Fertility and Sexual Function in Males With Hirschsprung Disease

Abstract

Objective:

To assess fertility, sexual function, and sexual quality of life in males with Hirschsprung disease (HSCR) in the Nordic countries with a cross-sectional study using self-reported validated questionnaires.

Background:

Data on fertility and sexual function in males with HSCR are limited.

Methods:

This multicenter study targeted all males born between 1970 and 2003 who underwent pull-through surgery at a pediatric surgery center in Sweden, Denmark, Norway, or Finland. Participants completed a multidomain questionnaire. Demographic data were collected retrospectively from the medical records. Patients with trisomy 21 and other syndromes associated with intellectual disability were excluded. The main outcomes were fertility, sexual function, and sexual quality of life.

Results:

A total of 169 patients (median age: 32 years) were included. Of 63 individuals attempting to father a biological child, 8 (12.7%) reported failure to conceive after 1 year, and 5 (7.9%) reported failure to conceive after 2 years. Our cohort did not report impaired fertility, a higher prevalence of erectile dysfunction, or lower sexual quality of life scores compared with normative summary data. Poor bowel function was associated with impaired fertility and erectile dysfunction (P = 0.0278 and P = 0.0026, respectively). The length of the aganglionic segment and surgical method did not seem to affect fertility, sexual function, or sexual quality of life.

Conclusions:

Males with HSCR who have undergone pull-through surgery do not seem to report overall reduced fertility, higher prevalence of erectile dysfunction, or reduced sexual quality of life compared with estimates from the general population. Impaired bowel function may correlate with erectile dysfunction and impaired fertility in affected individuals.

Hirschsprung disease (HSCR) is a congenital bowel disorder characterized by an aganglionic segment in the distal hindgut.¹ The birth prevalence of HSCR is 1:5000 with a 4:1 male-to-female ratio.¹ The condition requires surgical treatment, usually within the first year of life. The goal of the reconstructive surgery, pull-through surgery, is to resect the aganglionic segment and create an anastomosis between the normally innervated bowel and the anal canal, preserving the sphincter complex.^1,2 Despite a successful pull-through, impaired bowel function beyond childhood is common and might have a negative impact on quality of life.^3–6

The surgical procedure involves operating in the small pelvis, posing a risk for postoperative scarring or adhesions in the area as well as structural damage to urogenital innervation and fertility-related structures that may impair sexual function and fertility. Patients with other bowel conditions, such as inflammatory bowel disease, frequently report decreased sexual well-being and impaired fertility, with a negative impact on their quality of life. Psychogenic factors, disease perception, or structural damage after surgery may contribute to this.^7–10

There are few studies evaluating psychosexual well-being, sexual function, and fertility in patients with HSCR. Limited evidence suggests that women with HSCR may have reduced fertility, whereas no impairment has been observed in men.^11,12 Davidson et al reported that 83% of HSCR men were successful in their attempt to father a child.¹¹ Males with HSCR have the same number of children compared with controls, suggesting unimpaired fertility.¹² Current studies have failed to show an impact on sexual function or sexual quality of life in males with HSCR compared tonormative data.^11,13 In the study by Davidson et al, 97% of males reported an erection sufficient for penetration. In a smaller study, only 2 out of 20 males reported moderate to severe erectile dysfunction (ED).^11,13 An important limitation to previous studies is small cohorts, leading results to be severely underpowered with a risk of type II errors. Studied cohorts are also young with a risk of affecting external validity. Therefore, there is a need for larger studies evaluating fertility, sexual function, and sexual quality of life in males who have undergone pull-through surgery. Increased understanding would have a positive impact on clinical counseling and aid clinicians in identifying patients at risk of developing sexual dysfunction, thus paving the way for personalized treatment.

The primary aim of this study was to assess fertility, sexual function, and sexual quality of life in males with HSCR in the Nordic countries using self-reported validated questionnaires. The secondary aim was to explore factors associated with impaired fertility, reduced sexual function, and reduced sexual quality of life.

METHODS

Study Design

This was a cross-sectional multicenter study set in the Nordic countries.

Study Population

Inclusion criteria targeted all males born between 1970 and 2003 with accessible medical records who had biopsy-verified HSCR and had undergone pull-through surgery at one of the pediatric surgery centers in Sweden, Denmark, Norway, or Finland. Exclusion criteria were trisomy 21 or other syndromes causing intellectual disability, death, emigration, and inability to answer the questionnaire in the reference country’s language (Finland: Finnish or Swedish; Sweden: Swedish; Norway: Norwegian; Denmark: Danish).

Participating Centers

The participating centers were: Karolinska University Hospital, Stockholm; Skåne University Hospital, Lund; University Children’s Hospital, Uppsala; Queen Silvia’s Children’s Hospital, Gothenburg; Helsinki University Children’s Hospital, Helsinki; Odense University Hospital, Odense; and Oslo University Hospital, Oslo. Relevant data-sharing agreements were established before commencing the study. All statistical analyses were performed at the coordinating site at Karolinska University Hospital.

Data Collection and Measurements

Patients were invited to participate in the study through mail. Non-responders received one reminder. After written informed consent was obtained, study participants were asked to complete a validated questionnaire regarding bowel function score (BFS), urinary tract function International Prostate Symptom Score, fertility and sexual function International Index of Erectile Function (IIEF-5), sexual quality of life (SQoL-M), and general quality of life (SF-36). Fertility was defined as the capacity to father a child and infertility was defined per the World Health Organization as failure to conceive after 12 months despite regular (every 2–3 days) unprotected intercourse.¹⁴ The questionnaire also included the following demographic parameters: age, body mass index, sexual orientation, marital status, educational level and occupation, smoking habits, and previous abdominal and/or fertility organ related surgery. Disease-specific demographic data were collected retrospectively from the medical records. These included heredity, associated malformations and/or syndromes, age at diagnosis, length of the aganglionic segment, presence of preoperative stoma, age at surgery, type of surgery, postoperative complications within 30 days, and need for re-do pull-through. A flowchart for participant recruitment and inclusion in the study is shown in Figure 1.

FIGURE 1.

Flowchart for participant recruitment.

Included Questionnaires

Bowel function was assessed using the Rintala BFS, a 7-item questionnaire for pediatric anorectal disorders. Scores range from 0 to 20, with ≥17 indicating normal bowel function.^15–17 The International Prostate Symptom Score evaluated lower urinary tract symptoms across 7 voiding-related questions, classifying severity as mild (0–7), moderate (8–19), or severe (20–35).¹⁸ Sexual quality of life was measured by the 11-item SQoL-M, transformed to a 0 to 100 scale, with higher scores indicating a higher level of sexual quality of life.¹⁹ Erectile function was assessed using the IIEF-5, scored from 5 to 25, classifying ED as severe (5–7), moderate (8–11), mild to moderate (12–16), mild (17–21), and no ED (22–25).^20,21 Health-related quality of life was assessed with the 36-item short form health survey (SF-36), covering 8 health domains, with scores from 0 to 100.²²

Statistical Analysis

Statistical analysis was performed using the R programming language (version 4.2.1) in RStudio (version 2022.07.01). Data wrangling was performed using dplyr, tables were created using tibble and gt, and diagrams were created using ggplot2 unless otherwise specified. Data are presented as frequencies and percentages for categorical variables as well as median and interquartile range (Q₁–Q₃) for numerical variables. SQoL-M and IIEF-5 are presented by age groups. χ² was used for comparative statistics of categorical data when applicable and Fisher exact test when assumptions of χ² were violated. For numerical data, the Mann-Whitney U test was used when comparing 2 independent groups and the Kruskal-Wallis H test when comparing more than 2 groups. Statistical analysis of SF-36 was only performed in the Finnish and Norwegian populations due to missing data from other centers. Age-specific dropout rates did not include Norwegian patients due to local ethical prohibitions. Statistical significance was set at P ≤0.05.

Ethics

The study was approved by the Swedish Ethical Review Authority for the Swedish centers and for the local Ethical Review Boards at the other centers. All procedures were in accordance with the Helsinki Declaration and its later amendments.²³

RESULTS

Study Population

A total of 461 individuals were found to meet the inclusion criteria. After the invitation, 169 patients consented to participation and responded to the questionnaire, resulting in an overall response rate of 36.7%. Dropout rates per country did not differ significantly; Sweden (67.1%), Finland (65.8%), Norway (63%), and Denmark (52.7%)(P = 0.11). The dropout rate varied between each of the age groups: 15 to 19 years old (37.5%), 20 to 29 years old (71.9%), 30 to 39 years old (62,5%), 40 to 49 years old (59.3%), 50 to 59 years old (71.4%), and ≥60 years old (100%) (P = 0.20).

Patient Characteristics

Demographic features of participating males with HSCR are depicted in Table 1. Median age was 32 years. The largest age group was 20 to 29 years (63 individuals) and the smallest age group was 15 to 19 years (5 individuals). Active smoking was reported by 7.7% of the population. Associated malformations were present in 13 individuals (7.7%); 5 gastrointestinal, 3 musculoskeletal, 3 cardiovascular, 2 urogenital, and 4 “other” malformations. Endorectal pull-through and Duhamel procedure were the most frequently performed procedures (32% and 23.1%, respectively). Thirty-three individuals had undergone other abdominal surgery than pull-through.

TABLE 1.

Demographic Data for Males With Hirschsprung Disease

Patient characteristics	n = 169
Age (yr); median (Q1–Q3)	32 (25–41)
Associated malformations; n (%)	13 (7.7)
Other abdominal surgery; n (%)	33 (19.5)
Extent of aganglionosis; n (%)
RS	101 (59.8)
LS	16 (9.5)
TCA	6 (3.6)
Other/unknown	46 (27.2)
Surgery; n (%)
Endorectal pull-through	54 (32)
Swenson	6 (3.6)
Duhamel	39 (23.1)
Rehbein	21 (12.4)
Ileoanal anastomosis with J-pouch	1 (0.6)
Posterior sagittal ano-recto-plasty	1 (0.6)
Other/unknown	47 (27.8)
Sexual orientation; n (%)
Heterosexual	157 (92.9)
Homosexual	3 (1.8)
Bisexual	6 (3.6)
Other/unknown	3 (1.8)
Marital status; n (%)
Married/living together	82 (48.5)
Divorced	2 (1.2)
In a relationship	32 (18.9)
Single	51 (30.2)
Unknown/other	2 (1.2)

LS indicates long segment; RS, rectosigmoid; TCA, total colonic aganglionosis.

Median BFS was 18 (16–19). Impaired bowel function was found in 44 individuals (27.7%). Urinary tract symptoms were scored as follows: mild (132, 80.5%), moderate (28, 17.1%), and severe (4, 2.4%). Thirty-nine complete and valid SF-36 scores were collected with a median score of 78.7 (69.7–88) in the study population. Individual domains scored lowest to highest were as follows; energy 65 (41.2–75), perception of general health 75 (51.2–88.8), emotional well-being 80 (69–88), social functioning 87.5 (75–100), pain 90 (71.9–100), difficulties emotional role 100 (54.2–100), physical functioning 100 (95–100), and difficulties physical role 100 (100–100).

Fertility, Sexual Function, and Sexual Quality of Life

In total, 152 males (89.9%) had had sexual intercourse with a median age at sexual debut of 16.5 years (15–18 years; Table 2). Of 63 individuals attempting to father a biological child, 8 (12.7%) reported failure to conceive after 1 year, and 5 (7.9%) reported failure to conceive after 2 years. Eleven of these males had undergone a fertility investigation (17.5%) and 6 individuals reported need of medical assistance to conceive (9.5%). Overall, 63 males (37.3%) in our cohort had at least one child. Out of males who were successful in conceiving, the most common number of biological children for each male was 2. A total of 124 children were conceived by the group leading the cohort's total fertility to be 0.743. Comparing individuals with impaired and normal bowel function showed no differences in sexual debut (81.8% vs 92.2%; P = 0.11), age at sexual debut (16 vs 17; P = 0.54), or relationship status (61.4% vs 68.7%; ongoing relationship; P = 0.49). Thirteen males had undergone surgery on reproductive organs. In free text, 2 vasectomies, 1 orchidopexy, 1 preputioplasty, 1 intervention for hydrocele, 1 scrotal hernia repair, 1 intervention for testicular torsion and suture of scrotal laceration were reported.

TABLE 2.

Fertility Status in Males With Hirschsprung Disease

	n = 169
Fertility status	n (%)
Sexually debuted	152 (89.9)
Attempt to conceive	63 (41.4)
Failure to conceive (>1 yr)*	8 (12.7)
Failure to conceive (>2 yr)*	5 (7.9)
Undergone fertility investigation*	11 (17.5)
Partner examined for fertility issues*	9 (14.3)
Need of medical assistance to conceive*	6 (9.5)

^*Out of individuals who have attempted to conceive.

Sexual function, as measured by IIEF-5, showed that the median IIEF-5 score in the whole group was 24 (21–25; Fig. 2). ED was reported by 40 (26.5%) individuals. Four individuals (2.7%) reported moderate to severe ED. The lowest median IIEF-5 score was found in the age group 15 to 19 years (19.5) and the highest IIEF-5 score was in the age group 30 to 39 years (25).

FIGURE 2.

Prevalence of ED by age group in men with HSCR. Prevalence of ED and severity of ED are divided into 10-year age intervals. Number below the bar indicating the total number of individuals within the age group that have responded to the IIEF-5 questionnaire. Normative values from published data are indicated by the dashed bar (the groups mild to moderate ED and moderate ED were combined into one moderate ED group).²⁴

The SQoL-M questionnaire was completed by 157 individuals. Median score for all age groups was 95 (69–100). Individuals aged 15 to 19 had the lowest median SQoL-M score (75.5) and individuals aged 50 to 59 years had the highest (100; Fig. 3). Eight individuals scored lower than 40 points. Out of these, 6 reported impaired bowel function, 3 reported major social/psychological problems related to bowel function, and 7 had moderate to severe ED.

FIGURE 3.

Sexual quality of life by age group in men with HSCR. SQoL-M scores by age group visualized by boxplots. Width of the box indicating the number of individuals within the group. Dots represent individual values recorded. Normative values from published data indicated by background color: white=mean±1 SD; light blue = 1– 2 SD; dark blue >2 SD.¹⁹

Factors associated with fertility status, erectile function, and SQoL are presented in Table 3. Poor bowel function was associated with impaired fertility and lower IIEF-5 scores (P = 0.0278 and P = 0.0026, respectively). Males with moderate to severe urinary tract symptoms reported lower IIEF-5 scores compared with males with mild symptoms (23 vs 24, P = 0.0089). Lower educational level was significantly associated with impaired fertility (P = 0.0407), but not SQoL-M or IIEF-5. Young age was associated with both lower IIEF-5 and SQoL-M scores (P = 0.0006 and P = 0.0295, respectively). Low SQoL-M and IIEF-5 scores did not correlate with SF-36 significantly (P = 0.0574 and P = 0.0534, respectively). The relationship between SF-36 and impaired fertility could not be determined due to missing data. HSCR type and type of surgery did not correlate with reported fertility, IIEF-5, or SQoL-M.

TABLE 3.

Factors Associated With SQoL, Sexual Function and Fertility

	Bowel function (BFS)			Urinary tract function (IPSS)			Extent of aganglionosis				Surgery				Educational level
	Normal (BFS ≥ 17)	Poor (BFS < 17)	P	Normal/mild (IPSS ≤ 7)	Moderate/Severe (IPSS > 7)	P	RS	LS	TCA	P	TERP	Duhamel	Rehbein	P	Primary	Secondary	Folk high school	Tertiary	P
SQoL-M; median (Q1–Q3)	96.4 (78.2–100)	90.9 (59.1–100)	0.1026*	96.4 (80–100)	82.7 (55–100)	0.0547*	92.7 (63.6–100)	94.5 (79.1–100)	100 (93.2–100)	0.1799†	93.6 (69.5–100)	82.7 (60–98.2)	98.2 (80–100)	0.1504†	96.4 (70.9–99.1)	98.2 (84.5–100)	92.7 (59.1–99.1)	94.5 (67.7–100)	0.3947†
IIEF-5; median (Q1–Q3)	24 (22–25)	23 (18–24)	0.0026 *	24 (22–25)	23 (20–24)	0.0089 *	24 (20–25)	23 (22–25)	25 (25–25)	0.0679†	24 (22–25)	24 (20–25)	24 (20–25)	0.5229†	23 (22–24.5)	24 (21–25)	24 (18.5–24.5)	24 (23–25)	0.1394†
Impaired fertility; n (%)	3 (7)	5 (31.2)	0.0278 ‡	6 (11.8)	2 (18.2)	0.6233‡	6 (17.1)	0	1 (33.3)	0.5101‡	5 (26.3)	1 (5.9)	0	0.1719‡	3 (50)	3 (15)	0	2 (5.7)	0.0407 ‡

Bold values indicate statistical significance P ≤ 0.05.

Statistical test indicated by:

^* Mann-Whitney U test.

^† Kruskal-Wallis H test.

^‡ Fischer exact test.

LS indicates long segment; RS, rectosigmoid; TCA, total colonic aganglionosis; TERP, transanal endorectal pull-through.

DISCUSSION

Key Findings

With the largest cohort to date, this cross-sectional multicenter study aimed to describe fertility, sexual function, and sexual quality of life in males who had undergone surgery for HSCR. The patients did not report impaired fertility, higher prevalence of ED, or lower SQoL-M scores compared with normative summary data.^{14,19,24–27} Poor bowel function was associated with impaired fertility and lower IIEF-5 scores, whereas the length of the aganglionic segment and the type of surgical method did not seem to impact fertility, sexual function, or SQoL.

Interpretation

Our study showed that 12.7% of males with HSCR who attempted to father a biological child were unsuccessful within the first year. This is lower than the 17% reported by Davidson et al, as well as global population estimates by the World Health Organization (16.5% lifetime prevalence of infertility in the European region and 17.8% in high-income countries).^11,14 Overall, 37.3% of males in our cohort had at least one child, with a cohort total fertility of 0.743. This can be compared with the estimated cohort total fertility between 1.59 and 1.84 in males aged 45 in the Nordic countries (born 1965–1969).²⁸ The considerably low median age in our cohort, 32 years, may provide a possible explanation for the lower prevalence of infertility and low cohort total fertility as the average age at birth of first child ranges from 30.9 to 32.3 for fathers in the Nordic countries.^28,29 Recent data from the study by Byström et al corroborates this, reporting 35.3% of Swedish males, with a median age of 29.8 years, to have at least one child within normative population data (n = 2255).¹²

Erectile functioning, measured by IIEF-5, indicated any form of ED in 26.5% of the population and moderate-severe ED in 2.7%. Prevalence rates of ED vary significantly in the literature, partially due to differences in methodological approach. Incoherent definitions of ED ranging from non-validated single questions to a plethora of questionnaires often hamper the direct comparison of prevalence rates.³⁰ In a systematic review by Prins et al, the prevalence of ED ranged from 2% to 9% in males <40 years; however, only 3 of the 23 included studies used a validated instrument for evaluating ED.³⁰ A large survey-based study by Mark et al in the United States reported an overall ED prevalence, defined by IIEF-5, of 24.2% (age ≥18, n = 1882).²⁷ Another study by Ponholzer et al reported IIEF-5 scores in 2869 men aged 20 to 80 years participating in a health screening project in Vienna. They found an overall ED prevalence of 32.2% with a stable prevalence of ED from 20 to 30 years until 41 to 50 years (25.5%–28.9%).²⁴ By comparison to the normative results of Mark and Ponholzer, our study does suggest a higher prevalence of ED within our cohort.^24,27

Males in our study reported a median SQoL-M score of 95, which is slightly higher than the mean score of 88.2 observed by Davidson et al.¹¹ In the validation study of the SQoL-M for premature ejaculation and ED, 101 controls had a mean score of 87.13, while reference data from Roserira and colleagues, involving 398 patients, reported a mean score of 83.83.^19,25 Although the SQoL-M questionnaire does not define a cutoff score for impaired sexual quality of life, our data does not imply a lower sexual quality of life​​​ compared with normative reference data.^19,25

Even though our results may not suggest impaired fertility, sexual function, or sexual quality of life in males with HSCR on a group level, it is important to note that individuals with impaired bowel function may be at risk. Males with poor bowel function reported failure to conceive more frequently than those with normal bowel function (31.2% vs 7%) as well as a lower grade of erectile functioning (24 vs 25). As hypothesized in inflammatory bowel disease patients, we considered psychogenic factors, disease perception, and structural damage after surgery as possible causes. We could not find any association between the type of surgical treatment or the length of the aganglionic segment. To explore psychosocial elements of sexual behavior and relationship formation in patients with impaired bowel function, we analyzed the proportion of sexually debuted individuals, age at sexual debut, and relationship status with no significant differences. Even though impaired bowel function does not seem to hinder relationship development and intimate relations, the concern that social and self-stigma may affect psychosexual well-being remains. Although not statistically significant, it is noteworthy that patients with poor bowel function reported a median SQoL-M score of 90.9 compared with 96.4 in those with normal bowel function.

Another interesting aspect is that the lowest IIEF-5 and SQoL-M scores were reported in the youngest age group (15–19 years), with an improving trend until 30 to 39 years. It is well established that bowel function after pull-through surgery improves with age.^31–36 Evidence also suggests that young adults with chronic diseases report lower life satisfaction, more mental health problems, and lower peer support.³⁷ Considering this, both higher disease burden and psychological vulnerability may put this cohort at specific risk of decreased psychosexual well-being.

Limitations

There are several limitations in this study that need to be addressed. Firstly, the median age in our cohort is young, causing data to be more representative of this age group. Consequently, a significant proportion of our cohort may not have attempted to conceive at the time of the study. Secondly, the motivation of patients to participate in the study was unknown. It could be argued that participants who do experience problems related to fertility or sexual function are more inclined to participate as it would benefit them further. It could also be argued that sexual dysfunction and reduced fertility are linked to certain stigmas, leading patients who experience such problems to be reluctant to participate. Thirdly, as medical records span before the digitalized era, many patients eligible for inclusion might have been lost to follow-up or have incomplete medical records affecting the quality of retrospectively collected variables. Lastly, this study does not have a control group making the nature of the study more descriptive.

Generalizability and Clinical Implications

This study is the largest of its kind addressing male fertility, sexual function, and sexual quality of life in individuals with HSCR who have undergone pull-through surgery. It provides the most reliable cohort to date and considers many potential risk stratifiers, paving the way for personalized treatment and follow-up. However, the setting is limited to the Nordic countries, colored by its unique prerequisites regarding high age at family formation and relatively low cohort total fertility. In addition, prevailing cultural beliefs and stigma may affect the psychological burden of disease differently between countries.

Contrary to current evidence regarding women with HSCR, the results of our study suggest that males with HSCR as a group do not seem to report reduced fertility, sexual function, or sexual quality of life​​​ compared with normative data. However, a subset of individuals with impaired bowel function and/or young age may be at risk. We believe this aspect is important to consider when developing transitional care from adolescence to adulthood. As fertility and intimacy are important aspects to many young adults, it is likely advantageous to address these subjects as part of the disease-related education. Not only to increase knowledge for affected individuals but as a screening measure to identify patients at risk.

CONCLUSIONS

Males with HSCR who have undergone pull-through surgery do not seem to report reduced fertility, sexual functioning, or reduced sexual quality of life compared with the general population. Impaired bowel function may correlate with erectile dysfunction and impaired fertility.