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The reduced chance of a live birth in women with IBD receiving assisted reproduction is due to a failure to achieve a clinical pregnancy
  1. S Friedman1,2,3,
  2. P V Larsen1,
  3. J Fedder4,
  4. B M Nørgård1,2,3
  1. 1Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
  2. 2Crohn's and Colitis Center, Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3Department of Medicine, Division of Gastroenterology, Hepatology and Endoscopy, Harvard Medical School, Boston, Massachusetts, USA
  4. 4Department D, Centre of Andrology and Fertility Clinic, Odense University Hospital, and Research Unit of Human Reproduction, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
  1. Correspondence to Dr Sonia Friedman, Center for Crohn's and Colitis, 850 Boylston Street, Chestnut Hill, MA 02467, USA; sfriedman1{at}partners.org

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We recently reported that for women with UC receiving assisted reproductive technology (ART) treatment, the chance of a live birth after each embryo transfer cycle decreased significantly. In women with Crohn's disease (CD), the chance of a live birth after each embryo transfer cycle also decreased but was not significant in the fully adjusted regression model.1 In our study, we chose the outcome live birth because it was the most important clinical outcome for patients with UC and CD undergoing ART. After demonstrating the negative effects of UC and CD on chances of live birth, we wish to update our readers by exploring where along the process from fertilisation through pregnancy the risk of delivering a live born child decreases. Is the reduced chance of live birth due to (1) a reduced chance of conceiving after an ART cycle? and/or (2) a reduced chance of maintaining a fetus throughout the entire pregnancy and delivering a live born child? Using the dataset described in our previous paper,1 we chose a similar approach with cohorts of treatment cycles in women with UC, CD and an unexposed cohort of all other treatment cycles in women receiving ART treatments in Denmark from 1 January 1994 through 2013. The number of ART treatments in the cohorts is slightly different in these new analyses as a few ART cycles had missing or incomplete values according to relevant variables on measurements of human chorionic gonadotropin (hCG).

The outcomes in the new analyses were (1) clinical pregnancy, that is, measurement of hCG (positive or negative) or result of ultrasound 14–16 days after embryo transfer, and (2) among women with confirmed pregnancy, live birth. The results were adjusted for the confounders described in our previous paper.1 Both women with UC and CD had a reduced chance of becoming pregnant for each ART treatment cycle (see online supplementary table S1). although for women with CD, the results were not significant in the fully adjusted model (table 1). Among women with UC or CD who did become pregnant, the chance of delivering a live born child was similar to those in the unexposed cohort (table 2 and see online supplementary table S2).

Supplementary materials

Table 1

Adjusted OR, with 95% CI, for pregnancy in the study cohorts of assisted reproductive technology treatments in women with UC compared with women without chronic IBD; and similar result for women with CD

Table 2

Adjusted ORs, with 95% CI, for live birth in the study cohorts of assisted reproductive technology treatments in pregnant women with UC compared with pregnant women without chronic IBD; and similar result for pregnant women with CD

These results suggest that, compared with women without chronic IBD receiving ART treatment, women with UC and CD have a reduced chance of conceiving for each ART treatment cycle. Therefore, the reduced chance of live birth after ART treatment in women with UC and CD is likely related to the stages of fertilisation and implantation, and not the stage of pregnancy itself. The underlying cause of reduced ART efficacy may be due to the ART technique itself, subclinical inflammation, autoimmunity or other factors yet to be elucidated. We cannot rule out an effect of IBD medications or clinical IBD activity, although ART in Denmark is generally only done when patients with IBD are in remission.

This is the first study to suggest that the reduced chance of a live birth after ART in women with UC and CD might be due to a failure to achieve a pregnancy rather than a failure of carrying the pregnancy to term. Future studies should focus on the impact of factors related to the stages of fertilisation and implantation.

Reference

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Supplementary materials

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Footnotes

  • Contributors SF: funding, conception, interpretation of results, manuscript writing and editing, approved the final version. PVL: design, data collection, data analysis, interpretation of results, manuscript editing, approved the final version. JF: assistance with data analysis, interpretation of results, manuscript editing, approved the final version. BMN: funding, conception, design, data collection, assistance with data analysis, interpretation of results, manuscript writing and editing, approved the final version.

  • Funding The study was supported by a Crohn's & Colitis Foundation of America (CCFA), Senior Research Award.

  • Competing interests None declared.

  • Ethics approval The study was approved by the Danish Data Protection Agency (j.nr. 2014-41-3466). According to Danish law, there are no ethical approvals of register-based studies necessary.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • ▸ Additional material is published online only. To view, please visit the journal online (http://dx.doi.org/10.1136/gutjnl-2016-311805).

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