Perinatal outcomes of human singletons conceived naturally versus assisted reproductive technologies: analysis of the effect of stimulated IVF, modified natural IVF, and frozen embryo transfer

Background: Obstetrical outcomes in assisted reproduction techniques (ART) were compared with naturally conceived pregnancies and among each other in multiple reports. However, many important changes in the practice of in vitro fertilization (IVF) over the years, including single embryo transfers (sET) and the introduction of modified natural IVF (mnIVF), and the advances in the frozen embryo transfer (FET) might have impacted the outcomes. Our study is the first to our knowledge to assess four different groups, including spontaneous pregnancies, mnIVF, stimulated IVF (sIVF), and FET altogether in a head-to-head comparison. This is a retrospective study on perinatal outcomes of singleton babies conceived naturally or using three different ART protocols between 2011 and 2014. The primary objective was the comparison of gestational age and birth weight between spontaneously conceived pregnancies (NAT, n= 15,770), mnIVF (n=235), sIVF (n=389), and FET (n=222). Results: Our results show a significant difference in favor of naturally conceived pregnancies over ART in term of gestational age. In fact, the gestational age of babies in the NAT group was statistically higher compared to each one of the ART groups alone. Regarding the birth weight, the mean was significantly higher in the FET group compared to the other categories. Conclusion: Differences in perinatal outcomes are still found among babies born after different modes of conception. However, there is still need for well-designed high-quality trials assessing perinatal outcomes between naturally conceived pregnancies and different ART protocols based on different maternal and treatment characteristics.