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New research predicts miscarriage from foetal growth
7 January 2012
The clearest evidence yet to link an embryo’s growth to its risk of miscarriage will be presented at the British Fertility Society Annual Meeting in Leeds. The research, by scientists from the University of Nottingham’s School of Clinical Sciences, also challenges the notion that twins grow more slowly in the womb. A means of identifying singleton pregnancies that are at higher risk of miscarriage is one potential application of this work.
Researcher Dr Shyamaly Sur and team tested two hypotheses - whether twins grow more slowly than singletons in the womb, and whether restricted growth in the first trimester (from conception until 12-13 weeks) is associated with miscarriage. The team tracked the growth of 247 singleton and 264 twin embryos conceived through IVF, allowing them to know the embryos’ precise gestational age. For each embryo, the crown-rump length (CRL; distance from top of the embryo’s head to the bottom of its buttocks) was measured once during the first trimester from a transvaginal ultrasound scan and the pregnancy then monitored until birth. Using the CRL measurements, the researchers developed two growth curves to test their hypotheses: one to record the growth of singleton embryos and one for twin embryos. Sensitivity analysis was used to analyse whether embryos that went on to miscarry were growth restricted (defined as being in the smallest 5% of the normal sample; often called the 5th Centile).
In pregnancies resulting in a live birth, twin embryos grew at the same rate as singletons during the first trimester (F test, F=2.66, P=0.0713). For singleton pregnancies, growth restriction in the first trimester was a sensitive predictor of subsequent miscarriage. 77.8% (34/44) singleton pregnancies that miscarried were growth restricted, whilst 98.1% (209/213) of singleton pregnancies that did not miscarry were not growth restricted. This was not the case in twin pregnancies where only 28.6% (12/42) of pregnancies that miscarried were growth restricted although a similar number (98.5%: 193/196) of twin pregnancies that did not miscarry were not growth restricted.
The data show that we can potentially identify singleton pregnancies at higher risk of miscarriage through accurate measurement of growth during the first trimester. The next step in this research is to attempt to predict miscarriage prospectively using the 5th Centile for growth and also examine the relationship between restricted growth and miscarriage in more detail to elucidate the reasons behind this relationship.
Researcher Dr Shyamaly Sur, Subspecialty Trainee in Reproductive Medicine at the School of Clinical Sciences, based at Nottingham University Hospitals NHS Trust, said:
“Although it has been widely accepted that twin embryos exhibit slower growth in early pregnancy, this hypothesis has not been tested before. Our work shows that twin embryos actually grow at the same rate as singleton embryos in the early stages of pregnancy.
“Our study also provides the clearest evidence yet that restricted growth in single embryos during the early stages of pregnancy is related to subsequent miscarriage in that pregnancy. Our method of following women who have undergone IVF treatment meant that we were able to accurately date the pregnancies and therefore were able to relate their subsequent growth to the date of conception very precisely. This is not possible in spontaneous pregnancies as the exact date of conception is never known and simply estimated from the date of the last menstrual period.
“We hope that this work will go towards developing a new system to identify pregnancies at risk of miscarriage by using evidence of early growth restriction as a factor. More research is now needed to investigate the relationship between growth and the underlying causes of miscarriage in more detail. At NURTURE we are focussing on how blood flow to the womb lining and embryo quality influence conception rates and subsequent miscarriage.”
Notes for editors
This study will be presented as a lecture (OC1) by Dr Shyamaly Sur at the 2012 British Fertility Society Annual Meeting on Friday 6 January 2012 at 13:30. The proceedings from the meeting will be published in a supplement in the next edition of Human Fertility.
The British Fertility Society Annual Meeting is taking place on 6-7 January 2012 in Leeds, UK. Please see the full programme.
Please mention the British Fertility Society Annual Meeting in any story
For more information: contact the British Fertility Society press office
The British Fertility Society is a national multidisciplinary organisation representing professionals practising in the field of reproductive medicine. The British Fertility Society is committed to promoting good clinical practice and working with patients to provide safe and effective fertility treatment.
Abstract
Is growth restriction in the first trimester associated with multiple pregnancy and miscarriage?
Shyamaly Sur, Jeanette Clewes, Bruce Campbell, Nicholas Raine-Fenning
Division of Obstetrics and Gynaecology, School of Clinical Sciences, University of Nottingham, Nottingham, UK
Introduction: Growth restriction in the first trimester can predict miscarriage. Most studies have been performed in women conceiving naturally presenting with vaginal bleeding or pain, thus, the results may be biased. It is widely accepted that twin embryos exhibit slower growth in the first trimester compared to singletons, however the evidence for this is unclear.
Aims: To develop nomograms for first trimester growth for twin and singleton embryos.
Hypothesis: Twins are smaller than singletons at any gestational age. Growth restriction can be used to predict miscarriage.
Methods: A prospective study of women having IVF treatment with either a viable singleton or DCDA twin pregnancies. IVF patients were used to enable accurate estimation of gestation. Pregnancies continuing to term were included in the nomograms. All patients were scanned TV and the crown rump length measured.
Nomograms were developed for both twin and singleton embryos in the first trimester according to the methods suggested by Altman et al using non linear regression
Viable pregnancies that subsequently resulted in first trimester miscarriage were excluded from the nomogram and plotted separately. Sensitivity analysis was used to compare the 5th centile for each nomogram as a predictor for miscarriage.
Results: 247 singleton embryos were included in the nomogram. 44 subsequently miscarried.
264 twin embryos were included in the nomogram. 42 subsequent miscarriages.
F test: no significant difference between singleton or twin nomograms.
Using the 5th Centile:
Singletons: miscarriage predicted with sensitivity of 77.8%, specificity of 98.1%.
Twins: miscarriage predicted with sensitivity of 28.6%, specificity of 98.5%
Conclusions: CRL increases exponentially with gestation and is comparable between twin and singleton pregnancies, allowing us to reject our first hypothesis. The 5th centile was a highly specific predictor for miscarriage but not as sensitive in twin pregnancies. The data are consistent with our hypothesis that growth restriction is a good predictor of miscarriage and not a result of multiple pregnancy.