Traditionally, monochorionic (MC) twin gestation is generally considered as monozygosity (MZ).1 Since 1970, the possibility that MC twins are not invariably MZ is raised.1 Several case reports have reported that dizygotic (DZ) twins can also be MC.2–4
Although the mechanism of forming MCDZ is unclear, many have suggested that assisted reproductive technologies, particularly in vitro fertilization is a risk factor.2 Regardless of the mechanism of MCDZ, clinically, due to sharing one placenta, MCDZ carrying the same potential prenatal risks for MC twins including twin-to-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS).
Determination of chorionicity is the most important for twin gestation and is most reliable established sonographically early in gestation. Before 10 weeks’ gestation, evidence of two distinct gestational sacs on transvaginal ultrasound suggests dichorionicity (DC). Between 10 and 14 weeks, gestation, visualization of the interface between the placenta and the intervening twin membrane is an important determination of chorionicity.5 A lambda sign (also known as a twin peak sign) is the triangular projection of placental tissue into the base of the intertwin membrane. The presence of either a lambda sign or two separate placentas indicate a DC placentation with a sensitivity of 97% and a specificity of 100%. On the contrary, a “T” sign has been used to describe the ultrasound visualization in the cases of MC gestation. When combined with the presence of a single placental mass, it has a sensitivity of 100% and a specificity of 98% for MC.5
Traditionally, discordance of fetal sex by ultrasound is thought to have a positive predictive value that approaches 100% for predicting DC.6 However, when sex discordance is present in a MC pregnancy, not only MZ but also DZ must be considered. Amniocentesis should be offered as a part of the work up. In a MCMZ pregnancy with 46, XY karyotype, either a disorder of sexual development (gonadal dysgenesis or defective androgen synthesis or action) or postzygotic loss of the Y chromosome (Turner syndrome) in one twin may result in discordant phenotypes (Karyotypes 46, XY and 45, X, respectively).7 Similarly, a MCMZ pregnancy with 46, XX karyotype may also result in sex discordance, again because of a disorder in sexual development (virilizing forms of congenital adrenal hyperplasia) in one of the twins. On the other hand, in MCDZ twins, sex discordance is a possibility and a clue for the diagnose in the setting of confirmed MC twin.7 Therefore, discordance of fetal sex on ultrasound is not totally reliable to predict zygosity, and it is important to realize that MCDZ twin gestations exist.
Currently, spontaneous MCDZ twin gestation is very rare. The mechanism remains unclear since it is first reported in 1970. Several hypotheses have been proposed. First, assisted reproductive technologies techniques lead to changes in the nature of the cell surface and increase the chance of embryo fusion, such as assisted hatching of the zona pellucida, implantation of embryos close together by simultaneous embryo transfer, use of fertilized eggs that have developed to the blastocyst stage, and cell culture procedures.8 Second, binovular follicle fertilization, in which two oocytes are present within a single zona pellucida. This was reported in nonsimulated and simulated cycles. One or both of oocytes in a binovular follicle were reported to be fertilized in vivo.9,10 Third, chorions might fuse early in pregnancy and then complete disintegration of the two chorionic layers in the dividing septum would occur later.1 Fourth, spontaneous in vitro fusion of mammalian embryos under certain condition during the preimplantation period.11 Another study suggested that the product of two sperm fertilizing one oocyte result in each twin had distinct paternal genomes but identical maternal genomes.12 With the recognition of MCDZ twin pregnancy, further studies might be able to understand the mechanism of MCDZ twin.
Perinatal management and pregnant outcomes
In general, MCDZ and MCMZ might have similar perinatal course due to MC. MC twins are associated with increased perinatal risks compared with DC twins, and these risks necessitate close antenatal surveillance. In MC twins, fetuses share a single placenta and vascular anastomoses connect the blood circulations of both twins resulted in a continuous exchange of blood between the twins. Imbalance of this exchange is often the cause of severe pathology, including TTTS or TAPS.13 The diagnosis of TTTS is based on the presence of polyhydramnios in the recipient twin and oligohydramnios in the donor twin.14
In contrast to TTTS, TAPS involves a severe discordance in hemoglobin levels. TAPS appears to occur spontaneously in 5% of these pregnancies or iatrogenically following fetoscopic laser ablation in 3%–16% of these pregnancies.15,16 Currently the diagnosis is based on an increased middle cerebral artery peak systolic velocity in the donor twin (>1.5 multiples of the median) and a decreased in middle cerebral artery peak systolic velocity in the recipient twin (< 1 multiples of the median).17 Postnatally, TAPS can be diagnosed based on an intertwin hemoglobin difference of >80 g/L and one of the two following criteria: (1) a reticulocyte count ratio of >1.7; (2) the presence of only small vascular anastomoses (diameter ≤1 mm) on placental exam.18
The striking feature of TAPS placenta is the striking discordant ultrasound appearance of the placental parenchyma and the color difference noted during gross examination. In utero, placental echogenicity demonstrates a hyperechoic area associated with the anemic twin and hypoechoic area associated with the recipient twin.19 On gross examination, the pale gross appearance is associated with the anemic (donor) twin and the dark purple gross appearance is associated with the polycythemic (recipient) twin postnatally.19
It is very important to recognize that MCDZ has its own unique issues. MCDZ twins are prone to genetic problems. Reportedly, 90.3% of MCDZ twins have blood chimerism, where both twins possess two karyotypes: 46, XX and 46, XY.20 Blood chimerism occurs by the exchange of blood stem cells between fetuses through vascular anastomoses of the placenta in early gestation.21 It has been suggested that this exists persistently because twins are immunologically tolerant to each other and this phenomenon is more common than expected.22 Although this phenomenon was also reported among dichorionic twins, such cases are rare because anastomotic communication is rarely found within dichorionic placentas.23
This phenomenon may cause problems with blood typing or blood transfusion. Moreover, unrecognized chimerism may be misdiagnosed as hermaphroditism and lead to unnecessary gonadal removal. In female, it is known that XX and XY blood chimerism gradually becomes dominated by the XY cells because of the difference in cell division speed.24 Eventually, these females demonstrate an XY blood karyotype and female phenotype. If chimerism is not recognized early, these normal females run the risk of undergoing inappropriate gonadectomy.25 Therefore, precisely genetic counseling could only be performed with fully recognizing of this phenomenon, especially important for MCDZ twins. It is also reported that genital anomalies occur in 15.4% of MCDZ twins,20 including ambiguous external genitalia,26 absence of the uterus and fallopian tube in females,27 and testicular hypoplasia in males.28
It also has been suggested that fetal maternal chimerism plays a role in the pathogenesis of autoimmune disease such as systemic lupus erythematosus and Behçet's disease.29 It has been reported that fetal maternal chimerism could be expressed in maternal circulation,30,31 salivary glands,32 and in the skin33 of female patients with systemic sclerosis. Autoimmune thyroid diseases, especially Hashimoto thyroiditis and Grave's disease, also has been reported to be associated with fetal maternal chimerism.34 More specifically related to MCDZ twin chimeras, in 2010, De Bellefon reported a 40-year-old man diagnosed with a scleroderma-like disease which was hypothesized to be a result of twin twin blood exchange. Chimerism tests using fluorescent in-situ hybridization showed female cells in the peripheral blood and was initially assumed to be of maternal origin. Further human leucocyte antigen-specific quantitative polymerase chain reaction study led researcher to hypothesize that the female cells came from a previously unrecognized or “vanished” twin during pregnancy.35 These studies suggested that although the mechanism of autoimmune disease correlated with chimerism are unknown, MCDZ might be cautiously observed the clinical symptoms of autoimmune disease.
It is important to realize the existence of MCDZ. Traditionally, discordance of fetal gender by ultrasound is considered to have a positive predictive value that approaches 100% for predicting DC.6 But recent studies36,37 suggested that most MCDZ were discovered by incidentally following the finding of sex discordant in second trimester in MC placenta that were confirmed by first trimester ultrasound. Early identifying and confirmation of chorionicity combination with sex identification in second trimester is the key to identify MCDZ twin gestation. It is also important to realize that although the perinatal management of MCDZ twin gestation is about the same as monochorionic diamniotic twin pregnancy, amniocentesis should be offered, at least, for karyotype to rule out genital ambiguity prenatally. Postnatally, these twins have high possibility of blood chimerism that might be associated with health issues later in their life.
Conflicts of Interest
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