Higher obstetric complications, twin births with delayed embryo transfer during IVF
Delaying the transfer of embryo until the blastocyst stage during in-vitro fertilization (IVF) increased obstetric complications and twin births in a Nordic study. This finding is particularly important as there’s a spike in assisted reproduction technology (ART) treatments being performed with blastocyst transfer (BT) in recent years, according to the investigators.
“Extended embryo culture implies more time in vitro for the embryo, leaving it more exposed to external potential stressors such as temperature or oxygen concentration,” said lead investigator Dr Anne Lærke Spangmose Pedersen from the Copenhagen University Hospital-Rigshospitalet in Copenhagen, Denmark. “The types of culture media used for cleavage and blastocyst stage embryos are also different which may have an impact on perinatal outcomes.”
There were higher risks of preterm birth, rates of large for gestational age (LGA), and placental complications with extended culture to the blastocyst stage in this large cohort of the Committee of Nordic ART and safety (CoNARTas) study involving 90,000 ART births in Denmark, Norway, and Sweden. There were 69,751 singleton babies (8,368 born after BT and 61,383 born after a 3-day transfer) and 18,154 twins (1,167 and 16,987, respectively).
Selecting blastocysts embryos cultured for 5-6 days for IVF was associated with higher rates of infants born LGA and preterm births vs transfer of cleavage-stage embryos cultured for 3 days. There was also a higher likelihood of twin births with extended embryo culture. [ESHRE 2019, abstract O-035]
Of note, the risk of being born LGA was 4.3 percent in those conceived after BTs vs 3.7 percent in those conceived after cleavage-stage transfers (adjusted odds ratio [adjOR], 1.23, 95 percent confidence interval [CI], 1.05-1.44) for singleton births with fresh embryos. The incidence of having twins increased from 2.3 percent to 4 percent following fresh cleavage-stage transfers with fresh BTs (adjOR 1.79, 95 percent CI, 1.48-2.15), which Pedersen said, was a large increase considering the risks of perinatal and obstetric outcomes in twin births.
There was no increased risk for preterm births with fresh blastocysts. However, there was a small increased risk with frozen blastocysts vs cleavage-stage embryos when calculated either on second-trimester ultrasonography (adjOR 1.39, 95 percent CI, 1.18-1.65) or from the day of embryo transfer (adjOR 1.23, 95 percent CI, 1.07 –1.40).
“The findings suggest a small but higher obstetric risk with frozen BT vs day 3 transfers,” said Pedersen. Frozen BT was also associated with an increased, though less pronounced, risk of twin births (adjOR 1.30, 95 percent CI, 1.05-1.62).
To add to that, there was also a higher risk of placenta praevia with blastocyst vs cleavage-stage transfers for both fresh (adjOR 2.04, 95 percent CI, 1.73-2.41) and frozen embryos (adjOR 1.68, 95 percent CI, 1.16-2.44).
Previous research has shown that transferring longer, better developed embryos increases the chances of pregnancy and live birth. A 2016 Cochrane review even demonstrated that the rate of live birth increased from 29 percent with traditional cleavage-stage transfers to 32–42 percent with BTs.
“Blastocyst culture plays a crucial role in ART treatment but should be used with caution for embryo selection and enhancing success rates. We need to consider whether BT should be the gold standard in fresh ART cycles given the adverse risks found in our study,” said Pedersen.