The impact of fresh versus frozen-thawed embryos on maternal serum analyte levels in IVF singleton and twin pregnancies

Purpose To determine whether embryo cryopreservation is associated with a difference in maternal serum analyte levels in singleton and twin pregnancies conceived via in vitro fertilization (IVF). Methods This was a retrospective cohort study of singleton and twin pregnancies conceived via IVF from a university health system from 01/2014 to 09/2019. Patients with available first and second trimester serum analyte data were included and analyzed separately. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A, alpha-fetoprotein (AFP), Inhibin A, and unconjugated estriol (uE3) were compared between two groups: pregnancies conceived after the transfer of fresh embryos versus pregnancies conceived after the transfer of frozen-thawed embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. Results For singletons, fresh embryos were associated with a lower median first trimester free β-hCG (1.00 MoM vs. 1.14 MoM; parameter estimate [PE] 0.90, 95% CI 0.82–0.99, p = .03) compared to frozen-thawed embryos. Fresh embryos were also associated with a lower median second trimester uE3 (0.93 MoM vs. 1.05 MoM; PE 0.88, CI 0.83–0.95, p = .0004) and AFP (1.02 MoM vs. 1.19 MoM; PE 0.91, CI 0.84–0.99, p = .02) compared to frozen-thawed embryos in singletons. There were no significant differences between median first and second trimester serum analytes in twin pregnancies compared between the two groups. Conclusion Singleton pregnancies derived from fresh embryos had lower first (free β-hCG) and second (uE3 and AFP) trimester analytes compared to frozen-thawed embryos. Twin pregnancies demonstrated no difference between the groups.