Perinatal mortality following assisted reproductive technology treatment in Australia and New Zealand, a public health approach for international reporting of perinatal mortality

Abstract

BackgroundThere is a need to have uniformed reporting of perinatal mortality for births following assisted reproductive technology (ART) treatment to enable international comparison and benchmarking of ART practice.MethodsThe Australian and New Zealand Assisted Reproduction Database was used in this study. Births of ≥ 20 weeks gestation and/or ≥ 400 grams of birth weight following embryos transfer cycles in Australia and New Zealand during the period 2004 to 2008 were included. Differences in the mortality rates by different perinatal periods from a gestational age cutoff of ≥ 20, ≥ 22, ≥ 24, or ≥ 28 weeks (wks) to a neonatal period cutoff of either < 7 or < 28 days after birth were assessed. Crude and specific (number of embryos transferred and plurality) rates of perinatal mortality were calculated for selected gestational and neonatal periods.ResultsWhen the perinatal period is defined as ≥ 20 wks gestation to < 28 days after birth, the perinatal mortality rate (PMR) was 16.1 per 1000 births (n = 630). A progressive contraction of the gestational age groups resulted in marked reductions in the PMR for deaths at < 28 days (22 wks 11.0; 24 wks 7.7; 28 wks 5.6); and similarly for deaths at < 7 days (20 wks 15.6, 22 wks 10.5; 24 wks 7.3; 28 wks 5.3). In contrast, a contraction of the perinatal period from < 28 to < 7 days after birth only marginally reduced the PMR from 16.2 to 15.6 per 1000 births which was consistent across all gestational ages.The PMR for single embryo transfer (SET) births (≥ 20 weeks gestation to < 7 days post-birth) was significantly lower (12.8 per 1000 SET births) compared to double embryo transfer (DET) births (PMR 18.3 per 1000 DET births; p < 0.001, Fisher’s Exact Test). Similarly, the PMR for SET births (≥ 22 weeks gestation to < 7 days post-birth) was significantly lower (8.8 per 1000 SET births, p < 0.001, Fisher’s Exact Test) when compared to DET births (12.2 per 1000 DET births). The highest PMR (50.5 per 1000 SET births, 95% CI 36.5-64.5) was for twins following SET births (≥ 20 weeks gestation to < 7 days post-birth) compared to twins following DET (23.9 per 1000 DET births, 95% CI 20.8-27.1).ConclusionReporting of perinatal mortality of ART births is an essential component of quality ART practice. This should include measures that monitor the impact on perinatal mortality of multiple embryo transfer. We recommend that reporting of perinatal deaths following ART treatment, should be stratified for three gestation-specific perinatal periods of ≥ 20, ≥ 22 and ≥ 28 completed weeks to < 7 days post-birth; and include plurality specific rates by SET and DET. This would provide a valuable international evidence-base of PMR for use in evaluating ART policy, practice and new research.

Human forkhead box protein 3 gene variants associated with altered susceptibility to idiopathic recurrent pregnancy loss: A retrospective case‐control study

“…The retrospective nature of this study is another limitation as it questions the causal relationship, in limiting the analysis to four variants, and in the lack of testing all participants for chromosomal abnormalities due to financial considerations. While the chromosomal abnormalities are an important cause of miscarriage, with karyotypic abnormalities seen 2%–8% of couples with RPL in the first trimester of pregnancy, 44,45 RPL could happen even if the embryo has a normal genetic profile 46 . These limitations require further investigations in order to fully explain the role of FOXP3 in idiopathic RPL and to support or exclude the association of FOXP3 variants with altered FOXP3 expression and the pathophysiology of idiopathic RPL.…”

“…of couples with RPL in the first trimester of pregnancy, 44,45 RPL could happen even if the embryo has a normal genetic profile. 46 These limitations require further investigations in order to fully explain the role of FOXP3 in idiopathic RPL and to support or exclude the association of FOXP3 variants with altered FOXP3 expression and the pathophysiology of idiopathic RPL.…”

Applying developmental programming to clinical obstetrics: my ward round

“…However, singletons conceived by ART have also been demonstrated to have increased rates of prematurity, low birth weight and perinatal mortality. 75 Recently, two commonly used culture media were observed to be associated with a 200 g difference in birth weighta similar difference to that seen among women that smoke throughout pregnancy compared with non-smoking women. 76 Numerous studies in animal model systems have shown that ART can have important and lasting consequences on health in later life.…”

“…For example, in many countries the policy of transferring two or more embryos has now been restricted 73 because of unacceptably high multiple pregnancy rates, 74 with accompanying high perinatal morbidity and mortality. However, singletons conceived by ART have also been demonstrated to have increased rates of prematurity, low birth weight and perinatal mortality 75 . Recently, two commonly used culture media were observed to be associated with a 200 g difference in birth weight – a similar difference to that seen among women that smoke throughout pregnancy compared with non-smoking women 76 …”

Socioeconomic Risk Factors for Hospital-based Neonatal Death: A Population-based Study

“…The absence of antenatal care is a crucial factor that determines pregnancy outcomes. Clearly, neonatal deaths are higher among those mothers with poor antenatal attendance (1.6% versus 0.4%, with a p-value of 0.0001 and OR of 3.4) [12,13]. Kim et al demonstrated that even within both the United States and other developed countries, the evidence in two-thirds of studies suggests that low income, unemployment, poor neighborhood status, limited access to the health care system, and little or no antenatal care all play a role in infant mortality and neonatal outcome [14].…”