Search

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.

Background It is not known if impaired fertility in men with hypospadias is caused by decreased semen quality or other factors. Semen quality in men born with hypospadias may be impaired due to effects of androgens or testicular dysgenesis but has been very little studied. Objectives To study semen quality in men with hypospadias using dizygotic twinning rates as an epidemiological indicator. We further aimed to study men treated for cryptorchidism, given a hypothesized mutual etiology for decreased semen quality. Materials and methods We conducted a population-based study using national Swedish registers. A total of 4,363,165 births between 1964 and 2013 were included. The association between hypospadias and cryptorchidism, and fathering dizygotic multiple births was estimated using logistic regression and presented as odds ratios. The main analyses excluded births conceived using assisted reproductive technology (ART). Results We identified a total of 5317 births with fathers with hypospadias, including 26 dizygotic births conceived unassisted. No significant association was found between hypospadias and dizygotic twinning (OR 1.10, 0.75-1.61). We estimated a significantly increased odds for dizygotic multiple births in men treated for cryptorchidism (OR 1.35, 1.01-1.81) which was decreased after exclusion of ART, but the estimate was not significant (OR 0.75, 0.48-1.18). Discussion Using dizygotic twinning rates as an indicator of semen quality, we did not find any difference between fathers with hypospadias and controls. Due to sample size, we could not analyze phenotypes separately and can therefore not exclude impaired semen quality in severe hypospadias. We could not demonstrate any association between dizygotic twinning and cryptorchidism. Men treated for cryptorchidism were more likely than controls to use ART to conceive. Conclusion Men with hypospadias who conceived without ART were not shown to have impaired semen quality using dizygotic twinning as an epidemiological indicator.

In the course of twin studies whose main focus was elucidation of genetic and environmental factors on behavioral traits, many twin researchers became aware of the strong tendency for dizygotic (DZ) twinning to run in families. Over four decades, Nick Martin and others initiated hormone and ultrasound studies, performed segregation and pedigree analyses, tested candidate genes, carried out linkage projects in sister pairs and formed large collaborations to illuminate the genetics of DZ twinning by genome-wide association studies and meta-analysis. This article summarizes the early work on hormone and genetic studies and describes the meta-analyses that have at last met with success in finding the first genes that predispose to DZ twinning, which also appear to influence many other female reproductive traits.

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.

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