“Live birth and adverse birth outcomes in women with ulcerative colitis and Crohn’s disease receiving assisted reproduction: a 20-year nationwide cohort study”
Norgard, B.M. et al. (2016), Gut, 65: 767–776.
As the majority of patients with inflammatory bowel disease (IBD) are diagnosed in their fertile years, they are often faced with issues relating to fertility and pregnancy.
Trying to conceive and pregnancy are particularly delicate and vulnerable periods; most of the time, patients with IBD will be on some form of maintenance treatment during pregnancy to control their disease.
In the most recent ECCO Consensus (European Crohn’s and Colitis Organization) on Reproduction and Pregnancy in IBD states, there is no evidence that ulcerative colitis (UC) or Crohn’s disease (CD) in remission affect fertility. However, it is known that active CD may reduce fertility and so it is important to achieve remission. Moreover, disease activity at conception or during the pregnancy is associated with pre-term birth and low birthweight.
Below is a short summary of a nationwide study conducted in Denmark – a country with one of the highest reported incidence rate of IBD. In Denmark, the cumulative proportion of infertility is 16–26% in women who try to conceive for longer than 12 months, and more than 15,000 assisted reproductive technology treatments (ART) are initiated each year.
ART is an intervention for women who are unable to conceive naturally, which includes in vitro fertilisation (IVF), with or without fertilisation with intracytoplasmic sperm injection (ICSI), and transfer of frozen-thawed embryos (FER).
Reported causes of reduction in fertility in women with IBD include surgical interventions (e.g. ileoanal pouch anastomosis for women with UC), low ovarian reserve secondary to increased disease activity, and voluntary childlessness.
Prior to this study, there was little evidence of the efficacy of ART treatment in women with UC and CD, and no studies had examined the risk of adverse birth outcomes in children after ART treatments in women with UC and CD.
The authors of the study aimed to examine the chance of live births and adverse birth outcomes in women with UC and CD who have undergone ART treatments compared with women without IBD who have undergone ART treatments.
The data was available from the Danish health registries, comprising all women with an embryo transfer from 1994 to 2013. It was therefore on a larger scale in respect to previous studies, covering a time period of 20 years. The following groups were compared: 1,360 ART treatments in 432 women with UC, 554 ART treatments in 182 women with CD, 148,540 treatments in 52,489 women without IBD.
The main findings were as follows:
- In women with UC receiving ART, the chance of a live birth for each embryo transfer is reduced. This was not significantly found in women with CD. Increased pre-natal observation in UC pregnancies after ART should therefore be considered.
- UC surgery before ART treatment does not have a negative effect on the chance of live birth for each embryo transfer.
- CD surgery before ART treatment significantly reduces the chance of a live birth for each embryo transfer, thus women with CD may seek to initiate ART treatment before needing CD surgery.
- Though women with UC had a higher rate of pre-term births, no differences were observed in terms of birth weight at term and congenital abnormalities between women with IBD and women without IBD undergoing ART.
Strengths of this study include the topic itself, which is interesting and very current (in fact, more data is prompted in order to advise these patients appropriately); the large numbers; the long follow-up duration; and the solid methodology (including a detailed statistical analysis taking into account variables such as women’s and partners’ ages, other coexisting medical conditions, exposure to alcohol/smoke and surgery). A weakness of the study is the lack of specific information on medical treatment for underlying maternal diseases in the study population.
The take-home message in this study is that, although women with IBD receiving ART treatments cannot expect the same success for each embryo transfer as other women who are infertile without IBD, the overall results of this study do not discourage the use of ART in women with IBD. The most recent ECCO Guidelines should be referred to as solid guidance for clinicians and patients on this complex and highly relevant topic.