The changing impact of assisted reproductive techniques on preterm birth during the period 2007-2020 in Lombardy, Northern Italy

Objective: To assess the impact of Assisted Reproductive Techniques (ART) on the risk of preterm birth (PTB). Study design: This retrospective population-based study used healthcare utilization databases of the Lombardy Region to select all the deliveries occurred between 2007 and 2020. Log-binomial regression models were fitted to estimate prevalence ratio (PR) and the corresponding 95% confidence interval (CI) of PTB among deliveries after ART. Estimates were adjusted for maternal sociodemographic features. Furthermore, the population attributable fraction was computed. All the analyses were performed for calendar period and were repeated excluding multiple births. Results: In our cohort, an increasing trend in the number of ART emerged, with an overall rate of 25.8 per 1,000 deliveries (N = 28,742). ART was positively related to PTB (aPR = 2.83, 95 % CI: 2.76-2.91) with a downward trend. Over the period study, multiple births after ART decreased (from 20.4 % to 8.4 %) and were constantly burdened by a higher number of PTB. Excluding multiple births, the association was substantially lower (aPR = 1.72, 95 % CI: 1.65-1.79) and did not describe any trend. Moreover, stratifying for type of pregnancy, the as-sociation was observed only among singletons. Finally, the proportion of PTB considered attributable to ART increased from about 2-3 % to 6 % till the 2016, then decreased. Conclusion: The investigation suggested that ART was related to PTB; this association may be partly justified by the high rate of multiple births among women who conceived non spontaneously. However, excluding multiple births, ART remained associated with PTB.