Pediatric consequences of Assisted Reproductive Technologies

Outline Review of outcome studies regarding ART Comparison of different countries Multiple gestations Are there impacts of ART among singletons?

Twins and Singletons Among singletons there is an increase in prematurity and of growth restriction, leading to an increase in low birth weight Increased perinatal and neonatal mortality « Risks » of requiring ART increase with age and with some chronic illness, and are higher in older primigravidae Statistical correction for parity and age suggest residual impacts of ART Those residual impacts may be related to a history of subfertility

Singletons In one systematic review, Increased risks among singletons after ART, compared to adjusted risks (for age and parity) of all the adverse outcomes, persisted after adjustment for a history of subfertility In another review Risks were no longer significantly different.

Singletons For neonatologists the message is that the risks are increased compared to the general population This will increase pressure on NICU beds No evidence of other specific neonatal illnesses which are increased by ART Except for congenital anomalies Mothers are older, therefore more Gestational Diabetes, hypertension etc.

« Who’s my Dad? » Not just a question for the child Family history may be uncertain in a case of gamete donation (egg or sperm) Family history may be important for numerous neonatal issues If donors are anonymous obtaining family history may be impossible. Even if donors are identifiable, it may be extremely difficult to obtain the information.

Multiple problems Among twin pregnancies, the gestational age at birth is lower for those conceived by IVF than for spontaneous twins. In part because of a higher proportion of IVF mothers being primigravid, primigravidae carrying twins deliver earlier than multigravidae, even among spontaneous pregnancies

The more embryos you transfer the more babies are born

Transferring more embryos does not increase pregnancy rates

Trasnferring 3 or more embryos dramatically increases multiple deliveries

If you never transfer 3 embryos you (almost) never get triplets

Cost of irresponsibility Janvier A, Spelke B, and Barrington K Cost of irresponsibility Janvier A, Spelke B, and Barrington K. J Pediatr 2011 We analyzed data from our NICU, from 2007-2009 when there was little regulation in Québec At that time 30% of IVF pregnancies were multiples, triplets were not rare ART multiples accounted for nearly 20% of all our NICU admissions There were also frequent fetal reductions, from 4 or 3 to twins Those infants required intensive care, ventilation, TPN, etc Developed complications…

Human cost of irresponsible practices Morbidities Saved With Universal SET Selective SET NICU Admissions 67 63 Retinal Examinations 270 253 Patient-days of assisted ventilation 260 244 Patient-days of CPAP 171 160 Patient-days of Oxygen 643 604 Patient-days of TPN 950 893 Patient-days of gavage feeding 2001 1881 Patient-days of hospitalisation 3082 2897 Calculated the morbidities that would have been saved if those IVF procedures had all been SET Accounted for 2% twins, increased age and morbidities among mothers and increased prematurity even among singletons

We extrapolated those result to the whole of Canada. Pop. 23 million 840 NICU admissions per year 7300 ventilator patient days 4800 patient CPAP days 40 deaths 46 severe IVH 20 RoP surgeries Would be avoided by responsible single embryo transfers

Don’t forget maternal impact of multiples Hypertension Diabetes Antepartum hemorrhage Post-partum hemorrhage Cesarean delivery Pre-eclampsia Eclampsia Maternal depression Divorce

The long term? In the main, the long term impacts of ART are due to increased prematurity, and increased extreme prematurity Among ART singletons there may be an increase in cerebral palsy, probably also because of the increase in prematurity (mostly late preterms, with increased risk in the population of CP) Increase in epilepsy among ART singleton infants delivered at term (single study)

Conclusion ART is an enormous benefit to childless couples Unregulated ART carries huge risks to the babies, (and mothers) mostly as a result of multiple gestation Even singleton pregnancies are at higher risk, but those higher risks are mostly due to demographics and not due to the procedures Regulating multiple embryo transfers can be done effectively with very little impact on pregnancy rates and dramatic reductions in multiples Leads to dramatic reduction in NICU admissions, NICU costs, and baby complications