Objectives: This study evaluated the increase in risk of multiple births associated with ovulation induction and calculated the proportion of multiple births attributable to this treatment.
Methods: Cases were 350 multiple births and controls were 737 single births enrolled from April 1993 to March 1994 in the Mercurio Project, an investigation of reproductive outcomes in Italy.
Results: Ovulation induction was used in 45 case births (12.9%) and 24 control births (3.3%); the adjusted odds ratio was 4.1 (95% confidence interval [CI] = 2.4, 6.9). The odds ratio for triplet or higher order births was 72.2 (95% CI = 25.7, 202.8). When unlike-sexed multiple births were considered, the odds ratio increased for twin births, but not for triplet or higher births. The highest odds ratios were found when ovulation induction was used with assisted reproduction. The proportion of multiple births attributable to ovulation induction was 9.7% overall, 5.4% for twin births, and 69.8% for triplet or higher births.
Conclusions: Ovulation induction increases the risk of multiple births and has been responsible for the rise in the rate of triplet or higher order births in Italy in the last decade. Its indiscriminate and improper use should be avoided.