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