IVF Culture Medium and Post-natal Weight in Humans
IVF Culture Medium and Post-natal Weight in Humans
Study Question: Is post-natal growth during the first 2 years of life in IVF singletons affected by type of medium used for culturing human embryos during an IVF treatment?
Summary Answer: The in vitro culture of human embryos in medium from Cook resulted in singletons with a lower weight during the first 2 years of life compared with singletons born after embryo culture in medium from Vitrolife.
What is Known Already: In a previous study, we reported that type of medium used for culturing human IVF embryos during the first few days after fertilization until fresh embryo transfer significantly affects fetal growth and consequently birthweight of the resulting singletons.
Study Design, Size, Duration: From July 2003 to December 2006, a total of 1432 IVF treatment cycles with fresh embryo transfer were randomly allocated to have all embryos cultured in medium from Vitrolife AB (n = 715) or from Cook (n = 717). Two years after delivery, questionnaires were sent to the parents of all children requesting data about weight, height and head circumference around 1, 2, 3, 4, 6, 7.5, 9, 11, 14, 18 and 24 months of age. These measurements were collected as part of the children's health programme at municipal infant welfare centres in the Netherlands by health professionals unaware of this study.
Participants/Materials, Setting, Methods: Patients requiring donor oocytes or applying for PGD were excluded from the study. From the 294 live born singletons that fulfilled our inclusion criteria, 29 were lost to follow-up. The remaining 265 singletons (Cook group: 117, Vitrolife group: 148) were included in the analysis. Data analysis included linear regression, to compare cross-sectionally weight standard deviation score (SDS), height SDS and head circumference, and the first order Berkey-Reed model for a longitudinal analysis of the growth data.
Main Results and The Role of Chance: Singletons in the Vitrolife group were heavier during the first 2 years of life compared with singletons in the Cook group. Cross-sectional analyses showed that adjusted weight SDS differed between groups at 1 (0.35 ± 0.14, P = 0.010), 2 (0.39 ± 0.14, P = 0.006), 3 (0.35 ± 0.14, P = 0.011), 4 (0.30 ± 0.13, P = 0.020), 11 (0.28 ± 0.13, P = 0.036), 14 (0.32 ± 0.13, P = 0.014) and 24 (0.39 ± 0.15, P = 0.011) months of age, while adjusted height SDS was only significantly different at 1 (0.21 ± 0.11, P = 0.048) month of age. Head circumference was similar between the two groups at all ages. Longitudinal analyses showed that both post-natal weight (P = 0.005) and height (P = 0.031) differed between the groups throughout the first 2 years of life, while the growth velocity was not significantly different between the two groups.
Limitations, Reasons for Caution: Factors that might influence post-natal growth were included in the analysis; however, it was not possible to include all such factors, for example childhood diseases or nutrition, as this information was not available.
Wider Implications of the Findings: The effect of culture medium during the first few days after fertilization on prenatal growth and birthweight persists during the first 2 years of life. This suggests that the human embryo is sensitive to its very early environment, and that the culture medium used in IVF may have lasting consequences. Further monitoring of the long-term growth, development and health of IVF children is therefore warranted.
Study Funding/Competing Interest(S): W.V. was funded with an unrestricted research grant from the Stichting Fertility Foundation. The authors declare no conflict of interest.
Trial Registration Number: Not applicable.
The first child conceived by IVF was born 35 years ago (Steptoe and Edwards, 1978). Since then, the use of assisted reproduction technologies (ART) has increased substantially. In 2009, the percentage of children conceived with in vitro techniques ranged from 0.6% up to 4.5% of the national births in Europe (Ferraretti et al., 2013).
IVF singletons have a significantly increased risk of perinatal mortality, preterm birth, small for gestational age, low birthweight and birth defects (Helmerhorst et al., 2004; Jackson et al., 2004; Rimm et al., 2004; McDonald et al., 2009; Pandey et al., 2012) compared with naturally conceived singletons. Both patient-related factors, for example older age of the mother, time to pregnancy, and subfertility of the parents, and specific aspects of ART, for example hormonal stimulation and culture conditions, may be risk factors for the adverse perinatal outcome in IVF children (Pinborg et al., 2013).
Our group showed that the culture medium used during an IVF treatment affects birthweight (Dumoulin et al., 2010; Nelissen et al., 2012). The onset of the growth differentiation was already evident during the second trimester of pregnancy, as a more advanced fetus was seen in the Vitrolife group compared with the Cook group at 20 weeks of gestation, based on the differences between gestational age calculated by dating formulas using fetal biparietal diameter and the actual gestational age (Nelissen et al., 2013). It is important to monitor the post-natal growth of these children to investigate whether this effect of culture medium disappears, is still present or increases later in life.
The aim of our present study was to compare post-natal weight, height and head circumference at several time points (cross-sectional analysis) and post-natal growth (longitudinal analysis) during the first 2 years of life in the same singletons as our previous study.
Abstract and Introduction
Abstract
Study Question: Is post-natal growth during the first 2 years of life in IVF singletons affected by type of medium used for culturing human embryos during an IVF treatment?
Summary Answer: The in vitro culture of human embryos in medium from Cook resulted in singletons with a lower weight during the first 2 years of life compared with singletons born after embryo culture in medium from Vitrolife.
What is Known Already: In a previous study, we reported that type of medium used for culturing human IVF embryos during the first few days after fertilization until fresh embryo transfer significantly affects fetal growth and consequently birthweight of the resulting singletons.
Study Design, Size, Duration: From July 2003 to December 2006, a total of 1432 IVF treatment cycles with fresh embryo transfer were randomly allocated to have all embryos cultured in medium from Vitrolife AB (n = 715) or from Cook (n = 717). Two years after delivery, questionnaires were sent to the parents of all children requesting data about weight, height and head circumference around 1, 2, 3, 4, 6, 7.5, 9, 11, 14, 18 and 24 months of age. These measurements were collected as part of the children's health programme at municipal infant welfare centres in the Netherlands by health professionals unaware of this study.
Participants/Materials, Setting, Methods: Patients requiring donor oocytes or applying for PGD were excluded from the study. From the 294 live born singletons that fulfilled our inclusion criteria, 29 were lost to follow-up. The remaining 265 singletons (Cook group: 117, Vitrolife group: 148) were included in the analysis. Data analysis included linear regression, to compare cross-sectionally weight standard deviation score (SDS), height SDS and head circumference, and the first order Berkey-Reed model for a longitudinal analysis of the growth data.
Main Results and The Role of Chance: Singletons in the Vitrolife group were heavier during the first 2 years of life compared with singletons in the Cook group. Cross-sectional analyses showed that adjusted weight SDS differed between groups at 1 (0.35 ± 0.14, P = 0.010), 2 (0.39 ± 0.14, P = 0.006), 3 (0.35 ± 0.14, P = 0.011), 4 (0.30 ± 0.13, P = 0.020), 11 (0.28 ± 0.13, P = 0.036), 14 (0.32 ± 0.13, P = 0.014) and 24 (0.39 ± 0.15, P = 0.011) months of age, while adjusted height SDS was only significantly different at 1 (0.21 ± 0.11, P = 0.048) month of age. Head circumference was similar between the two groups at all ages. Longitudinal analyses showed that both post-natal weight (P = 0.005) and height (P = 0.031) differed between the groups throughout the first 2 years of life, while the growth velocity was not significantly different between the two groups.
Limitations, Reasons for Caution: Factors that might influence post-natal growth were included in the analysis; however, it was not possible to include all such factors, for example childhood diseases or nutrition, as this information was not available.
Wider Implications of the Findings: The effect of culture medium during the first few days after fertilization on prenatal growth and birthweight persists during the first 2 years of life. This suggests that the human embryo is sensitive to its very early environment, and that the culture medium used in IVF may have lasting consequences. Further monitoring of the long-term growth, development and health of IVF children is therefore warranted.
Study Funding/Competing Interest(S): W.V. was funded with an unrestricted research grant from the Stichting Fertility Foundation. The authors declare no conflict of interest.
Trial Registration Number: Not applicable.
Introduction
The first child conceived by IVF was born 35 years ago (Steptoe and Edwards, 1978). Since then, the use of assisted reproduction technologies (ART) has increased substantially. In 2009, the percentage of children conceived with in vitro techniques ranged from 0.6% up to 4.5% of the national births in Europe (Ferraretti et al., 2013).
IVF singletons have a significantly increased risk of perinatal mortality, preterm birth, small for gestational age, low birthweight and birth defects (Helmerhorst et al., 2004; Jackson et al., 2004; Rimm et al., 2004; McDonald et al., 2009; Pandey et al., 2012) compared with naturally conceived singletons. Both patient-related factors, for example older age of the mother, time to pregnancy, and subfertility of the parents, and specific aspects of ART, for example hormonal stimulation and culture conditions, may be risk factors for the adverse perinatal outcome in IVF children (Pinborg et al., 2013).
Our group showed that the culture medium used during an IVF treatment affects birthweight (Dumoulin et al., 2010; Nelissen et al., 2012). The onset of the growth differentiation was already evident during the second trimester of pregnancy, as a more advanced fetus was seen in the Vitrolife group compared with the Cook group at 20 weeks of gestation, based on the differences between gestational age calculated by dating formulas using fetal biparietal diameter and the actual gestational age (Nelissen et al., 2013). It is important to monitor the post-natal growth of these children to investigate whether this effect of culture medium disappears, is still present or increases later in life.
The aim of our present study was to compare post-natal weight, height and head circumference at several time points (cross-sectional analysis) and post-natal growth (longitudinal analysis) during the first 2 years of life in the same singletons as our previous study.
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