The risk of infertility in women with IBD who have had surgery

What is inflammatory bowel disease?
There are two types of inflammatory bowel disease (IBD): Crohn's disease and ulcerative colitis. IBD is a lifelong disease of the digestive system. Patients with IBD can experience diarrhea, abdominal pain, and fatigue, among other symptoms. IBD is most often diagnosed in teenagers and young adults, around the time of family planning decisions. Previous studies have suggested that women who have undergone surgery to remove their colon and create an ileal anal pouch anastomosis (IPAA or J-pouch) may have trouble getting pregnant. This type of surgery is common in women with ulcerative colitis when medications do not work. The impact that other types of IBD surgeries can have on a woman's ability to become pregnant is unknown.

What types of surgery do people with IBD require?
When medication fails, a person with IBD may require surgery to remove part of the intestine or colon, which can result in the need for an ostomy - an opening in the skin created to allow drainage of fecal matter into a collection bag outside the body. An additional surgery that patients with ulcerative colitis may have is an IPAA, also called a J-pouch. This procedure creates a reservoir using part of the small intestine, which allows the ostomy to be closed. People with Crohn’s disease may also have their colon removed. However, people with Crohn’s disease rarely receive a J-pouch because the pouch often becomes inflamed. Additionally, people with Crohn’s disease may have part of their small intestine removed or a strictureplasty to widen the intestine where it has become narrowed because of scarring. These surgeries can be performed via a laparoscopic approach or an open approach. In laparoscopic surgery, cameras and tools are inserted through small incisions and a slightly larger incision is made to remove the diseased portion of the intestine. In open surgery, a single large cut is made in the abdomen, allowing the surgeon to directly see and remove the diseased portions of bowel.

What did researchers investigate?
Researchers reviewed the literature to identify previous studies that reported the risk of infertility in women with IBD who had previous IBD-related surgeries as well as studies that reported the impact of previous surgery on pregnancy outcomes (miscarriage, stillbirth, prematurity, low birth weight, and small for gestational age) or pregnancy complications (gestational diabetes, gestational hypertension, postpartum depression, and bleeding).

What did researchers find?
Researchers found 16 studies that reported the impact of surgery on infertility or pregnancy outcomes in women with IBD. Nine studies compared women with and without previous surgery. Four of these studies reported on the impact of surgery on a woman’s ability to become pregnant. We were unable to reach conclusions about the association between surgery and infertility because of the low quality of evidence from these studies. Eight reported on pregnancy outcomes and complications. Evidence from these studies was also of very low quality, and we are unable to draw conclusions about the impact of IBD surgery on pregnancy outcomes. Evidence from the one study comparing infertility among women undergoing open and laparoscopic surgery was also of low quality. Thus, we could not draw conclusions about the impact of open and laparoscopic procedures on infertility. The remaining six studies compared women before and after surgery. One study that compared women with IBD who did and did not have surgery also compared women before and after surgery. These seven studies comparing women before and after surgery provided low-quality evidence on differences in women’s ability to get pregnant and on outcomes of pregnancy before and after surgery.

Conclusions
Studies on the impact of IBD-related surgery on a woman's ability to get pregnant and on the outcomes of pregnancy are rare and of low quality. As a result, information reviewed in the present study on associations between IBD-related surgery and adverse pregnancy outcomes has high risk of bias, and we have very little confidence in these conclusions. Our results should be interpreted with caution. Additional well-designed studies on this topic are needed.

Authors' conclusions: 

The effect of surgical therapy for IBD on female infertility is uncertain. It is also uncertain if there are any differences in infertility among those undergoing open versus laparoscopic procedures. Previous surgery was associated with higher risk of miscarriage, use of ART, Caesarean section delivery, and giving birth to a low birth weight infant, but was not associated with risk of stillbirth, preterm delivery, or delivery of a small for gestational age infant. These findings are based on very low-quality evidence. As a result, definitive conclusions cannot be made, and future well-designed studies are needed to fully understand the impact of surgery on infertility and pregnancy outcomes.

Read the full abstract...
Background: 

Women with inflammatory bowel disease (IBD) may require surgery, which may result in higher risk of infertility. Restorative proctocolectomy with ileal anal pouch anastomosis (IPAA) may increase infertility, but the degree to which IPAA affects infertility remains unclear, and the impact of other surgical interventions on infertility is unknown.

Objectives: 

Primary objective

• To determine the effects of surgical interventions for IBD on female infertility.

Secondary objectives

• To evaluate the impact of surgical interventions on the need for assisted reproductive technology (ART), time to pregnancy, miscarriage, stillbirth, prematurity, mode of delivery (spontaneous vaginal, instrumental vaginal, or Caesarean section), infant requirement for resuscitation and neonatal intensive care, low and very low birth weight, small for gestational age, antenatal and postpartum hemorrhage, retained placenta, postpartum depression, gestational diabetes, and gestational hypertension/preeclampsia.

Search strategy: 

We searched MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to September 27, 2018, to identify relevant studies. We also searched references of relevant articles, conference abstracts, grey literature, and trials registers.

Selection criteria: 

We included observational studies that compared women of reproductive age (≥ 12 years of age) who underwent surgery to women with IBD who had a different type of surgery or no surgery (i.e. treated medically). We also included studies comparing women before and after surgery. Any type of IBD-related surgery was permitted. Infertility was defined as an inability to become pregnant following 12 months of unprotected intercourse. Infertility at 6, 18, and 24 months was included as a secondary outcome. We excluded studies that included women without IBD and those comparing women with IBD to women without IBD..

Data collection and analysis: 

Two review authors independently screened studies and extracted data. We used the Newcastle-Ottawa Scale to assess bias and GRADE to assess the overall certainty of evidence. We calculated the pooled risk ratio (RR) and 95% confidence interval (CI) using random-effects models. When individual studies reported odds ratios (ORs) and did not provide raw numbers, we pooled ORs instead.

Main results: 

We identified 16 observational studies for inclusion. Ten studies were included in meta-analyses, of which nine compared women with and without a previous IBD-related surgery and the other compared women with open and laparoscopic IPAA. Of the ten studies included in meta-analyses, four evaluated infertility, one evaluated ART, and seven reported on pregnancy-related outcomes. Seven studies in which women were compared before and after colectomy and/or IPAA were summarized qualitatively, of which five included a comparison of infertility, three included the use of ART, and three included other pregnancy-related outcomes. One study included a comparison of women with and without IPAA, as well as before and after IPAA, and was therefore included in both the meta-analysis and the qualitative summary. All studies were at high risk of bias for at least two domains.

We are very uncertain of the effect of IBD surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57; 114 participants; 2 studies) and at 24 months (RR 3.59, 95% CI 1.32 to 9.73; 190 participants; 1 study). Infertility was lower in women who received laparoscopic surgery compared to open restorative proctocolectomy at 12 months (RR 0.70, 95% CI 0.38 to 1.27; 37 participants; 1 study).

We are very uncertain of the effect of IBD surgery on pregnancy-related outcomes, including miscarriage (OR 2.03, 95% CI 1.14 to 3.60; 776 pregnancies; 5 studies), use of ART (RR 25.09, 95% CI 1.56 to 403.76; 106 participants; 1 study), delivery via Caesarean section (RR 2.23, 95% CI 1.00 to 4.95; 20 pregnancies; 1 study), stillbirth (RR 1.96, 95% CI 0.42 to 9.18; 246 pregnancies; 3 studies), preterm birth (RR 1.91, 95% CI 0.67 to 5.48; 194 pregnancies; 3 studies), low birth weight (RR 0.61, 95% CI 0.08 to 4.83), and small for gestational age (RR 2.54, 95% CI 0.80 to 8.01; 65 pregnancies; 1 study).

Studies comparing infertility before and after IBD-related surgery reported numerically higher rates of infertility at six months (before: 1/5, 20.0%; after: 9/15, 60.0%; 1 study), at 12 months (before: 68/327, 20.8%; after: 239/377, 63.4%; 5 studies), and at 24 months (before: 14/89, 15.7%; after: 115/164, 70.1%; 2 studies); use of ART (before: 5.3% to 42.2%; after: 30.3% to 34.3%; proportions varied across studies due to differences in which women were identified as at risk of using ART); and delivery via Caesarean section (before: 8/73, 11.0%; after: 36/75, 48.0%; 2 studies). In addition, women had a longer time to conception after surgery (two to five months; 2 studies) than before surgery (5 to 16 months; 2 studies). The proportions of women experiencing miscarriage (before: 19/123, 15.4%; after: 21/134, 15.7%; 3 studies) and stillbirth (before: 2/38, 5.3%; after: 3/80: 3.8%; 2 studies) were similar before and after surgery. Fewer women experienced gestational diabetes after surgery (before: 3/37, 8.1%; after: 0/37; 1 study), and the risk of preeclampsia was similar before and after surgery (before: 2/37, 5.4%; after: 0/37; 1 study). We are very uncertain of the effects of IBD-related surgery on these outcomes due to poor quality evidence, including confounding bias due to increased age of women after surgery.

We rated evidence for all outcomes and comparisons as very low quality due to the observational nature of the data, inclusion of small studies with imprecise estimates, and high risk of bias among included studies.

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