Transfer of embryos cultured until the blastocyst phase during in-vitro fertilization (IVF) was associated with an increased risk of obstetric complications and twin births, a large retrospective cohort study found.
In the study of nearly 90,000 assisted reproduction (ART) births, selecting blastocysts (embryos cultured for 5-6 days) for IVF was associated with higher rates of infants born large for gestational age and preterm births compared with transfer of cleavage-stage embryos (those cultured for 2-3 days), and a higher likelihood of having twins, reported Anne Lærke Spangmose, MD, of Copenhagen University Hospital in Denmark.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
For singleton births with fresh embryos, the rate of infants born large for gestational age was 4.3% for those conceived after blastocyst transfer compared to 3.7% for cleavage-stage transfers (adjusted odds ratio [aOR] 1.23, 95% CI 1.05-1.44), according to the research presented at the European Society of Human Reproduction and Embryology (ESHRE) annual meeting in Vienna.
No increased risk for preterm births was observed with fresh blastocysts, but there was a small increased risk with frozen blastocysts compared with cleavage-stage embryos when calculated either on second-trimester ultrasonography (aOR 1.39, 95% CI 1.18-1.65) or from the day of embryo transfer (aOR 1.23, 95% CI 1.07-1.40).
And further analysis found that the incidence of having twins increased from 2.3% following fresh cleavage-stage transfers to 4.0% with fresh blastocyst transfers (aOR 1.79, 95% CI 1.48-2.15).
"I would say this is a large increase," Spangmose said in a , "considering the risks of perinatal and obstetric outcomes in twin births."
Frozen blastocyst transfer was also associated with an increased, though less pronounced, risk of twin births (aOR 1.30, 95% CI 1.05-1.62).
Alan Penzias, MD, a reproductive endocrinologist at Boston IVF, who was not involved with the research, said that the small difference in large-for-gestational-age rates found between blastocyst and cleavage-stage transfers is reassuring from such a large cohort study.
"Blastocyst transfer is increasingly favored as an aid to embryo selection," he said. "The choice of blastocyst versus cleavage-stage embryo transfer is one that continues to require consideration of numerous variables that pertain to the individual medical history of each woman."
Blastocyst transfer has become increasingly common in fertility clinics in recent years, with prior research showing that transferring these longer, better developed embryos boosts the chances of pregnancy and live birth. A 2016 found that the rate of live birth increased from 29% with traditional cleavage-stage transfers to rates of 32% to 42% with blastocyst transfers.
Along with the increased risk of preterm birth and infants born large for gestational age, a higher risk of placenta previa was also observed with blastocyst versus cleavage-stage transfers with both fresh (aOR 2.04, 95% CI 1.73-2.41) and frozen embryos (aOR 1.68, 95% CI 1.16-2.44).
Spangmose acknowledged that blastocyst culture plays a crucial role in ART treatment. "But we still need to consider whether blastocyst transfer should be the gold standard in fresh ART cycles given the adverse risks found in our study," she said.
The current study included ART births in Denmark, Norway, and Sweden from 1997 to 2015, and included 69,751 singleton babies (8,368 born after blastocyst transfer and 61,383 born after a 3-day transfer) and 18,154 twins (1,167 and 16,987, respectively).
Researchers used data from the Committee of Nordic ART and Safety (CoNARTaS) cohort to compare obstetric and perinatal outcomes, as well as the risk of having same-sex twins after both fresh and frozen blastocyst and cleavage transfer. They adjusted for fertilization method (IVF or intracytoplasmic sperm injection [ICSI]), sex, country, birth year, parity, and maternal age, the abstract noted.
Limitations of the research included potential confounding factors that were not adjusted for, though they said residual confounding was likely limited.
Primary Source
European Society of Human Reproduction and Embryology
Spangmose AL, et al "Obstetric and perinatal risks in 8,368 singletons and 1,167 twins conceived after fresh and frozen blastocyst transfers in the Nordic countries -- A CoNARTaS collaboration" ESHRE 2019; Abstract O-035.