Association of infertility cause with perinatal outcomes in a freeze-all policy: an analysis including 10,151 singleton newborns

Abstract

In vitro fertilization-conceived babies, even singletons, are at a higher risk of poor birth outcomes such as low birthweight and preterm birth than naturally conceived counterparts. It remains unclear as to what extent these adverse outcomes are attributed to the underlying causes of infertility. Evidence on this topic is scarce and has mainly focused on fresh embryo transfer cycles. This study aimed to investigate the effect of infertility cause on perinatal outcomes when a freeze-all strategy is applied. We conducted a retrospective cohort study involving singleton live births born to women who had undergone frozen-thawed embryo transfer during the period from January 2014 to December 2019 at a single center. Subjects were categorized into 7 groups as follows according to the sole cause of infertility: tubal disorder, polycystic ovary syndrome, diminished ovarian reserve, uterine factor infertility, endometriosis, male factor, and unexplained infertility. The perinatal outcomes evaluated were as follows: birthweight, newborn gender, gestational age, preterm birth, low birthweight, small for gestational age, large for gestational age, and macrosomia. Multivariable regression analyses were introduced to control for several important confounders, with unexplained infertility as a reference group. A total of 10,151 women were included for the final analysis. The most common maternal infertility diagnosis of the entire cohort was tubal disorder (42.5%), followed by diminished ovarian reserve (9.5%), endometriosis (9.4%), polycystic ovary syndrome (5.7%), and uterine factor infertility (1.6%). Male factor infertility was present in 19.8% of cycles, and infertility was diagnosed as unexplained in 11.4% of cycles. In the unadjusted analyses, the prevalence of low birthweight (odds ratio, 2.05; 95% confidence interval, 1.24-3.38) and preterm birth (odds ratio, 1.97; 95% confidence interval, 1.33-2.92) was higher among singletons in the polycystic ovary syndrome group than in those from the unexplained infertility group. However, these differences were no longer significant after correction for parental characteristics, treatment variables, and pregnancy complications (adjusted odds ratio, 1.50; 95% confidence interval, 0.98-2.28 for preterm birth; adjusted odds ratio, 1.70; 95% confidence interval, 0.99-2.91 for low birthweight). The risks of preterm birth (adjusted odds ratio, 2.66; 95% confidence interval, 1.53-4.63) and low birthweight (adjusted odds ratio, 3.51; 95% confidence interval, 1.79-6.90) with uterine factor infertility were significantly increased vs the reference group in both unadjusted and adjusted analyses. In addition, the perinatal outcomes in women with other infertility causes were comparable with unexplained infertility in terms of the rates of preterm birth, low birthweight, small for gestational age, large for gestational age, and macrosomia. With the exception of uterine factor infertility, other infertility causes do not seem to compromise perinatal outcomes when compared with unexplained infertility in a freeze-all approach. With the ever-increasing use of frozen-thawed embryo transfer globally, our data hold relevant clinical implications, as they can guide physicians in patient counseling.