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Assisted reproduction is presumed to increase monozygotic twin rates, with the possible contribution of laboratory and medical interventions. Monozygotic dichorionic gestations are supposed to originate from the splitting of an embryo during the first four days of development, before blastocyst formation. Single embryo transfers could result in dichorionic pregnancies, currently explained by embryo splitting as described in the worldwide used medical textbooks, or concomitant conception. However, such splitting has never been observed in human in vitro fertilization, and downregulated frozen cycles could also produce multiple gestations. Several models of the possible origins of dichorionicity have been suggested. However, some possible underlying mechanisms observed from assisted reproduction seem to have been overlooked. In this review, we aimed to document the current knowledge, criticize the accepted dogma, and propose new insights into the origin of zygosity and chorionicity.

In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007−2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg’s method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007−2010, 2011−2014 and 2015−2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.

Low birth weight is associated with perinatal and long-term morbidity and mortality, and may be a result of abnormal placental development and function. In studies of singletons, associations have been reported between features of placental morphology and birth weight. Evaluating similar associations within twin pairs offers a unique opportunity to control for key confounders shared within a twin pair, including gestational age, parental characteristics, and intrauterine environment. Data from 3 studies in the United States that were completed from 2012 to 2013, 2006 to 2008, and 1959 to 1966 were used in our analysis of 208 sets of dichorionic twins with unfused placentas. We used linear regression to model difference in birth weight within a twin pair as a function of differences in placental characteristics (i.e., thickness, 2-dimensional surface area, intraplacental difference in diameter). After controlling for sex discordance, a 75.3- cm(2) difference in placental surface area, which reflects the interquartile range, was associated with a difference in birth weight of 142.1 g (95% confidence interval (CI): 62.9, 221.3). The magnitude of the association also may be larger for same-sex male pairs than same-sex female pairs (males: 265.8 g, 95% CI: 60.8, 470.8; females: 133.0 g, 95% CI: 15.7, 250.3). Strong associations between surface area and birth weight are consistent with reported results for singleton pregnancies.

Dizygotic twinning, the simultaneous birth of siblings when multiple ova are released, is an evolutionary paradox. Twin-bearing mothers often have elevated fitness, but despite twinning being heritable, twin births occur only at low frequencies in human populations. We resolve this paradox by showing that twinning and non-twinning are not competing strategies; instead, dizygotic twinning is the outcome of an adaptive conditional ovulatory strategy of switching from single to double ovulation with increasing age. This conditional strategy, when coupled with the well-known decline in fertility as women age, maximizes reproductive success and explains the increase and subsequent decrease in the twinning rate with maternal age that is observed across human populations. We show that the most successful ovulatory strategy would be to always double ovulate as an insurance against early fetal loss, but to never bear twins. This finding supports the hypothesis that twinning is a by-product of selection for double ovulation rather than selection for twinning.

Introduction: Intertwin birthweight (BW) difference is associated with an increased risk of adverse outcome. Ultrasound estimated fetal weight (EFW) is the current method to predict intertwin BW difference, however, the sensitivity is poor. Therefore, new methods are needed. Placental T2* estimated by magnetic resonance imaging (MRI) provides non-invasive information about the placental function. This study aimed to investigate placental T2* difference as a new predictor of BW difference, and to compare it to the EFW. Methods: We included 25 dichorionic twin pairs at 19–38 weeks’ gestation. Placental T2* was obtained by MRI and EFW by ultrasound. Correlations between each predictor and BW difference were examined by simple linear regression, and the combined model was analyzed by multiple linear regression and likelihood ratio test. Results: Strong positive correlations were demonstrated between intertwin differences in placental T2* and BW (r = 0.80, p < 0.005), and EFW and BW (r = 0.64, p < 0.005). Placental T2* difference was a strong independent predictor of BW difference (p < 0.001), and the combined model performed better than each predictor alone (p < 0.0001). Discussion: This pilot study demonstrates that placental T2* difference may be a predictor of intertwin BW difference irrespectively of fetal size. The clinical potential of this method deserves further investigation in a larger clinical study

Supplemental Digital Content is available in the text, Background: Published findings on perinatal outcomes of multifetal pregnancy reduction (MPR) of dichorionic diamniotic (DCDA) twin pregnancy to singleton are controversial. We performed a meta-analysis to appraise the effects of MPR of DCDA twin pregnancy versus expectant management on perinatal outcomes. Methods: Four electronic databases were searched from their inception to June 15, 2019, to identify publications that appraised MPR before 15 weeks of gestation. Studies reporting perinatal outcomes of both MPR of DCDA twin pregnancy to singleton and expectant management were considered. The relative risks (RRs) and mean differences with 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Six studies involving 7398 participants showed that MPR of DCDA twin pregnancy to singleton was associated with a lower risk of preterm birth (5 studies with 7297 participants; RR: 0.30, 95% CI: 0.22–0.40; P