Study Question: Have changes in culture media used for IVF resulted in changes in offspring birthweight or placental weight that differed from the trends in offspring from spontaneous conceptions during the corresponding time periods?

Summary Answer: Changes in culture media used for IVF were associated with significant differences in offspring birthweight and in placental weight to birthweight ratio when compared with the trend in offspring from spontaneous conceptions during the time periods.

What Is Known Already: The effect of culture media used for IVF on offspring birthweight has varied between studies. There is a large variation in birthweight between newborns, and birthweight may vary across populations and over time. Such variations may therefore have influenced previous results.

Study Design, Size, Duration: We included all singleton births from IVF at one treatment center in Norway during the years 1999-2011(n = 2435) and all singleton births from spontaneous conceptions in Norway during the same years (n = 698 359).

Participants/materials, Setting, Methods: Three different media were used for embryo culture; Medicult Universal IVF (1999 through 2007, n = 1584), Medicult ISM1 (2008 until 20 September 2009, n = 402) and Vitrolife G-1 PLUS (21 September 2009 through 2011, n = 449). We estimated mean birthweight and placental weight in IVF pregnancies by culture media. We also estimated mean weights in IVF and in spontaneous pregnancies by year of birth. Thereafter, we studied whether the changes in mean weights in IVF pregnancies differed from the changes in weight in spontaneous pregnancies in the periods corresponding to culture media changes by applying a grouped difference-in-difference analysis. Adjustments were made for parity, maternal age and gestational age at birth.

Main Results And The Role Of Chance: In singleton offspring from IVF the mean birthweight was 3447.6 g with Medicult Universal, 3351.7 g with Medicult ISM1 and 3441.4 g with Vitrolife G-1 PLUS (P < 0.05). The corresponding mean placental weights were 684.1, 693.4 and 704.3 g (P < 0.05). In offspring from spontaneous conceptions the mean birthweight decreased (56.9 g) and the placental weight increased (9.3 g) during the study period. The adjusted difference in birthweight in offspring from IVF decreased with 35.0 g by the change from Medicult Universal to Medicult ISM1 (P = 0.16) and increased with 79.9 g by the change from Medicult ISM1 to Vitrolife G-1 PLUS (P = 0.01) when compared with changes in offspring after spontaneous conceptions, We also found a significant increase in placental weight in relation to birthweight by the change from Medicult ISM1 to Vitrolife G-1 PLUS (P = 0.02).

Limitations, Reasons For Caution: There may be underlying factors that have influenced both birthweight and the use of culture media in IVF pregnancies. Lack of adjustment for such possible factors may have biased our results.

Wider Implications Of The Findings: We found a significant effect of culture media used for IVF on birthweight and on placental weight in relation to birthweight. Also the population changes over time should encourage identification of factors in very early embryonic life that may influence birthweight and placental weight.

Study Funding/competing Interests: We received funding from the South-Eastern Regional Health Authority in Norway for this study (2011136-2012). None of the authors has any conflicts of interest to declare.

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