Blastocyst quality and reproductive and perinatal outcomes: a multinational multicentre observational study.

study questionDoes the transfer of single low-grade blastocysts result in acceptable reproductive and perinatal outcomes compared to the transfer of single good-grade blastocysts? SUMMARY ANSWER: The transfer of single low-grade blastocysts resulted in a reduced live birth rate of around 30% (14% for very low-grade blastocysts) compared to 44% for single good-grade blastocysts, but does not lead to more adverse perinatal outcomes. WHAT IS KNOWN ALREADY: It is known that low-grade blastocysts can result in live births. However, the current studies are limited by relatively small sample sizes and single-centre designs. Furthermore, evidence on perinatal outcomes after transferring low-grade blastocysts is limited. STUDY DESIGN, SIZE, DURATION: We conducted a multi-centre, multi-national retrospective cohort study of 10 018 women undergoing 10 964 single blastocyst transfer cycles between 2009 and 2020 from 14 clinics across Australia, China, and New Zealand. PARTICIPANTS/MATERIALS, SETTING,

methodsBlastocysts were graded individually based on assessment of the morphology and development of the inner cell mass (ICM) and trophectoderm (TE), and were grouped into three quality categories: good- (AB, AB, or BA), moderate- (BB), and low-grade (grade C for ICM or TE) blastocysts. CC blastocysts were individually grouped as very low-grade blastocysts. Logistic regression with generalized estimating equation was used to analyse the association between blastocyst quality and live birth as well as other reproductive outcomes. Binomial, multinomial logistic, or linear regression was used to investigate the association between blastocyst quality and perinatal outcomes. Odds ratio (OR), adjusted OR (aOR), adjusted regression coefficient, and their 95% CIs are presented. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: There were 4386 good-grade blastocysts, 3735 moderate-grade blastocysts, and 2843 low-grade blastocysts were included in the analysis, for which the live birth rates were 44.4%, 38.6%, and 30.2%, respectively. Compared to good-grade blastocysts, the live birth rate of low-grade blastocysts was significantly lower (aOR of 0.48 (0.41-0.55)). Very low-grade blastocysts were associated with an even lower live birth rate (aOR 0.30 (0.18-0.52)) and their absolute live birth rate was 13.7%. There were 4132 singleton live births included in the analysis of perinatal outcomes. Compared with good-grade blastocysts, low-grade blastocysts had comparable preterm birth rates (<37 weeks, aOR 1.00 (0.65-1.54)), birthweight Z-scores (adjusted regression coefficient 0.02 (0.09-0.14)), and rates of very low birth weight (<1500 g, aOR 0.84 (0.22-3.25)), low birth weight (1500-2500 g, aOR 0.96 (0.56-1.65)), high birth weight (>4500 g, aOR 0.93 (0.37-2.32)), small for gestational age (aOR 1.63 (0.91-2.93)), and large for gestational age (aOR 1.28 (0.97-1.70)). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the retrospective design, residual confounding could not be excluded. In addition, the number of events for some perinatal outcomes was small. Between-operator and between-laboratory variations in blastocyst assessment were difficult to control. WIDER IMPLICATIONS OF THE

findingsPatients undergoing IVF should be informed that low-grade blastocysts result in a lower live birth rate, however they do not increase the risk of adverse perinatal outcomes. Further research should focus on the criteria for embryos that should not be transferred and on the follow-up of long-term outcomes of offspring. STUDY FUNDING/COMPETING INTEREST(S): H.Z. is supported by a Monash Research Scholarship. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437). R.W. is supported by an NHMRC Emerging Leadership Investigator grant (2009767). B.W.J.M. reports consultancy, travel support, and research funding from Merck. The other authors do not have competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.