Human Reproduction, Vol. 14, No. 5, 1378-1380,
May 1999
© 1999 European Society of Human Reproduction and Embryology
Case Report:Trisomy 2 in an acardiac twin in a triplet in-vitro fertilization pregnancy
1 Mayday University Hospital, Croydon, Surrey, 2 Fetal Medicine Unit and 3 SW Thames Regional Genetics Service, St George's Hospital Medical School, London, UK
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Abstract |
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A case is reported of twin reversed arterial perfusion (TRAP) sequence in a triamniotic dichorionic triplet pregnancy conceived by in-vitro fertilization which was diagnosed at 25 weeks of gestation by colour Doppler sonography. It highlights the risk of monochorionicity-associated morbidity in multiple pregnancies obtained by assisted conception and stresses the importance of chorionicity determination by early ultrasound examination. Cytogenetic analysis of skin from the acardius showed trisomy 2 in all cells, whereas the karyotype in the monochorionic triplet was normal. This is an example of heterokaryotypic monozygotism where the chromosomal abnormality must have occurred during the early cleavage divisions. Aneuploidy as a possible aetiological factor of TRAP sequence is discussed.
Key words: acardia/chorionicity/IVF/TRAP
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Introduction |
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The twin reverse arterial perfusion (TRAP) sequence is a rare complication occurring in 1 in 35 000 pregnancies but in up to 1 in 100 monochorionic twin pregnancies (Moore et al., 1990
). The risk in multiple pregnancies of a higher order is even greater (Nicolaidis et al., 1990). The anatomically normal twin is termed the pump twin whilst the recipient twin is malformed. The recipient twin functions as a parasite to the pump twin and receives retrograde blood flow of poorly oxygenated blood from the pump twin via the abdominal aorta, resulting in a wide spectrum of malformations. The abnormal haemodynamics created in this situation can result in congestive heart failure, hydrops and consequent premature delivery of the pump twin such that the mortality rate may be as high as 50%.
We present a case of TRAP sequence in a triplet pregnancy conceived by in-vitro fertilization (IVF) which was diagnosed at 25 weeks of gestation. It highlights the risk of monochorionicity-associated morbidity in multiple pregnancies obtained by assisted conception and stresses the importance of chorionicity determination by early ultrasound examination. Aneuploidy as a possible aetiological factor of TRAP sequence is discussed.
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Case report |
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A 30 year old woman underwent IVF treatment with transfer of three embryos resulting in a dichorionic triplet pregnancy. One of the fetuses in the diamniotic monochorionic component was an acardiac twin.
A mass attached to the placenta next to that of twin was first noted on a scan performed at 11 weeks of gestation. The diagnosis of an acardiac twin in a monochorionic diamniotic pregnancy (one normal male fetus and one acardius), and a dichorionic triplet (normal female fetus) was only made at 25 weeks. The acardius measured 92x88x84 mm, lacked a cephalic pole and had primitive and phocomelic limbs in an oligohydramniotic cavity. Both normal fetuses were well grown with no evidence of cardiac insufficiency. An artery-to-artery superficial anastomosis was visualized by colour Doppler. The acardius had a single umbilical artery.
The pregnancy was scanned weekly thereafter and both fetuses maintained good growth without any evidence of cardiac decompensation in the pump twin. The acardius remained stable in size. Expectant management and weekly dexamethasone courses were continued until 33 weeks of gestation when ultrasound revealed redistribution of arterial blood flow in the pump twin. In view of the risk of further haemodynamic instability of the pump twin, a Caesarean section was performed at 34 weeks of gestation. The acardius weighed 622 g, the neonates weighed 2.2 kg and 2.39 kg and were in good condition with normal haemoglobin concentrations. Both were discharged from the special care baby unit 1 week later along with their mother.
Examination of the placentae confirmed a dichorionic triplet pregnancy. The umbilical cord of the abnormal triplet contained only two vessels, whereas the umbilical cords of triplets 1 and 2 contained three. Sections confirmed that the common membrane between triplets 1 and 2 contained chorion but that between triplet 1 and the abnormal triplet was composed only of amnion and no intervening chorion and there was a direct artery-to-artery anastomosis.
The analysed cells from the skin of the acardius showed 47 chromosomes with an extra chromosome 2 in all cells (47, XY, +2; trisomy 2). Triplet 1 showed a normal male (46, XY) karyotype.
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Discussion |
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In assisted conception programmes, serial early scans are routinely performed and multiple pregnancies are more frequent, hence chorionicity is almost always established in these early scans. The great majority of IVF twin and triplet pregnancies are dichorionic and trichorionic respectively. However, the incidence of monochorionic twin pregnancy in these patients is increased eightfold above the background rate, and may be due to a delay in early development process or abnormal hatching with a reported risk of monochorionicity of 3.2% compared to 0.4% in the general population (Wenstrom et al., 1993
).
It has been suggested that the delayed ovum transport and implantation seen with both the oral contraceptive and with assisted reproduction techniques, might predispose to monochorionicity (Bressers et al., 1987). Manipulation of the embryo prior to transfer should also be considered as a possible aetiological factor.
Our case highlights the risk of monochorionicity and monochorionicity-associated morbidity in multiple pregnancies obtained by assisted conception including TRAP and twin-to-twin transfusion. Information concerning the chorionicity of a multiple pregnancy is therefore of critical importance in these patients as well as in pregnancies conceived naturally; this is best determined by first trimester ultrasound examination. The presence of anastomsoses in the placenta from artery-to-artery and vein-to-vein seen here are consistent with this diagnosis and are thought to develop at 3–4 weeks of gestation when the placenta connects to the umbilical–allantoic vessels of the embryo. This is also an issue in embryo reduction programmes since the risk of selective fetocide on a monochorionic fetus is likely to be associated with a higher morbidity in its co-twin (Maymon et al., 1995).
Two major theories have been advanced to explain the aetiology and pathogenesis of TRAP sequence. The first theory (Benirschke et al., 1977) postulated that the primary conditions required are (i) a severe genetic or other primary defect sufficient to cause failure of cardiac development in one of the twins, and (ii) anastomoses formed between the vessels of the two umbilical cords. This view was supported by reports suggesting that the genetic abnormality may arise only in one of monozygotic twins either after the occurrence of twinning as a form of post-zygotic non-disjunction (Scott et al., 1973) or primarily by means of independent fertilization of an ovum and its diploid first polar body, thus resulting in possibly different-sexed twins, one of which is triploid (Bieber et al., 1981). The alternative pathogenic theory (Benirschke et al., 1977) suggests that the development of artery-to-artery anastomosis between the twins in the presence of a fused placenta early in the first trimester would lead to vascular disruption of one twin and the development of TRAP sequence. Although zygocity was not assessed by molecular genetics in this monochorionic pregnancy, monochorionicity is generally accepted to reflect monozygoticity in human pregnancies (Husby et al., 1991; Keith et al., 1997). This case strongly supports the former theory and to our knowledge is the first report of trisomy 2 associated with an acardiac acephalic fetus. In this case, three embryos had been replaced 24 h post-fertilization. Histopathology of the placenta confirmed a dichorionic–triamniotic triplet pregnancy; hence, it is most likely that one embryo did not implant, one implanted normally and one split into two between day 4 and day 8 post-fertilization. This is an example of heterokaryotypic monozygotism where the chromosomal abnormality must have occurred during the early cleavage divisions. One possibility is non-disjunction during the second or subsequent divisions, with loss of the non-viable monosomic cell. Other possible mechanisms to explain this case are trisomic rescue or asynchronous endoreduplication of a single chromosome resulting in the gain of a chromosome in one cell without reciprocal loss from another cell. The actual mechanism is uncertain, but this finding illustrates that errors in postzygotic mitoses can produce trisomic states. Given the fact that the karyotype in the other monozygotic triplet is normal, it is most likely that this karyotypic abnormality arose after splitting of the fertilized ovum. The presence of trisomy 2 is unusual in that affected fetuses are usually aborted in the first trimester and it is reported as the second commonest autosomal trisomy found in spontaneous abortuses (Byrne et al., 1985). True mosaic trisomy 2 is extremely rare and as a result very few cases have been described; however, these have been recorded in association with multiple congenital abnormalities (Robinson et al., 1997; Sago et al., 1997). In this case, fetal demise presumably would have been the fate of the abnormal fetus but for the presence and support of its monochorionic co-triplet via their vascular anastomoses.
Management strategies for these pregnancies in the second half of gestation aim at improving the survival of the pump twin. The diagnosis of an acardiac tumour next to a normally grown pump twin without evidence of heart failure in the third trimester calls for conservative management and close observation for signs of cardiac decompensation in the pump twin. Whilst the recurrence rate for TRAP is unknown, it is likely to be low and couples can therefore be counselled optimistically for future pregnancies.
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4 To whom correspondence should be addressed at: Service de Gynécologie-Obstétrique, CH Poissy-St Germain, Rue du champ Gaillard, 78303 Poissy Cedex 03 France
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Submitted on September 11, 1998; accepted on January 26, 1999.
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