Single vs Multiple Embryo Transfer
Authors: Pooja Mehta, Mark Pauly
Journal: JAMA Pediatrics (2014)

The equivalent efficacy and superior safety of elective single embryo transfer (SET) compared with elective multiple embryo transfer (MET) after in vitro fertilization (IVF) has been established in recent medical literature. The transfer of a single high-quality embryo selected from a larger number of available embryos after IVF does not decrease implantationratescomparedwithMETanddecreases the rateof twins from 30% to between 1% and 2%.1 To reduce the complications associated with twin and higher-order multiple births—including medical and delivery complications for mothers, infant low birth weight, preterm birth, stillbirth, neonatal and infant mortality, and cerebral palsy2—practice guidelines have urged health care professionals to recommend SET in women younger than 35 years who have more than 1 top-quality embryo, who may have had a previous successful IVF cycle, and who are on a first or second treatment cycle.3 There has been a resulting decrease in the proportion of transfers of 3 or more embryos from 70% to 39%. However, the United States has lagged behind the rest of the world in adoption of SET, with rates of twin pregnancy due to MET after IVF actually increasing in recent years.4 Until recently, cost-effectiveness studies comparing electiveSETwithMEThave focusedontheeasier-to-measurecosts of achieving pregnancy and medical costs up to 4 to 6 weeks postpartum,withconflicting results.5-7Toourknowledge, longer-termexaminations of the relative cost ofMET to families, payers, and society, aswell as studies thatmore directly elicit patient perspectives, are lacking. The study by Chambers et al8 in this issue of JAMA Pediatrics attempts to fill this gap by assessing the contribution of assisted reproductive technology to the frequency, duration, and cost of hospitalization in singleton, twin, and higher-order multiple children up to 5 years of life in Western Australia. The authors were able to take advantage of a validated linkage system between a regional birth registry, a reproductive technology registry, death certificates, and an inpatient hospital admission database to perform one of the largest population assessments of costs attributable to SET vs MET to date.8 The study’s authors demonstrated that, compared with singletons, twins andhigher-ordermultiple childrenwere 3.4 and 9.6 timesmore likely to be stillborn, respectively, and 6.4 and 36.7 times more likely to die during the neonatal period, respectively. Twins and higher-ordermultipleswere 18.7 and 525.1 more times likely to be preterm and small for gestational age, respectively. The average hospital cost of singleton, twin, and higher-order multiple children to 5 years was $2730, $8993, and $24 411, respectively, with cost differences concentrated to the first year of life. Fifteen percent of inpatient costs could have been avoided if twins and higher-order multiples conceivedwithassisted reproductionhadbeenborn as singletons. The study’s greatest strength was that it achieved longterm follow-up of a large population of 233 850 infants born over a 10-year period. A 100% linkage rate between the birth registry and the reproductive technology registry is reported, creating a rich source of datawhen combinedwith childhood hospital use records. However, the study likely underestimated the costs attributable to assisted reproductive technology because outpatient costs are not accounted for. Additionally, only qualifiednewborn admissionswere included in the cost analysis—in Australia, an infant is classified as qualified if he or she is in the hospital for more than 9 daysafterbirth, receives special care, remains inhospitalwithout the mother, or is the second or subsequent liveborn of a multiple birth. The large number of births excludedmay distort results and affect generalizability of the study to settings where reimbursement for neonatal care is structured differently. In general, trends in hospital use and absolute monetary value of hospital care are likely to be different in other countries. The study’s authors attempted to address this issue by reporting results in terms of relative differences rather than absolute costs. Howcanwecontextualize these findings?A2002studytold us that, in theUnitedStates, insurance coverageof IVF is a key factor in howparents, like those in the Chambers et al study,8 make their decisions around embryo transfer. Statemandated insurance coverage of IVF services in 5 states was shown to increase overall IVFuse but decrease the number of embryos transferredper cycle and thepercentage of pregnancieswith3ormore fetuses.9Nevertheless, todate,only15states have laws requiring insurance coverage for IVF treatment. Beyondexpanding state-based legislation, creative financingoptions that respect reproductive freedom, while encouraging what is safe, reasonable, and efficient, could include adding anextra charge to the insurancepremiumsofprospectiveparents whowant to retain themultiple embryo option, thereby approximating the average incremental cost ofMETover SET. But if insurance covers the consequences but not the cost of IVF, individuals are set up tomake less rational decisions than if insurers covered both costs and consequences. In light of studies that have shown that patients in settings with no mandated insurance coverage of IVF services make very different decisions regarding embryo transfer, we must recognize the dangerous and potentially discriminatoryways inwhicheveneducated reproductivedecisionmaking seems to be constrainedby a restrictive coverage environment.Efforts to restructure insurancecoverageof IVFservices, expand patient education, and elicit patient perspectives are still needed, with lack of action implicitly facilitating use of METand therefore comingat ahigh financial cost. Indeed, the Related article page 1045 Editorial Opinion