The influence of IVF/ICSI treatment on human embryonic growth trajectories.

STUDY QUESTION: Is in vitro fertilization treatment with or without intracytoplasmatic sperm injection (IVF/ICSI) associated with changes in first and second trimester embryonic and fetal growth trajectories and birthweight in singleton pregnancies?

SUMMARY ANSWER: Embryonic and fetal growth trajectories and birthweight are not significantly different between pregnancies conceived with IVF/ICSI treatment and spontaneously conceived pregnancies with reliable pregnancy dating.

WHAT IS KNOWN ALREADY: IVF/ICSI treatment has been associated with increased risks of preterm birth, fetal growth restriction and low birthweight. Decreased first-trimester crown-rump length (CRL) in the general population has been inversely associated with the same adverse pregnancy outcomes.

STUDY DESIGN, SIZE, DURATION: In a prospective periconception birth cohort study conducted in a tertiary centre, 146 singleton pregnancies with reliable pregnancy dating and nonmalformed live borns were investigated, comprised of 88 spontaneous and 58 IVF/ICSI pregnancies.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Serial 3D ultrasound scans were performed from 6 to 12 weeks of gestation. As estimates of embryonic growth, CRL and embryonic volume (EV) were measured using the I-Space virtual reality system. General characteristics were obtained from self-administered questionnaires at enrolment. Fetal growth parameters at 20 weeks and birthweight were obtained from medical records. To assess associations between IVF/ICSI and embryonic growth trajectories, estimated fetal weight and birthweight, stepwise linear mixed model analyses and linear regression analyses were performed using square root transformed CRL and fourth root transformed EV.

MAIN RESULTS AND THE ROLE OF CHANCE: In 146 pregnancies, 934 ultrasound scans were performed of which 849 (90.9%) CRLs and 549 (58.8%) EVs could be measured. Embryonic growth trajectories were comparable between IVF/ICSI pregnancies and spontaneously conceived pregnancies (CRL: βIVF/ICSI = 0.10√mm; P = 0.10; EV: βIVF/ICSI = 0.03(4)√cm³; P = 0.13). Estimated fetal weight and birthweight were also comparable between both groups (βIVF/ICSI = 6 g; P = 0.36 and βIVF/ICSI = 80 g; P = 0.24, respectively).

LIMITATIONS, REASONS FOR CAUTION: Variations in embryonic growth trajectories of spontaneously conceived pregnancies with reliable pregnancy dating may partially be a result of less precise pregnancy dating and differences in endometrium receptivity compared with IVF/ICSI pregnancies.

WIDER IMPLICATIONS OF THE FINDINGS: The absence of a significant difference in embryonic and fetal growth trajectories suggests safety of IVF/ICSI treatment with regard to early embryonic growth. However, further research is warranted to ascertain the influence of IVF/ICSI treatments in a larger study population, and to estimate the impact of the underlying causes of the subfertility and other periconceptional exposures on human embryonic and fetal growth trajectories.

FUNDING STATEMENT: This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Centre.

CONFLICT OF INTEREST: No competing interests are declared.