Birth size after embryo cryopreservation: larger by all measures?

Area of Science:

• Reproductive Medicine
• Perinatal Epidemiology
• Developmental Biology

Background:

• Pregnancies following frozen embryo transfer (frozen-ET) are associated with higher birthweight, but the underlying reasons related to fetal growth and placental efficiency are not fully understood.
• Existing knowledge suggests a potential link between frozen-ET and increased birth size, yet its association with symmetrical growth and placental efficiency requires further investigation.
• Fresh embryo transfer (fresh-ET) has also been linked to altered birth outcomes compared to natural conception, necessitating a comparative analysis with frozen-ET.

Purpose of the Study:

• To investigate whether changes in birthweight after frozen and fresh embryo transfer are associated with corresponding changes in other measures of fetal growth and placental efficiency.
• To compare fetal growth and placental efficiency between singletons conceived via frozen-ET, fresh-ET, and natural conception.

Main Methods:

• A Norwegian nationwide registry-based cohort study included 3093 singletons from frozen-ET, 15,510 from fresh-ET, and 1,125,366 from natural conception (1988-2015).
• Data from the Medical Birth Registry of Norway and National Education Database were analyzed for birth length, birthweight, head circumference, ponderal index, placental weight, and birthweight:placental weight ratio.
• Sibship analyses were conducted to control for maternal factors, comparing outcomes within families conceived through different methods.

Main Results:

• Within sibships, frozen-ET singletons exhibited longer length and larger head circumference but similar ponderal index compared to naturally conceived infants.
• Fresh-ET singletons showed shorter length, smaller head circumference, and lower ponderal index compared to naturally conceived infants.
• Both frozen-ET and fresh-ET were associated with larger placental weight and reduced birthweight:placental weight ratio compared to natural conception.

Conclusions:

• The increased birthweight in frozen-ET singletons is linked to symmetrically increased birth size and larger placentas, even after accounting for maternal factors.
• Reduced placental efficiency is observed in both frozen-ET and fresh-ET compared to natural conception.
• Further research is crucial to identify specific treatment factors and long-term health outcomes associated with these findings, especially given the rise in elective embryo freezing.