Female and Male Fertility after Colectomy and Reconstructive Surgery in Inflammatory Bowel Disease: A National Cohort Study from Sweden

Abstract

Background and Aims

Colectomy and reconstruction in patients with inflammatory bowel disease [IBD] may adversely affect fertility, but few population-based studies on this subject are available.

Methods

Fertility was assessed in 2989 women and 3771 men with IBD and prior colectomy during 1964–2014, identified from the Swedish National Patient Register, and in 35 092 matched individuals.

Results

Reconstruction with ileoanal pouch anastomosis [IPAA] was as common as ileorectal anastomosis [IRA] in ulcerative colitis [UC] and IBD-unclassified [IBD-U] but rare in Crohn’s disease [CD]. Compared with the matched reference cohort, women with IBD had lower fertility overall after colectomy (hazard ratio [HR] 0.65, confidence interval [CI] 0.61–0.69), with least impact with leaving the rectum intact [HR 0.79, CI 0.70–0.90]. Compared with colectomy only, fertility in female patients remained unaffected after IRA [HR 0.86, CI 0.63–1.17 for UC, 0.86, CI 0.68–1.08 for IBD-U and 1.07, CI 0.70–1.63 for CD], but was impaired after IPAA, especially in UC [HR 0.67, CI 0.50–0.88], and after completion proctectomy [HR 0.65, CI 0.49–0.85 for UC, 0.68, CI 0.55–0.85 for IBD-U and 0.61, CI 0.38–0.96 for CD]. In men, fertility was marginally reduced following colectomy [HR 0.89, CI 0.85–0.94], regardless of reconstruction.

Conclusions

Fertility was reduced in women after colectomy for IBD. The least impact was seen when a deviated rectum was left intact. IRA was associated with no further reduction in fertility, whereas proctectomy and IPAA were associated with the strongest impairment. IRA therefore seems to be the preferred reconstruction to preserve fertility in selected female patients. Fertility in men was only moderately reduced after colectomy.

1. Introduction

Surgery is one of the factors with the strongest association to reduced fertility [number of children born] and fecundity [biological reproductive capacity] in patients with inflammatory bowel disease [IBD].^1–4 Plausible contributing factors include damage to autonomic nerves, altered anatomy, fibrosis and psychological factors.

After colectomy, patients with IBD may choose to keep the ileostomy or to restore bowel continuity with the construction of either an ileal pouch anal anastomosis [IPAA] or ileorectal anastomosis [IRA]. Continent ileostomy is a further alternative for a few patients. IBD patients with a disconnected rectum may need completion proctectomy for symptomatic proctitis, a rectum not amenable for endoscopic surveillance, or development of dysplasia or rectal cancer. As the dissection is more extensive in proctectomy, with or without IPAA,⁵ IRA has been proposed as an alternative for patients of child-bearing age⁶ but it is also a controversial method due to the risk of developing rectal cancer.^7,8

The objective of this study was to examine fertility in a nationwide cohort of women and men with IBD after colectomy and possible subsequent reconstruction.

2. Methods

2.1. Data sources

All Swedish residents are assigned a unique personal identification number used in all official registers, enabling linkage between them.⁹ The Swedish National Patient Register [NPR] contains the discharge diagnoses and surgical interventions for all hospital admissions since 1964, reaching full national coverage by 1987, and for all outpatient specialist contacts since 2001.^10,11 The NPR has been validated and found to be reliable regarding medical diagnoses of IBD and IBD-related surgical procedures.^12,13 The Medical Birth Register [MBR] includes data on all deliveries in Sweden since 1973. The Swedish Multi-Generation Register [MGR] contains information on children born in Sweden since 1932. In the register, the child’s paternity automatically applies to the husband of the mother at the time of birth or ‘by the putative father’s acknowledgment’. Adoption or other non-biological relations are marked in the register.¹⁴ In this study all non-biological relations were excluded from the analyses.

2.2. Study populations

From the NPR we identified a cohort of all IBD patients of fertile age [15–45 years] with an ICD [International Classifications of Diseases] code for ulcerative colitis [UC], Crohn’s disease [CD] or indeterminate colitis [IC] on at least two separate occasions and a procedure code indicating colectomy from 1964 until the end of 2014 [Supplementary Information]. Statistics Sweden [SCB] provided a comparison cohort of individuals from the general population, matched for sex and birthdate. For each IBD patient at least five matched referent individuals were identified. As the NPR initially did not have complete national coverage, the comparison cohort was also matched for place of residence at date of diagnosis to avoid ascertainment bias. Information regarding the number of children born to the IBD and reference cohorts was obtained by linkage with the MBR and MGR.^2,4

It may sometimes be difficult to differentiate between UC and CD. The term IC is reserved for patients without a definitive diagnosis even after complete histological analysis of a colectomy specimen.¹⁵ The term IBD unclassified [IBD-U] is increasingly used for patients with their colon still in place where the clinical presentation is atypical or varying over time. From several schemes proposed to categorize patients with inconsistent coding in the registers we used a slightly modified variant of the classification promoted by Everhov et al.^2,4,16

The final IBD diagnosis was defined as UC or CD in patients who had a consistent discharge diagnosis. Patients with an initial diagnosis of IC followed by a consistent diagnosis of UC or CD were accepted as having UC or CD, respectively. Patients with a consistent IC diagnosis as well as patients with any other combination of IBD diagnoses were defined as having IBD-U. UC patients with an additional ICD-code for typical CD-related conditions such as perianal disease or small bowel involvement was classified as having IBD-U, as proposed by Everhov, minimizing misclassifications and keeping the UC and CD cohorts as ‘clean’ as possible.

2.3. Statistical analysis

Characteristics, including age at diagnosis, duration of follow-up and parity at specified occasions [at diagnosis, at colectomy, at restorative surgery if performed, and at end of follow-up], were estimated for each IBD sub-cohort and the corresponding matched cohorts.

The fertility of the women and men in the IBD sub-cohorts was compared with the corresponding matched referent sub-cohorts, expressed as the hazard ratio [HR] of childbirth over time using Cox regression, adjusting for covariates. For recurrent birth events we used the Andersen–Gill proportional hazards regression model where applicable, taking account of the reduced fertility during pregnancy and 1 year postpartum by using each pregnancy as a time-varying covariate. The stratification of sets of IBD patients and matched individuals allowed for different baselines but assumed equal HRs across strata. To compare the impact of different surgical reconstructions and completion proctectomy on fertility, further analyses were performed within the IBD cohort following colectomy, with patients keeping their ileostomy with the rectum intact as the reference. Analyses were adjusted for age at disease onset, year of colectomy and parity at colectomy. As our data were based on national official registries of high quality, we had no issues with missing values or loss of follow-up.

For the IBD patients and their matched referent individuals, follow-up started on the date when the IBD patient was diagnosed, had colectomy and had restorative surgery. Follow-up ended when the IBD patients turned 45 years or on December 31, 2014, whichever occurred earliest.

Differences in proportions were analysed with the chi-square test. All tests were two-tailed and p < 0.05 was considered statistically significant. All analyses were performed in Stata 15 [Stata Statistical Software: Release 15, StataCorp.].

This research was done without patient or public involvement. Due to this being a register-based cohort study, involvement of patients and the public was not considered possible. Patients were not invited to contribute to the writing or editing of this document for readability or accuracy.

The study was approved by the Regional ethical review board in Linköping [registration number of ethical approvals including amendments: 2011/419–31, 2014/226–32, 2014/492–32 and 2015/123–32].

3. Results

From the NPR, 2989 females [UC 1191; CD 415; IBD-U 1383] and 3771 males [UC 1850; CD 321; IBD-U 1600] with colectomy for IBD in 1964–2014 were identified. Corresponding matched cohorts of 15 590 women and 19 502 men were obtained from SCB [Table 1]. The IBD and referent cohorts were well matched at baseline in terms of age, parity and age at first child [Supplementary Table S1]. The average follow-up time was 12.2 [SD 7.6] years for women and 11.2 [SD 7.2] for men. Demographic information is given in Table 1 [women] and Table 4 [men].

Table 1.

Demography and characteristics of the study cohorts including female IBD patients following colectomy and a matched referent cohort from the general population.

				IBD subcohorts
Characteristics		Matched cohort [n = 15 590]	IBD cohort [n = 2989]	UC [n = 1191]	CD [n = 415]	IBD-U [n = 1383]
Age at diagnosis, years, mean [SD]		26.09 [8.73]	26.12 [8.75]	28.00 [8.71]	25.93 [8.42]	24.56 [8.58]
Age at colectomy, years, mean [SD]		29.99 [8.32]	30.01 [8.33]	31.38 [8.22]	29.52 [7.95]	28.99 [8.38]
Age at reconstruction, years, mean [SD]		35.21 [12.57]	35.29 [12.58]	36.22 [12.17]	35.77 [14.17]	34.33 [12.37]
Follow-up time, years, mean [SD]		12.43 [7.61]	12.24 [7.62]	10.64 [7.12]	13.60 [7.82]	13.22 [7.73]
Time to colectomy, years, mean [SD]		3.90 [5.10]	3.89 [5.09]	3.38 [4.80]	3.59 [5.34]	4.42 [5.20]
Time to reconstruction, years, mean [SD]		5.22 [10.13]	5.27 [10.17]	4.85 [9.66]	6.25 [11.95]	5.35 [10.00]
Age at first child, years, mean [SD]		26.24 [5.19]	26.19 [5.39]	26.22 [5.13]	24.99 [5.53]	26.52 [5.52]
Parity at diagnosis, mean [SD]		0.85 [1.14]	0.84 [1.11]	1.01 [1.17]	0.77 [1.03]	0.71 [1.07]
Parity at colectomy, mean [SD]		1.12 [1.22]	1.06 [1.18]	1.21 [1.21]	0.95 [1.07]	0.97 [1.17]
Achieved parity at end of follow-up, mean [SD]		1.76 [1.26]	1.48 [1.19]	1.57 [1.20]	1.38 [1.14]	1.43 [1.19]
No child at diagnosis, no. [%]		8855 [56.8%]	1673 [56.0%]	581 [48.8%]	237 [57.1%]	855 [61.8%]
No child at colectomy, no. [%]		7075 [45.4%]	1364 [45.6%]	482 [40.5%]	191 [46.0%]	691 [50.0%]
No child at end of follow up, no. [%]		3,408 [21.9%]	801 [26.8%]	305 [25.6%]	121 [29.2%]	375 [27.1%]
Year of colectomy, no. [%]	1950–1979	2819 [18.1%]	537 [18.0%]	188 [15.8%]	116 [28.0%]	233 [16.8%]
	1980–1989	4254 [27.3%]	824 [27.6%]	289 [24.3%]	138 [33.3%]	397 [28.7%]
	1990–1999	4183 [26.8%]	804 [26.9%]	339 [28.5%]	92 [22.2%]	373 [27.0%]
	2000–2009	3027 [19.4%]	578 [19.3%]	247 [20.7%]	49 [11.8%]	282 [20.4%]
	2010–2014	1307 [8.4%]	246 [8.2%]	128 [10.7%]	20 [4.8%]	98 [7.1%]

Inflammatory bowel disease [IBD], ulcerative colitis [UC], Crohn’s disease [CD], IBD unclassified [IBD-U].

Table 4.

Demography and characteristics of the study cohorts including male IBD patients following colectomy and a matched referent cohort from the general population.

					IBD subcohorts
Characteristics		Matched cohort [n = 19 502]	IBD-cohort [n = 3771]	UC [n = ,850]	CD [n = 321]	IBD-U [n = 1600]
Age at diagnosis, years, mean [SD]		26.34 [8.55]	26.36 [8.58]	27.64 [8.42]	25.16 [8.32]	25.11 [8.60]
Age at colectomy, years, mean [SD]		30.40 [8.12]	30.41 [8.13]	31.20 [7.99]	29.18 [8.49]	29.73 [8.14]
Age at reconstruction, years, mean [SD]		35.62 [12.27]	35.62 [12.28]	35.77 [11.86]	36.91 [14.73]	35.19 [12.20]
Follow-up time, years, mean [SD]		11.63 [7.12]	11.34 [7.21]	10.37 [6.76]	13.90 [8.09]	11.95 [7.33]
Time to colectomy, years, mean [SD]		4.06 [5.37]	4.05 [5.38]	3.57 [5.13]	4.02 [5.74]	4.61 [5.53]
Time to reconstruction, years, mean [SD]		5.22 [9.90]	5.21 [9.90]	4.56 [9.15]	7.73 [13.60]	5.46 [9.77]
Age at first child, years, mean [SD]		28.96 [5.44]	29.29 [5.41]	29.41 [5.32]	28.11 [5.28]	29.39 [5.52]
Parity at diagnosis, mean [SD]		0.63 [1.03]	0.57 [0.97]	0.64 [1.01]	0.50 [0.91]	0.51 [0.93]
Parity at colectomy, mean [SD]		0.88 [1.15]	0.78 [1.07]	0.83 [1.10]	0.73 [1.04]	0.74 [1.04]
Achieved parity at end of follow-up, mean [SD]		1.57 [1.31]	1.38 [1.25]	1.37 [1.26]	1.38 [1.28]	1.39 [1.23]
No child at diagnosis, no. [%]		12 993[66.6%]	2594 [68.8%]	1211 [65.5%]	229 [71.3%]	1154 [72.1%]
No child at colectomy, no. [%]		10 770 [55.2%]	2210 [58.6%]	1049 [56.7%]	191 [59.5%]	970 [60.6%]
No child at end of follow-up, no. [proportion]		5,799 [29.7%]	1325 [35.1%]	660 [35.7%]	114 [35.5%]	551 [34.4%]
Year of colectomy, no. [%]	1950–1979	2563 [13.1%]	493 [13.1%]	211 [11.4%]	87 [27.1%]	195 [12.2%]
	1980–1989	4330 [22.2%]	835 [22.1%]	382 [20.6%]	115 [35.8%]	338 [21.1%]
	1990–1999	5387 [27.6%]	1047 [27.8%]	529 [28.6%]	67 [20.9%]	451 [28.2%]
	2000–2009	4853 [24.9%]	940 [24.9%]	488 [26.4%]	30 [9.3%]	422 [26.4%]
	2010–2014	2369 [12.1%]	456 [12.1%]	240 [13.0%]	22 [6.9%]	194 [12.1%]

Inflammatory bowel disease [IBD], ulcerative colitis [UC], Crohn’s disease [CD], IBD unclassified [IBD-U].

3.1. Characteristics of the female cohort

After colectomy, a majority of the female patients remained with an ileostomy without restoration of intestinal continuity, either with the rectal stump left in place [614, 20.5%] or removed by completion proctectomy [1146, 38.3%]. In total, 1229 [41.1%] of the women underwent reconstructive surgery. IPAA and IRA were almost equally common in UC and IBD-U whereas few female CD patients had an IPAA [Table 2].

Table 2.

Impact of colectomy with or without subsequent reconstructive surgery or proctectomy on female fertility for IBD subtypes, expressed as hazard ratio for giving birth compared with matched individuals from the general population, with adjustment for pregnancy and first year postpartum.

	IBD cohort				IBD subcohorts
					UC				CD				IBD-U
	No.	HR	95% CI	p-value	No.	HR	95% CI	p-value	No.	HR	95% CI	p-value	No.	HR	95% CI	p-value
Colectomy only	614	0.79	0.70–0.90	<0.001	268	0.81	0.66–0.98	0.032	84	0.69	0.47–1.00	0.052	262	0.80	0.68–0.96	0.015
IRA	685	0.67	0.60–0.76	<0.001	193	0.75	0.58–0.97	0.026	160	0.67	0.53–0.83	<0.001	332	0.65	0.55–0.77	<0.001
IPAA	544	0.61	0.53–0.71	<0.001	298	0.57	0.46–0.72	<0.001	2	N/A			244	0.65	0.54–0.79	<0.001
Proctectomy	1,146	0.52	0.47–0.58	<0.001	432	0.60	0.51–0.72	<0.001	169	0.39	0.30–0.52	<0.001	545	0.52	0.45–0.60	<0.001

Inflammatory bowel disease [IBD], ulcerative colitis [UC], Crohn’s disease [CD], IBD unclassified [IBD-U]. Ileoanal pouch anastomosis [IPAA], ileorectal anastomosis [IRA]. Hazard ratio [HR] with 95% confidence interval [95% CI].

The female IBD cohort and sub-cohorts had similar parity as their matched cohorts at diagnosis. A total of 1215 live births occurred following colectomy in women with IBD. Parity was slightly higher in the matched cohort at colectomy, and this difference became more pronounced at the end of the follow-up [after both colectomy and reconstruction]. The mean parity achieved at the end of follow-up was 1.5 [SD 1.2] in the IBD cohort, markedly lower than the observed 1.8 [SD 1.3] in the matched cohort [p < 0.001]. The parity achieved at the end of follow-up was less affected in UC [mean 1.6, SD 1.2] than in CD [mean 1.4, SD 1.2] and IBD-U [mean 1.4, SD 1.2] [Table 1]. Parity was higher at the time of reconstruction in patients having IPAA than in those reconstructed with IRA [Supplementary Table S1].

3.2. Fertility in women following colectomy compared with the matched cohort

Women with IBD following colectomy had a substantially lower fertility compared with the matched cohort from the general population (HR 0.65, confidence interval [CI] 0.61–0.69). Fertility was least affected in women with rectum in situ and ileostomy [HR 0.79, CI 0.70–0.90]. Female fertility appeared to be further affected by reconstructive surgery with IRA [HR 0.67, CI 0.60–0.76] and IPAA [HR 0.61, 0.53–0.71] but appeared to be most dramatically reduced after completion proctectomy for any IBD subtype [HR 0.52, CI 0.47–0.58] [Table 2].

3.3. Impact of reconstruction following colectomy within the female IBD cohort

The impact of reconstruction and proctectomy after colectomy was further analysed within the IBD cohort compared with those who had ileostomy and the rectum intact, with adjustment for age at disease onset, year of colectomy and parity at colectomy. In UC, fertility was more severely impacted after completion proctectomy [HR 0.65, CI 0.49–0.85] and IPAA [0.67, 0.50–0.88] than after IRA [HR 0.86, 0.63–1.17] compared to no further surgery [Table 3]. The difference between IPAA [HR 0.85, CI 0.88–1.08] and IRA [HR 0.86, CI 0.68–1.08] was not as clear in IBD-U patients, but fertility was clearly reduced after completion proctectomy [HR 0.68, CI 0.55–0.85]. In CD, analysis of fertility after IPAA was not possible due to few eligible patients. As with the other IBD subtypes, there was less impact on fertility following IRA [HR 1.07, CI 0.70–1.63] compared with procedures involving proctectomy [HR 0.61, CI 0.38–0.96] [Table 3].

Table 3.

Impact on fertility from reconstructive surgery or proctectomy after colectomy in women with IBD.

	UC			CD			IBD-U
	HR	95% CI	p-value	HR	95% CI	p-value	HR	95% CI	p-value
Unadjusted
Colectomy only	1.00			1.00			1.00
IRA	0.89	0.66–1.21	0.472	1.21	0.81–1.83	0.355	0.83	0.66–1.04	<0.001
IPAA	0.64	0.49–0.84	0.002	N/A			0.79	0.62–1.01	<0.001
Proctectomy	0.61	0.48–0.78	<0.001	0.70	0.45–1.10	1.121	0.63	0.51–0.78	<0.001
Adjusted for age at disease onset, year of colectomy and parity at colectomy
Colectomy only	1.00			1.00			1.00
IRA	0.86	0.63–1.17	0.329	1.07	0.70–1.63	0.772	0.86	0.68–1.08	0.196
IPAA	0.67	0.50–0.88	0.005	N/A			0.85	0.66–1.08	0.081
Proctectomy	0.65	0.49–0.85	0.002	0.61	0.38–0.96	0.032	0.68	0.55–0.85	0.001

Ulcerative colitis [UC], Crohn’s disease [CD], inflammatory bowel disease unclassified [IBD-U]. Ileoanal pouch anastomosis [IPAA], ileorectal anastomosis [IRA]. Hazard ratio [HR] with 95% confidence interval [95% CI].

3.4. Characteristics of the male cohort

Among men, 1635 [43.4%] underwent reconstructive surgery following colectomy at a mean age of 35.6 [SD 12.3] years, whereas 885 [23.5%] remained with ileostomy and a rectal stump and 1251 [33.2%] underwent completion proctectomy with ileostomy.

The most frequent reconstruction in men with UC was IPAA. IPAA and IRA were almost as common in IBD-U patients, whereas few CD patients had an IPAA [Table 6].

Table 6.

Impact on fertility from reconstructive surgery or proctectomy after colectomy in men with IBD.

	UC			CD			IBD-U
	HR	95% CI	p-value	HR	95% CI	p-value	HR	95% CI	p-value
Unadjusted
Colectomy only	1.00			1.00			1.00
IRA	0.97	0.77–1.21	0.795	1.12	0.77–1.62	0.555	1.00	0.81–1.23	0.973
IPAA	1.00	0.83–1.20	0.968	1.61	0.39–6.65	0.504	1.12	0.93–1.34	0.249
Proctectomy	1.08	0.91–1.29	0.368	1.01	0.72–1.43	0.934	1.15	0.97–1.36	0.114
Adjusted for age at disease onset, year of colectomy and parity at colectomy
Colectomy only	1.00			1.00			1.00
IRA	0.98	0.78–1.22	0.875	1.05	0.72–1.53	0.792	1.00	0.81–1.24	0.972
IPAA	0.92	0.76–1.11	0.378	1.46	0.24–8.71	0.680	1.14	0.94–1.38	0.192
Proctectomy	1.17	0.97–1.41	0.095	0.91	0.64–1.28	0.582	1.07	0.89–1.27	0.482

Ulcerative colitis [UC], Crohn’s disease [CD], inflammatory bowel disease unclassified [IBD-U]. Ileoanal pouch anastomosis [IPAA], ileorectal anastomosis [IRA]. Hazard ratio [HR] with 95% confidence interval [95% CI].

The male IBD cohort and sub-cohorts had similar parity to their matched cohorts at diagnosis. A total of 1914 live births occurred among partners to men with IBD following colectomy. The mean parity achieved at the end of follow-up [1.38, SD 1.25] was lower than that in the matched cohort [1.57, SD 1.31] [p < 0.001]. Patients eventually reconstructed with IPAA were throughout slightly older at diagnosis, colectomy and reconstruction than patients reconstructed with IRA. Parity was also higher at the time of reconstruction in patients having IPAA than in those reconstructed with IRA [Supplementary Table S2].

3.5. Fertility in men following colectomy compared with the matched cohort

After colectomy, the cohort of men with IBD had a slightly reduced fertility compared with the matched cohort [HR 0.89, CI 0.85–0.94], with no clear differences between the surgical/restorative alternatives: colectomy only with intact rectum [HR 0.85, CI 0.77–0.94], IRA [HR 0.88, CI 0.78–0.98], IPAA [HR 0.88, CI 0.80–0.96] and completion proctectomy [HR 0.91, CI 0.84–0.98]. The largest impact was seen in men with CD and completion proctectomy [HR 0.77, CI 0.62–0.97] [Table 5].

Table 5.

Impact of colectomy with or without subsequent reconstructive surgery or proctectomy on male fertility for IBD subtypes, expressed as hazard ratio for partner giving birth compared with matched individuals from the general population.

	IBD-cohort				IBD-subcohorts
					UC				CD				IBD-U
	No.	HR	95% CI	p-value	No.	HR	95% CI	p-value	No.	HR	95% CI	p-value	No.	HR	95% CI	p-value
Colectomy only	885	0.85	0.77–0.94	0.002	417	0.94	0.81–1.10	0.435	82	0.75	0.56–1.00	0.054	386	0.81	0.69–0.94	0.005
IRA	699	0.88	0.78–0.98	0.026	299	0.95	0.79–1.15	0.625	92	0.85	0.65–1.11	0.227	308	0.83	0.70–0.99	0.038
IPAA	976	0.88	0.80–0.96	0.006	559	0.85	0.75–0.96	0.011	2	1.43	0.29–7.11	0.664	375	0.91	0.79–1.05	0.186
Proctectomy	1,251	0.91	0.84–0.98	0.012	575	0.93	0.83–1.04	0.217	145	0.77	0.62–0.97	0.024	531	0.93	0.83–1.03	0.178

Inflammatory bowel disease [IBD], ulcerative colitis [UC], Crohn’s disease [CD], IBD unclassified [IBD-U]. Hazard ratio [HR] with 95% confidence interval [95% CI].

3.6. Impact of reconstruction following colectomy within the male IBD cohort

Reconstruction and proctectomy after colectomy had no further impact on fertility compared with those who had colectomy with ileostomy and the rectum intact [Table 6]. This result remained also after adjusting for age at diagnosis, time of colectomy and parity at colectomy.

4. Discussion

This is the first population-based study comparing fertility after colectomy and different reconstructive alternatives in both women and men with IBD compared with a matched referent population. All patients with IBD undergoing colectomy in Sweden between 1964 and 2014 were included alongside five matched individuals, allowing a long follow-up time. In addition, we had access to the entire reproductive history, allowing us to estimate the total number of offspring for the patients and their matched individuals. Women with IBD had a lower fertility following colectomy compared with the matched cohort from the general population. Colectomy with end ileostomy had the least impact on fertility, followed by IRA, while fertility after IPAA and completion proctectomy was affected to a greater extent. The impact of colectomy and reconstructive surgery in men with IBD was only minor but highest after completion proctectomy. Pelvic surgery itself and more extensive dissection needed to remove the chronically inflamed rectum may be contributing factors to the impaired fertility after completion proctectomy in both sexes.

A recent French cohort study found a lower rate of successful pregnancy in women after colectomy for IBD or polyposis compared to the general population, consistent with our findings. Unlike us, they found no difference in fertility between the reconstructive options but did not present fertility data after reconstruction stratified by IBD subtype. Further limitations were a short follow-up time and an uneven distribution of open and laparoscopic surgery between reconstruction types.¹⁷ Several meta-analyses have found that IPAA in women with IBD leads to a 2- to 3-fold increased risk of infertility compared with medical treatment only.^18–20 Fertility was most affected during the first year after IPAA and gradually recovered over the following years in a Finnish study,²¹ suggesting a reduction in the probability of conception rather than complete infertility.²² Higher rates of hydrosalpinx, fimbrial damage and tubal obstruction following pelvic surgery are considered the most likely contributing mechanisms.²³ In the present study, fertility was equally reduced after completion proctectomy, supporting the theory that pelvic dissection reduces fertility.

Fertility treatment is more common in women with IBD, particularly those reconstructed with IPAA.²⁴ This group had a 3-fold greater incidence of in vitro fertilization [IVF] compared to controls and every third child born after IPAA was a product of IVF in Denmark.²⁵ Their success rate after IVF is unfortunately also lower than for other women with impaired fertility.²⁶

It has been proposed that fertility may be less affected by laparoscopically performed IPAA compared to open surgery due to fewer adhesions.^17,27,28 Laparoscopic IPAA and IRA have also been found to be beneficial in terms of fertility in a population-based setting.¹⁷ Unfortunately, laparoscopic interventions were too infrequent in our material to allow further analyses. In future studies, comprehensive evaluation of fertility and fecundity after laparoscopic IPAA and IRA is of the essence.

IPAA is the most common surgical reconstructive option after colectomy in UC in most countries. In Sweden, as an exception, IRA is equally common.²⁹ Fertility after IRA has been less well studied, but may theoretically affect fertility less as it avoids pelvic dissection,²⁷ supported by the results from our study. Against IRA is the disadvantage of risk of cancer in the rectum. However, the actual cancer risk associated with IRA is moderate, in particular during the first 10 years.^7,8 For patients, particularly women, who wish to have one or more children, IRA could therefore be a good alternative to postpone proctectomy with or without IPAA. Importantly in this context, IPAA performed secondary to an IRA has the same long-term survival as a primarily constructed IPAA.³⁰

A reduced fertility in women with IBD may partially be due to family planning. Women with IPAA had a higher fertility rate before the reconstructive surgery, suggesting that women electively complete their families before restorative surgery,³ and this is also seen in our study. It is also likely that the patients, in consultation with their physician, have chosen IRA to preserve fertility. Nevertheless, our study has shown that IRA is associated with a better fertility after reconstruction, and possibly a way to preserve fertility following colectomy in women with IBD.

In the present study, fertility was negatively affected to some extent in men with IBD compared to matched individuals. However, regardless of diagnosis, surgical reconstruction was not associated with a further reduction in fertility. Retrograde ejaculation and erectile dysfunction have been reported in men with UC after IPAA.³¹ However, overall no change or even an improvement in sexual function occurs after surgery.³² In a Danish study, an increase in birth rates was observed after IPAA.³³

A limitation of the present study was that the ICD system has been revised four times during the study period. The same condition may therefore have been coded differently at different time periods. Most obviously, there was no separate code for IC in ICD-9. It is also known that colitis is sometimes difficult to categorize as either UC or CD, and may therefore be variably classified over time. Mistaken registration also occurs. We therefore chose to create the IBD-U group in order not to compromise the results for other IBD subtypes. This group by definition is a mixture of IBD subtypes, which makes the results more difficult to interpret.

Treatment regimens have completely changed over the long study period. This may have had an impact both on fecundity and the desire to have children. However, the matched cohorts representing the general population allowed us to take into account changes in fertility pattern that have taken place in the general society. Data were taken from Swedish registers of high quality^11,14 Unfortunately the registers offer no information on smoking, known to affect both fertility and the clinical course of both CD and UC, including need for surgery and surgical outcome.

5. Conclusion

In this nationwide study, fertility was reduced among women with IBD undergoing colectomy with or without subsequent reconstruction in comparison with matched individuals. Colectomy with ileostomy and preserved rectum affected fertility the least, while colectomy with proctectomy affected it the most. Following reconstruction after colectomy, fertility was more affected after IPAA than after IRA in women with UC. IRA may therefore be an alternative to preserve fertility in women. The impact of colectomy and reconstructive surgery in men with IBD was only minor.

Conference

An abstract was presented as an oral presentation at the annual meeting of the Swedish Surgical Society [Kirurgveckan 2022] and as a poster and oral presentation at ECCO 2023.

Funding

This work was supported by grants from FORSS—Medical Research Council of Southeast Sweden [Grant number: FORSS-570791]; and Futurum—Academy for Health and Care, Region Jönköping County, Sweden [Grant number: FUTURUM-962541].

Conflict of Interest

The authors declare that they have no conflicts of interest. This manuscript, including related data, figures and tables has not been previously published and is not under consideration elsewhere.

Author Contributions

Study concept and design: ED, RA, KL, PM. Acquisition of data: RA. Statistical analysis: RA, ED. Interpretation of data: ED, RA, KL, PM. Drafting the manuscript: ED. Critical revision of the manuscript for important intellectual content: RA, KL, PM. Obtained funding; ED, KL, RA. Study supervision: RA, KL, PM. All authors read and approved the final manuscript.

Data Availability

We do not have permission to share extracts from the nationwide registries but will display all analyses and results upon request.