Factors Associated With Embryo Splitting And Clinical Outcome Of Monozygotic Twins In Pregnancies After Ivf And Icsi

STUDY QUESTION: What factors are associated with monozygotic twins (MZT) after autologous IVF/ICSI with fresh and frozen/thawed single embryo transfer (SET) and what is the outcome of MZT?SUMMARY ANSWER: Factors associated with increased MZT were blastocyst transfer and elective single embryo transfer (eSET), with MZT showing a lower gestational age at birth and neonatal weight but higher perinatal mortality only after fresh transfer.WHAT IS KNOWN ALREADY: ART is associated with an increased incidence of MZT, which carries higher perinatal mortality. However, risk factors associated with MZT are still controversial.STUDY DESIGN, SIZE, DURATION: A population-based retrospective analysis of data extracted from ART cycles reported to the Latin American Registry of ART between January 2012 and December 2016 was used in order to study the frequency and outcome of MZT after SET.PARTICIPANTS/MATERIAL, SETTING, METHODS: In total, 2925 clinical pregnancies obtained after autologous IVF/ICSI with fresh SET were used to study biomedical factors possibly associated with MZT, such as maternal age, type of insemination, use of assisted hatching, stage of embryo development at transfer, elective or non-elective SET and preimplantation genetic testing. Another group of 3085 clinical pregnancies obtained after SET of frozen-thawed embryo transfer (FET) was also used to study the possible association between embryo freezing and MZT. Only pregnancies with complete follow-up until birth were included in this analysis. The diagnosis of MZT was established by transvaginal ultrasound performed at 6-8 weeks of amenorrhea. The rate of MZT for each potential risk factor was obtained and a multivariable logistic regression was performed in order to account for the above-mentioned factors. Pregnancies were followed until birth and the early neonatal period in order to assess the rate of miscarriage and stillbirths, gestational age at birth, neonatal weight and early neonatal mortality.MAIN RESULTS AND ROLE OF CHANCE: There were 76 MZT out of 2925 clinical pregnancies with fresh SET (2.6%) and 69 MZT out of 3085 clinical pregnancies after FET (2.2%) (odds ratio (OR)=0.85, 95% CI 0.61-1.19). A statistically significantly increase in MZT rate was observed with blastocyst compared with cleavage stage ET (3.4 versus 2.0%, respectively; OR=1.70, 95% CI 1.05-2.76). When confounding variables were considered, eSET was also significantly associated with an increase in the odds of MZT (OR=1.74, 95% CI 1.04-2.92). Overall perinatal mortality was higher in MZT compared with singletons, but this rise was only significant after fresh ET.LIMITATIONS, REASONS FOR CAUTION: Limitations of the current study result from the fact that MZT were diagnosed with ultrasound performed at 6-8 weeks of amenorrhea; therefore, spontaneous embryo reductions taking place earlier were missed.WIDER IMPLICATIONS OF THE FINDINGS: Reproductive health providers must inform their patients that blastocyst transfer and eSET of fresh embryos are associated with a statistically significantly increase in the odds of MZT and that perinatal mortality after fresh ET is significantly higher in MZT than in singletons.