Abstract
PurposeThe risk of monozygotic (MZT) twinning is increased in pregnancies after assisted reproductive technologies (ART). However, determinants remain poorly understood. To shed more light on this issue, we analyzed the estimated frequency of MZT twins from ART in Lombardy, Northern Italy, during the period 2007–2017.MethodsThis is a population-based study using regional healthcare databases of Lombardy Region. After having detected the total number of deliveries of sex-concordant and sex-discordant twins from ART, we calculated MZT rate using Weinberg’s method. Standardized ratios (SRs) and corresponding 95% confidence intervals (CI) of MZT deliveries, adjusted for maternal age, were computed according to calendar period, parity, and type of ART.ResultsOn the whole, 19,130 deliveries from ART were identified, of which 3,446 were twins. The estimated rate of MZT births among ART pregnancies was higher but decreased over time (p-value = 0.03); the SRs being 1.33 (95% CI: 1.18–1.51), 0.96 (95% CI: 0.83–1.11), and 0.92 (95% CI: 0.79–1.07) for the periods 2007–2010, 2011–2014, and 2015–2017, respectively. The SRs of MZT among women undergoing first-level techniques, conventional in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) were 0.47 (95% CI: 0.38–0.57), 1.02 (95% CI: 0.88–1.17), and 1.43 (95% CI: 1.27–1.61) (p-value < 0.0001). The ratio of MZT births was significantly higher in women younger than 35 years (p-value < 0.0001) and slightly higher among nulliparae (p-value < 0.0001).ConclusionDespite a reduction of MZT rate from ART over the time, the risk remains higher among ART pregnancies rather than natural ones. Younger women and women undergoing ICSI showed the highest risk of all.
Highlights
Several clinical and population-based studies have consistently reported that the risk of monozygotic twin (MZT) is increased in pregnancies achieved by assisted reproductive technologies (ART) [1, 2] when compared with the natural incidence of MZT that is established to be about 0.4% of all births [3]
We identified all deliveries that took place in Lombardy Region between 1 January 2007 and 31 December 2017 from women who had benefited from the National Health System (NHS) and resident in Lombardy
We excluded 7,685 records because they did not match to a hospital ICD-9-CM code or to a diagnosis-related group (DRG) code related to childbirth, 458 records because the infant could not be linked to the mother because of a missing identification code, 742,968 records related to pregnancy conceived spontaneously, and 196 records related to multiple births
Summary
A recent systematic review and meta-analysis of the literature suggested that this risk is about 2.5-fold higher in ART pregnancies compared with natural conception [2]. Two recent systematic reviews and meta-analyses tried to disentangle risk factors for MZT in pregnancies achieved by ART but failed to provide robust and consistent findings. The meta-analysis from Hviid highlighted a significant association only with the embryo transfer at blastocyst stage (OR 2.18, 95% CI: 1.93–2.48) [4]. In this regard, it has to be pointed out that the studied risk factors tend to correlate one another and meta-analyses on raw data are incapable to provide firm conclusions. Such analyses can be carried out only in single-center studies that, have a low statistical power due to the rarity of the examined condition [5]
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