Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies

Infertility, defined as the inability to conceive within 1 year of unprotected intercourse, affects an estimated 80 million individuals worldwide, or 10-15% of couples of reproductive age. Assisted reproductive technology includes all infertility treatments to achieve conception; in vitro fertilization is the process by which an oocyte is fertilized by semen outside the body; non-in vitro fertilization assisted reproductive technology treatments include ovulation induction, artificial insemination, and intrauterine insemination. Use of assisted reproductive technology has risen steadily in the United States during the past 2 decades due to several reasons, including childbearing at older maternal ages and increasing insurance coverage. The number of in vitro fertilization cycles in the United States has nearly doubled from 2000 through 2013 and currently 1.7% of all live births in the United States are the result of this technology. Since the birth of the first child from in vitro fertilization >35 years ago, >5 million babies have been born from in vitro fertilization, half within the past 6 years. It is estimated that 1% of singletons, 19% of twins, and 25% of triplet or higher multiples are due to in vitro fertilization, and 4%, 21%, and 52%, respectively, are due to non-in vitro fertilization assisted reproductive technology. Higher plurality at birth results in a >10-fold increase in the risks for prematurity and low birthweight in twins vs singletons (adjusted odds ratio, 11.84; 95% confidence interval, 10.56-13.27 and adjusted odds ratio, 10.68; 95% confidence interval, 9.45-12.08, respectively). The use of donor oocytes is associated with increased risks for pregnancy-induced hypertension (adjusted odds ratio, 1.43; 95% confidence interval, 1.14-1.78) and prematurity (adjusted odds ratio, 1.43; 95% confidence interval, 1.11-1.83). The use of thawed embryos is associated with higher risks for pregnancy-induced hypertension (adjusted odds ratio, 1.30; 95% confidence interval, 1.08-1.57) and large-for-gestation birthweight (adjusted odds ratio, 1.74; 95% confidence interval, 1.45-2.08). Among singletons, in vitro fertilization is associated with increased risk of severe maternal morbidity compared with fertile deliveries (vaginal: adjusted odds ratio, 2.27; 95% confidence interval, 1.78-2.88; cesarean: adjusted odds ratio, 1.67; 95% confidence interval, 1.40-1.98, respectively) and subfertile deliveries (vaginal: adjusted odds ratio, 1.97; 95% confidence interval, 1.30-3.00; cesarean: adjusted odds ratio, 1.75; 95% confidence interval, 1.30-2.35, respectively). Among twins, cesarean in vitro fertilization deliveries have significantly greater severe maternal morbidity compared to cesarean fertile deliveries (adjusted odds ratio, 1.48; 95% confidence interval, 1.14-1.93). Subfertility, with or without in vitro fertilization or non-in vitro fertilization infertility treatments to achieve a pregnancy, is associated with increased risks of adverse maternal and perinatal outcomes. The major risk from in vitro fertilization treatments of multiple births (and the associated excess of perinatal morbidity) has been reduced over time, with fewer and better-quality embryos being transferred.