Cognitive and psychomotor development of 5- to 6-year-old singletons born after PGD: a prospective case-controlled matched study.

STUDY QUESTION: Do preschool preimplantation genetic diagnosis (PGD) children differ in their cognitive and psychomotor development from children born after ICSI and spontaneous conception (SC)? SUMMARY ANSWER: The cognitive development of PGD pre-schoolers was comparable to children born after ICSI and SC but motor development differed between ICSI and SC groups. STUDY DESIGN, SIZE DURATION: The cognitive abilities and motor skills of 5- to 6-year-old singletons born after PGD (n = 47) were assessed in comparison with 49 ICSI and 48 SC children in a prospective, case-controlled, matched follow-up study between April 2011 and May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGD singletons, ICSI and SC children of preschool age were examined with the Wechsler Preschool and Primary Scale of Intelligence (WPSSI-III-NL) and the Movement ABC (M ABC). The WPSSI-III-NL revealed scores for Full IQ, Verbal IQ and Performance IQ. The M ABC yields a total score and comprising scores for measurements of balance, dexterity and ball skills. Since embryo biopsy is the only technical difference between the PGD and ICSI procedures, ICSI children were included as controls. These children were part of a Dutch-speaking cohort of children conceived after assisted reproduction technology (ART) at the Universitair Ziekenhuis Brussel (UZ Brussel) who received longitudinal follow-up. The SC children acted as a second control group similar to the fertile PGD sample and in contrast to the ICSI group. The SC group was recruited through announcements in a variety of media. The children were matched for age, gender, birth order and educational level of the mother. The assessments carried out for the ART groups were blinded whenever possible. The data were analysed using analysis of covariance (ANCOVA) and partial eta squared (η(2)), which was used as a measurement of effect size. MAIN RESULTS AND THE ROLE OF CHANCE: The overall cognitive development of PGD singletons did not differ from controls [P = 0.647, η(2) = 0.006; 95% confidence interval (CI) (0, 0.043)]. The partial IQ scores for Verbal and Performance intelligence revealed similar results. Analysis of motor development based on the total score as well as subscales did indicate a significant difference between the three conception groups [P = 0.033, η(2) = 0.050, 95% CI (0, 0.124)]. Post hoc analysis indicated that the significant difference was situated between performances of ICSI and SC children. Balance capacities [P = 0.004, η(2) = 0.079, 95% CI (0.025, 0.163)] and its post hoc analysis yielded equivalent results. Motor capacities of PGD singletons, however, did not differ from any of the two other conception groups. LIMITATIONS, REASONS FOR CAUTION: Given that we only assessed Caucasian singletons born after PGD, caution is required when drawing more general inferences from our results. The small sample size may be a limitation. A priori power analysis, however, revealed that at least 52 children per group were needed to detect a medium effect and 80% power using ANCOVA. Originally our sample met this threshold but we had to exclude six cases in order to remove outliers and due to missing data. WIDER IMPLICATIONS OF THE FINDINGS: Long-term follow-up of children born after embryo biopsy, in this case for PGD, is needed to confirm that the development of these children remains comparable to ICSI and SC children. Our findings do support the safety of the PGD technique and will reassure patients with hereditary genetic diseases regarding the health of their future offspring conceived with PGD. STUDY FUNDING/COMPETING INTERESTS: Funding for this study was obtained from the OZR (Research group of the Vrije Universiteit Brussel), the FWO (Fonds Wetenschappelijk Onderzoek) and the Wetenschappelijk Fonds Willy Gepts. The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection. UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection, from IBSA, Ferring, Organon, Shering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speaker's fees from Organon, Serono Symposia and Merck.

Body composition and blood pressure in 6-year-old singletons born after pre-implantation genetic testing for monogenic and structural chromosomal aberrations: a matched cohort study.

STUDY QUESTION: Does Day 3 embryo biopsy for pre-implantation genetic testing for monogenic (PGT-M) and structural chromosomal aberrations (PGT-SR) affect body composition and blood pressure readings of 6-year-old singletons? SUMMARY ANSWER: This study of 87 PGT-M and PGT-SR conceived singletons showed no differences in anthropometric measurements and blood pressure readings in comparison with a matched cohort of peers born after ICSI without embryo biopsy. WHAT IS KNOWN ALREADY: While neonatal outcomes after PGT conception have been found comparable to those after ICSI without embryo biopsy, only a few studies have reported outcomes after PGT at older ages. Moreover, embryo biopsy is also applied in couples who opt for PGT-M and PGT-SR and hence are not necessarily infertile. Health parameters and in particular body composition data in this group of children are lacking. STUDY DESIGN SIZE DURATION: This single-centre matched-pair cohort study evaluated body composition of 6-year-old children born after fresh blastocyst embryo transfer with or without embryo biopsy performed at Day 3 for the purpose of PGT-M and PGT-SR. For each child born after embryo biopsy, a singleton born after transfer of a fresh ICSI embryo at the blastocyst stage and reaching the age of 6 years between May 2011 and June 2017 was matched as closely as possible for gender, age, maternal educational level and birth order. PARTICIPANTS/MATERIALS SETTING METHODS: Anthropometry (weight, height, BMI, skinfold thickness, waist and mid-upper arm circumference) and blood pressure readings in a longitudinally followed cohort of 87 singletons conceived by PGT-M and PGT-SR and a pairwise matched sample of 87 children conceived by ICSI are described. Results are adjusted for current, neonatal and parental characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: From the 124 eligible PGT-M and PGT-SR families, 110 could be reached of whom 23 refused and 87 (87/110 = 79%) participated. All anthropometric measurements, including z-scores of BMI, waist and mid-upper arm circumference, were comparable between the PGT-M and PGT-SR (-0.23; 0.27; 0.17, respectively) and ICSI (-0.29; 0.11; 0.11, respectively) groups (all P > 0.05). Furthermore, indices of peripheral (triceps) and central (subscapular) adiposity derived from skinfold thickness were comparable (PGT-M and PGT-SR: 14.7 mm; 11.6 mm and ICSI: 15.5 mm; 11.5 mm) as well as the percentage total body fat mass derived from these (PGT-M and PGT-SR: 13.7% and ICSI: 13.9%) (all P > 0.05). Z-scores for blood pressure were also comparable between the PGT and ICSI groups (all P > 0.05). Results did not change when adjusted for neonatal (birthweight, birth order), current (age) and parental (smoking during pregnancy, parental BMI) characteristics. Hospitalization rate and surgical intervention rate were not different for PGT-M and PGT-SR children compared to matched peers born after ICSI. LIMITATIONS REASONS FOR CAUTION: Although our study describes the largest cohort of singletons born after embryo biopsy worldwide, we were only able to detect moderate differences in anthropometrics and blood pressure with our sample size. WIDER IMPLICATIONS OF THE FINDINGS: Although Day 3 embryo biopsy followed by blastocyst transfer is not associated with adverse outcomes regarding anthropometry and blood pressure, future studies should focus on outcomes in children born after trophectoderm biopsy and/or transfer of warmed embryos after vitrification. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts; all issued by the Vrije Universiteit Brussel (VUB). All co-authors, except M.B. declared no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough, Merck for establishing the database for follow-up research and organizing the data collection.