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International Urology and Nephrology

, Volume 44, Issue 6, pp 1617–1622 | Cite as

The impact of simple orchiectomy on semen quality and endocrine parameters in postpubertal cryptorchid men

  • Hasan Cem IrkilataEmail author
  • Yusuf Kibar
  • Seref Basal
  • Bulent Kurt
  • Armagan Gunal
  • Bilal Fırat Alp
  • Ender Oral
  • Ugur Musabak
  • Lutfu Tahmaz
  • Murat Dayanc
Urology - Original Paper

Abstract

Purpose

The main objectives of this retrospective cohort study were to evaluate reproductive endocrine and semen profiles before and after simple orchiectomy in patients with unilateral postpubertal cryptorchidism and to investigate the relationship between hormone levels and histopathology of the removed testis.

Methods

We evaluated 40 adult males who were admitted to our clinic, between 2001 and 2007, with unilateral undescended testis. Right orchiectomy was performed in 27 patients and left orchiectomy in 13. Semen analysis, serum inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were examined in before and 3 months after orchiectomy. Orchiectomy materials were evaluated histopathologically.

Results

Semen parameters, as well as testosterone and LH levels, did not change in any histopathological subgroups in the postoperative follow-up. In patients with maturation arrest, mean serum inhibin B level statistically significantly decreased from 160.9 to 83.5 pg/ml, and mean FSH level significantly increased from 4.8 to 7.6 mIU/ml after orchiectomy (p value, 0.008 and 0.008, respectively). Though, the levels were still within the normal range of the two hormones.

Conclusions

Simple orchiectomy does not have any effect on semen parameters and testosterone level in patients with postpubertal cryptorchidism. The change in inhibin B and FSH levels after orchiectomy in patients with maturation arrest is not clinically significant.

Keywords

Cryptorchidism Adult Fertility Hormone 

Introduction

Orchiectomy is routinely performed in the treatment for malignant and benign disorders of testis in the urology practice. The impact of removal of one testis on semen quality and reproductive hormones was determined clearly [1, 2, 3]. After radical and simple orchiectomy, sperm concentration and serum inhibin B level decrease, whereas serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels increase and testosterone level does not change [1, 2, 3].

Cryptorchidism is the most common genitourinary disorder in boys. Although timing and benefits of orchiopexy remain controversial, the optimal age at surgery is recommended to be between 6 and 18 months [4]. After puberty, there are three treatment options for the management of cryptorchid men: active surveillance, orchiopexy, and orchiectomy. Active surveillance has been recommended for patients older than 50, because the relative risk of death from perioperative anesthetic complications is higher than the relative risk of death from germ cell neoplasia [5]. Postpubertal orchiopexy has been preferred because of its potential hormonal, possible fertility benefit, as well as psychological factors, while orchiectomy is recommended since adult cryptorchid testes have an increased malignancy risk [5, 6, 7] and low sperm recovery chance [8]. Patient preference is the main determining factor for the decision of the treatment modality.

We have not encountered any information about the effect of simple orchiectomy on exocrine and endocrine testicular function in unilateral postpubertal cryptorchids in the literature. We aimed to evaluate fertility status of patients with unilateral postpubertal cryptorchidism after orchiectomy through sperm analysis and reproductive hormone levels, and to investigate the relationship between endocrine and histopathological findings.

Materials and methods

Ethical approval was taken from the local ethical committee of Gulhane Military Medical Academy. The charts were retrospectively reviewed to obtain demographic data on the patients with postpubertal cryptorchidism. Location and laterality of undescended testis, fertility status, and histopathology of removed testis were determined. Semen analysis and hormonal profiles were obtained before and after surgery.

Participants

Forty adult males were referred to our clinic with unilateral undescended testis between January 2001 and July 2007. Testicular location and laterality of undescended testis were determined by physical examination. Scrotal ultrasonography was performed to measure undescended and contralateral descended testes volume, by using the formula for an ellipsoid: length × width × height × 0.52, before and 3 months after (for contralateral testis) orchiectomy. We excluded patients with bilateral postpubertal cryptorchidism and those who had a history of previous orchiopexy and unilateral testicular absence (monorchy). Orchiectomy was performed for 27 right and 13 left unilateral cryptorchid testes, 3 of which were removed laparoscopically.

Semen analyses

Semen analyses were performed two times with 3-day interval between the visits, before and 3 months after orchiectomy, by microscopic examinations at our academy laboratories, certified for having systemic quality controls for semen analyses. Sperm concentration and motility were defined in accordance with world health organization standards 2010 [9]. Sperm morphology was determined according to Kruger’s strict criteria [10].

Histopathologic examinations

Orchiectomy specimens were sampled and fixed in the Bouin’s solution. Slides of random sections taken from testicles were evaluated by two pathologists (B. K. and A. G.). Based on the morphological view, a basic histological classification was assigned for the cases. The three subgroups of the classification were maturation arrest (some germ cells in the tubules, but not completed spermatogenesis), sertoli cell only (SCO) with germ cell aplasia (no germ cells in the tubules, but Sertoli cells detected), and end-stage testis (sclerotic tubules caused by fibrosis).

Hormonal assays

Serum inhibin B, FSH, LH, testosterone levels, and sperm analysis were examined before and 3 months after orchiectomy. Serum FSH, LH, and total testosterone levels were measured with radioimmunoassay (RIA), and inhibin B levels were measured with enzyme-linked immunosorbent assay (ELISA) [11].

Statistical analysis

The results were analyzed statistically via Wilcoxon signed ranks test by using SPSS® for Windows® 10.0 (SPSS, Inc., Chicago, IL).

Results

General characteristics of the study cohort are seen in Table 1. Physical examination revealed that 37 of 40 testes were palpable in the inguinal region and 3 were nonpalpable, which were found in the intra-abdominal region by diagnostic laparoscopy. The semen analyses in preoperative period revealed that 16 had oligozoospermia and 9 had azoospermia. Microscopic evaluation of the removed testes revealed 3 histopathologic subgroups, maturation arrest in 9 patients, SCO with germ cell aplasia in 28, and end-stage tubular atrophy in 3. None of them had normal or hypospermatogenesis. None of the removed testis showed signs of malignancy, but one of the specimens revealed severe atypia.
Table 1

General characteristics of study cohort

Number patients, n

40

Mean age (range), years

22.5 (20.2–30.1)

Location of testis, n

 Inguinal canal

25

 Superficial inguinal pouch

12

 Intra-abdominal

3

Laterality, n

 Right

27

 Left

13

Fertility status, n

 Normozoospermia

15

 Oligozoospermia

16

 Azoospermia

9

Histopathology, n

 Normal spermatogenesis

0

 Hypospermatogenesis

0

 Maturation arrest

9

 SCO with germ cell aplasia

28

 End-stage tubular atrophy

3

Exocrine functions of testis (sperm concentration, motility, and Kruger morphology) did not change in any histopathologic subgroup in the postoperative follow-up (Table 2). Endocrine functions of testis were significantly affected by orchiectomy in only patients with maturation arrest. In the maturation arrest subgroup, mean serum inhibin B level statistically significantly decreased from 160.9 to 83.5 pg/ml after orchiectomy (Table 2; p value, 0.008), remaining in the normal range. However, there were no changes in total testosterone levels. Gonadotropins were also affected in postorchiectomy period in the maturation arrest subgroup; mean FSH level significantly increased from 4.84 to 7.59 mIU/ml, and mean LH level insignificantly increased from 6.12 to 7.18 mIU/ml (Table 2; p value, 0.008 and 0.138, respectively). A decrease in inhibin B level and an increase in FSH level were observed in seven of nine patients with maturation arrest. Reproductive hormone levels did not change statistically significantly after orchiectomy in patients with SCO with germ cell aplasia. Patients with end-stage tubular atrophy were excluded in statistical comparisons.
Table 2

Mean ± SD levels of semen parameters and reproductive hormones before and after orchiectomy in patients with different histopathologic subgroups

Parameters (mean ± SD)

Reference ranges

Maturation arrest (n = 9)

SCO with germ cell aplasia (n = 28)

End-stage testis (n = 3)

Before

After

p value

Before

After

p value

Before

After

Sperm concentration, ×106/ml

15

50 ± 47

51 ± 45

0.722

37 ± 44

35 ± 50

0.185

0

0

Sperm motility,  % motile sperm

>50

46 ± 16

45 ± 16

0.634

35 ± 27

33 ± 26

0.255

0

0

Sperm morphology,  % normal

>14

6.9 ± 5

6.1 ± 5

0.068

5.7 ± 6

6.0 ± 6

0.245

0

0

Testicular volume cryptorchid testis, ml

>10

13.9 ± 3.9

9.5 ± 2.7

7.1 ± 3.3

7.1 ± 3.3

Testicular volume contralateral testis, ml

>10

19.5 ± 3.4

19.5 ± 3.5

0.931

16.6 ± 5.9

16.7 ± 6.0

0.527

14.5 ± 4.5

14.6 ± 4.6

Inhibin B, pg/ml

31-443

160.9 ± 92.3

83.5 ± 52.5

0.008

55.0 ± 34.0

48.9 ± 33.4

0.712

4.3 ± 4.0

3.2 ± 3.7

FSH, IU/l

1.4–12.1

4.8 ± 2.8

7.6 ± 5.3

0.008

8.9 ± 7.6

9.5 ± 7.8

0.062

26.3 ± 12.9

28.5 ± 14.2

LH, IU/l

1.5–9.3

6.1 ± 2.0

7.2 ± 3.1

0.138

6.4 ± 4.5

7.1 ± 5.0

0.245

17.4 ± 17.4

19.8 ± 17.1

Total testosterone, nmol/l

7.7–27.8

17.6 ± 6.7

17.7 ± 7.1

0.515

19.6 ± 7.0

18.2 ± 5.8

0.148

17.9 ± 2.1

18.0 ± 0.5

Contralateral testicular volume did not change in any histological subgroups in the postoperative period (Table 2).

Discussion

Preservation of fertility potential and androgen production are two important issues for candidates of orchiectomy. According to the reason of orchiectomy, patient might need semen preservation before and androgen replacement therapy after orchiectomy. Both spermatogenetic and hormonal functions are affected by orchiectomy according to clinical trials [1, 2, 3]. In patients with testicular cancer, radical orchiectomy causes decrease in median sperm concentration, total sperm count, and serum inhibin B level, and increase in median serum FSH and LH levels, but it does not change testosterone level [1]. Orchiectomy due to benign testicular diseases leads to a similar decrease in sperm concentration, increase in gonadotropins, and no change in testosterone level [2, 3]. Orchiectomy is one of the treatment options for adult patients with cryptorchidism. To our knowledge, information about the effects of orchiectomy on gonadal function in patients with adult cryptorchidism is lacking. In the present study unlike the previous studies, simple orchiectomy did not adversely affect the semen quality, but testosterone level was similarly not affected.

Fertility potential of patients with cryptorchidism is evaluated with different methods, such as testicular volume, testicular histology, semen analysis, time to conception, paternity rate, hormonal evaluation, and the probability to find sperm by testicular sperm extraction (TESE). Testicular volume of patients with cryptorchidism is smaller both under and over 2 years [12]. Histologic studies have shown that progressive deterioration of germ cells (adult dark spermatogonia) starts during the first year of life in both unilateral and bilateral cryptorchidism. The lack of germ cells is associated with subsequent risk of infertility, and frequency increases with age [13, 14]. In patients with unilateral cryptorchidism, the lack of germ cells in the cryptorchid testis was found in 18 % [14] and semen quality was reported as abnormal in a wide range (abnormal in 24–75 %) [15, 16, 17]. However, paternity rate was reported as 89.7 % in the patients with unilateral cryptorchidism and 93.7 % in the control group [18].

Untreated patients with cryptorchidism are a special group, and this patient group reveals the consequence of cryptorchidism. Rogers et al. [6] reported histological studies on postpubertal cryptorchidism, and they found Sertoli cell only and/or atrophy in 30 patients (65 %), maturation arrest in 15 (33 %), and hypospermatogenesis in only 1 (2 %) by analyzing whole testicular specimen. Our results are similar to their histological results, 77, 23, and 0 %, respectively. In most of the boys after puberty, semen quality is abnormal (abnormal in 70–83.5 %) [19, 20], but paternity rate is unknown. Another way to assess the fertility potential of cryptorchid testis is the examination held by embryologist to find spermatozoa. Spermatozoa were successfully retrieved in azoospermic patients with a history of orchiopexy in 52–74 % of patients [21, 22]. Success rate for sperm retrieval was higher in the patient whose age at orchiopexy was lower than 10 years [21, 22]. However, the probability to find spermatozoa from adult cryptorchid testis is very low, 0–4 % [8, 23]. In this study, we demonstrated that the removal of cryptorchid testicles in adulthood did not affect the contralateral testicular functions. This is a new evidence on fertility potential of untreated cryptorchid testicle.

Younger adults with cryptorchid testis have been surgically treated with orchiopexy or orchiectomy. However, there is no consensus on which treatment option is essential for a patient. Postpubertal orchiopexy may contribute to fertility and androgen production, and testis can easily be monitored. Orchiopexy is mandatory for patients with bilateral cryptorchidism, atrophic contralateral testis, or infertility. After successful adult orchiopexy, spermatozoa can be retrieved by TESE according to some case reports [24, 25, 26, 27]. However, clinical studies on postpubertal orchiopexy revealed that probability of retaining fertility is low [20] and spermatozoa could be retrieved from the contralateral scrotal testis, not from the cryptorchid testis by TESE [23]. Spermatozoa were found in only one patient whose cryptorchid testis was in superficial inguinal pouch in our previous report [8]. Rogers et al. histologically showed that the presence of germ cells occurred more frequently in cryptorchid testis in the superficial inguinal pouch or distal inguinal canal compared to those in the proximal inguinal canal or inside the deep ring [6]. Consequently, preserving fertility after postpubertal orchiopexy is possible in cryptorchid testis, which is in inguinal pouch or distal inguinal canal.

On the other hand, because of increased malignancy risk of cryptorchid testes, some patients prefer orchiectomy [7]. Testicular cancer risk is 2–6 times higher in patients who undergo orchiopexy after 12 years or no orchiopexy than those who undergo prepubertal orchiopexy [7]. Moreover, intra-abdominal testis has fourfold greater incidence of testicular cancer than the inguinal cryptorchid testis [28]. According to our present study, orchiectomy does not affect their spermatogenetic and androgenic production. Although adult cryptorchid testes have low fertility potential, patients should be informed that histologically maturation arrest or even spermatogenesis may exist in these testis. Therefore, all of these findings suggest that orchiectomy could be recommended in unilateral postpubertal cryptorchid patients with intra-abdominal or proximal inguinal testis (generally having short spermatic cord). More importantly, patient preference is a crucial issue to decide on the treatment modality. Some patients with unilateral cryptorchidism may prefer to get rid of the malignancy risk or inguinal pain in spite of the location of the cryptorchid testis, no matter whether it is in distal inguinal canal or in superficial inguinal pouch. To sum up, the management of postpubertal cryptorchidism must be held on individual basis. Location and size of testis, laterality of cryptorchidism, fertility status of patient, condition of contralateral testis, and patient preference are important factors for decision making.

Changes in other reproductive hormones (inhibin B, FSH, and LH) are revealed in our study, but these changes are clinically insignificant. In maturation arrest subgroup, inhibin B levels decreased and FSH levels increased as in the previous studies on orchiectomy [1, 2, 3]. In patients with SCO with germ cell aplasia, inhibin B levels decreased slightly, but the decrease was not statistically significant. It is well known that inhibin B is a joint product with Sertoli cells providing the α-subunit and certain stages of germ cells providing the βB-subunit in adult men, but immunostaining for βB-subunit was observed in a few Leydig cells [29]. In our study, serum inhibin B levels significantly decreased in patients with maturation arrest. Thus, we thought that this decrease might be mainly due to the lost premature spermatogenetic cells (pachytene spermatocytes to round spermatids) producing inhibin B βB-subunit. By the way, inhibin B levels decreased slightly (statistically insignificantly) in patients with SCO. Thus, this slight decrease may be attributed to the production of inhibin B βB-subunit by Leydig cells.

The functional relationship between spermatogenesis and serum inhibin B concentrations is clearly demonstrated [30, 31]. However, inhibin B with or without FSH is inadequate to predict the presence of spermatozoa and to envisage the type of spermatogenetic damage in patients with nonobstructive azoospermia, in clinical practice [32, 33]. In other words, inhibin B is a marker of a certain stage of spermatogenesis, but not a marker of spermatozoa. Our study provided another evidence for this relationship by showing no change in sperm concentration alongside a significant decrease in inhibin B levels.

There are some limitations of this study. Since all patients were single and testicular biopsy might have reduced their fertility potential, we could not perform a biopsy on the contralateral testis for ethical causes. Another limitation is short follow-up period for semen parameters. However, semen parameters did not decrease at the end of the third month after orchiectomy.

The main conclusion of our study is that removal of a cryptorchid testicle in a young adult with a normal contralateral testicle does not adversely affect the semen quality and testosterone level. Although other reproductive hormone (inhibin B and FSH) levels are affected by orchiectomy in patients with maturation arrest, the change is not clinically significant. Further large studies with long follow-up period are needed to validate these findings.

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Copyright information

© Springer Science+Business Media, B.V. 2012

Authors and Affiliations

  • Hasan Cem Irkilata
    • 1
    • 4
    Email author
  • Yusuf Kibar
    • 1
  • Seref Basal
    • 1
  • Bulent Kurt
    • 2
  • Armagan Gunal
    • 2
  • Bilal Fırat Alp
    • 1
  • Ender Oral
    • 1
  • Ugur Musabak
    • 3
  • Lutfu Tahmaz
    • 1
  • Murat Dayanc
    • 1
  1. 1.Department of UrologyGulhane Military Medical AcademyAnkaraTurkey
  2. 2.Department of PathologyGulhane Military Medical AcademyAnkaraTurkey
  3. 3.Department of Immunology and AllergyGulhane Military Medical AcademyAnkaraTurkey
  4. 4.Department of UrologyGulhane School of MedicineAnkaraTurkey

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