Michael T. Coughlin

Fertility after Bilateral Cryptorchidism

Purpose: Evaluation of the fertility of a cohort of formerly bilaterally cryptorchid men in comparison with a group of formerly unilaterally cryptorchid men, and a group of control men. Materials and Methods: Using a detailed questionnaire concerning paternity and factors related to paternity, a cohort of formerly bilateral cryptorchid men were studied and compared with men who had undergone orchiopexy for unilateral cryptorchidism, and a group of control men. All study subjects had had surgery at the Children’s Hospital of Pittsburgh, Pittsburgh, Pa., between 1955 and 1975. A subset of the full cohort underwent clinical evaluation that included a physical examination, serum hormonal determination and semen analyses. Results: Paternity rates are significantly lower among the formerly bilaterally cryptorchid men who have attempted to father a child (65.3%) as compared to the formerly unilaterally cryptorchid (89.7%; p < 0.001) and control men (93.2%; p < 0.001). Differences in the ability to father children are also apparent when semen and hormone levels are compared between the three groups. The bilateral group has significantly lower sperm density and inhibin B levels, and higher FSH and LH levels, than the unilateral and control groups. Conclusions: Men born with bilateral cryptorchidism have severely compromised fertility in adulthood. This reduction in fertility is clearly shown in comparisons of both paternity rates, and in semen and hormone analyses, between the formerly bilateral, formerly unilateral, and control groups.

Fertility after Unilateral Cryptorchidism

Objective: To further evaluate whether fertility is decreased among a cohort of men with previous unilateral cryptorchidism as compared with a control group of men. Subjects and Methods: Formerly unilateral cryptorchid men who had undergone orchiopexy between the years of 1955 and 1975 at the Children’s Hospital of Pittsburgh and a control group of men who were matched for age of an unrelated surgery at the same institution were evaluated by review of medical records and by completion of a questionnaire. 359 previously cryptorchid men were identified as having attempted paternity. Of these men, 320 had information concerning preoperative testicular location and 163 for preoperative testicular size. 106 of these men had levels of testosterone, inhibin B, FSH, and LH measured, while 95 of the men had semen analyses. Results: Among men who had attempted paternity, there was no statistical difference in success of paternity between the previously unilateral group (89.7%) and the control group (93.7%). There was no difference in the mean time to conception (7.1 ± 0.7 months for the unilateral group vs. 6.9 ± 2.3 for the control group). Within the unilateral group in regard to success at paternity, no difference was found compared with the age of orchiopexy, preoperative testicular location, or preoperative testicular size. Inhibin B levels were lower among the unilateral group. FSH, LH, testosterone, sperm density, motility and morphology were not different, but considerable variation was noted within the cryptorchid group. Conclusions: In this continued evaluation of a cohort of previously cryptorchid men who had undergone unilateral orchiopexy, paternity does not appear to be significantly compromised after unilateral cryptorchidism. Unilateral cryptorchidism appears to be one of several factors contributing to infertility, similar to those found in the general population. No correlation was found between success at paternity and the age of orchiopexy, preoperative testicular size or preoperative testicular location. Inhibin B levels were lower while FSH, LH, T and sperm parameters did not differ.

AGE AT UNILATERAL ORCHIOPEXY: EFFECT ON HORMONE LEVELS AND SPERM COUNT IN ADULTHOOD

PURPOSE We determined whether there are differences in hormone levels, such as inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone and testosterone, and sperm density in men with a history of unilateral cryptorchidism as stratified by age at orchiopexy. MATERIALS AND METHODS A total of 84 men with a history of unilateral cryptorchidism presented to our institution for serum hormone measurement and semen analysis. These parameters were compared using Pearsons correlations and analysis of variance among 4 groups stratified according to age at orchiopexy (range 1 month to 11 years). RESULTS Comparison by Pearsons correlation analysis showed that age at orchiopexy significantly correlated inversely with inhibin B (r = -0.274, p = 0.012) and positively correlated with FSH (r = 0.229, p = 0.036). Comparison of mean hormone levels and sperm density by analysis of variance for linear trend revealed a significant relationship between age at surgery with inhibin B (p = 0.032) and testosterone (p = 0.029), while sperm density, FSH and luteinizing hormone were not significantly related. Post hoc comparison of individual means at surgery and at the time of this study demonstrated a significantly higher inhibin B level in the youngest age group than in 2 of the 3 older groups. CONCLUSIONS Men who previously had unilateral cryptorchidism and who underwent orchiopexy by age 2 years have higher inhibin B and lower FSH profiles than those who underwent surgery later in life. This finding suggests an overall beneficial effect of early orchiopexy in boys born with unilateral cryptorchidism.

Do men become infertile after having sexually transmitted urethritis? An epidemiologic examination

OBJECTIVE To critically assess the possibility that gonorrhea or chlamydia causes male infertility. DESIGN Comprehensive literature review structured to evaluate the epidemiologic tenets for causality, including biologic plausibility, strength of association, dose response, consistency, temporality, and treatment effect. RESULT(S) It is biologically plausible that gonorrhea and/or chlamydia could cause male infertility. There is clinical and pathologic evidence linking these pathogens to urethritis, linking urethritis to epididymo-orchitis, and linking epididymo-orchitis to infertility. Retrospective epidemiologic results also support an association between chlamydia serologies and male infertility, which in most of these small studies does not reach the level of statistical significance. However, there is no consistent epidemiologic evidence that these pathogens alter sperm characteristics. We discuss the methodologic limitations of previous epidemiologic studies and suggest strategies for future research. CONCLUSION(S) Whether gonorrhea and/or chlamydia cause male infertility is currently unclear. Sound methodologic research strategies must be applied to future studies.

Leydig Cell Function After Cryptorchidism: Evidence Of The Beneficial Result Of Early Surgery

PURPOSE We determined whether there are differences indicative of the function of the Leydig cell-pituitary axis in formerly unilateral cryptorchid men. Parameters were compared with those in control men. MATERIALS AND METHODS We determined luteinizing hormone, testosterone, free testosterone, follicle-stimulating hormone, inhibin B, sperm density, motility and morphology, testicular volume, patient weight and age at orchiopexy or at other nonrelated childhood surgery in controls. RESULTS Significant correlations were noted between hormone levels and other parameters. An inverse correlation between age of surgery and testosterone suggested the detrimental effect of deferring orchiopexy during childhood. Correlations of testosterone with sperm density, motility and morphology suggested a direct relationship between spermatogenesis and testosterone in cryptorchid men. An inverse relationship between body weight and testosterone was observed in each group. There was considerable variation in the range of parameters, sometimes extending into the abnormal range. However, results indicated no differences in mean free testosterone, testosterone or luteinizing hormone in the formerly cryptorchid and control groups, and no difference in time to conception in fertile, formerly cryptorchid men and controls. Furthermore, there were no differences in hormone levels in fertile (as indicated by paternity) and infertile formerly cryptorchid men. CONCLUSIONS This study suggests that men who underwent orchiopexy in later childhood have subclinically decreased Leydig cell function. It may result in a less than optimal hormonal milieu for adult reproductive function. These data provide support for orchiopexy during infancy to preserve Leydig cell function and, thereby, potentially enhance fertility.

Paternity and hormone levels after unilateral cryptorchidism: association with pretreatment testicular location.

PURPOSE We determined differences in paternity and levels of the hormones inhibin B, follicle- stimulating hormone, luteinizing hormone, testosterone and free testosterone based on the preoperative location of the undescended testis in men with previous unilateral cryptorchidism. MATERIALS AND METHODS Testicular location was determined by a review of the medical records and paternity or attempted paternity using a detailed questionnaire administered to 320 men with previous unilateral cryptorchidism. In 103 cases we performed semen analysis and measured the levels of the hormones inhibin B, luteinizing hormone, follicle-stimulating hormone, testosterone and free testosterone. Paternity, sperm count and hormonal parameters were compared with cryptorchid testicular location using analysis of variance and chi-square analysis. Logistic regression was done to analyze pretreatment testicular location as a risk factor for infertility. RESULTS Paternity, duration of attempted conception in men who achieved paternity, sperm count and hormone levels did not differ based on pretreatment abdominal, internal ring, inguinal canal, external ring, upper scrotum or ectopic testicular location. The overall paternity rate was 90% with the lowest rate of 83.3% in the abdominal group. More than 12 months were required to achieve conception in 28.9% of the study group overall and in 39.4% of the abdominal group. Varicocele and a partner with fertility problems were risk factors for infertility, while abdominal testicular location caused borderline significant risk. CONCLUSIONS Preoperative testicular location in men with previous unilateral cryptorchidism is not a major determinant of fertility according to paternity, sperm count or hormone levels.

CORRELATIONS AMONG HORMONE LEVELS, SPERM PARAMETERS AND PATERNITY IN FORMERLY UNILATERALLY CRYPTORCHID MEN

PURPOSE We compared characteristics related to fertility between formerly unilaterally cryptorchid men. MATERIALS AND METHODS We compared sperm counts and gonadotropin levels before and after gonadotropin-releasing hormone stimulation between formerly unilaterally cryptorchid men and controls who had completed a detailed questionnaire on fertility and other pertinent paternity information. These parameters were also compared between the subsets of formerly cryptorchid men who reported paternity and unsuccessful attempts at paternity. RESULTS Sperm density and total count, and basal and gonadotropin-releasing hormone stimulated follicle-stimulating hormone (FSH) levels were different in the cryptorchidism and control groups. Higher FSH levels and lower sperm counts correlated inversely in the cryptorchidism group, while luteinizing hormone, testosterone and other results of semen analysis did not differ. Furthermore, FSH levels were higher and sperm counts were lower in the subset who reported unsuccessful attempts at paternity compared with those reporting paternity. Other measured parameters did not differ between these groups. CONCLUSIONS FSH levels are significantly higher and sperm counts are significantly lower in formerly cryptorchid men than in controls. In the cryptorchidism group the same differences are found in fertile and infertile men. Thus, elevated FSH and low sperm counts may be considered risks for infertility in formerly cryptorchid men.

THE SINGLE TESTIS: PATERNITY AFTER PRESENTATION AS UNILATERAL CRYPTORCHIDISM

PURPOSE We determine if paternity is reduced among men with monorchidism (absent or removed testis) compared to men with unilateral cryptorchidism corrected during childhood by orchiopexy and controls. The group of men with an absent testis was determined among males presenting during childhood with only 1 descended testis. MATERIALS AND METHODS Data were obtained by medical record review and a detailed questionnaire. Only men who had been successful at or attempted paternity for whom we had complete data were included in the study from the entire cohort of 584 men with former cryptorchidism, 23 with absent testis, 26 treated with orchiectomy and 706 controls. RESULTS Percentages of men reporting success after attempting paternity did not differ among men with an absent testis (15 of 15, 100%), treated with orchiectomy (17 of 20, 85.0%), with corrected unilateral cryptorchidism (313 of 349, 89.7%) and controls (412 of 442, 93.2%). There was no difference for a subgroup of men with cryptorchidism judged to have an atrophic testis at orchiopexy (17 of 20, 85%) or those who underwent orchiectomy at initial attempted orchiopexy (8 of 10, 80%) and men who had subsequently undergone orchiopexy (9 of 10, 90.0%). Paternity was also not reduced in the group of men with only 1 testis (32 of 35, 91.4%) (monorchism plus orchiectomy) compared to either the corrected unilateral cryptorchid group or the control group. Of 637 testes 183 were recorded as impalpable on examination before surgery and 23 testes were absent, including 7 recorded as palpable. In fact, 12.1% (23 of 190) of testes that should have been recorded as impalpable were absent. CONCLUSIONS This study failed to indicate that paternity is diminished among men with a single testis compared with the general population, regardless of the origin of the loss. About 12% of unilateral impalpable testes judged to be impalpable on examination before surgery were found to be absent after surgical exploration.

Testicular suture: A significant risk factor for intertility among formerly cryptorchid men

BACKGROUND/PURPOSE Although fertility is decreased after cryptorchidism, the importance of risk factors, including parenchymal testicular suture, is unknown. The aim of this study was to examine the relationship between parenchymal testicular suture and failure to conceive a child for 1 year or longer among formerly cryptorchid men. METHODS Men who underwent orchidopexy between 1955 and 1972 at the Childrens Hospital of Pittsburgh (n = 619) were surveyed by questionnaire and their medical records reviewed. Only the men who attempted to conceive a child (n = 387) are included. RESULTS Logistic regression analysis determined significant risk factors for infertility. Testicular suture was strongly related to infertility (RR, 7.56; 95% CI, 1.66, 34.39) as were bilateral cryptorchidism (RR, 5.51; 95% CI, 1.58, 19.24), varicocele (RR, 4.72; 95% CI, 1.42, 15.75), hormone treatment before surgery (RR, 3.69; 95% CI, 1.22, 11.11), and partner conception problem (RR, 3.32; 95% CI, 1.11, 9.90). CONCLUSIONS Testicular suture was a potent independent determinant of infertility among formerly cryptorchid men who have orchidopexy. Bilateral cryptorchidism, hormone treatment, varicocele, and partner conception problems also were associated with increased infertility.

Time to conception after orchidopexy : evidence for subfertility?

OBJECTIVE To determine whether time to conception is increased among men who were formerly bilaterally or unilaterally cryptorchid compared with a group of matched control men. DESIGN Retrospective cohort study. SETTING Human volunteers in an academic research environment. PATIENT(S) Men who underwent orchidopexy between 1955 and 1971 at the Childrens Hospital of Pittsburgh (n = 547) and a group of matched control men (n = 463) were surveyed by questionnaire. RESULT(S) Of the men who attempted paternity, the mean time to conception for the bilateral cases, unilateral cases, and control men was 33.90, 11.11, and 8.78 months, respectively. Kaplan-Meier survival analysis showed a significantly longer time to conception among bilateral cases compared with unilateral cases and controls, but not between unilateral cases and control men. Adjustment for confounders and covariates using a Cox Proportional Hazards model showed that former bilaterally cryptorchid men were 68% (95% CI = 55% to 81%) less likely than former unilaterally cryptorchid men or controls to conceive per month of unprotected intercourse. CONCLUSION(S) Time to conception was increased among former bilaterally cryptorchid men compared with both former unilaterally cryptorchid and control men. However, there were no significant differences in time to conception between the unilateral cryptorchid men and the control men.