**5. Conclusion**

factor than that of maternal age [33]. In Australia where fertility treatment is subsidised by the state and rates of health insurance are high, the rate of single embryo transfer is over 75% and reflected in the multiple pregnancy rate from IVF being below 6% [34]. In comparison, in the United States sET recorded in the same year was less than 25% [35]. This is also a reflection of

Regulations and policy governing single embryo transfer also exist in many Scandinavian and some European countries, such as Belgium, as well as Australia, with reflective low rates of multiple pregnancy and high rates of cycle success. The transfer of more than two embryos is banned in Australia and double embryo transfer only allowed in the setting of significant advanced maternal age or multiple failed attempts at single embryo transfer [36]. In comparison, other European countries like Greece, Montenegro and Lithuania have few regulations governing IVF protocols and treatment and overall data from Europe show rates of double embryo transfer well over 50% and rates of transfer of three or more embryos as high as 12.5% [37]. The multiple birth rate is reflected in this practice with the multiple birth rate following IVF being 18.7% in Europe compared with 5.6% in Australia and New Zealand [37]. The multiple birth rate following IVF is even higher in the United States at 26.6% [35]. This is despite slightly higher rates of double embryo transfer in Europe, however this is thought to reflect the high rate of fetal

reductions that occur in Europe as a management strategy for multiple pregnancy.

ning following IVF [40].

54 Multiple Pregnancy - New Challenges

Despite implementing a single embryo transfer an IVF cycle may still result in a multiple pregnancy due to monozygotic twinning. Monozygotic twins are at increased risk of significant complications including Twin-Twin Transfusion Syndrome (TTTS) and Twin Anaemia-Polycythaemia Sequence (TAPS), fetal anomalies and perinatal morbidity. The rate of monozygotic twinning is increased in IVF pregnancy by 6 times compared with spontaneously conceived pregnancies [38], occurring at a rate of around 2.5% [39]. The reason for this is likely multifactorial. Culture media, embryo quality, use of gonadotropins and manipulation of the zona pellucida are all thought to play a role in the increased rates of monozygotic twin-

In natural conception the rate of monozygotic twinning increases with age, likely a reflection of egg quality, however the inverse has been seen in pregnancies conceived with IVF. Women under 35 are twice as likely to have a monochorionic twin pregnancy following IVF treatment compared with women aged over 35 [41]. The mechanism for this may include the zona pellucida experiencing increased thickening with advancing maternal age, resulting in the embryo of an older patient being more robust to the manipulation exerted on it during IVF or Intracytoplasmic Sperm Injection (ICSI), or during embryo biopsy. This is an important observation and further supports the argument for single embryo transfer for younger patients with a good chance of implantation per embryo transfer. If a patient is at increased risk of monozygotic twinning, and has a double embryo transfer the risk of a higher order multiple

The stress that a developing blastocyst and embryo undergoes during an IVF cycle may rationalise the increased rates of monozygotic twinning. Monozygotic twin pregnancies are more likely in day 5 blastocyst transfer than day 2 or 3 cleavage stage transfer, perhaps reflective of the strain that may be put on the embryo the day of transfer. Monozygotic twinning occurs due

pregnancy, with the added complication of a monozygotic twin pair develops.

the strict regulations that exist in Australia governing IVF treatment.

The rate of multiple pregnancy associated with ART has fallen steadily with the implementations of better practices. As pregnancy success rates have increased the belief that more follicles or more embryos equates to better outcomes has been disproven. Close monitoring of ovulation stimulation protocols, and a practice of single embryo transfer for IVF has resulted in far lower multiple pregnancy rates and safer practices for women. An awareness of the risk of multiple pregnancy with ART and the ways in which this can be avoided is paramount to the future direction of ART, both for research and regulatory bodies.

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