Skip to main content

Rare spontaneous monochorionic dizygotic twins: a case report and a systematic review

Abstract

Background

Monochorionic dizygotic twins are a rare condition, mostly related to assisted reproductive technology. This type of twinning is burdened by the same risk of pregnancy complications found in monochorionic monozygotic pregnancies.

Case presentation

We report a case of spontaneous monochorionic dizygotic twins sharing situs inversus abdominalis and isolated levocardia, with only one twin affected by biliary atresia with splenic malformation syndrome. We also conducted a literature review of the 14 available documented monochorionic dizygotic twin gestations spontaneously conceived.

Conclusions

It is still unclear how this unusual type of twinning can occur in spontaneous conception. The evidence so far suggest the importance to timely diagnose the chorionicity, in order to adequately manage the typical complications associated with monochorionicity.

Peer Review reports

Background

Monochorionic dizygotic (MCDZ) twins are a rare condition, mostly related to assisted reproductive technology (ART) [1]. Here we present a case of spontaneous monochorionic dizygotic twins with isolated levocardia and a normal cardiac structure, situs inversus abdominalis, discordant for abdominal anomalies, with only one twin affected by biliary atresia with splenic malformation syndrome (BASM).

We reviewed all cases of spontaneous monochorionic dizygotic twins reported in literature, highlighting the clinical features, the obstetrical implications and the challenges related to this unusual and still not fully known twinning event.

Case presentation

A 27-year-old woman, gravida 2, para 0, with no history of previous disease and no family history of congenital anomalies, smoker and with a BMI of 18.3 received a diagnosis of spontaneous twin pregnancy at 12 weeks. The assessment of chorionicity in this gestational age was however hampered by the presence of an hematoma measuring 44 × 38 mm separating the two membranes, thus preventing the identification of the “lambda” or “T” sign.

The anatomy scan at 20 weeks revealed two female fetuses, both presenting isolated levocardia (IL) with normal heart and situs inversus abdominalis with a left-sided liver and right-sided stomach and spleen (Fig. 1). Noteworthy, in one fetus (A) the gallbladder was not visible.

Fig. 1
figure 1

Situs inversus abdominalis with isolated levocardia of one twin at anomaly scan: stomach lies on the right, whereas the cardiac apex is pointing toward the left

An amniocentesis was performed, with conventional cytogenetic evaluation indicating normal karyotype 46XX for both fetuses. No genetic anomaly was reported with the Chromosomal Microarray Analysis (CMA). Zygosity was assessed by microsatellite analysis; as shown in Table 1, twins share only a fraction of paternal and maternal alleles, indicating dizygosity.

Table 1 Microsatellites analysis of twins and parents. Numbers indicate alleles

At 36 weeks one fetus was diagnosed to be growth restricted, having an abdominal circumference and an estimated fetal weight less than 3rd centile. At 37 weeks and 1 day, the pulsatility index (PI) of the umbilical artery of the growth restricted fetus, with an estimated fetal weight of 2171 g (below the 3rd centile, according to Hadlock growth chart), was 0.89 (corresponding to 46° centile), while the PI of the middle cerebral artery was 1.45 (26° centile). By contrast, the other twin had an estimated fetal weight of 2521 g with normal Doppler parameters. At 37 weeks and 3 days the mother underwent a scheduled cesarean delivery. The birthweight of the two female neonates were 2430 g and 2185 g.

The histological analysis of the placenta confirmed the monochorionicity of the twin pregnancy, revealing the juxtaposition of an amnion on each surface of the dividing membrane (Fig. 2: Hematoxillin-Eosin image obtained using ECLPISE Ni-U equipment, with 10 × magnification, acquired through DS-Fi3 Nikon Digital Camera). The chorion was not visible between the two amnion surfaces, thus excluding the rare occurrence of partially fused placentas [2, 3]. Postnatally, by using DNA extracted from blood samples, the molecular analysis confirmed the dizygosity of the twins, as already previously determined through amniocentesis.

Fig. 2
figure 2

Cross-section through the placental septal membrane roll demonstrates a septum with two layers of amnion, without intervening central chorion (Hematoxillin-Eosin image obtained using ECLPISE Ni-U equipment, with 10 × magnification, acquired through DS-Fi3 Nikon Digital Camera)

Moreover, the two babies turned out to have the same situs anomaly, with IL and situs inversus, thus confirming the prenatal diagnosis. In order to identify possible genetic causes of such a concordant abnormal phenotype, the twins were subjected to clinical exome analysis with evaluation of 17 genes known to be associated to situs inversus. However, according to the variant classification ACMG (The American College of Medical Genetics and Genomics), no pathogenic or probably pathogenetic variants have been identified. By opening the analysis to the whole clinical exome (4490 genes), the twins did not share pathogenic or probably pathogenetic variants. In addition, the twin whose gallbladder was not visualized prenatally, developed jaundice with acholic stool in her neonatal period.

The complete abdominal scan performed at 20 days of extrauterine life showed a left sided, damage-free liver with regular size (lateral diameter of 6,3 cm), a reversed relation between superior mesenteric vein and artery and right-placed inferior vena cava in relation to the aorta. These findings perfectly fit with abdominalis situs inversus with isolated levocardia. The scan revealed for the first time a shriveled gallbladder, which led to the diagnosis of biliary atresia type IV associated with splenic malformations syndrome (Fig. 3). The clinical exome analysis was unable to identify the genetic cause of these abdominal abnormalities.

Fig. 3
figure 3

Abdominal ultrasound at 35 days of extrauterine life of the twin with jaundice: in the liver, a small and atretic gallbladder, not expanding after 3 h fasting, confirmed suspicion of biliary atresia

The twin with BASM at 38 days of extrauterine life underwent Kasai portoenterostomy, second-hand appendectomy and Ladd bridle dissection. Later, during the fifth month of extrauterine life, the baby was diagnosed to have a subclinical acute cholangitis, which was treated with continuous infusion of piperacillin tazobactam during hospitalization. Unfortunately, the baby had recurrent cholangitis during the whole first year of extrauterine life, and these are still occurring.

Discussion and conclusions

A systematic review was conducted using Pubmed, Scopus, OVID, and Cochrane Library electronic databases. The citations were identified with the use of a combination of the following key words: “monochorionic dizygotic twins”; “monochorionic dizygotic chimerism”; “monochorionic dizygotic freemartinism”; “spontaneous monochorionic dizygotic twins”; “spontaneous monochorionic heterosexual twins” from the inception of each database through January 2022. Only articles in English language were selected, while no restrictions for geographic location were applied (Supplementary material).

Overall 14 cases of spontaneously conceived and 4 cases of monochorionic dizygotic twins conceived after ovulation induction were identified. All available articles were case reports. A description of each case is provided in two tables: Table 2 describes case reports on spontaneously conceived monochorionic dizygotic twins [4,5,6,7,8,9,10,11,12,13,14,15,16,17], while Table 3 describes case reports on monochorionic dizygotic twins conceived after ovulation induction [18,19,20,21]. The mean maternal age at delivery in the group of spontaneously conceived monochorionic dizygotic twins was 31.08 weeks (SD ± 4.69). The sonographic assessment of chorionicity was established in the first trimester in 11 cases [5, 6, 8,9,10,11,12,13,14,15,16]. Follow-up scans revealed the following complications during pregnancy: 2 cases of Twin-to-Twin Transfusion syndrome (TTTS) [5, 14],  1 case of Twin Reversed Arterial Perfusion sequence (TRAP) [7], 1 case of Twin Anemia Polycythemia sequence (TAPS) [13] and 1 case of discordant growth pattern [10]. Sex discordance between twins in monochorionic pregnancy was reported in 4 cases [12, 13, 15, 16]. Amniocentesis was performed to validate dizygosity in 2 cases [12, 15], while in 1 case it was done to exclude trisomy 21 [6]. Out of 14 cases reported, 1 case underwent miscarriage after laser procedure performed at 18 weeks gestation for TTTS [5], 1 case underwent a voluntary termination of pregnancy because of the diagnosis of trisomy 21 in one twin [6], 6 cases had a cesarean delivery which occurred at a mean gestational age of 35.83 weeks (SD ± 2.31) [9, 11, 12, 14,15,16], 3 cases had a spontaneous vaginal delivery at a mean gestational age of 35 weeks (SD ± 2.64) [7, 8, 10] and 3 cases did not report the delivery mode [4, 13, 17]. A monochorionic pregnancy was confirmed at gross examination in all cases. Dizygosity was demonstrated by the phenotypical evidence of sex discordance between twins in 2 cases [4, 13] and it was proven by cytogenetic analysis showing sex discordant karyotypes between twins in 3 cases [5, 7, 8]. Chimerism was found to be confined to blood in 6 cases [6, 8, 10, 14, 16, 17], to be present in a non-shared tissue in 3 cases [9, 12, 15] and it was detected in blood as well as in tissue in 1 case [11]. The mean maternal age at delivery in the group of monochorionic dizygotic twins conceived after ovulation induction was 31.00 weeks (SD ± 3.36) [18,19,20,21]. The sonographic assessment of chorionicity was determined in the first trimester in all cases. No typical monochorionic complications were detected during the follow up scans. However, TAPS was found in one case at delivery [21]. Sex discordance between twins in monochorionic pregnancy was reported in 3 cases [18, 20, 21]. Invasive prenatal diagnosis aiming at validating dizygosity was performed in only one case [18]. Preterm delivery occurred in all cases; twins were delivered through cesarean section in 2 cases [19, 20]. A monochorionic pregnancy was confirmed at gross examination in all cases. Chimerism was found to be confined to blood in 2 cases [19, 20], to be present in a non-shared tissue in 1 case [18], and it was detected in blood as well as in tissue in 1 case [21]. In this review, we present a case of spontaneous monochorionic dizygotic twins with isolated levocardia and a normal cardiac structure, situs inversus abdominalis, discordant for abdominal anomalies, with only one twin affected by BASM. Moreover, we reviewed 14 cases of spontaneously conceived MCDZ twins [4,5,6,7,8,9,10,11,12,13,14,15,16,17]. Monochorionicity has been traditionally considered to be a guarantee of monozygosity. A growing body of evidence has now demonstrated that monochorionic twins could be dizygotic. A very rare phenomenon of “sesquizygosis” has been described in the literature [12]. In this case, the twins share the same haploid genome from one parent and, therefore, are intermediate between mono and dizygotic twinning. The microsatellite analysis of our twins excluded sesquizygosis (Table 1). A previous systematic review on this issue showed that assisted reproductive technology is the major responsible for the origin of this unusual way of twinning [1]. Several hypotheses have been advanced to explain a monochorionc dizygotic twin pregnancy: the fusion of the trophoblasts from two different embryos before implantation [22], the presence of binovular follicles where a single zona pellucida includes two distinct oocytes leading to close contact between embryos [19] and the penetration of an oocyte and second polar body surrounded by one zona pellucida by more than one sperm [23]. The chance of cell fusion seems to be small in a natural pregnancy, but not impossible to occur as proven by the number of cases found in our systematic research. Based on this review, this type of twinning is burdened by the same risk of pregnancy complications found in MCMZ pregnancies, i.e. TTTS, TRAP, TAPS and selective Fetal Growth Restriction (sFGR). These findings suggest the importance of a correct diagnosis of chorionicity in the first trimester of pregnancy, in order to timely and adequately manage possible complications. Chorionicity should be determined before 14 weeks of gestation, examining the dividing membrane carefully. In dichorionic diamniotic (DCDA) twin pregnancy, the twins are separated by a thick layer of fused chorionic membranes with two thin amniotic layers, one on each side (the so-called “full lambda” sign), while in monochorionic diamniotic (MCDA) pregnancy only two thin amniotic layers separate the two fetuses (the T-sign). In this case report the ultrasonographic examination of these signs was prevented by the presence of a large hematoma at the site of insertion of the amniotic membrane into the placenta. Since 3% of monochorionic pregnancies have two placental masses (also defined “bipartite placenta” [24]) on ultrasound and dichorionic placentae are commonly appearing as a single mass, the reliability of the number of placental masses at ultrasound is questionable. Therefore, we did not consider this feature for the diagnosis of chorionicity. Interestingly, bipartite placenta seems to have some relevant clinical implications. A recent study found bipartite placenta in five MCDA pregnancies and showed that this occurrence was associated with a higher rate of complications, such as TTTS and sFGR and might impair prenatal surgical interventions [24]. The diagnosis of monochorionicity is even more important in the context described in our case report, since sex discordance of twins could lead to the automatic assumption of dichorionicity. Chimerism is characterized by cells originating from more than one genetically distinct zygote. Chimerism was found in most reviewed cases. Blood confined chimerism is likely to be consequent to the blood sharing between the dizygotic twins via the unique placenta. It has been theorized that the “outer cell mass” of the two distinct dizygotic embryos undergo fusion with the development of a single chorion and anastomoses. However, in 21.42% of cases tissue chimerism was found, which is more difficult to explain [9, 11, 15]. It is unknown whether chimerism has clinical consequences. Bogdanova et al. reported a possible case of human freemartinism in a female twin with aplasia of the uterus [25]. According to the Author the lack of Mullerian structures in this female was caused by her exposition to the effect of the Mullerian inhibiting substance transferred from the male twin via the common placenta in early pregnancy. Recently, Peters et al. investigated whether there is a prevalence of male microchimerism in women with Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome [26]. However, their observational case–control study, involving 95 women with MRKH syndrome and 99 control women, showed that the prevalence of male microchimerism was significantly higher in the control group than in the MRKH group, thus rejecting the initial hypothesis. We compared our case report with the cases of spontaneously conceived MCDZ twins present in our systematic review. Molecular analysis performed on tissue and blood samples of the two female twins confirmed dizygosity. What is peculiar of our case report, is the very rare anomaly shared by both twins, though in a different way. Both have IL and situs inversus abdominalis, but only one twin is affected by biliary atresia with splenic malformation syndrome. No genetic cause of these abnormalities was identified by clinical exome analysis; but this should not rule out genetic determinants of the phenotypic abnormalities. There are indeed several distinct methodological features able to explain the non-identification of genetic causes. Among them, the fact that the clinical exome evaluates only genes known to be associated to human diseases or the possibility that the putative causative variant might be located in control regions of gene expression (promoter or enhancers, for example), not analyzed by the exome approach. Biliary atresia is recognized as a key feature in two distinct types of syndromes: the Cat-eye syndrome (CES) and the Biliary Atresia Splenic Malformation (BASM) syndrome. The first one is determined by aneuploidy of chromosome 22 and patients affected typically have coloboma, cardiac anomalies and anorectal malformations. On the other hand, BASM is characterized by a constellation of visceral anomalies in different combinations. Patients with BASM could have polysplenia, asplenia or double spleen, situs inversus with and without malrotation; preduodenal portal vein, a complete absence of intrahepatic vena cava and cardiac anomalies. According to some researchers [27, 28] the association between BA and laterality defects of the abdominal viscera may suggest a defect in the embryonic development to explain the etiology of BASM. The bile duct development begins at 4 gestational weeks and ends at about 13 weeks; in the same period laterality defects, such as development of left–right axis reversal (GA 2–3 weeks), splenic malformations (GA 3–6 weeks), preduodenal portal vein (GA 4–8 weeks), and interrupted vena cava (GA 6–8 weeks) are thought to occur [27]. A recent metanalysis, aiming at analyzing the characteristics of biliary atresia in twins, found that 97% of twins were discordant for the anomaly. In more than half of the cases twins were monozygotic, thus indicating that zygosity is not the main causative factor of the onset of the disease [29]. However, even assuming the role of epigenetic factors in the pathogenesis of BA, our case report still remains a fascinating enigma. It is hard to find an explanation of why two monochorionic dizygotic sex concordant twins should share a very rare laterality anomaly of the abdominal viscera, sparing one twin from developing biliary atresia. The main strength of this study is the singularity and originality of our case report, where two MCDZ twins share the same malformation in a slight different way, with important clinical consequences on one twin. Moreover, we did a comprehensive systematic review on MCDZ pregnancies naturally conceived, which is the first in the literature to the best of our knowledge. It is interesting to note that when spontaneously conceived MCDZ pregnancies were affected by a malformation, this was present in one twin only, according to our review. Our case report is therefore unique. However, some limitations should be recognized too. First of all, we did not perform the whole exome sequencing, thus preventing the possibility to identify some variants located in control region of gene expression. In addition we did not investigate the occurrence of chimerism, either in blood and in other different tissues.

Table 2 Case reports of spontaneously conceived monochorionic dizygotic twins
Table 3 Case reports of monochorionic dizygotic twins conceived after ovulation induction

In conclusion, spontaneously conceived MC-DZ twins are a rare condition, with only 14 cases described in literature. The evidence so far suggests the importance to timely diagnose the chorionicity, in order to adequately manage the typical complications associated with monochorionicity. Furthermore, the clinician should keep in mind that monochorionicity does not always correspond to monozygosity. Rarely, MC twins could be DZ, even in naturally conceived pregnancies, as shown in this comprehensive review. It is still unclear how this unusual type of twinning can occur in spontaneous conception. The mystery deepens considering the peculiarity of our case report, where the two MCDZ twins share a very rare anomaly, for which no genetic cause has been found through clinical exome analysis.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

MC-DZ:

Monochorionic dizygotic

ART:

Assisted reproductive technology

BASM:

Biliary atresia with splenic malformation syndrome

IL:

Isolated levocardia

CMA:

Chromosomal Microarray Analysis

PI:

Pulsatility index

ACMG:

The American College of Medical Genetics and Genomics

TTTS:

Twin-to-Twin Transfusion syndrome

TRAP:

Twin Reversed Arterial Perfusion sequence

TAPS:

Twin Anemia Polycythemia sequence

MCMZ:

Monochorionic monozygotic

sFGR:

Selective fetal growth restriction

DCDA:

Dichorionic diamniotic

MCDA:

Monochorionic diamniotic

MRKH:

Mayer–Rokitansky–Küster–Hauser

CES:

Cat-eye syndrome

BA:

Biliary atresia

References

  1. Peters HE, König TE, Verhoeven MO, Schats R, Mijatovic V, Ket JC, Lambalk CB. Unusual Twinning Resulting in Chimerism: A Systematic Review on Monochorionic Dizygotic Twins. Twin Res Hum Genet. 2017;20(2):161–8. https://doi.org/10.1017/thg.2017.4. Epub 2017 Feb 27. PMID: 28236812.

    Article  PubMed  Google Scholar 

  2. Lopez-Tello J, Sferruzzi-Perri AN. Fused placentas: till birth do us part. Placenta. 2021;1(103):177–9. https://doi.org/10.1016/j.placenta.2020.10.036. Epub 2020 Nov 2. PMID: 33157350.

    Article  Google Scholar 

  3. Galjaard S, Moerman P, Corveleyn A, Devlieger R, Lewi L. Partial monochorionic and monoamniotic twin pregnancies: a report of two cases. Ultrasound Obstet Gynecol. 2014;44:722–4. https://doi.org/10.1002/uog.13403.

    CAS  Article  PubMed  Google Scholar 

  4. Nylander PP, Osunkoya BO. Unusual monochorionic placentation with heterosexual twins. Obstet Gynecol. 1970;36(4):621–5. PMID: 5506469.

    CAS  PubMed  Google Scholar 

  5. Quintero RA, Mueller OT, Martínez JM, Arroyo J, Gilbert-Barness E, Hilbelink D, Papenhausen P, Sutcliffe M. Twin-twin transfusion syndrome in a dizygotic monochorionic-diamniotic twin pregnancy. J Matern Fetal Neonatal Med. 2003;14(4):279–81. https://doi.org/10.1080/jmf.14.4.279.281. PMID: 14738176.

    CAS  Article  PubMed  Google Scholar 

  6. Shalev SA, Shalev E, Pras E, Shneor Y, Gazit E, Yaron Y, Loewenthal R. Evidence for blood chimerism in dizygotic spontaneous twin pregnancy discordant for Down syndrome. Prenat Diagn. 2006;26(9):782–4. https://doi.org/10.1002/pd.1503. PMID: 16927328.

    CAS  Article  PubMed  Google Scholar 

  7. Lattanzi W, De Vincenzo RP, De Giorgio F, Stigliano E, Capelli A, Arena V. An acephalus acardius amorphous fetus in a monochorionic pregnancy with sex discrepancy. Twin Res Hum Genet. 2006;9(5):697–702. https://doi.org/10.1375/183242706778553453. PMID: 17032553.

    Article  PubMed  Google Scholar 

  8. Hackmon R, Jormark S, Cheng V, O’Reilly Green C, Divon MY. Monochorionic dizygotic twins in a spontaneous pregnancy: a rare case report. J Matern Fetal Neonatal Med. 2009;22(8):708–10. https://doi.org/10.1080/14767050902763159. PMID: 19562637.

    Article  PubMed  Google Scholar 

  9. Umstad MP, Short RV, Wilson M, Craig JM. Chimaeric twins: why monochorionicity does not guarantee monozygosity. Aust N Z J Obstet Gynaecol. 2012;52(3):305–7. https://doi.org/10.1111/j.1479-828X.2012.01445.x. Epub 2012 May 8. PMID: 22563999.

    Article  PubMed  Google Scholar 

  10. Kanda T, Ogawa M, Sato K. Confined blood chimerism in monochorionic dizygotic twins conceived spontaneously. AJP Rep. 2013;3(1):33–6. https://doi.org/10.1055/s-0032-1331377. Epub 2013 Jan 2. PMID: 23943707; PMCID: PMC3699156.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rodriguez-Buritica D, Rojnueangnit K, Messiaen LM, Mikhail FM, Robin NH. Sex-discordant monochorionic twins with blood and tissue chimerism. Am J Med Genet A. 2015;167A(4):872–7. https://doi.org/10.1002/ajmg.a.37022. Epub 2015 Feb 23. PMID: 25708669.

    Article  PubMed  Google Scholar 

  12. Gabbett MT, Laporte J, Sekar R, Nandini A, McGrath P, Sapkota Y, Jiang P, Zhang H, Burgess T, Montgomery GW, Chiu R, Fisk NM. Molecular Support for Heterogonesis Resulting in Sesquizygotic Twinning. N Engl J Med. 2019;380(9):842–9. https://doi.org/10.1056/NEJMoa1701313. PMID: 30811910.

    CAS  Article  PubMed  Google Scholar 

  13. Chen K, Kuhlmann R, Bell A, Rader J, Baumgartner M, Lemmens K, Merrill D. Twin anemia-polycythemia sequence in sex-discordant monochorionic dizygotic twins. Ultrasound Obstet Gynecol. 2020;56(3):461–2. https://doi.org/10.1002/uog.22073. PMID: 32395871.

    CAS  Article  PubMed  Google Scholar 

  14. Armitage AM, Kundra MA, Ghiam N, Atwal PS, Morel D, Hruska KS, Torene R, Harbour JW, Forghani I. Chimerism involving a RB1 pathogenic variant in monochorionic dizygotic twins with twin-twin transfusion syndrome. Am J Med Genet A. 2021;185(1):208–12. https://doi.org/10.1002/ajmg.a.61913. Epub 2020 Oct 9. PMID: 33037780.

    CAS  Article  PubMed  Google Scholar 

  15. Daum H, Frumkin A, Meiner V, Werner M, Macarov M, Gillis D, Israel S, Abed El Latif M, Meir K, Gielchinsky Y. Non-confined long-standing blood chimerism in a spontaneous monochorionic dizygotic twin pregnancy. Int J Gynaecol Obstet. 2020;148(3):399–400. https://doi.org/10.1002/ijgo.13022. Epub 2019 Nov 26. PMID: 31671208.

    Article  PubMed  Google Scholar 

  16. Yoshida A, Kaji T, Sogawa E, Yonetani N, Suga K, Nakagawa R, Iwasa T. Monochorionic Dizygotic Twins Conceived Spontaneously Showed Chimerism in Karyotype and Blood Group Type. Twin Res Hum Genet. 2021;24(3):184–6. https://doi.org/10.1017/thg.2021.20. Epub 2021 Jun 15. PMID: 34127172.

    Article  PubMed  Google Scholar 

  17. Chen J, Xu J, Chen ZH, Yin MN, Guo XY, Sun L. Case Report: Identification of Germline Chimerism in Monochorionic Dizygotic Twins. Front Genet. 2021;19(12):744890. https://doi.org/10.3389/fgene.2021.744890. PMID:34868215;PMCID:PMC8641794.

    Article  Google Scholar 

  18. Ginsberg NA, Ginsberg S, Rechitsky S, Verlinsky Y. Fusion as the etiology of chimerism in monochorionic dizygotic twins. Fetal Diagn Ther. 2005;20(1):20–2. https://doi.org/10.1159/000081363. PMID: 15608454.

    Article  PubMed  Google Scholar 

  19. Aoki R, Honma Y, Yada Y, Momoi MY, Iwamoto S. Blood chimerism in monochorionic twins conceived by induced ovulation: case report. Hum Reprod. 2006;21(3):735–7. https://doi.org/10.1093/humrep/dei379. Epub 2005 Nov 3. PMID: 16269445.

    Article  PubMed  Google Scholar 

  20. Mayeur Le Bras A, Petit F, Benachi A, Bedel B, Oucherif S, Martinovic J, Armanet N, Tosca L, Gautier V, Parisot F, Labrune P, Tachdjian G, Brisset S. Confined blood chimerism in a monochorionic dizygotic sex discordant twin pregnancy conceived after induced ovulation. Birth Defects Res A Clin Mol Teratol. 2016;106(4):298–303. https://doi.org/10.1002/bdra.23457. Epub 2016 Mar 2. PMID: 26931099.

    CAS  Article  PubMed  Google Scholar 

  21. Suzuki T, Kagami K, Mitani Y, Yamazaki R, Ono M, Fujiwara H. Twin anemia-polycythemia sequence with blood chimerism in monochorionic dizygotic opposite-sex twins. J Obstet Gynaecol Res. 2019;45(6):1201–4. https://doi.org/10.1111/jog.13949. Epub 2019 Feb 28. PMID: 30821075.

    Article  PubMed  Google Scholar 

  22. Souter VL, Kapur RP, Nyholt DR, Skogerboe K, Myerson D, Ton CC, Opheim KE, Easterling TR, Shields LE, Montgomery GW, Glass IA. A report of dizygous monochorionic twins. N Engl J Med. 2003;349(2):154–8. https://doi.org/10.1056/NEJMoa030050. PMID: 12853588.

    Article  PubMed  Google Scholar 

  23. Dyban AP, De Sutter P, Dozortsev D, Verlinsky Y. Visualization of second polar body chromosomes in fertilized and artificially activated mouse oocytes treated with okadaic acid. J Assist Reprod Genet. 1992;9(6):572–9. https://doi.org/10.1007/BF01204256. PMID: 1299391.

    CAS  Article  PubMed  Google Scholar 

  24. Walter A, Strizek B, Berg C, Geipel A, Gembruch U, Engels AC. Outcome of monochorionic twins with prenatally diagnosed bipartite placenta. Arch Gynecol Obstet. 2020;302(6):1549–52. https://doi.org/10.1007/s00404-019-05364-w. Epub 2019 Nov 25. PMID: 31768742.

    Article  PubMed  Google Scholar 

  25. Bogdanova N, Siebers U, Kelsch R, Markoff A, Röpke A, Exeler R, Tsokas J, Wieacker P. Blood chimerism in a girl with Down syndrome and possible freemartin effect leading to aplasia of the Müllerian derivatives. Hum Reprod. 2010;25(5):1339–43. https://doi.org/10.1093/humrep/deq048. Epub 2010 Feb 26. PMID: 20190264.

    CAS  Article  PubMed  Google Scholar 

  26. Peters HE, Johnson BN, Ehli EA, Micha D, Verhoeven MO, Davies GE, Dekker JJML, Overbeek A, Berg MHVD, Dulmen-den Broeder EV, Leeuwen FEV, Mijatovic V, Boomsma DI, Lambalk CB. Low prevalence of male microchimerism in women with Mayer-Rokitansky-Küster-Hauser syndrome. Hum Reprod. 2019;34(6):1117–25. https://doi.org/10.1093/humrep/dez044. PMID:31111890; PMCID:PMC6554047.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Mysore KR, Shneider BL, Harpavat S. Biliary Atresia as a Disease Starting In Utero: Implications for Treatment, Diagnosis, and Pathogenesis. J Pediatr Gastroenterol Nutr. 2019;69(4):396–403. https://doi.org/10.1097/MPG.0000000000002450. PMID:31335837; PMCID:PMC6942669.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Davenport M, Muntean A, Hadzic N. Biliary Atresia: Clinical Phenotypes and Aetiological Heterogeneity. J Clin Med. 2021;10(23):5675. https://doi.org/10.3390/jcm10235675. PMID:34884377; PMCID:PMC8658215.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Xu X, Zhan J. Biliary atresia in twins: a systematic review and meta-analysis. Pediatr Surg Int. 2020;36(8):953–8. https://doi.org/10.1007/s00383-020-04690-4. Epub 2020 Jun 5. PMID: 32504124.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Funding information is not applicable.

Author information

Authors and Affiliations

Authors

Contributions

LD, SX and GT managed the pregnancy antenatally. SX, GT and GD wrote the manuscript. DF, ED and GD performed the genetic analysis. SX performed the literature review, GT was responsible for acquisition and interpretation of the images. GD and LD revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Giuseppe Damante or Serena Xodo.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

The patient signed informed consent for the publication of this case report and any associated images. A copy of the consent form is available for review by the Editor of this journal.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Supplementary figure S1. 

Flow diagram of inclusion of articles.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Trombetta, G., Fabbro, D., Demori, E. et al. Rare spontaneous monochorionic dizygotic twins: a case report and a systematic review. BMC Pregnancy Childbirth 22, 564 (2022). https://doi.org/10.1186/s12884-022-04866-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12884-022-04866-x

Keywords

  • Monochorionic dizygotic twins
  • Situs inversus
  • Biliary atresia splenic malformation