We used raw data from the available literature to perform a meta‐analysis of the RR of infertility in UC patients who had undergone IPAA compared with those on medical therapy. We found that the RR of infertility was threefold greater after IPAA, and that half of the surgically treated women who attempt to conceive will be unsuccessful after 12 months.
We were unable to identity any patient or procedure related variables that consistently affected risk, including adhesion barriers, intraoperative lysis of adhesions, pouch type (S v
J), and pouch anti‐adhesives. In a single study, Gorgun et al
did show that intraoperative transfusion during IPAA was associated with an increased risk of infertility.12
The limited data available from Oresland's study7
suggest that post‐IPAA infertility may be largely due to scarring of the fallopian tubes after IPAA surgery, and this is supported by Asztely's previous study of hysterosalpingography in women after proctocolectomy.18
We would like to advocate collection of potential risk factors for infertility in future studies, both to identify the women at highest risk of infertility and any potentially modifiable risk factors.
Identification of intraoperative transfusion as a risk factor raises the question of whether there are modifiable procedure related variables that could affect fertility outcome. Transfusion, rather than directly causing infertility, may be a proxy for difficult pelvic dissection. An increased surface area of dissection would contribute to increased development of fibrin bridges, which are considered precursors to the formation of adhesions.19,20
It is reasonable to believe that patients undergoing a two stage operation (versus three stage) might have a lower likelihood of pelvic scarring and infertility. It is also possible that hand sewn anastomoses may pose greater risk than stapled anastomoses, due to increased distal dissection and tissue manipulation, potentially increasing the formation of adhesions. It is unclear whether future advancements in laparoscopic colectomy or adhesion barriers may decrease the rate of infertility after proctocolectomy. If infertility is associated specifically with fallopian tube occlusion, it is conceivable that wrapping the fallopian tubes in an adhesion barrier may reduce the risk of infertility. On the other hand, anecdotal reports of increased tissue inflammation at the site of intraoperative hyaline membrane placement suggest that further study is required before a change in surgical technique can be recommended.
This study had several limitations. Firstly, subjects in individual studies were not randomised to medical therapy or colectomy, potentially resulting in selection bias. Patients undergoing colectomy may have been more debilitated, resulting in higher baseline fertility impairment. Secondly, we identified variable response rates in each study. Subjects who attributed their infertility to colectomy may have been more likely to respond to surveys, as suggested by the higher response rate of the IPAA group in the study of Johnson and colleagues.13
Thirdly, several studies included only women post‐IPAA, and therefore relied more on distant recall for data on infertility and attempted conception during medical therapy. Reliance on recall may have systematically affected the medical therapy data more than the post‐IPAA data on infertility. Fourthly, two studies included an unknown number of patients with FAP rather than UC. However, our sensitivity analysis showed that this did not have a substantial effect on the summary estimate. In addition, we only evaluated studies of IPAA surgery. A recent small study of fertility after colectomy and ileorectal anastomosis (IRA) found a postoperative infertility rate of only 33%.21
Larger studies are needed to determine whether IRA offers a better approach for young women, as this approach leaves the inflamed rectum in place, which has its own drawbacks. We were also limited by the heterogeneity of the study designs and definitions of infertility. Despite these differences, after excluding the Cleveland Clinic study, we were able to identify a set of seven homogeneous studies to produce a summary estimate of RR. While the Cleveland Clinic study was an outlier, it had the same direction of effect: colectomy with IPAA significantly increases the risk of infertility in women with UC. It is plausible that these patients were referred to a tertiary centre due to more severe preoperative illness, resulting in the appearance of a decreased effect of surgery on infertility in this study.
Our study found that colectomy with IPAA increased the risk of infertility by approximately threefold in women with UC compared with medical management. Infertility increased from approximately 15% in UC before proctocolectomy with J pouch to approximately 50% after the surgery. Additional research is needed to identify modifiable procedure related risks and to determine whether interventions to reduce scarring of the fallopian tubes may have an ameliorative effect. We wish to emphasise that in patients with more severe disease, postoperative infertility rates may be higher, as suggested by the Cleveland Clinic study. These findings may influence physicians to more strongly consider potentially hazardous rescue therapies, including ciclosporin and infliximab, in young women with severe UC before committing to colectomy. For those patients who experience infertility after colectomy and reconstruction, in vitro fertilisation should be considered, as this has been successful in these patients.11
We advocate the presentation of all medical and surgical options, including a clear statement of the infertility risk associated with proctocolectomy, to patients with severe UC to encourage informed decision making.