Background
Hypospadias is a defect in penile development. The natural history of mild hypospadias is unclear but could have a mostly benign course without treatment [
1]. However, patients with more severe hypospadias undergo repair during infancy, in the hope that with corrected penis, the patient will subsequently have a normal reproductive function as a male. However, long-term consequences in patients with repaired hypospadias have been unclear.
Population based studies have reported decreased paternity in hypospadias patients, but precise disease and surgical background were not implicated in those studies [
2,
3]. Several groups have recently conducted long-term follow-up studies, [
4‐
9] and a Swedish group reported that sexual function and fertility of adult patients with hypospadias are equivalent to those of their age-matched controls but inferior in proximal type patients [
7]. In our previous report, we introduced a survival analysis method for analyzing the outcome of patients with hypospadias operated at our institute. We also reported that patients with hypospadias in general had equivalent intercourse and marriage rates compared with the general population [
10]. Our study also revealed that while sexual intercourse, marriage, and paternity occurred in serial order, overlap was scant in the factors associated with these three events. The intercourse rate was lower in patients with proximal hypospadias, and the marriage rate was lower in those without stable jobs. These were expected findings, but were statistically proven for the first time using multivariate survival analysis.
An unexpected finding in that study was the lower paternity rate in those who underwent reoperation after the initial repair. We did not analyze this finding further, because that study had included patients who had undergone diverse surgical procedures including two-stage repair, one-stage repair, and reoperative procedures after multiple repairs. Therefore, in this study, we analyzed the paternity data of our hypospadias patient cohort, exclusively limited to those who underwent the same initial two-stage repair operation in relation to surgical complications requiring reoperation. We hypothesized that reoperation for urethral obstruction after initial hypospadias repair could be related with decreased paternity, and aimed to clarify the association between them.
Discussion
This study reports that reoperation for obstructive complications after the initial pediatric urethroplasty was associated with a decreased paternity rate in adult hypospadias patients who had undergone a two-stage procedure at our institution. This type of study, linking a childhood surgical outcome with the adult potential for paternity, is scarce in literature.
This study was conducted as a sub-analysis of our previous report, which unexpectedly revealed that urethral reoperation was related to decreased paternity. Out of 108 patients in our earlier study, we selected out 90 patients who underwent a two-stage repair by a single surgeon from mild to severe type of hypospadias. Thus, we could analyze the surgical results without being confounded by differences in the surgical procedure. The two-stage repair was the mainstay for most of the hypospadias patients at the time. Among the 518 mailed patients with the exclusion of 80 cases in which operative procedure was not identified, 81.7% (358/438) underwent the same two-stage repair, which is equivalent to 83.3% (90/108) of the present and previous studies. This may indicate that our responders represent the total patient group treated during that period without significant selection bias with regard to the operation procedure.
We analyzed the type of reoperations the patients underwent and found that reoperations have been performed for more than 20 years after the initial repair. Such accumulation of reoperations in longer studies has also been reported by other authors [
17]. This finding could explain why the final reoperation rate was as high as 28.9% in the surgeon’s series who documented less than 10% reoperation rate in up to 5 years of follow-up [
16]. The timing of urethrocutaneous fistula repair after the initial repair was relatively shorter than that of the other types of reoperation. The total fistula rate, 7.8% (7/90), was similar to the short-term result of the same surgeon’s series, which reported a fistula rate of around 7.9–8.9% for all degrees of hypospadias [
16]. Reoperations for other two major complications, urethral obstruction and meatal regression, typically occurred after a longer interval. Interestingly, in our patients, the complication rates between the proximal cases and the non-proximal cases were similar, presumably due to the uniformity of the procedure.
The most important finding in this study was that in a sharp contrast to that in the Study controls, paternity was absent in the Study group patients who were reoperated for obstructive complications of the urethra, despite the longer follow-up period and the higher age of the participants at the time of study. This is a novel finding, as paternity data in hypospadias patients have not previously been associated with a surgical outcome during childhood in the existing literature. While one relevant article from Sweden reported lower paternity in patients with proximal hypospadias, the surgical complications were not implicated as a cause, and the patients in that study had undergone diverse surgical procedures by multiple surgeons [
7].
The cause of lower paternity in our Study group patients may be multifactorial. The z-test revealed that the marriage rate of the Study group at 32.5 years old was significantly lower than that of the General population, implying that these patients married later in life. We cannot infer whether reoperation for urethral obstruction delayed their marriage, either for psychological or physical reasons. Mureau et al. reported that, the later the patients underwent surgery, the greater were their inhibitions in seeking sexual contact and the later they made the first sexual contacts [
18]. However, between the patients reoperated for obstructive or non-obstructive cause, the timing of the first and last reoperation was not statistically significant, nor was the age of first intercourse.
As another point, a later marriage may have reduced the child-bearing period, with presumably more aged partner that those who married earlier. There were 5 married patients in the study group, all of whom did not achieve paternity. Since we did not ask them whether they had attempted to have children, we cannot conclude whether they were infertile or simply elected to remain childless. It is plausible that urethral obstruction had an adverse effect on sperm emission, since the Study group documented difficulties with ejaculation at a rate significantly higher than the Study controls. Since 4 out of the 5 married Study group patients underwent only palliative surgery such as 3 internal urethrotomy and 1 urethral dilatation, they might still have had urethral obstruction persisting into adulthood. However, we lack the seminalysis, uroflow, and concrete penile shape data, which is a major limitation of our study, as we relied mainly on questionnaires to collect data. One interesting point is that, after exclusion of the patients reoperated for obstructive causes, the final paternity rate of the married patients in the Study controls reached nearly 80% on the Kaplan–Meier curve (Fig.
4d), which is equivalent to that of the general population at 83.3% [
15]. We may thus infer that if there had been no obstructive pathology that required reoperation, the final paternity rate of hypospadias patients might have been closer to that of the general population.
Because this study is a sub-analysis of our previous study, it has the same kind of limitation as have been already documented in the earlier report. One drawback, inevitable in this type of study, was the limited response rate to the questionnaires, although our response rate at 28.4% was comparable to that in other similar studies [
6,
14]. Limited response can cause selection bias, but we would like to note that there was no significant difference in background between the responders and non-responders with respect to hypospadias severity as reported in the previous study [
15] and the type of initial repair procedure as described in this report. Another limitation is that the majority of the information regarding the present condition of the participants was obtained through a survey, and there is a lack of objective data, such as seminalysis or uroflowmetry. Since our data derive from limited number of patients, with 12 Study group patients without offsprings, of which only 5 were married, our findings should be further tested by future study by different groups and by ourselves. To overcome this drawback in such future studies, we may have to maintain a prospective follow-up protocol up to adulthood when we discharge our patients from outpatient visit today. Lastly, the data were obtained from patients who underwent a hypospadias repair surgery different from more recent procedures, and the patients were generally older at the time of initial repair than today. Over the last two decades, surgery for hypospadias correction has shifted to different types of one-stage repair, with the urethral plate as the preferred material compared to preputial skin used earlier [
19,
20] and patients tend to be treated at a younger age. Although current repair like tubularized incised plate method may have better results than the procedures performed in this article, twenty to thirty year follow up should be needed to obtain final outcome, as described in this report.
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