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• W1529136187 abstract "When the world says, “Give up,” Hope whispers, “Try one more time.”AnonymousInfertility is defined as the inability to achieve pregnancy after 1 year of regular, unprotected intercourse. Causes of female infertility include male factors, ovulatory dysfunction, uterine abnormalities, tubal obstruction, peritoneal factors, or cervical factors. Unfortunately, infertility has been shown to adversely affect both health and life-satisfaction.1Rostad B. Schmidt L. Sundby J. et al.Infertility experience and health differentials–a population-based comparative study on infertile and non-infertile women (the HUNT Study).Acta Obstet Gynecol Scand. 2014; 93: 757-764Google Scholar Infertility-related stress has been shown to directly impact both emotional distress and marital satisfaction.2Gana K. Jakubowska S. Relationship between infertility-related stress and emotional distress and marital satisfaction.J Health Psychol. 2014; (Epub ahead of print)Google Scholar Individuals with infertility often struggle with maintaining hope, and pursuing their dreams of parenthood. Inflammatory bowel diseases (IBDs), including both Crohn’s disease (CD) and ulcerative colitis (UC), often are diagnosed in young women of childbearing age. Therefore, fertility and fecundability can be of utmost importance when treating women with IBD. Current recommendations are to induce remission before conception and continue appropriate medical therapies to maintain remission during pregnancy.3Mahadevan U. Kane S. American Gastroenterological Association Institute medical position statement on the use of gastrointestinal medications in pregnancy.Gastroenterology. 2006; 131: 278-282Google Scholar Data have shown that women who enter pregnancy with active disease are twice as likely to have active disease during pregnancy when compared with women with IBD who enter pregnancy in remission.4Abhyankar A. Ham M. Moss A.C. Meta-analysis: the impact of disease activity at conception on disease activity during pregnancy in patients with inflammatory bowel disease.Aliment Pharmacol Ther. 2013; 38: 460-466Google Scholar Prior studies of pregnancy and IBD have focused largely on drug safety, and maternal and neonatal outcomes, rather than conception factors. Interestingly, women with CD report much greater voluntary childlessness than the general population in the United States (18% vs 6%; P = .001).5Marri S.R. Ahn C. Buchman A.L. Voluntary childlessness is increased in women with inflammatory bowel disease.Inflamm Bowel Dis. 2007; 13: 591-599Google Scholar Many factors could influence this childlessness, including concerns about pregnancy and disease activity, medications, or passing IBD on to offspring. Patients’ overall knowledge about aspects of fertility in IBD also is lacking. Two separate studies, from Australia and the United States, have shown that more than 40% of women with IBD report a fear of infertility, which is a substantial overestimate of infertility risk.6Mountifield R. Bampton P. Prosser R. et al.Fear and fertility in inflammatory bowel disease: a mismatch of perception and reality affects family planning decisions.Inflamm Bowel Dis. 2009; 15: 720-725Google Scholar, 7Selinger C.P. Eaden J. Selby W. et al.Inflammatory bowel disease and pregnancy: lack of knowledge is associated with negative views.J Crohns Colitis. 2013; 7: e206-e213Google Scholar In a study of pregnancy-related knowledge in women with IBD, nearly half of the women had poor scores, showing the need for further patient-centered education on pregnancy factors.8Selinger C.P. Eaden J. Selby W. et al.Patients' knowledge of pregnancy-related issues in inflammatory bowel disease and validation of a novel assessment tool (‘CCPKnow').Aliment Pharmacol Ther. 2012; 36: 57-63Google Scholar In this month’s issue of Clinical Gastroenterology and Hepatology, Oza et al9Oza S.S. Pabby V. Dodge L.E. et al.In vitro fertilization in women with inflammatory bowel disease is as successful as in women from the general infertility population.Clin Gastroenterol Hepatol. 2015; 13: 1641-1646Google Scholar present data on in vitro fertilization (IVF) in women with IBD, including both CD and UC patients. They detail outcomes of IVF therapy and conclude that overall live birth rates are similar among infertile women with and without IBD. This group of investigators evaluated assisted reproductive technology in IBD patients. Prior data have focused on the subgroup of women undergoing colectomy and ileal pouch–anal anastomosis (TAC/IPAA) for UC, in which infertility has been linked to surgical factors, including adhesions surrounding the fallopian tubes.10Ording Olsen K. Juul S. Berndtsson I. et al.Ulcerative colitis: female fecundity before diagnosis, during disease, and after surgery compared with a population sample.Gastroenterology. 2002; 122: 15-19Google Scholar This same group previously showed that IVF outcomes in women with TAC/IPAA are not different from those of women with UC and no prior surgery or from women without IBD.11Pabby V. Oza S.S. Dodge L.E. et al.In vitro fertilization is successful in women with ulcerative colitis and ileal pouch anal anastomosis.Am J Gastroenterol. 2015; 110: 792-797Google Scholar In this retrospective cohort, the investigators identified women with IBD seen at one of 2 centers in Boston (Beth Israel Deaconess Medical Center and Brigham and Women’s Hospital) from 1998 to 2011 who underwent at least 1 cycle of IVF during this time period. The records from these women were matched to women undergoing IVF who had no diagnosis of IBD in their records. The primary outcome was delivery of 1 or more live infants (cumulative live birth rate) in up to 6 IVF cycles. A total of 132 patients with IBD underwent IVF and were matched to 470 women without IBD. Of the women with IBD, 71 women had UC, 49 women had CD, and 1 woman had IBD unclassified. Perhaps most interesting is the fact that 53.5% of the women with CD were not taking any medications at the time of IVF. A total of 53.1% of these patients reported prior surgery for CD. Therefore, this was a group with significant prior disease activity, who for the most part were not taking any type of medication for IBD. Some of this lack of medication use may have been related to prior protocolectomy and end ileostomy, although only 16.3% of patients underwent this surgery. A similar trend was seen in the UC group, with 56.7% not using medications at the time of IVF and more than a third of women with UC had a prior TAC/IPAA. This lack of medication use is surprising and generates several important questions. First, could there be a misclassification bias in which women have been mislabeled with IBD? Second, does this medication utilization pattern show a lack of knowledge in regards to safety of medical therapies during conception and pregnancy? Third, could there be a selection bias in which women with mostly mild disease were included, limiting the generalizability of these results? Although the authors determined diagnoses of IBD retrospectively from chart review, word searches, and diagnosis codes, women were required to have seen one of the gastrointestinal divisions, which likely substantiated the IBD diagnoses and made misclassification less likely. Knowledge and/or misconception of the safety of medical therapies during pregnancy could be prevalent in this cohort given the low IBD medication utilization rates. Discontinuation of medications before conception is not recommended in guidelines for IBD and pregnancy management, although certainly tailoring and adjusting medical therapy for an individual is appropriate. Biologic anti–tumor necrosis factor α medications currently are pregnancy class B and have been shown to be safe during pregnancy.12Katz J.A. Antoni C. Keenan G.F. et al.Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis.Am J Gastroenterol. 2004; 99: 2385-2392Google Scholar, 13Mahadevan U. Kane S. Sandborn W.J. et al.Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease.Aliment Pharmacol Ther. 2005; 21: 733-738Google Scholar, 14Casanova M.J. Chaparro M. Domenech E. et al.Safety of thiopurines and anti-TNF-alpha drugs during pregnancy in patients with inflammatory bowel disease.Am J Gastroenterol. 2013; 108: 433-440Google Scholar The thiopurine class, azathioprine and mercaptopurine, are pregnancy class D, but have been shown to be safe and have not shown evidence of congenital malformations in patients with IBD.14Casanova M.J. Chaparro M. Domenech E. et al.Safety of thiopurines and anti-TNF-alpha drugs during pregnancy in patients with inflammatory bowel disease.Am J Gastroenterol. 2013; 108: 433-440Google Scholar, 15Francella A. Dyan A. Bodian C. et al.The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study.Gastroenterology. 2003; 124: 9-17Google Scholar, 16Ban L. Tata L.J. Fiaschi L. et al.Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications.Gastroenterology. 2014; 146: 76-84Google Scholar The majority of the mesalamine compounds are pregnancy class B and are safe to continue during pregnancy. Recently, Asacol and Asacol high dose (Warner Chilcolt, Rockaway, NJ) (both brands of mesalamine) were moved to pregnancy category C. This is owing to an inactive ingredient in the enteric coating of these specific agents, dibutyl phthalate, which has been associated with external and skeletal malformations and adverse effects on the male reproductive system in animal studies. Methotrexate is a pregnancy class X and should be discontinued in women before conception owing to teratogenic effects. In this cohort, 32.6% of patients with CD were taking oral mesalamine, 9.3% were taking biologics, and only 4.7% were taking immunomodulators. There is a potential mismatch between the reported medication use and severity of CD. The overall rate of surgery of more than 50% in CD, which can be a marker for more severe disease, may not be consistent with the relatively low use of immunomodulators and biologics, which is typically seen with mild disease. Supporting the hypothesis that tubal factors from surgery may play a role in infertility in women with IBD, the authors found that tubal factor infertility was more common in the CD population compared with the non-IBD population (24.5% vs 14.0%; P = .05). However, a history of prior surgery in both the CD and UC cohorts did not influence the outcome of live birth rates. IVF bypasses this factor and obviates the need for functional fallopian tubes. It is reassuring that adhesion-related factors potentially can be overcome by assisted reproductive techniques such as IVF. Overall live birth rates after the first cycle of IVF were similar among women with and without IBD in this study (33.8% for UC, 30.6% for CD, and 30.2% for the non-IBD group). After a total of 6 cycles of IVF, the live birth rates were 69% for UC, 57% for CD, and 53% for non-IBD. There were no significant differences in these rates for any subgroup. These overall rates provide hope for women with IBD and infertility, outcomes should not be any different for them as compared with other women with infertility. However, at best, more than a third of women who wish to become pregnant and who undergo IVF therapy are not able to conceive. This can be heartbreaking for the families involved. There can be emotional and financial implications. The American Society of Reproductive Medicine and RESOLVE (National Infertility Association) list the average price of an IVF cycle in the United States to be $12,400.17Available: http://www.resolve.org/family-building-options/making-treatment-affordable/the-costs-of-infertility-treatment.html. Accessed: May 1, 2015.Google Scholar This cost can be out of reach for many families, particularly when multiple cycles are attempted (in this cohort the median number of cycles attempted for all groups was 2). The information provided in this study is potentially reassuring, and provides further hope for infertile couples with IBD. However, we also must recognize the limitations of these data from selection bias and the potential lack of generalizability based on the medication use patterns of the cohort. Most importantly, there may be a lack of knowledge, among both the provider and patient populations, on the importance of continuing medical therapies in women with IBD during conception and pregnancy to maintain remission. My hope is that we can improve educational efforts, correct misconceptions, and encourage women with IBD that assisted reproductive techniques such as IVF can be effective. As a medical community, we need to strive to reduce costs and improve access to infertility services. Rather than give up, women with IBD who wish to conceive, armed with education, can move forward toward hope. In Vitro Fertilization in Women With Inflammatory Bowel Disease Is as Successful as in Women From the General Infertility PopulationClinical Gastroenterology and HepatologyVol. 13Issue 9PreviewInflammatory bowel disease (IBD) affects women of reproductive age, so there are concerns about its effects on fertility. We investigated the success of in vitro fertilization (IVF) in patients with IBD compared with the general (non-IBD) IVF population. Full-Text PDF" @default.
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• W1529136187 title "Infertility in Inflammatory Bowel Diseases: A Cause for Hope?" @default.
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