NIHR Signal Assisted reproduction using donated eggs has higher risk of complications for mothers and babies

Published on 13 December 2016

Assisted reproduction with donated eggs carries about double the chance of some risks for mothers and babies when compared to pregnancies from natural conceptions or assisted reproduction using the woman’s own eggs. These risks include high blood pressure and pre-eclampsia, preterm birth, low birthweight and a higher risk of caesarean section. In multiple pregnancies, high blood pressure and pre-eclampsia can affect more than 25% of mothers carrying multiple pregnancies following donated eggs.

This systematic review included a large sample of 16,000 women receiving donor eggs from 35 observational studies and national registers. The authors adjusted for the influence of maternal characteristics and multiple pregnancies which can also affect risk of these complications.

People deciding upon assisted reproduction treatment with their healthcare practitioners should be made aware of the potential risks with the different options.

Assisted reproduction using donated eggs has higher risk of complications for mothers and babies

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Why was this study needed?

In 2013, about 4-5% of IVF treatment cycles in the UK used donated eggs – approximately 1,940 cycles.

The first successful assisted reproduction involving donated eggs was in 1984. Since then, several studies have reported that high blood pressure during pregnancy, including pre-eclampsia, is more common in women who receive IVF using donor eggs. Pre-eclampsia is a major cause of maternal illness and mortality. Other studies have suggested that babies of egg donation pregnancies may also have poorer outcomes.

This systematic review aimed to pool the results of these observational studies, to get a clearer picture of the potential risks to mothers and babies during egg donation pregnancies. This is not an intervention that can be tested by randomised controlled trial.

What did this study do?

The review included 35 studies comparing outcomes for mothers and babies from egg donation pregnancies with those from IVF or ICSI pregnancies using the mother’s own eggs, and from natural conceptions. Twenty-two were cohort studies, including four national registry studies, and 13 were annual reports from US organisations. The studies covered a large sample size of 16,000 egg donation pregnancies, 118,000 IVF or ICSI and 1,000,000 natural conceptions.

The main outcomes were high blood pressure of pregnancy, pre-eclampsia, pregnancy diabetes, serious bleeding after birth (postpartum haemorrhage), caesarean section, preterm birth, and low birthweight and small-for-dates babies.

Despite the large number of studies, only eight were pooled in the meta-analyses. The studies included a mix of fresh and frozen eggs or embryos, and maternal characteristics and history varied.

What did it find?

  • In single pregnancies, after adjustment egg donation increased risk of the following outcomes compared with conventional IVF or ICSI:
    • high blood pressure of pregnancy (odds ratio [OR] 2.30, 95% confidence interval [CI] 1.60 to 3.32, 5 studies)
    • pre-eclampsia (OR 2.11, 95% CI 1.42 to 3.15, 6 studies)
    • preterm birth (OR 1.75, 95% CI 1.39 to 2.20, 4 studies)
    • low birthweight (OR 1.53, 95% CI 1.16 to 2.01, 3 studies)
    • caesarean section (OR 2.20, 95% CI 1.85 to 2.60, 3 studies)
    • postpartum haemorrhage (OR 2.40, 95% CI 1.49 to 3.88, 2 studies)
  • Egg donation in single pregnancies also increased risk of the following compared with natural conceptions after adjusting for other factors:
    • pre-eclampsia (OR 2.94, 95% CI 2.29 to 3.76, 3 studies)
    • preterm birth (OR 2.30, 95% CI 1.09 to 4.87, 2 studies)
    • low birthweight (OR 1.94, 95% CI 1.10 to 3.41. 2 studies)
    • caesarean section (OR 2.38, 95% CI 2.01 to 2.81, 2 studies)
  • Compared with conventional IVF or ICSI, egg donation increased risk in multiple pregnancies for:
    • high blood pressure of pregnancy (OR 2.45, 95% CI 1.53 to 3.93, 2 studies)
    • pre-eclampsia (OR 3.31, 95% CI 1.61 to 6.80, 2 studies)
  • Risk of small-for-dates babies following egg donation was no different from conventional IVF or ICSI (four studies of single pregnancies, two of multiple) or natural conceptions (two studies). Two studies found no difference in pregnancy diabetes rates between single pregnancies conceived with egg donation or conventional IVF or ICSI.

What does current guidance say on this issue?

The NICE guideline on assessing and treating fertility problems outlines circumstances when donor eggs may be considered, including if the ovaries have been removed, have stopped working, or after chemotherapy/radiotherapy. People using egg donation should be offered counselling about the physical and psychological implications of treatment. NICE recommend transferring a maximum of two embryos in any IVF cycle. If donor eggs are used they suggest a transfer strategy based on the woman’s age, but give no further specifics.

The NICE guideline on hypertension in pregnancy does not list assisted reproduction as a risk factor for pre-eclampsia.

What are the implications?

This evidence suggests that assisted reproduction techniques involving donated eggs may carry increased risk of several maternal and newborn complications. The authors adjusted for other factors that might also increase risk. However, the possibility that maternal characteristics and other variables might still influence the links, can’t be completely discounted.

Nevertheless, people considering egg donation can now be better informed about the extent of possible risks to mother and baby, including information about the risks of single versus multiple pregnancies. The findings may inform future guideline updates.

Citation and Funding

Storgaard M, Loft A, Bergh C, et al. Obstetric and neonatal complications in pregnancies conceived after oocyte donation - a systematic review and meta-analysis. BJOG. 2016. [Epub ahead of print].

This study was funded by a grant from the Hvidovre Hospital Research Fund and supported by Finox.

Bibliography

HFEA. Egg and sperm donation in the UK: 2012-2013. London: Human Fertilisation and Embryology Authority; 2014.

HFEA. Fertility treatment 2014: trends and figures. London: Human Fertilisation and Embryology Authority; 2016.

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.

Why was this study needed?

In 2013, about 4-5% of IVF treatment cycles in the UK used donated eggs – approximately 1,940 cycles.

The first successful assisted reproduction involving donated eggs was in 1984. Since then, several studies have reported that high blood pressure during pregnancy, including pre-eclampsia, is more common in women who receive IVF using donor eggs. Pre-eclampsia is a major cause of maternal illness and mortality. Other studies have suggested that babies of egg donation pregnancies may also have poorer outcomes.

This systematic review aimed to pool the results of these observational studies, to get a clearer picture of the potential risks to mothers and babies during egg donation pregnancies. This is not an intervention that can be tested by randomised controlled trial.

What did this study do?

The review included 35 studies comparing outcomes for mothers and babies from egg donation pregnancies with those from IVF or ICSI pregnancies using the mother’s own eggs, and from natural conceptions. Twenty-two were cohort studies, including four national registry studies, and 13 were annual reports from US organisations. The studies covered a large sample size of 16,000 egg donation pregnancies, 118,000 IVF or ICSI and 1,000,000 natural conceptions.

The main outcomes were high blood pressure of pregnancy, pre-eclampsia, pregnancy diabetes, serious bleeding after birth (postpartum haemorrhage), caesarean section, preterm birth, and low birthweight and small-for-dates babies.

Despite the large number of studies, only eight were pooled in the meta-analyses. The studies included a mix of fresh and frozen eggs or embryos, and maternal characteristics and history varied.

What did it find?

  • In single pregnancies, after adjustment egg donation increased risk of the following outcomes compared with conventional IVF or ICSI:
    • high blood pressure of pregnancy (odds ratio [OR] 2.30, 95% confidence interval [CI] 1.60 to 3.32, 5 studies)
    • pre-eclampsia (OR 2.11, 95% CI 1.42 to 3.15, 6 studies)
    • preterm birth (OR 1.75, 95% CI 1.39 to 2.20, 4 studies)
    • low birthweight (OR 1.53, 95% CI 1.16 to 2.01, 3 studies)
    • caesarean section (OR 2.20, 95% CI 1.85 to 2.60, 3 studies)
    • postpartum haemorrhage (OR 2.40, 95% CI 1.49 to 3.88, 2 studies)
  • Egg donation in single pregnancies also increased risk of the following compared with natural conceptions after adjusting for other factors:
    • pre-eclampsia (OR 2.94, 95% CI 2.29 to 3.76, 3 studies)
    • preterm birth (OR 2.30, 95% CI 1.09 to 4.87, 2 studies)
    • low birthweight (OR 1.94, 95% CI 1.10 to 3.41. 2 studies)
    • caesarean section (OR 2.38, 95% CI 2.01 to 2.81, 2 studies)
  • Compared with conventional IVF or ICSI, egg donation increased risk in multiple pregnancies for:
    • high blood pressure of pregnancy (OR 2.45, 95% CI 1.53 to 3.93, 2 studies)
    • pre-eclampsia (OR 3.31, 95% CI 1.61 to 6.80, 2 studies)
  • Risk of small-for-dates babies following egg donation was no different from conventional IVF or ICSI (four studies of single pregnancies, two of multiple) or natural conceptions (two studies). Two studies found no difference in pregnancy diabetes rates between single pregnancies conceived with egg donation or conventional IVF or ICSI.

What does current guidance say on this issue?

The NICE guideline on assessing and treating fertility problems outlines circumstances when donor eggs may be considered, including if the ovaries have been removed, have stopped working, or after chemotherapy/radiotherapy. People using egg donation should be offered counselling about the physical and psychological implications of treatment. NICE recommend transferring a maximum of two embryos in any IVF cycle. If donor eggs are used they suggest a transfer strategy based on the woman’s age, but give no further specifics.

The NICE guideline on hypertension in pregnancy does not list assisted reproduction as a risk factor for pre-eclampsia.

What are the implications?

This evidence suggests that assisted reproduction techniques involving donated eggs may carry increased risk of several maternal and newborn complications. The authors adjusted for other factors that might also increase risk. However, the possibility that maternal characteristics and other variables might still influence the links, can’t be completely discounted.

Nevertheless, people considering egg donation can now be better informed about the extent of possible risks to mother and baby, including information about the risks of single versus multiple pregnancies. The findings may inform future guideline updates.

Citation and Funding

Storgaard M, Loft A, Bergh C, et al. Obstetric and neonatal complications in pregnancies conceived after oocyte donation - a systematic review and meta-analysis. BJOG. 2016. [Epub ahead of print].

This study was funded by a grant from the Hvidovre Hospital Research Fund and supported by Finox.

Bibliography

HFEA. Egg and sperm donation in the UK: 2012-2013. London: Human Fertilisation and Embryology Authority; 2014.

HFEA. Fertility treatment 2014: trends and figures. London: Human Fertilisation and Embryology Authority; 2016.

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.

Obstetric and neonatal complications in pregnancies conceived after oocyte donation - a systematic review and meta-analysis

Published on 7 September 2016

Storgaard, M.,Loft, A.,Bergh, C.,Wennerholm, U. B.,Soderstrom-Anttila, V.,Romundstad, L. B.,Aittomaki, K.,Oldereid, N.,Forman, J.,Pinborg, A.

Bjog , 2016

BACKGROUND: Approximately 50 000 oocyte donation (OD) treatment cycles are now performed annually in Europe and the US. OBJECTIVES: To ascertain whether the risk of adverse obstetric and perinatal/neonatal outcomes is higher in pregnancies conceived by OD than in pregnancies conceived by conventional in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) or spontaneously. SEARCH STRATEGY: A systematic search was performed in the PubMed, Cochrane and Embase databases from 1982-2016. Primary outcomes were hypertensive disorders of pregnancy, pre-eclampsia (PE), gestational diabetes mellitus, postpartum haemorrhage, caesarean section, preterm birth, low birthweight and small for gestational age. SELECTION CRITERIA: Inclusion criteria were original studies including at least five OD pregnancies with a control group of pregnancies conceived by conventional IVF/ICSI or spontaneous conception, and case series with >500 cases reporting one or more of the selected complications. Studies not adjusting for plurality were excluded. DATA COLLECTION AND ANALYSIS: Thirty-five studies met the inclusion criteria. A random-effects model was used for the meta-analyses. MAIN RESULTS: For OD pregnancies versus conventional IVF/ICSI pregnancies the risk of PE was adjusted odds ratio (AOR) 2.11 (95% CI, 1.42-3.15) in singleton and AOR 3.31 (95% CI, 1.61-6.80) in multiple pregnancies. The risks of preterm birth and low birthweight in singletons were AOR 1.75 (95% CI, 1.39-2.20) and 1.53 (95% CI, 1.16-2.01), respectively. CONCLUSIONS: OD conceptions are associated with adverse obstetric and neonatal outcomes. To avoid the additional increase in risk from multiplicity, single-embryo transfer should be the choice of option in OD cycles. TWEETABLE ABSTRACT: Oocyte donation pregnancies have increased risk of a range of obstetric and neonatal complications.

Assisted reproduction is the name given to treatments to help people if they can’t get pregnant naturally. There a variety of treatments available, depending on circumstances.  These include in vitro fertilisation (IVF), where the egg is incubated with multiple sperm, and intracytoplasmic sperm injection (ICSI), where the egg is injected with a single sperm. ICSI may be used when there is reduced chance of conception happening without help, for example if the man has a low sperm count or there are problems with sperm shape or movement. Both techniques may be carried out either with the couple’s own eggs and sperm, or with donor sperm or eggs. Egg donation is sometimes referred to as oocyte donation.

Expert commentary

Many women undergo egg donation treatment for subfertility due to various reasons, and it accounts for 5.5% of all IVF cycles in the UK. The reported increase in adverse outcome for mothers and babies during pregnancy resulting from egg donation may partly be related to the underlying health factors of women having treatment. Although, further data is needed to confirm the findings in this study, egg donation pregnancies should be considered as “high risk”, warranting pre-pregnancy counselling with specialists, strict adherence to single embryo transfer policy and close antenatal and postnatal observation and care.

Kanna Jayaprakasan, Subspecialist & Honorary Associate Professor in Reproductive Medicine, Royal Derby Hospital, Derby & University of Nottingham; IVF Consultant, CARE Fertility, Nottingham

Categories

  •   Fertility and childbirth, Neonates and neonatal care