Perinatal and maternal outcome after vitrification of blastocysts: a Nordic study in singletons from the CoNARTaS group

Abstract

STUDY QUESTION Is transfer of vitrified blastocysts associated with higher perinatal and maternal risks compared with slow-frozen cleavage stage embryos and fresh blastocysts? SUMMARY ANSWER Transfer of vitrified blastocysts is associated with a higher risk of preterm birth (PTB) when compared with slow-frozen cleavage stage embryos and with a higher risk of a large baby, hypertensive disorders in pregnancy (HDPs) and postpartum hemorrhage (PPH) but a lower risk of placenta previa when compared with fresh blastocysts. WHAT IS KNOWN ALREADY Transfer of frozen-thawed embryos (FETs) plays a central role in modern fertility treatment, limiting the risk of ovarian hyperstimulation syndrome and multiple pregnancies. Following FET, several studies report a lower risk of PTB, low birth weight (LBW) and small for gestational age (SGA) yet a higher risk of fetal macrosomia and large for gestational age (LGA) compared with fresh embryos. In recent years, the introduction of new freezing techniques has increased treatment success. The slow-freeze technique combined with cleavage stage transfer has been replaced by vitrification and blastocyst transfer. Only few studies have compared perinatal and maternal outcomes after vitrification and slow-freeze and mainly in cleavage stage embryos, with most studies indicating similar outcomes in the two groups. Studies on perinatal and maternal outcomes following vitrified blastocysts are limited. STUDY DESIGN, SIZE, DURATION This registry-based cohort study includes singletons born after frozen-thawed and fresh transfers following the introduction of vitrification in Sweden and Denmark, in 2002 and 2009, respectively. The study includes 3650 children born after transfer of vitrified blastocysts, 8123 children born after transfer of slow-frozen cleavage stage embryos and 4469 children born after transfer of fresh blastocysts during 2002–2015. Perinatal and maternal outcomes in singletons born after vitrified blastocyst transfer were compared with singletons born after slow-frozen cleavage stage transfer and singletons born after fresh blastocyst transfer. Main outcomes included PTB, LBW, macrosomia, HDP and placenta previa. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were obtained from the CoNARTaS (Committee of Nordic ART and Safety) group. Based on national registries in Sweden, Finland, Denmark and Norway, the CoNARTaS cohort includes all children born after ART treatment in public and private clinics 1984–2015. Outcomes were assessed with logistic multivariable regression analysis, adjusting for the country and year of birth, maternal age, body mass index, parity, smoking, parental educational level, fertilisation method (IVF/ICSI), single embryo transfer, number of gestational sacs and the child’s sex. MAIN RESULTS AND THE ROLE OF CHANCE A higher risk of PTB (<37 weeks) was noted in the vitrified blastocyst group compared with the slow-frozen cleavage stage group (adjusted odds ratio, aOR [95% CI], 1.33 [1.09–1.62]). No significant differences were observed for LBW (<2500 g), SGA, macrosomia (≥4500 g) and LGA when comparing the vitrified blastocyst with the slow-frozen cleavage stage group. For maternal outcomes, no significant difference was seen in the risk of HDP, placenta previa, placental abruption and PPH in the vitrified blastocyst versus the slow frozen cleavage stage group, although the precision was limited. When comparing vitrified and fresh blastocysts, we found higher risks of macrosomia (≥4500 g) aOR 1.77 [1.35–2.31] and LGA aOR 1.48 [1.18–1.84]. Further, the risks of HDP aOR 1.47 [1.19–1.81] and PPH aOR 1.68 [1.39–2.03] were higher in singletons born after vitrified compared with fresh blastocyst transfer while the risks of SGA aOR 0.58 [0.44–0.78] and placenta previa aOR 0.35 [0.25–0.48] were lower. LIMITATIONS, REASONS FOR CAUTION Since vitrification was introduced simultaneously with blastocyst transfer in Sweden and Denmark, it was not possible to explore the effect of vitrification per se in this study. WIDER IMPLICATIONS OF THE FINDINGS The results from the change of strategy to vitrification of blastocysts are reassuring, indicating that the freezing technique per se has no major influence on the perinatal and maternal outcomes. The higher risk of PTB may be related to the extended embryo culture rather than vitrification. STUDY FUNDING/COMPETING INTEREST(S) The study is part of the ReproUnion Collaborative study, co-financed by the European Union, Interreg V ÖKS. The study was also financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (LUA/ALF 70940), Hjalmar Svensson Research Foundation and NordForsk (project 71 450). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER ISRCTN11780826.

Separating parental and treatment contributions to perinatal health after fresh and frozen embryo transfer in assisted reproduction: A cohort study with within-sibship analysis

“…This enabled us to explore whether any differences between population and sibling results might be driven by families with only 1 child being different to those with 2 or more. Finally, we restricted the ART population to single embryo transfers and to blastocyst transfers (i.e., culture duration 5-6 days) to account for changes in practice over the study period that could potentially influence our results [5,27,28]. Single, compared with double, embryo transfer is associated with higher AU : Thephraseembryotransferisassociatedwithhigherisincompete : higherwhat?Pleasefix: [29] and eliminates vanishing twin syndrome, which may also influence birthweight and gestational duration [30].…”

Perinatal outcome in children born after assisted reproductive technologies

“…When comparing vitrification and slow freezing of day-3 embryos ( 43 ) or blastocysts ( 44 ), similar outcomes were found. A Nordic study compared vitrified blastocyst transfers with slow freezing day-2–3 embryo transfer ( 45 ). Except for a higher risk of preterm birth in the vitrified blastocyst group (aOR 1.33, 95% CI 1.09–1.62), there were no other differences.…”

Progesterone Intramuscularly or Vaginally Administration May Not Change Live Birth Rate or Neonatal Outcomes in Artificial Frozen-Thawed Embryo Transfer Cycles

“…The analysis only included patients with their first FET cycles to assure the relative good quality embryo transferred and exclude the recurrent embryo failure cases. We excluded blastocyst transfer to alleviate prolonged in vitro embryo culture impact on neonatal outcomes (43,44). To control for infant gender and gestational age bias, z score was calculated across two groups.…”