Guidelines for the Number of Embryos toTransfer Following In Vitro Fertilization

Objective: To review the effect of the number of embryos transferredon the outcome of in vitro fertilization (IVF), to provide guidelineson the number of embryos to transfer in IVF-embryo transfer (ET)in order to optimize healthy live births and minimize multiplepregnancies. Options: Rates of live birth, clinical pregnancy, and multiplepregnancy or birth by number of embryos transferred arecompared. Outcomes: Clinical pregnancy, multiple pregnancy, and live birthrates. Evidence: The Cochrane Library and MEDLINE were searched forEnglish language articles from 1990 to April 2006. Search termsincluded embryo transfer (ET), assisted reproduction, in vitrofertilization (IVF), intracytoplasmic sperm injection (ICSI), multiplepregnancy, and multiple gestation. Additional references wereidentified through hand searches of bibliographies of identifiedarticles. Values: Available evidence was reviewed by the ReproductiveEndocrinology and Infertility Committee and the Maternal-FetalMedicine Committee of the Society of Obstetricians andGynaecologists of Canada and the Board of the Canadian Fertilityand Andrology Society, and was qualified using the Evaluation ofEvidence Guidelines developed by the Canadian Task Force onthe Periodic Health Exam. Benefits, Harms, and Costs: This guideline is intended to minimizethe occurrence of multifetal gestation, particularly high-ordermultiples (HOM), while maintaining acceptable overall pregnancyand live birth rates following IVF-ET. Recommendations: The recommendations made in this guideline were derived mainlyfrom studies of cleavage stage embryos-those cultured for two orthree days.1.Individual IVF-ET programs should evaluate their own data toidentify patient-specific, embryo-specific, and cycle-specificdeterminants of implantation and live birth in order to developembryo transfer policies that minimize the occurrence of multifetalgestation while maintaining acceptable overall pregnancy and livebirth rates. (III-B)2.In general, consideration should be given to the transfer of fewerblastocyst stage embryos than cleavage stage embryos,particularly in women with excellent prognoses and high-qualityblastocysts. (I-A)3.In women under the age of 35 years, no more than two embryosshould be transferred in a fresh IVF-ET cycle. (II-2A)4.In women under the age of 35 years with excellent prognoses, thetransfer of a single embryo should be considered. Women withexcellent prognoses include those undergoing their first or secondIVF-ET cycle or one immediately following a successful IVF-ETcycle, with at least two high-quality embryos available for transfer.(I-A)5.In women aged 35 to 37 years, no more than three embryos shouldbe transferred in a fresh IVF-ET cycle. In those with high-qualityembryos and favourable prognoses, consideration should be givento the transfer of one or two embryos in the first or second cycle.(II-2A)6.In women aged 38 to 39 years, no more than three embryos shouldbe transferred in a fresh IVF-ET cycle. (III-B) In those withhigh-quality embryos and favourable prognoses, considerationshould be given to the transfer of two embryos in the first orsecond cycle. (III-B)7.In women over the age of 39 years, no more than four embryosshould be transferred in a fresh IVF-ET cycle. (III-B) In those olderwomen with high-quality embryos in excess of the number to betransferred, consideration should be given to the transfer of threeembryos in the first IVF-ET cycle. (III-B)8.In exceptional cases when women with poor prognoses have hadmultiple failed fresh IVF-ET cycles, consideration may be given tothe transfer of more embryos than recommended above insubsequent fresh IVF-ET cycles. (III-C)9.In donor-recipient cycles, the age of the oocyte/embryo donorshould be used when determining the number of embryos totransfer. (II-2B)10.In women with obstetrical or medical contraindication to multifetalgestation, fewer embryos should be transferred to minimize thechance of multifetal gestation. In such cases, pre-treatmentconsultation with a maternal-fetal medicine specialist should be pursued. (III-C) Whenever reasonable, consideration should begiven to the transfer of a single embryo. (II-3B)11.Couples should be adequately counselled regarding theobstetrical, perinatal, and neonatal risks of multifetal gestation tofacilitate informed decision making regarding the number ofembryos to transfer. (II-3B) Emphasis on healthy singleton livebirth as the measure of success in IVF-ET may be beneficial inpromoting a reduction in the number of embryos transferred. (III-C)12.A strategy for public funding of IVF-ET must be developed for theeffective implementation of guidelines limiting the number ofembryos transferred. In the context of this strategy, total healthcare costs would be lower as a result of reductions in the incidenceof multifetal pregnancies and births. (III-C)13.Efforts should be made to limit iatrogenic multiple pregnanciesresulting from non-IVF-ET ovarian stimulation through thedevelopment of suitable guidelines for cycle cancellation and theremoval of financial barriers to IVF-ET. (III-B). Summary Statement: The following recommendations are generally intended forcleavage stage embryos transferred on day two or three. Because blastocyst stage embryos have higher implantation rates thancleavage stage embryos, fewer blastocyst stage embryos mayneed to be transferred. (II). Validation: This guideline was reviewed by the ReproductiveEndocrinology and Infertility Committee and the Maternal-FetalMedicine Committee and approved by the Executive and Councilof the Society of Obstetricians and Gynaecologists of Canada andthe Board of the Canadian Fertility and Andrology Society. Sponsor: Society of Obstetricians and Gynaecologists of Canada.The quality of evidence reported in this document has beendescribed using the Evaluation of Evidence criteria outlined in theReport of the Canadian Task Force on the Periodic Health Exam(Table 1).