJECTIVE
  Is there a difference in birthweight distribution in ART singletons born after IVF culture in two different culture media?
  
  
  CONCLUSIONS
  There is no effect of culture media on both crude and adjusted birthweight distributions in ART singletons from nulliparous mothers.
  
  
  BACKGROUND
  Studies on human ART singletons have reported a difference in birthweight in singletons following IVF culture in different culture media. However, other studies comparing different culture media have not shown any significant differences in birthweight.
  
  
  METHODS
  This study was a retrospective comparison of birthweights in IVF/ICSI singletons conceived after fresh embryo transfer following embryo culture in Cook or Medicult medium and in a national cohort of naturally conceived singletons in nulliparous women. The study compares four independent groups consisting of singletons in nulliparous women from Cook-d2: 2-day culture in Cook medium at Rigshospitalet (n = 974), Medicult-d2: 2-day culture in Medicult EmbryoAssist medium at Rigshospitalet (n = 147), Medicult-d3: 3-day culture in Medicult EmbryoAssist medium with and without added GM-CSF (n = 204), and DK: pregnancies from the Danish birth registry (n = 106842).
  
  
  METHODS
  The study compares the birthweights of singletons from nulliparous women in the four independent groups mentioned above; Cook-d2: Medicult-d2: Medicult-d3: and DK. In addition, distributions of large and small for gestational age infants were compared between the groups and a multiple linear regression analysis was used to determine which factors determined birthweight.
  
  
  RESULTS
  We found no significant difference in the crude birthweight distributions between singletons born after culture in Cook-d2 or Medicult-groups. Singleton girls from the Cook-d2 group weighed 3302 ± 28 g, versus 3252 ± 76 in the Medicult-d2 group (difference 50 g; P = 0.547). Singleton boys from the Cook-d2 group weighed 3430 ± 27 g, versus 3354 ± 56 in the Medicult-d2 group (difference 76 g; P = 0.279). In the background population, mean birthweights for singleton girls and boys were 3383 ± 2.4 g and 3494 ± 2.5 g, respectively. The mean birthweights of girls, 3315 ± 61 g, and boys, 3383 ± 64 g, in the Medicult-d3 group were not significantly different from that in the Medicult-d2 group. When pooling data from all culture media groups, we found the same slightly lower mean birthweight in IVF/ICSI singletons when compared with the national birth cohort as has been previously reported (Cook-d2 + Medicult-d2 + d3 versus birth cohort; girls: P < 0.001, boys: P < 0.001). We also pooled data on boys and girls and calculated the mean birthweight for the Cook-d2, Medicult-d2 and Medicult-d3 groups and found no significant differences.
  
  
  CONCLUSIONS
  The retrospective design and the inherent risk of confounding factors is a limitation. Selection bias cannot be excluded as the embryos cultured in Cook-d2 and Medicult-d2 were from single centre studies while data in Medicult-D3 group were derived from a multicentre study.
  
  
  CONCLUSIONS
  This large cohort of singletons born after IVF/ICSI shows no difference in crude mean birthweight after culture in two different culture media, indicating that if such a difference exists, this must be specific for certain culture media. As expected we found a slightly lower mean birthweight in ART compared with naturally conceived singletons. This suggests that parental characteristics or IVF technique related factors other than type of culture medium may influence the birthweight in ART singletons.
  
  
  BACKGROUND
  No external funding was used for this study. No conflicts of interest are declared.
authors: Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark jlem0002@regionh.dk.
authors: J G
authors: JG
authors: Lemmen
authors: Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark Present Address: Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, 2650 Hvidovre, Denmark.
authors: A
authors: A
authors: Pinborg
authors: Department of Clinical Microbiology, Hvidovre Hospital, 2650 Hvidovre, Denmark.
authors: S
authors: S
authors: Rasmussen
authors: Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.
authors: S
authors: S
authors: Ziebe
mesh_terms: D000328:Adult; D001724:Birth Weight; D003470:Culture Media; D046149:Embryo Culture Techniques; D004624:Embryo Transfer; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D027724:Reproductive Techniques, Assisted; D012189:Retrospective Studies
chemical_list: D003470:Culture Media
keywords: IVF/ICSI; birthweight; culture media; outcome; singleton