Growth and other health outcomes of 2-year-old singletons born after IVM versus controlled ovarian stimulation in mothers with polycystic ovary syndrome.

STUDY QUESTION: Does In vitro maturation (IVM) of immature oocytes affect health, including growth at 2 years of age, in singletons born to mothers with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: This study of 92 singletons born after IVM in mothers with PCOS showed no significant differences in anthropometry and health outcome parameters in comparison with a cohort of 74 peers born after intracytoplasmic sperm injection (ICSI) and conventional controlled ovarian stimulation (COS) in mothers with PCOS. WHAT IS KNOWN ALREADY: IVM has been used worldwide in women with PCOS. However, the paucity of available data related to children's health following IVM is an important impediment to a more widespread use of the technology. Although previous reports on the neonatal outcome after IVM are generally reassuring, these studies have flaws that hamper the interpretation of outcomes. Moreover, few studies have reported on health outcomes after IVM beyond infancy, and particularly growth data in children born after IVM of immature oocytes from mothers with PCOS are lacking. STUDY DESIGN SIZE DURATION: This single-center cohort study compared anthropometry and health outcomes in 92 singletons born after ICSI of in vitro matured oocytes with 74 singletons born after ICSI without IVM (COS). All participants were born to mothers who were diagnosed with PCOS phenotype A, B, C or D and reached the age of 2 years between November 2012 and June 2019. Singletons born after COS were randomly selected for follow-up until young adulthood. PARTICIPANTS/MATERIALS SETTING METHODS: Anthropometric parameters and health status data were prospectively collected at birth, 4 months and 2 years in cohorts of singletons followed since birth. Results were adjusted for neonatal (birthweight z-score, birth order), treatment (day of transfer, number of embryos transferred, mode of transfer) and parental (maternal smoking, age, body mass index (BMI), anti-Müllerian hormone level, PCOS phenotype, gestational diabetes, hypertensive disorder and paternal BMI) characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no differences were found for bodyweight, height and head circumference z-score between IVM and COS children at birth, at 4 months or at 2 years (all P > 0.05). In addition, z-scores of waist and mid-upper arm circumference at 2 years were comparable in IVM and COS children. Adjustment for covariates did not change the conclusion. Surgical intervention rate as well as the hospital admission rate were comparable between the IVM and COS group (all P > 0.05). The proportion of children born to mothers with metabolically unfavorable PCOS phenotypes (A and C) was comparable in the two groups (52.1% in IVM and 45.9% in COS). Mothers giving birth to a child conceived using IVM were younger than mothers in the COS group but their BMI was comparable. LIMITATIONS REASONS FOR CAUTION: Although our study describes the largest cohort to date of singletons born after IVM applied in mothers with well-defined PCOS phenotypes, the current sample size only allowed us to detect moderate differences in anthropometry. Also, follow-up of children born after IVM for indications other than PCOS, for example fertililty preservation after cancer diagnosis, is highly recommended. WIDER IMPLICATIONS OF THE FINDINGS: We did not observe adverse effects of IVM on growth parameters in offspring ~2 years of age compared to COS, but future studies should focus on cardiovascular and metabolic outcomes in these children and adolescents given their mother's PCOS condition. 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., M.D.V. and H.T. declared no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. M.D.V. has received fees for lectures from MSD, Ferring, Gedeon Richter and Cook Medical. H.T. has received consultancy fees from Gedeon Richter, Merck, Ferring, Abbott and ObsEva. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Center for Medical Genetics have received several educational grants from IBSA, Ferring, MSD and Merck for establishing the database for follow-up research and organizing the data collection.

Growth and health outcome of 102 2-year-old children conceived after preimplantation genetic diagnosis or screening.

OBJECTIVE: The major objective of this study was to determine whether the embryo biopsy procedure might cause growth restriction or affect health outcome of children. STUDY DESIGN: Auxological data and physical findings were compared at birth and age 2 for 102 children (70 singletons and 32 twins) born after PGD/PGS and 102 matched children born after intracytoplasmic sperm injection (ICSI) in a prospective study. RESULTS: No statistically significant differences regarding weight, height and head circumference standard deviation scores (SDS) at birth and at age two years were observed. At two years of age the mean BMI SDS tended to be lower in PGD/PGS children (p=0.058). PGD/PGS babies had been more often breastfed (p=0.013), but mostly during a shorter time. The prevalence of major as well as minor congenital anomalies, hospital admissions and surgical interventions was similar. CONCLUSION: Children born after embryo biopsy applied in PGD/PGS present similar prenatal and postnatal growth and health outcome in the first two years of life compared to ICSI children. Up till now, PGD and PGS appear not to be associated with a higher risk for health problems.

Preimplantation genetic diagnosis for myotonic dystrophy type 1: upon request to child.

Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis for patients at risk of transmitting an inherited disease such as myotonic dystrophy type 1(DM1) to their offspring. In this paper, the clinical application of preimplantation diagnosis for DM1 upon request to children born is described in a large cohort of risk couples. PGD could be offered to all 78 couples opting for PGD regardless of the triplet repeat size. The incidence of major complications was minimalised following a careful assessment in affected DM1 females anticipating possible cardiological, obstetrical and anaesthetical problems. A live-birth delivery rate per cycle with oocyte retrieval of 20% was the outcome. Forty-eight of the 49 children born are in good health and have normal psychomotor development.

Two-year auxological and medical outcome of singletons born after embryo biopsy applied in preimplantation genetic diagnosis or preimplantation genetic screening.

BACKGROUND: Embryo biopsy is an essential but invasive procedure to perform preimplantation genetic diagnosis (PGD) or preimplantation genetic screening (PGS). The major objective of this study was to determine whether embryo biopsy might cause post-natal growth restriction. METHODS: We compared growth data and physical findings at birth and 2 years for singletons born either after PGD/PGS (n = 70), ICSI (n = 70) or natural conception (NC) (n = 70). Children were matched for gender, maternal educational level, mother tongue and birth order. RESULTS: No significant differences were found between the three groups regarding weight, height and head circumference standard deviation scores (SDS) at birth and at age 2 years, although the PGD/PGS children tended to have a lower birthweight compared with the NC children. At 2 years, the mean BMI SDS in PGD/PGS children was significantly lower compared with NC children (P = 0.005). PGD/PGS children were more frequently born after Caesarian section than ICSI children, but had no more congenital malformations, hospital admissions and surgical interventions compared with ICSI and NC children. CONCLUSIONS: Singleton children at age 2 years born after embryo biopsy applied in PGD/PGS present a similar post-natal linear growth compared with ICSI and NC children. PGD/PGS singletons appear not to be at higher risk for congenital malformations and surgical interventions during the first 2 years of life. To date, there have been no observable detrimental effects of the PGD/PGS procedure on children.

Socio-emotional and language development of 2-year-old children born after PGD/PGS, and parental well-being.

BACKGROUND: The objective of this study was to assess socio-emotional and language development in 2-year-old children born after preimplantation genetic diagnosis (PGD) and genetic aneuploidy screening (PGS), intracytoplasmic sperm injection (ICSI) and natural conception (NC) and to assess parental well-being. METHODS: Parents of 2-year-old PGD/PGS (n = 41), ICSI (n = 35) and NC (n = 53) singleton children were recruited. The socio-emotional development of the children was assessed using the Child Behavioural Checklist (CBCL) and the Short Temperament Scale for Toddlers. Parental stress and health status was measured with the Parent Stress Index and the General Health Questionnaire. Language development was assessed with the McArthur Communicative Development Inventories. RESULTS: No differences were found for temperament, language development, parental stress or health status. The mothers in the PGD/PGS and ICSI group reported significantly fewer CBCL Total problems than their NC counterparts, whereas for the CBCL Externalizing problems, only the ICSI mothers reported fewer problems than their PGD/PGS and NC counterparts. Fathers in the ICSI group also rated their children as having fewer Externalizing and Total behavioural problems. CONCLUSIONS: PGD/PGS conception does not adversely affect children's socio-emotional and language development at age 2, nor did parents differ from ICSI and NC parents for parental stress and health status.

Mental and psychomotor development of 2-year-old children born after preimplantation genetic diagnosis/screening.

BACKGROUND: Embryo biopsy is a new invasive procedure applied in ART for diagnostic purposes in preimplantation genetic diagnosis (PGD) or to increase pregnancy rate in preimplantation genetic screening (PGS). The objective of this study is to assess mental and psychomotor developmental outcomes in 2-year-old children born after PGD/PGS, intracytoplasmic sperm injection (ICSI) and natural conception (NC). METHODS: Two-year-old PGD/PGS (n = 70), ICSI (n = 70) and naturally conceived (n = 70) singleton children were recruited. The participation rate in the NC group was 88.6% and 94.5% in both ART conception groups. The mental and psychomotor development of the children was assessed using the Dutch version of the Bayley Scales of Infant Development. The mothers were questioned about socio-demographic characteristics. RESULTS: Even after controlling for socio-demographic variables, no differences were found between the three conception groups for the mental and psychomotor developmental outcomes. Moreover, an equal number of PGD/PGS, ICSI and NC children obtained scores within the mildly delayed, the normal and the accelerated performance category of the BSID-II-NL. CONCLUSIONS: Children conceived after PGD/PGS show similar mental and psychomotor developmental outcomes at age 2 to children conceived after ICSI or naturally.