Relationship Between Inflammatory Bowel Disease, Fertility,
and Pregnancy
Inflammatory bowel disease (IBD), which includes
Crohn’s disease (CD) and ulcerative colitis (UC), is characterized
by chronic inflammation at various sites in the gastrointestinal (GI)
tract.8294 This
inflammation results from an inappropriate activation of the mucosal
immune system. Crohn’s disease may occur in any part of the
GI tract but most commonly affects the distal ileum and colon, while
UC is generally restricted to the colon. Both diseases may have extraintestinal
manifestations. Inflammatory bowel disease commonly occurs in people
of reproductive age and may impact fertility and pregnancy outcomes
in these individuals. Several studies have evaluated the effects of
IBD on fertility and pregnancy and the influence of pregnancy on disease
status. A summary is provided here.
Inflammatory Bowel Disease and Female Fertility
Initial reports in the published literature suggested
higher infertility rates and smaller family size in individuals with
UC and CD.4853,4854,4856,4857 However,
these early studies failed to take into account several factors, including
severity of disease, voluntary childlessness, and the fertility status
of the husband or partner.4858 Other
variables, such as the effects of systemic disease and its effect
on libido, as well as concerns about the child inheriting the genetic
component of IBD or being affected by treatment in utero, can lead to voluntary childlessness and should be taken into consideration
when studying this population.11905 More
recent studies comparing fertility of females with IBD to healthy
controls have indicated that, overall, IBD does not reduce fertility
and that most females with quiescent and mildly active disease can
anticipate a normal pregnancy outcome.4855,4885 However,
active disease at time of conception may negatively impact fertility
and increase the risk of obstetric complications throughout a pregnancy.4855
In an effort to understand whether, and to what
extent, IBD patients’ perceptions of risk influence their reproductive
behavior, Mountifield, et al., conducted a survey by questionnaire
to all contactable patients age 18-50 years from one Australian hospital-based
IBD database.12545 Of
the 355 patients contacted, 217 participated in the survey (59% completion
rate). Of the responders, 127 had CD, 85 had UC, and 5 had indeterminate
colitis (IC). Seventy-seven percent of all IBD patients reported being
in a current relationship, while 5.5% reported never having been partnered.
The average fertility rate among responders did not differ between
UC and CD (UC, 1.2 live births per female; CD, 1.0 live birth per
female); however, during the same time period the average Australian
female’s pregnancy rate was 1.81. In total, 42% of IBD responders
reported being childless, with 14% making this decision as a direct
result of IBD. Of those who had children, 25% reported having fewer
children than desired or planned. While approximately 43% of responders
reported a fear of infertility, only 19.4% of patients reported consulting
a fertility specialist with their concerns. This fear was greater
in CD patients than in UC patients (47.2% and 25.8% respectively, P=0.0032). Further, the fear of infertility
was higher in females compared with males (P=0.035), and in those with a history of prior IBD surgery.
Patients cited IBD heritability, the risk of congenital abnormalities,
and medication teratogenicity as specific concerns that lead to voluntary
childlessness.
Fertility in Ulcerative Colitis
Several studies suggest that fertility is not
likely impaired in patients with UC who are treated nonoperatively,4858,4855,4859 but
may be diminished in those treated operatively. One study reported
that females who had ileal pouch-anal anastomosis (IPAA) for treatment
of UC had a significantly higher rate of infertility post surgery
than females with UC who were managed nonoperatively.4860 In
this study, researchers reported an infertility rate of 38.6% after
IPAA, compared to a rate of 13.3% in patients treated nonoperatively
and a rate of 10.2% reported in the general population in the U.S.
While IPAA may impair fertility, it has not been shown to jeopardize
pregnancy and childbirth.4861 Reduced
fertility post-IPAA may be due to the presence of postoperative adhesions
in the pelvis that obstruct the fallopian tubes or alter the normal
tubo-ovarian relationship necessary for ovum capture and transport.4885
Fertility in Crohn’s Disease
Several reports indicate that CD status may negatively
impact fertility. Reduced fertility in CD has been attributed to disease-associated
inflammation in the ovaries or fallopian tubes,4899 proximity
of disease to fallopian tubes, disease severity at time of conception,
adhesions or scarring from surgery,4859,4862,4865 poor
nutritional status, specifically vitamin B12 deficiencies,4890 or
disease-associated decrease in libido.4860 One study suggests that fertility may be further reduced
when CD includes colonic involvement rather than ileal involvement,4856 while other reports suggest that fertility is reduced in
CD regardless of disease site.4857,4858 Still, other studies report similar fertility
rates in females with CD compared to those without CD,4875,4876 suggesting
that differences in rates may result from voluntary infertility.4865,4867
Inflammatory Bowel Disease and Male Fertility
Inflammatory bowel disease often affects young
males during their prime reproductive years; however, few studies
have evaluated the impact of disease on male fertility. Some studies
have shown reduced fertility in males with IBD.11934,11935 One
study found that males with more severe IBD activity had a higher
rate of erectile dysfunction (ED), whereas the rate of ED in those
with mild to moderate disease activity was similar to that seen in
healthy controls.11908 Still,
it is unclear whether diminished fertility is due to disease-specific
factors or to voluntary contraception.4897,4898,11908
Inflammatory Bowel Disease and Pregnancy
A number of studies have examined the effects
of IBD on the course of pregnancy. Some studies found that IBD did
not adversely affect the course of pregnancy or pregnancy outcomes.4900,4901,4924,4925 However,
other reports associate CD and certain types of UC with an elevated
risk of pregnancy-related complications, such as preterm birth, spontaneous
abortion, lower birth weight infants, fetal malformation, and fetal
loss compared to a control population.4899,4900 Further, active disease status at time
of conception, disease flares during pregnancy, and a history of surgery
for the treatment of IBD have been associated with an increase in
obstetric complications.4890
One retrospective, community-based cohort study
conducted in a large non-referral population (N=954) in California
showed that pregnant females with CD or UC had a reduced likelihood
of live birth (P=0.01) and an
increased rate of cesarean section (P=0.05), adverse conception outcome (P=0.03), and pregnancy complications (P=0.01) compared to females without IBD.11910 However,
the rate of therapeutic abortion and congenital abnormalities was
similar between the groups.11910
Another study, reviewing the Nationwide Inpatient
Sample from 2005, estimated the occurrence of pregnancy in females
with UC and CD in the United States and compared pregnancy outcomes
between the IBD and nonIBD population.11912 Results
showed that adverse pregnancy and maternal outcomes occurred more
frequently in females with IBD. Females with CD and UC were found
to be at an increased risk for cesarean delivery (adjusted odd ratio [aOR]=1.72, 95% confidence interval [CI]: 1.44-2.04 for
CD and aOR=1.29, 95% CI: 1.01-1.66 for UC), venous
thromboembolism (aOR=6.12, 95% CI: 2.91-12.9 for
CD and aOR=8.44, 95% CI: 3.71-19.2 for UC), and
protein-calorie malnutrition (aOR=20.0, 95% CI:
8.8-45.4 for CD and aOR=60.8, 95% CI: 28.2-131.0
for UC).
A recent population-based study evaluated the
breast-feeding practices among females with IBD and the impact of
breast-feeding on disease course during the postpartum period.12546 A
total of 204 of 314 eligible females (age 15-40) participated in a
questionnaire asking them to detail their pregnancies, birth outcomes,
and disease activity before, during, and immediately following each
pregnancy. Of these females, 132 had CD, 39 had UC, and 3 had IC.
Seventy-nine females became pregnant after being diagnosed with IBD
(51 CD, 25 UC, 3 IC) for a total of 156 children born after IBD diagnosis
(94 CD, 57 UC, 5 IC). The average disease duration for these females
was 14.8 years at the time of study. Breast-feeding was reported in
83.3% of females with IBD vs. 77.1% in the general population. Of
the females with IBD, 56.1% breast-fed for >24 weeks. During the
postpartum year, the rate of disease flare was 26% in women with CD
who breast-fed vs. 29.2% in those who did not (P=0.76) and 29.2% vs. 44.4% in women with UC (P=0.44). In this study, breast-feeding did not
increase the risk of disease flare (OR: 0.58, 95% CI: 0.24-1.43 for
IBD total; OR: 0.84, 95% CI: 0.19-9.87 for CD, and OR: 0.51, 95% CI:
0.12-2.2 for UC).
Effects of Crohn’s Disease on Pregnancy
Crohn’s disease commonly occurs in females
of reproductive age. Chronic disease generally produces systemic symptoms,
including malnutrition, weight loss, and extraintestinal manifestations
that can influence the course and outcomes of pregnancy.8183 Thus,
females with CD who seek pregnancy may be concerned with the effects
of CD on a pregnancy and the possible risks to the neonate.
A number of studies have implicated active disease
at the time of conception and the exacerbation of symptoms of CD during
pregnancy as risk factors for premature birth, lower birth weight
infants, and fetal loss.4910,4913 Females
who had quiescent disease or mildly active disease at conception were
found to have significantly more abnormal pregnancy outcomes, defined
as those ending in spontaneous abortion, premature birth, birth weight <2500 g , or respiratory distress if their disease
became more active throughout the pregnancy.4918 Conversely,
females who conceive during a period of inactive disease and whose
disease remains inactive during the pregnancy are more likely to have
normal pregnancies without obstetric complications.4919
Prior surgery for the treatment of CD and ileal
involvement has been shown to be predictors of preterm delivery and
small-for-gestational-age births.4912 However,
others have found no evidence that site of disease and prior resection
adversely affects pregnancy duration, compared to a nonCD population.4901,4920
Effects of Ulcerative Colitis on Pregnancy
Ulcerative colitis is a chronic inflammatory
and ulcerative condition of the colonic mucosa, which commonly occurs
in adolescence or early adulthood and, therefore, can affect females
of reproductive age.8184 Some
research has shown that the status of UC may affect pregnancy outcomes.
Thus, females with UC who want to become pregnant may be concerned
with the effects of the disease on a pregnancy and the possible risks
to the neonate.
In general, there is no evidence to suggest that
inactive UC has any effect on a female’s ability to carry a
pregnancy to term or have a vaginal delivery.4925 However,
some research has implicated active UC, at the time of conception
or in very early pregnancy, with an increased risk of lower birth
weight infants despite adequate maternal weight gain during pregnancy.4923 Moreover,
higher rates of maternal death and infant loss have been found in
females who have been treated operatively for UC than in those who
have been treated medically.4925 However, other studies have found rates of lower birth weight
infants and spontaneous abortions to be consistent with that of the
general population.4901,4922
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Content on this page was last changed on
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Pregnancy outcome for women with Crohn’s disease: a follow-up
study based on linkage between national registries.
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with inflammatory bowel disease: a large community-based study from
northern California.
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2007;133(4):1106-1112.
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doi:10.1038/ajg.2009.362.