1 Department of Obstetrics and Gynaecology, Monash University, and 2 Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia
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Introduction |
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Natural and IVF monozygotic twinning |
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Monozygous twins occur in IVF programmes and are associated with consequences similar to naturally conceived monozygous twins. In two thirds of monozygous twins, monochorionic placentation occurs.
Vascular anastomosis occur between the two halves of the shared placenta. In most cases this is a normal event (Table I). Imbalance in the placental support between the twins may lead to clinical sequelae of intertwin transfusion, which may be acute, chronic or reversed (Table II
).
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Acute intertwin transfusion |
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The impending fetal death of one twin represents a complex management issue: (i) delivery of both twins which at 2528 weeks exposes the healthy twin to the risks of prematurity; (ii) conservative management which allows a single fetal death but exposes the surviving fetus to the risks of acute intertwin transfusion. Fetal sampling and fetal blood transfusion may succeed if the diagnosis can be made at an appropriate time; and (iii) selective feticide occluding the circulation of the compromised fetus to avoid acute intertwin transfusion. This has been achieved by laparoscopy (Denbow and Fisk, 1998).
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Chronic intertwin transfusion |
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The clinical changes are thought to be due to intertwin transfusion in a state of flux or free mixing of blood between the twins. The differences between the twins, a large amniotic sac (hydramnios) enlarged heart and oedema, and the growth restricted small amniotic volume of the other, are due to volume changes rather than haematological differences, the haemoglobin in utero being similar.
Treatment options are suboptimal and include, serial aggressive amniotic fluid reduction, laser ablation or ligation of placental vasculature, amniotic septostomy to join the two unequal sized sacs, or selective feticide.
The long-term sequelae in FFTS are cerebral white matter lesions with neurological impairment, cardiac dysfunction and morbidity associated with prematurity (Denbow and Fisk, 1998).
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Twin reversed arterial perfusion sequence |
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Conservative treatment or separation of the twins cardiovascular systems are the two options in management. Separation techniques (laser, suture ligation, ultrasound-guided or laparoscopic) have been used but may cause premature labour.
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Monozygotic twins may not be identical in genotype and phenotype |
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While it is true that most monozygotic twins are phenotypically very similar, there are significant numbers of monozygotic pairs who are neither genotypically nor phenotypically identical (Machin, 1996). Cohorts of monozygotic twin pairs have been monitored to determine non-genetic influences on the risks of developing diseases and on behaviour, the assumption being that studies comparing genetically identical monozygotic twin pairs eliminate genetic variability when the twins are reared apart. Any differences that have been attributed to environmental factors in twins reared apart may overestimate the effect of the environment as genetic or placental influences may produce differences between the twins. The percentage of discordant genetic monozygotic twins is unknown (Edwards and Beard, 1998
). Presumably there may also be genetic differences in artificial twins.
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Artificial twinning in cattle and humans |
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The immediate concern is whether artificial twinning could result in identical twins where complications occur. Artificial identical twins would represent the one third of naturally occurring monozygotic twins having their own placenta, which can still be separate or fused and their own amniotic sacs, and would result from separation of the inner cell mass and trophoblast. This avoids those complications which occur in natural monozygotic twins which include cord entanglement, locked twins during birth and cross circulation between twins leading to acute, chronic, or retrograde intertwin transfusion.
Artificial twinning has been used extensively in cattle (Lewis, 1994; Hygate, 1995). Many thousands of calves have been born worldwide and there have been no reports of the technique producing abnormalities in the offspring, including an extensive Australian experience (Lewis, 1994
). The health of the calves resulting from embryo duplication is not different from normal calves. The establishment of a pregnancy depends upon an `all or nothing' effect. If there are enough viable cells in the demi-embryo to establish a pregnancy, a normal offspring results. If not, then no offspring result.
Most demi-embryos that have been split are transferred individually to separate cows and birth and rearing is normal. When the two demi-embryos are transferred to the same cow the only problems are the same as natural twins with possibly difficulty at birth or mothering, but no refusion of embryos to form Siamese twins.
The success of the embryo bisection is greatest at the blastocyst to expanded blastocyst stage (Lewis, 1994; Hygate et al., 1995
). This is probably due to the fact that there are more cells in the inner cell mass of a blastocyst, and after bisection there are more cells left in the demi-embryo to establish a pregnancy (I.M.Lewis, personal communication). This hypothesis agrees with the finding that the technique does not work well in poor quality embryos, which have fewer cells and possibly other cell defects. Poor quality embryos are transferred whole as bisection results in a lower overall chance of pregnancy.
Transfer of good quality whole cattle embryos result in a pregnancy rate of ~70% per transfer. Where good quality embryos are bisected the pregnancy rate of the resulting demi-embryos are ~5055%, resulting in a 100110% pregnancy rate for the original whole embryo. This gives a 3040% greater chance of conception. Poor quality embryos result in a pregnancy rate of around 40% and after bisection only 20% (I.M.Lewis, personal communication).
Demi-embryos may be cryopreserved as blastocysts and are viable after thawing and transfer (I.M.Lewis, personal communication). New cryopreservation methods enable the high survival of in-vitro produced, demi-and cloned embryos devoid of their zona (I.M.Lewis, personal communication).
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Prevention of monochorionic twins |
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It has been observed that monozygotic pregnancy is higher than expected with new embryo culture methods. Following the transfer of human blastocysts, the incidence of monozygotic twins is 2.7% of pregnancies (Rijnders et al., 1998). It could be argued that separation of the trophoblast of embryos with two distinct inner cell masses by microsurgery would benefit the probability of survival of both embryos formed and this would be the preferred ethical position. This is an argument for splitting embryos with naturally occurring twin inner cell masses.
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Artificial twinning may help infertile couples |
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Ethics |
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IVF has already been generally accepted and involves an artificial method of reproduction and manipulation and possible destruction of embryos if these are abnormal. Monozygotic twins do occur in natural reproduction, the effect on each twin being accepted. The violation of an inherent uniqueness of an individual already exists in natural reproduction with the occurrence of monozygotic twins. The use of artificial twinning may be controlled by the government as it has been in the use of donor eggs, donor spermatozoa and surrogacy in Australia. For example, a restriction could be placed on couples wishing to create embryos to produce organs and tissues for children who need transplants.
Twins are associated with some disadvantages, a four-fold increase in perinatal death rate, three per 100, and if severe prematurity occurs an increased risk of mental deficiency in offspring. The mother has double the chance of requiring Caesarean section (42%, compared to 19%) (Lancaster et al., 1995). The risk to artificial twins may be less than to natural monozygotic twins. Separate placenta and amnion are formed, so that cord entanglement, locking of twins during birth and cross circulation of placental vasculature, which may cause fetal death or growth retardation, would be avoided.
Artificial twinning has the second advantage that the twinning is planned and the parents informed of risks, which does not occur in natural twinning. Bryan emphasized the psychological effects of being born as a monozygotic twin (Bryan, 1998). Problems exist because of the unique situation of two similar individuals growing up together but neither behaviour problems nor long-term psychological disturbance are significantly greater than singletons (Rutter and Redshaw, 1991
; Kendler et al., 1996
).
Artificial twinning may provide donor embryos for infertile couples who cannot conceive naturally or with IVF. The shortage of adopted children and donor embryos may be overcome by the production of artificial twins. The offspring of the original embryo could be checked before using the frozen stored copy. Adoption or unwanted donor embryos can give little or no information relevant to the future health of the child. The donated embryo would enable the infertile woman to experience pregnancy, birth and early rearing. A donor embryo would also be advantageous for a couple with increased genetic risks to offspring from their own spermatozoa or oocytes.
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Notes |
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This debate was previously published on Webtrack 99, December 13, 1999
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