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Perinatal outcomes after assisted reproductive technology treatment in Australia and New Zealand: single versus double embryo transfer

Yueping A Wang, Elizabeth A Sullivan, David L Healy and Deborah A Black
Med J Aust 2009; 190 (5): 234-237. || doi: 10.5694/j.1326-5377.2009.tb02381.x
Published online: 2 March 2009

Abstract

Objective: To compare the perinatal outcomes of babies conceived by single embryo transfer (SET) with those conceived by double embryo transfer (DET).

Design, setting and participants: A retrospective population-based study of embryo transfer cycles in Australia and New Zealand between 2002 and 2006, using data from the Australia and New Zealand Assisted Reproduction Database.

Main outcome measures: Proportion of SET procedures; comparison of SET and DET procedures with respect to multiple births, low birthweight (LBW), preterm birth and fetal death.

Results: The proportion of SET procedures has increased from 28.4% in 2002 to 32.0% in 2003, 40.5% in 2004, 48.2% in 2005 and 56.9% in 2006. The multiple birth rate for all babies conceived by SET (4.0%) was 10 times lower than for those conceived by DET (39.1%) (P < 0.01). The average birthweight for all liveborn babies conceived by SET (3290 g) was higher than for those conceived by DET (2934 g) (P < 0.01). The preterm birth rate of all DET-conceived babies (30.3%) was higher than for SET-conceived babies (12.3%) (adjusted odds ratio [AOR], 3.19 [95% CI, 3.01–3.38]). All babies conceived by DET were more likely to be stillborn than those conceived by SET (AOR, 1.49 [95% CI, 1.21–1.82]). Singletons conceived by DET were more likely to be born preterm than singletons conceived by SET (AOR, 1.13 [95% CI, 1.05–1.22]). Liveborn singletons conceived by DET were 15% more likely to have LBW than liveborn singletons conceived by SET (AOR, 1.15 [95% CI, 1.05–1.26]). There was no significant difference in fetal death rate between DET- and SET-conceived singletons.

Conclusion: The increase in proportion of SET procedures has resulted in a lower rate of multiple births and in better perinatal outcomes in Australian and New Zealand assisted reproduction programs.

Since 2002, the Reproductive Technology Accreditation Committee in Australia and New Zealand has advocated reducing the number of embryos transferred to women undergoing assisted reproductive technology (ART) treatment, with the aim of minimising the number of multiple births.1 Studies suggest that the high incidence of multiple births following ART is responsible for most adverse perinatal outcomes (preterm birth, low birthweight [LBW] and perinatal death).2-4

The high rate of multiple births following ART is largely explained by the number of embryos transferred. Transferring two embryos (double embryo transfer [DET]) increases the odds of a multiple gestation by more than 60 times5 compared with single embryo transfer (SET). Recent studies from Finland concluded that babies conceived by SET had better neonatal outcomes than those conceived after transferring two or more embryos.6 This is the case even among singletons.7,8 Belgium and the Scandinavian countries have endorsed SET as best practice, with Sweden reporting that SET is used in 70% of its embryo transfer cycles.9

The Assisted reproduction technology in Australia and New Zealand 2006 report10 showed that the proportion of embryo transfer cycles using SET had increased from 28.4% in 2002 to 56.9% in 2006 in Australia and New Zealand. Over the same period, the twin rate declined from 18.8% to 11.3%.

The aim of our study was to compare the perinatal outcomes of babies conceived by SET with those conceived by DET using data from the Australia and New Zealand Assisted Reproduction Database (ANZARD).

Methods
Results
Perinatal outcomes

Over the period 2002–2006, 40 483 babies (73.0% singletons, 26.3% twins, 0.7% triplets or higher) were born to women who had either SET or DET cycles in Australia and New Zealand. Of these babies, 14 022 (34.6%) were conceived by SET and 26 461 (65.4%) by DET. The multiple birth rate for babies born to women who had SET cycles (4.0%) was about 10 times lower than for those born to women who had DET cycles (39.1%) (P < 0.01; χ= 5768.3; df = 1) (Box 1).

The overall preterm birth rate was 24.1%. The mean birthweight of liveborn babies was 3058 g, with 19.2% of babies having LBW. There were 520 fetal deaths (12.8 fetal deaths per 1000 births) after either SET or DET.

Perinatal outcomes of multiples

Unlike singletons, multiples conceived by DET had better perinatal outcomes than those conceived by SET (Box 5). However, more than half of liveborn multiples (whether conceived by DET or SET) were LBW and 60% of multiples were born preterm.

Discussion

Consistent with other studies,6,8,11 we found that babies conceived by SET had better perinatal outcomes than those conceived by DET. This was the case even for singletons. Regardless of maternal age, DET-conceived singletons had 15% greater odds of LBW and 13% greater odds of preterm birth than SET-conceived singletons.

Our analysis showed that the multiple birth rate for babies conceived by DET was nearly 10-fold higher than for babies conceived by SET. Multiple births are strongly associated with poorer perinatal outcomes.4,12 LBW and preterm birth have been shown to be directly related to fetal and neonatal death, and short- and long-term morbidity and mortality.13,14

The rationale for favouring DET over SET, until recently, has been that the transfer of two or more embryos results in a higher clinical pregnancy rate than the transfer of only one embryo, especially in younger women.15 However, a higher clinical pregnancy rate does not mean better perinatal outcomes for the baby.

Multiple gestations not only increase the risk for babies, but also for mothers.16,17 Threatened miscarriage, hyperemesis, thromboembolism, hypertension, haemorrhage and maternal mortality are all significantly increased in multiple gestations.17 There is also a greater risk of depression and marital decline after multiple gestations.16

In addition, multiple gestations place a greater economic and social burden on the parents and on the health care system.18,19 In Australia in 2003, the average combined cost of infant and maternal birth admission following ART treatment was $8053 for singletons compared with $23 214 for twins and $90 742 for higher-order multiples.20

One of the findings of our study was that preterm birth and LBW were less likely to occur in babies conceived by thawed embryo transfer than fresh embryo transfer. This is consistent with other studies3,21 showing that cryopreservation does not adversely affect fetal development or perinatal outcomes, but in fact appears to have a protective effect. The better outcomes of babies conceived from frozen embryos are likely to be related to the more similar ovarian and uterine conditions in thawed embryo transfer cycles to those for non-ART conceptions.21

Twins conceived by SET are considered to be monozygotic twins.22 In general, monozygotic twins have worse perinatal outcomes than dizygotic twins.23 Consistent with other studies,22 our data showed a significantly higher rate of twins following blastocyst transfer (both SET and DET) than cleavage-stage embryo transfer. But overall outcomes were more favourable for babies following blastocyst transfer than cleavage-stage embryo transfer. This may largely be explained by more DET in cleavage-stage embryo transfer cycles than in blastocyst transfer cycles, and hence an overall higher multiple birth rate following cleavage-stage embryo transfer cycles. A significantly lower LBW rate was observed for singletons following blastocyst transfer in our study, which supports the suggestion that the blastocyst culture could have had an impact on higher birthweight.24

Strengths of our study were the large study population and the two-nation coverage. One limitation was that elective embryo transfer procedures could not be distinguished from all embryo transfer procedures. (A Belgian study has shown that babies conceived by elective SET have better perinatal outcomes than those conceived by DET.25) Another limitation of our study was the potential variability in case reporting. The follow-up information on pregnancy and birth outcomes was collected in a number of ways, including follow-up by the treatment doctors and self-report by patients to fertility clinics. A further limitation was that data on the 2002–2006 study population were incomplete: information on pregnancy and birth outcomes was not stated for 1.7% of clinical pregnancies.

Our study confirms that the Reproductive Technology Accreditation Committee’s policy of shifting towards greater use of SET in ART is working. In 2006, more than half of embryo transfer cycles were SETs, resulting in a fall in the multiple delivery rate to 12%, the lowest rate ever reported in Australia and New Zealand. Given the fewer maternal complications, lower rate of adverse perinatal outcomes and higher cost-effectiveness ratio for SET compared with DET, continuing to encourage SET will benefit women and their babies, as well as society in general.

  • Yueping A Wang1
  • Elizabeth A Sullivan1
  • David L Healy2
  • Deborah A Black3

  • 1 Perinatal and Reproductive Epidemiology Research Unit, University of New South Wales, Sydney, NSW.
  • 2 Department of Obstetrics and Gynaecology, Faculty of Medicine, Monash University, Melbourne, VIC.
  • 3 Faculty of Health Sciences, University of Sydney, Sydney, NSW.


Correspondence: alex.wang@unsw.edu.au

Acknowledgements: 

The Fertility Society of Australia is the funding body for the ANZARD collection. We acknowledge the contribution of fertility clinics in Australia and New Zealand in the provision of data to ANZARD.

Competing interests:

None identified.

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