Comparison of perinatal outcomes after frozen or fresh embryo transfer: separate analyses of singleton, twin, and sibling live births from a linked national in vitro fertilization registry

Singletons conceived from frozen embryos have a lower risk of preterm birth and small size for gestational age and higher risk of large for gestational age vs. siblings conceived from fresh embryos.

VOLUME 118, ISSUE 2, P323-334


Edwin-Amalraj Raja, Ph.D., Siladitya Bhattacharya, M.D., Abha Maheshwari, M.D., David J. McLernon, Ph.D.



To determine whether perinatal outcomes following frozen vs. fresh embryo transfer (ET) differ within singletons, within sets of twins, and between siblings.


Population-based retrospective cohort study.


Academic Medical School


200,075 live births in 151,561 women who underwent in vitro fertilization with frozen or fresh ET between 1992 and 2017.

Main Outcome Measure(s)

Gestational age at birth, birthweight, congenital anomaly, and healthy baby (≥37 weeks of gestation, birthweight 2,500–4,000 g, no congenital malformations).


There were 200,075 live births in 151,561 women including 132,679 singletons, 33,698 sets of twins, and 5,723 pairs of singleton siblings. In singletons, frozen ET was associated with a lower risk of very preterm birth (adjusted relative risk [aRR], 0.83; 95% confidence interval [CI], 0.73, 0.94), preterm birth (aRR, 0.93; 95% CI, 0.88, 0.97), low birthweight (<2,500 g) (aRR, 0.72; 95% CI, 0.68, 0.77), small for gestational age (aRR, 0.66; 95% CI, 0.62, 0.70) and congenital anomaly (aRR, 0.85; 95% CI, 0.78, 0.94), but higher risk of high birthweight (>4,000 g) (aRR, 1.64; 95% CI, 1.58, 1.72) and large for gestational age (aRR, 1.62; 95% CI, 1.55, 1.70) in comparison with fresh ET. In twins, frozen ET was associated with lower risk of very preterm birth (aRR, 0.84; 95% CI, 0.73, 0.97), and low birthweight (aRR, 0.72; 95% CI, 0.68, 0.77), but with a higher chance of a healthy baby (aRR, 1.11; 95% CI, 1.06, 1.16) compared to fresh ET. Singletons conceived following frozen ET had a lower risk of low birthweight (aRR, 0.56; 95% CI, 0.44, 0.74) and being small for gestational age (aRR, 0.54; 95% CI, 0.42, 0.68) than a singleton sibling born after a fresh ET. Frozen ET also was associated with higher risk of high birthweight (aRR, 1.85; 95% CI, 1.54, 2.24) and being large for gestational age (aRR, 1.81; 95% CI, 1.50, 2.20), and also were less likely to be preterm (aRR, 0.81; 95% CI, 0.67, 0.99).


Our key finding is that singletons born following a frozen ET are less likely to be small for gestational age than a singleton sibling born following fresh ET but are more likely to be large for gestational age.

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