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NIHR Signal Donor eggs may be linked to higher risk of pregnancy complications following IVF

Published on 26 May 2016

doi: 10.3310/signal-000243

Women who use donor eggs in their IVF may have significantly higher rates of pregnancy complications than those who use their own eggs, a systematic review and meta-analysis has found. Use of donor eggs was linked to up to four times the risk of developing high blood pressure in pregnancy. Other risks associated with donor eggs were low birth weight in the baby, caesarean section and premature delivery.

It is always possible that other factors, such as the age of women who use donor eggs, may have influenced the study results. Advanced maternal age is itself associated with pregnancy complications, including high blood pressure. Nevertheless it seems likely from this research that donor eggs are an independent risk factor for some pregnancy complications.

As the authors argue, it is important that women considering IVF using egg donation are aware of the risks and that donor pregnancies are monitored in specialist units.

Share your views on the research.

Why was this study needed?

Egg donation has enabled many women without eggs of their own - because of advanced age or premature menopause, for example - to achieve successful pregnancies. In the UK, the number of IVF cycles using donor eggs has grown from 1,262 in 2009 to 1,866 in 2013, while over half of women aged 45 and over having IVF use donated eggs.

Donor eggs have been linked to an increase in pregnancy complications, the most common of which is high blood pressure. This remains a major cause of maternal illness in the UK and can lead to pre-eclampsia, which can be life-threatening if left untreated.

It is not certain if other factors, such as multiple pregnancy or advanced maternal age, cause or contribute to this higher risk. This review looks at whether donor eggs are an independent risk for pregnancy complications.

What did this study do?

The review included observational studies comparing the risk of high blood pressure in IVF pregnancies using donor eggs, with IVF pregnancies using the woman’s own eggs.

Other outcomes included caesarean delivery, the development of diabetes in the mother, low birth weight baby, premature delivery and stillbirth.

The researchers also analysed separately whether the risk of pregnancy complications in singleton and twin pregnancies and in women older than 40 years, was higher when donor eggs were used.

A total of 11 studies were included, ten of which examined the risk of high blood pressure in pregnancy. The ten studies included 970 women who became pregnant using donor eggs and 10,569 women who became pregnant using their own eggs.

Researchers combined figures from the studies in a meta-analysis. Results relating to low birth weight are less reliable than the rest due to lack of a consistent definition across studies.

What did it find?

  • Women who had IVF using donor eggs were at higher risk of developing high blood pressure in pregnancy (odds ratio[OR] 3.92, 95% confidence interval 3.21 to 4.78). Thirty five per cent of those using donor eggs developed high blood pressure in pregnancy, compared with 17% of those using their own eggs.
  • The results were similar when women with twin pregnancies, one child or over 40 years old were analysed. For twin pregnancies, those using donor eggs had a higher risk of high blood pressure in pregnancy (OR 3.69, 95% CI 2.62 to 5.19). For those older than 40 years, in two studies, those using donor eggs had a higher risk of high blood pressure in pregnancy (OR 2.33, 95% CI 1.21 to 4.49).
  • Women using donor eggs also had a higher risk of low birth weight babies (OR 1.81, 95% CI 1.26 to 2.60), Caesarean section (OR 2.71, CI 95% CI 2.23 to 3.30), and premature delivery (OR 1.34, 95% CI 1.08 to 1.66). 
  • The authors’ analysis suggests that the increased risks associated with donor eggs were independent of maternal age and multiple pregnancies. However, it is not clear how this was adjusted for in the underlying studies, so we can’t be sure that the confounding effect of age is completely avoided.

What does current guidance say on this issue?

In its 2013 guidance on fertility problems, NICE advises that both potential egg donors and recipients should be offered independent counselling about the physical and psychological implications of treatment for themselves and their children.

For England and Wales, the NICE guidelines also set out the criteria for IVF treatment on the NHS, although currently, decisions about funding are often made locally.

Egg donation and egg sharing, where a woman shares her eggs in exchange for free or reduced cost fertility treatment, is regulated by the Human Fertilisation and Embryology Authority (HFEA).

What are the implications?

This systematic review suggests that women considering use of egg donation for IVF should be carefully counselled about the higher risk of pregnancy complications. The authors argue women who choose to go ahead should be individually monitored and managed in high risk obstetric clinics, to reduce complications. But the effectiveness or cost-benefit implications of this approach is not known. Further research is needed on these issues and the full cost and funding implications explored.

What is most important is to know that women using egg donation for IVF are quite likely to have some problems in pregnancy, sufficient to need careful monitoring and management. The risk over and above standard IVF or even natural conception is less important than their personal risk. 

Citation and Funding

Jeve YB, Potdar N, Opoku A, Khare M. Donor oocyte conception and pregnancy complications: a systematic review and meta-analysis. BJOG. 2016 February 8 [Epub ahead of print]. DOI: 10.1111/1471-0528.13910

No external funding was received for this study.

Bibliography

HFEA. Fertility treatment in 2013. Trends and figures. London: Human Fertilisation and Embryology Authority.

HFEA. Egg donation and egg sharing. London: Human Fertilisation and Embryology Authority.

NHS Choices. IVF. Introduction. London: Department of Health; updated 2015.

NICE. Fertility problems: assessment and treatment. CG156. London: National Institute for Health and Care Excellence; 2013.

NICE. Hypertension in pregnancy: diagnosis and management. CG107. London: National Institute for Health and Care Excellence; 2010.

Sauer, M. Gestational hypertension and donor eggs: elusive yet dangerous. BJOG. 2016 March 10 [Epub ahead of print]. DOI: 10.1111/1471-0528.13973.

Why was this study needed?

Egg donation has enabled many women without eggs of their own - because of advanced age or premature menopause, for example - to achieve successful pregnancies. In the UK, the number of IVF cycles using donor eggs has grown from 1,262 in 2009 to 1,866 in 2013, while over half of women aged 45 and over having IVF use donated eggs.

Donor eggs have been linked to an increase in pregnancy complications, the most common of which is high blood pressure. This remains a major cause of maternal illness in the UK and can lead to pre-eclampsia, which can be life-threatening if left untreated.

It is not certain if other factors, such as multiple pregnancy or advanced maternal age, cause or contribute to this higher risk. This review looks at whether donor eggs are an independent risk for pregnancy complications.

What did this study do?

The review included observational studies comparing the risk of high blood pressure in IVF pregnancies using donor eggs, with IVF pregnancies using the woman’s own eggs.

Other outcomes included caesarean delivery, the development of diabetes in the mother, low birth weight baby, premature delivery and stillbirth.

The researchers also analysed separately whether the risk of pregnancy complications in singleton and twin pregnancies and in women older than 40 years, was higher when donor eggs were used.

A total of 11 studies were included, ten of which examined the risk of high blood pressure in pregnancy. The ten studies included 970 women who became pregnant using donor eggs and 10,569 women who became pregnant using their own eggs.

Researchers combined figures from the studies in a meta-analysis. Results relating to low birth weight are less reliable than the rest due to lack of a consistent definition across studies.

What did it find?

  • Women who had IVF using donor eggs were at higher risk of developing high blood pressure in pregnancy (odds ratio[OR] 3.92, 95% confidence interval 3.21 to 4.78). Thirty five per cent of those using donor eggs developed high blood pressure in pregnancy, compared with 17% of those using their own eggs.
  • The results were similar when women with twin pregnancies, one child or over 40 years old were analysed. For twin pregnancies, those using donor eggs had a higher risk of high blood pressure in pregnancy (OR 3.69, 95% CI 2.62 to 5.19). For those older than 40 years, in two studies, those using donor eggs had a higher risk of high blood pressure in pregnancy (OR 2.33, 95% CI 1.21 to 4.49).
  • Women using donor eggs also had a higher risk of low birth weight babies (OR 1.81, 95% CI 1.26 to 2.60), Caesarean section (OR 2.71, CI 95% CI 2.23 to 3.30), and premature delivery (OR 1.34, 95% CI 1.08 to 1.66). 
  • The authors’ analysis suggests that the increased risks associated with donor eggs were independent of maternal age and multiple pregnancies. However, it is not clear how this was adjusted for in the underlying studies, so we can’t be sure that the confounding effect of age is completely avoided.

What does current guidance say on this issue?

In its 2013 guidance on fertility problems, NICE advises that both potential egg donors and recipients should be offered independent counselling about the physical and psychological implications of treatment for themselves and their children.

For England and Wales, the NICE guidelines also set out the criteria for IVF treatment on the NHS, although currently, decisions about funding are often made locally.

Egg donation and egg sharing, where a woman shares her eggs in exchange for free or reduced cost fertility treatment, is regulated by the Human Fertilisation and Embryology Authority (HFEA).

What are the implications?

This systematic review suggests that women considering use of egg donation for IVF should be carefully counselled about the higher risk of pregnancy complications. The authors argue women who choose to go ahead should be individually monitored and managed in high risk obstetric clinics, to reduce complications. But the effectiveness or cost-benefit implications of this approach is not known. Further research is needed on these issues and the full cost and funding implications explored.

What is most important is to know that women using egg donation for IVF are quite likely to have some problems in pregnancy, sufficient to need careful monitoring and management. The risk over and above standard IVF or even natural conception is less important than their personal risk. 

Citation and Funding

Jeve YB, Potdar N, Opoku A, Khare M. Donor oocyte conception and pregnancy complications: a systematic review and meta-analysis. BJOG. 2016 February 8 [Epub ahead of print]. DOI: 10.1111/1471-0528.13910

No external funding was received for this study.

Bibliography

HFEA. Fertility treatment in 2013. Trends and figures. London: Human Fertilisation and Embryology Authority.

HFEA. Egg donation and egg sharing. London: Human Fertilisation and Embryology Authority.

NHS Choices. IVF. Introduction. London: Department of Health; updated 2015.

NICE. Fertility problems: assessment and treatment. CG156. London: National Institute for Health and Care Excellence; 2013.

NICE. Hypertension in pregnancy: diagnosis and management. CG107. London: National Institute for Health and Care Excellence; 2010.

Sauer, M. Gestational hypertension and donor eggs: elusive yet dangerous. BJOG. 2016 March 10 [Epub ahead of print]. DOI: 10.1111/1471-0528.13973.

Donor oocyte conception and pregnancy complications: a systematic review and meta-analysis

Published on 9 February 2016

Jeve, Y. B.,Potdar, N.,Opoku, A.,Khare, M.

Bjog , 2016

BACKGROUND: Observational studies showed that women with a donor oocyte (DO) pregnancy have an increased risk of pregnancy complications. OBJECTIVES: Systematic review and meta-analysis to compare pregnancy complications of DO pregnancy with autologous oocyte in vitro fertilisation (IVF), and whether DO pregnancy acts as an independent risk factor. SEARCH STRATEGY: Online searches of databases from 1 January 1980 to 31 January 2015 were performed using a set of relevant keywords. SELECTION CRITERIA: All studies comparing pregnancy complications of women with donor oocyte IVF and autologous oocyte IVF were included. DATA COLLECTION AND ANALYSIS: Data collected included demographics and pregnancy complications. Methodological quality assessment was performed using the Newcastle-Ottawa scale. Statistical analysis was performed using review manager 5.3 and stata 13.0. Meta-regression was performed for age. MAIN RESULTS: In total, 11 studies (n = 81 752) were included. Ten studies (n = 11 539) examined the primary outcome. The risk of developing hypertensive disorders in pregnancy was significantly higher for DO pregnancy (odds ratio, OR 3.92; 95% confidence interval, 95% CI 3.21-4.78). Further subgroup analysis for singleton and twin pregnancies showed that the risk was significantly higher for DO pregnancy in each group. Secondary outcomes including small for gestational age (OR 1.81), caesarean section (OR 2.71), and preterm delivery (OR 1.34) were significantly higher with DO pregnancy. Meta-regression for the covariate of age suggested that risk was independent of age. AUTHOR'S CONCLUSIONS: Donor oocyte pregnancy acts as an independent risk factor for pregnancy complications, including hypertensive disorders, small for gestational age, and preterm delivery. Women should be counselled carefully before undergoing DO-assisted conception. TWEETABLE ABSTRACT: Donor oocyte conception is an independent risk factor for obstetric complications.

‘High blood pressure in pregnancy’ (hypertensive disorders) included:

  • Pregnancy-induced hypertension defined as a blood pressure of ≥140/90 mmHg on two or more occasions, at least 6 hours apart, without proteinuria, and later than 20 weeks of gestation.
  • Pre-eclampsia defined as a blood pressure of ≥140/90 mmHg on two or more occasions, at least 6 hours apart, with proteinuria of ≥0.3 g/day, and later than 20 weeks of gestation.

Expert commentary

This meta-analysis brings together for the first time confirmatory evidence that donated oocyte treatment carries additional materno-foetal risk to those accepted for assisted conception treatment. The independent risks of pregnancy-induced hypertension, pre-eclampsia and intra-uterine growth retardation are demonstrated, perhaps unsurprisingly, but importantly also independent of maternal age and it is a salutary reminder that whilst a great benefit to such women/couples oocyte donation does not remove all ills.

Without over-complicating a pregnancy it is clearly important to consider and manage such risks appropriately for the best outcome for mother and child in such hard-won pregnancies.

Dr Jane Stewart, Consultant in Reproductive Medicine, Newcastle Fertility Centre, International Centre for Life