| |

Received: 25 July 2020    Revised: 5 December 2020    Accepted: 16 December 2020

DOI: 10.1111/andr.12964

ORIGINAL ARTICLE

Fertility potential in adult men treated for uncorrected bilateral

cryptorchidism: A systematic literature review and analysis of
case reports

Wade Muncey1,2  | Rahul Dutta3 | Ryan P. Terlecki3 | Lynn L. Woo1,2,4 |

Kyle Scarberry1,2,4

1
Case Western Reserve University School
of Medicine, Cleveland, OH, USA
2
University Hospitals Cleveland Medical
Center, Cleveland, OH, USA
3
Wake Forest Baptist Health, Winston-
Salem, NC, USA
4
Rainbow Babies and Children's Hospital,
Cleveland, OH, USA
Correspondence
Wade Muncey, Urology Institute,
University Hospitals – Cleveland Medical
Center, Mailstop LKS 5046, 11100 Euclid
Ave, Cleveland, OH 44106, USA.
Email: wade.muncey@UHhospitals.org
Abstract
Objective: Reports of adult orchidopexy for bilateral undescended testicles (bUDT)
are sparse, and fertility outcomes are not well established. Our aim was to determine
prognosis for restoration of spermatogenesis among adult men (≥18 years) undergo-
ing orchidopexy for bUDT.
Methods: A systematic literature review, conforming to the PRISMA statement, was
conducted using the PubMed/MEDLINE and EMBASE databases through March
2020 using search terms "adult” AND “bilateral orchidopexy" OR "bilateral cryptor-
chidism.” Relevant referenced articles from non-indexed journal were identified by
Google Scholar search and additionally included.
Results: Fifty-seven publications including adult men with uncorrected bilateral UDTs
were identified. Baseline semen analysis was reported in 157 men, all of whom dem-
onstrated azoospermia. Testosterone values were reported in 82 cases and were nor-
mal in 89%. Germ cells could not be identified in 72.6% of histologic specimens from
62 testicles. Abdominal testicles more frequently lacked germ cells (90%, p = 0.038)
on univariate analysis.
Eleven cases identified ejaculated spermatozoa following adult bilateral orchidopexy
(8 publications). Sperm extraction (TESE) during orchidopexy or orchiectomy was re-
ported in 13 men without success. Delayed TESE (median 10 months) was performed
in 22 persistently azoospermic men with success in 10 (45.5%), none of whom had
abdominal testicles prior to orchidopexy. Six men experienced successful paternity
via natural conception (3) or assisted reproduction (3).
Conclusion: Fertility is possible in adult men with inguinal bUDT following orchi-
dopexy. Subsequent sperm retrieval may involve ejaculated specimens or delayed
TESE. TESE performed prior to or at time of orchidopexy is unlikely to be of benefit.

KEYWORDS
infertility, bilateral cryptorchidism, spermatogenesis, orchidopexy

© 2020 American Society of Andrology and European Academy of Andrology

Andrology. 2021;00:1–11.  |
wileyonlinelibrary.com/journal/andr     1
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2      MUNCEY et al.
1  |  I NTRO D U C TI O N
Cryptorchidism is the most common male sexual development
anomaly, affecting up to 4% of full-term infants.1 Failure of testicu-
lar descent is associated with impaired spermatogenesis, hormonal
abnormalities, and increased risk of testicular neoplasm.1 In order
to preserve future fertility and decrease risk of malignancy, orchi-
dopexy for recognized cases is typically performed at 6–12 months
of age. 2 Only 1% of infants with cryptorchidism reach adulthood
without surgical intervention. 3 Given the rarity of delayed recogni-
tion and the potential for differences in management, the benefits
of surgery for cryptorchidism in adults are not well established.4
Unlike children, adults with unilateral cryptorchidism are usually
advised to undergo orchiectomy because of increased risk of malig-
nancy and low perceived spermatogenic potential. 5 Compromised
fertility has been identified in nearly 50% of men with a history of
childhood orchidopexy for bilateral undescended testicles (bUDT),6
but very little is known regarding fertility potential and hormonal
function in adults who have not undergone orchidopexy. The liter-
ature is limited to case reports or small series, with many published
before the advent of testicular sperm extraction (TESE) techniques
and other advances in assisted reproductive technologies. The pur-
pose of this systematic review is to examine the available research
to characterize fertility potential following adult orchidopexy for
bUDT.
2  |  M E TH O D S
A comprehensive literature search was conducted using the
electronic databases PubMed/MEDLINE and EMBASE through
October 2019. The search was restricted to articles written in
English. The following search terms were utilized: “Adult” AND “bi-
lateral orchidopexy” OR “bilateral cryptorchidism”. Following this
screening process, eligible articles underwent a full-text review
with inclusion of all studies involving any adult men presenting
with bUDT. Publications were excluded if they were not available
online or in English, if orchidopexy was performed as a child (age
<18), or reports were limited to adults with a unilateral unde-
scended testicle only. Studies included case reports, case series,
case-control, and cohort designs. References within identified ar-
ticles were screened for additional studies. References that ap-
peared relevant, but were absent within indexed databases, were
located by free-text searching within Google Scholar to identify
the full text. Two individual authors (KS and WM) independently
performed the initial review, extraction, and data screening, with
relevant titles and abstracts identified We applied the Preferred
Reporting Items for Systematic Reviews and Meta-Analysis
(PRISMA) statement to report results.7 Figure 1 depicts the results
of the systematic search.
Patient data relevant to fertility and outcomes following orchi-
dopexy were extracted and included for analysis. This included de-
mographic data such as age and comorbidities, laboratory values
including semen analysis and hormone values, histology and sperm
retrieval from testis tissue, and paternity. Hypogonadism was defined
as a testosterone value <300 ng/dl. Four histopathologic patterns
were assigned to biopsy or orchiectomy specimens: reduced sper-
matogenesis with all germ cell types present (hypospermatogenesis);
arrest of spermatogenesis with any area demonstrating germ cells
without mature spermatozoa (maturation arrest [MA]); complete ab-
sence of germ cells (Sertoli cell only; SCO); or neither germ cells nor
Sertoli cells present (tubular atrophy).8 TESE success was defined by
the publication authors, but in general was characterized by retrieval
of one or more spermatozoa. TESE performed with microdissection
was not analyzed separately, but is represented as “mTESE” when
possible in our results.
Statistical associations were assessed with Stata SE, version 13.0
(StataCorp, College Station, TX). Mean variable values are reported
with standard deviation (±), and median values are presented with
range or interquartile range (IQR) as a measure of variability. Two-sided
Student’s t test was used to compare continuous variables. Fisher’s
exact and Pearson’s chi-square tests were used to compare categorical
variables. A p value <0.05 was considered to be statistically significant.
3  |  R E S U LT S
Using the aforementioned criteria, 57 publications were included for
analysis, yielding 231 cases of uncorrected bUDT (Figure 1). Included
publications were from twenty-eight countries, with most patients
from reports from Turkey (7 reports, n = 50), India (9 reports, n = 42),
China (3 reports, n = 32), the United States (8 reports, n = 21), Japan
(3 reports, n = 13), the United Kingdom (3 reports, n = 13), Nigeria
(1 report, n = 10), and Sudan (1 report, n = 8) (Table S1). The reason
for men presenting to a healthcare provider was not frequently de-
scribed: 62 (26.8%) presented for infertility and 34 (14.7%) for tes-
ticular cancer. Associated developmental abnormalities were rarely
reported, consisting of nine cases of persistent Müllerian duct syn-
drome (8 of which had associated germ cell malignancy), one case of
unspecified ambiguous genitalia, one case of androgen insensitivity
syndrome, and one case of Klinefelter syndrome.
At least one semen analysis was obtained in 157 men at initial
presentation, all of which demonstrated azoospermia. Testosterone
levels were reported in 82 cases, with hypogonadism identified in 9
(11%) after excluding men with cancer or associated developmental
conditions. Exact laboratory values were reported in 35 men, with
a median testosterone of 383 ng/dl (range 90–780), and a median
FSH of 23.5 mIU/ml (range 5.6–65). Age was not associated with
laboratory diagnosis of hypogonadism (mean 36 ± 10.8 vs. 29 ± 7.7
years, p = 0.078), nor was testis location as patients with abdominal
testicles experienced low testosterone at similar rates as those with
non-abdominally located testes (9.1% vs. 12.2%, p = 0.734)
Men with hypogonadism were not associated with age (mean 36
± 10.8 vs. 29 ± 7.7 years, p = 0.078), nor was it more common in men
with abdominal cryptorchidism compared with inguinal/unidentified
locations (9.1% vs. 12.2%, p = 0.734) on univariate analysis.
MUNCEY et al. |
      3

Idenficaon
Records idenfied through Addional records idenfied
database searching through other sources
(n = 1,233) (n = 27)

Records aer duplicates removed

(n = 1,239)
Screening

Records screened Records excluded

(n = 1,239) (n = 1,128)

Full-text arcles assessed Full-text arcles excluded

for eligibility (n = 54)
Eligibility

(n = 111)

Studies included in
Included

qualitave synthesis
(n = 57)

F I G U R E 1  Literature search results

Histologic assessment of cryptorchid testis biopsy or orchi-
ectomy specimens was reported for 41 men (62 testicles) across
18 studies, with no samples exhibiting normal histology or hy-
pospermatogenesis. Germ cells with MA were identified in 17
testicles (27.4%), with the remainder exhibiting SCO (56.5%) or
tubular atrophy (16.1%). Associations between specimens with or
without germ cells identified are described in Table 1, with germ
cells less likely to be identified in abdominally located testicles
(10.0% vs. 35.7%, p = 0.038) on univariate analysis. Five stud-
ies involving a total of 13 men reported results from concomi-
tant TESE at time of orchidopexy or orchiectomy. None of these
procedures (19 testicles—6 abdominal and 13 inguinal) identified
spermatozoa.
Orchidopexy was performed by varied methods for 165 men
across 37 reports with a median age at orchidopexy of 28 years
(range 18–56, IQR 23–34). In total, 34 underwent unilateral (24.3%)
and 106 underwent bilateral orchidopexy (75.7%), despite all men
having bUDT. At presentation, both testicles were located intra-ab-
dominally in 66 (40.0%), one inguinal and one abdominal in 8 (4.9%),
inguinal bilaterally in 33 (20.0%), and an unspecified location in the
remainder (n = 58, 35.1%). Reported testosterone values following
orchidopexy were normal in 24 of 29 men (82.8%) in five publica-
tions, with no statistically significant associations observed with tes-
tis location or bilateral procedure (p > 0.05).
Postoperative semen analyses were reported in 51 men across
17 reports. At a median follow-up of 12 months (range 2–168),
 |
4      MUNCEY et al.

TA B L E 1  Patient characteristics by
Germ cells identified No germ cells All results
histology result
(n = 17 testes) (n = 45 testes) (n = 62 testes) p

Age, median 27 (18–38) 31 (20–56) 31 (18–56) 0.070

(range)
Location, n (%)
Abdominal 2 (10) 18 (90) 20 (32.3) 0.038
Inguinal 13 (32.5) 27 (67.5) 40 (65.5)
Unknown 2 (100) 0 (0.0) 2 (3.2)
Median FSH, 19.1 (5.6–43) 23.5 (9.1–67.1) 23.4 (5.6–67.1) 0.082
IU/ml
(range)
Median testis 5.9 (1–13) 6.8 (2–18.1) 6.4 (1–18.1) 0.207
size, ml
(range)
Specimen, n (%)
Biopsy 15 (88.2) 35 (77.8) 50 (80.7) 0.352
Orchiectomy 2 (11.8) 10 (22.2) 12 (19.4)

persistent azoospermia was reported in 78.4%. Eleven cases iden-
tifying ejaculated spermatozoa following adult bilateral orchidopexy
have been described in the literature (8 publications), with patient
characteristics listed in Table 2. A younger mean orchidopexy age
was observed in men who developed spermatozoa in their ejaculate
(24 ± 3.9 vs. 29 ± 5.9, p = 0.026) but preoperative testosterone (518
± 132.0 vs. 372 ± 164.6, p = 0.061) and FSH levels (26.1 ± 18.3 vs.
28.8 ± 11.2, p = 0.680) were similar.
TESE performed in a delayed fashion (median 10 months post-orchi-
dopexy) has been reported in 22 persistently azoospermic men across
seven publications (Tables 3a and 3b). Successful retrieval was noted in 10
men, none of whom had intra-abdominal testicles prior to orchidopexy.
No variables were significant associated with TESE success (p > 0.05).
Successful paternity was reported in six men: via natural conception (3),
intracytoplasmic sperm injection (ICSI) with ejaculated spermatozoa (1),
or ICSI with spermatozoa obtained by TESE (2). One patient had success-
ful TESE 7 years after orchidopexy even though TESE at time of surgery
and mTESE 10 months postoperatively were both unsuccessful.
4  |  D I S C U S S I O N
In his 1911 report of one of the earliest large orchidopexy series,
Dr. William Coley (the “Father of Cancer Immunotherapy”) noted

TA B L E 2  Studies with ejaculated sperm obtained (N = 11)

Age at
Author/Year Study orchidopexy Location Right/Left Operation

Hand et al. 1956 Case Series 25 Bilateral orchidopexy

Comhaire et al. 1978 Case Report 25 Inguinal/Inguinal Bilateral orchidopexy

20
Silber Case Report 18 Abdominal Bilateral autotransplantation

Heaton et al. 1993 Case Report 23 Inguinal/Inguinala  Bilateral orchidopexy

Shin et al. 28 Case Report 23 Inguinal/Inguinal Bilateral orchidopexy and varicocelectomy

Giwercman et al. 29 Case Report 27 Inguinal/Inguinal Bilateral orchidopexy

Giwercman et al. 29 Case Report 27 Inguinal/Inguinal Bilateral orchidopexy

Zhang et al.19 Cohort Study 18 Inguinal/Inguinal Bilateral orchidopexy

19
Zhang et al. Cohort Study 31 Inguinal/Inguinal Bilateral orchidopexy
Zhang et al.19 Cohort Study 27 Abdominal/Inguinal Orchiectomy/Orchidopexy
18
Duong et al. Case Report 26 Abdominal/Inguinal Bilateral orchidopexy

SA, Semen analysis; blank cell, not reported.

a
Testicles described to be at the external ring or “suprascrotal” position.
MUNCEY et al.       5 |

something of particular interest to him: a “patient suffering from
double undescended testes” had become a father. He described a
thirty-year-old man who underwent orchidopexy in 1885 and sub-
sequently fathered a child in 1903 after a year of marriage.9 At the
time, Dr. Coley described this as only the second reported case
of paternity by a man with bUDT. More than a century later, only
six additional reports have been identified. Given the rarity of this
presentation, providers are limited in guidance for counseling of
affected patients. The literature consists largely of case reports or
small series, often in non-indexed journals and with pertinent details
frequently buried within the discussion. As such, we sought to ag-
gregate available data, such that an analysis may offer some useful
input for clinical efforts. Our study supports what was well under-
stood before recognition and treatment of cryptorchidism in child-
hood became common: uncorrected bilateral cryptorchidism results
in universal fertility impairment.
Although baseline azoospermia was seen in all men undergoing
semen analysis in the reports identified by our literature search, there
were three reports describing men with uncorrected bUDT who were
fathers.10–12 Interestingly, all three had intra-abdominal testicles found
at the time of surgery for removal of large (≥15 cm) pelvic masses, sub-
sequently identified to be metastatic germ cell tumors. Two of the men
had persistent Müllerian duct syndrome, and semen analysis revealed
azoospermia in one. As such, the validity of the paternity claims is sus-
pect, and inaccuracies in history and/or reporting seem likely.
Pediatric patients treated in a timely manner for unilateral
cryptorchidism can achieve normal or near-normal rates of pater-
nity in adulthood.13,14 Adults presenting with uncorrected unilat-
eral cryptorchidism may frequently demonstrate abnormalities on
semen analysis, but many still achieve pregnancy by natural means.4
Orchiectomy has generally been advocated to reduce the risk of
future testicular malignancy.15 The unilateral cryptorchid testicle
has been thought to add little fertility potential in the presence of a
normally descended contralateral testicle, and these men generally
have normal testosterone levels.16 Historically, men with bUDT who
undergo a post-pubertal orchidopexy have been described as having
irreversible gonadal damage along with an increased risk of malig-
nancy.15 The role for surgery in these cases has been less clear. The
potential for fertility following orchidopexy has seldom been evalu-
ated, and bilateral orchiectomy eliminates any possibility of fertility,
results in the need for hormonal replacement, and may result in psy-
chologic stress/negative self-image.
4.1  |  Return of spermatozoa to ejaculate
Despite declarations of futility relative to bilateral orchidopexy in
adult men,17 our review uncovered 11 patients with return of sper-
matozoa to ejaculate following surgery (Table 2). The location of the
undescended testicle was identified in 10 of these men, with nine
undergoing bilateral or unilateral inguinal orchidopexy. A case re-
port by Duong et al. in 2019 described a patient undergoing repair
of both an abdominal and inguinal testis, and a patient from a 2018
cohort study by Zhang et al. underwent an inguinal orchidopexy
with contralateral orchiectomy.18,19 The sole report of fertility fol-
lowing treatment of an adult with bilateral abdominally located tes-
ticles was by Silber in 1982, who described an autotransplantation
technique in which a microanastomosis of the spermatic vessels to
the inferior epigastrics was performed. 20 Barring this isolated case
of autotransplanation, our review would suggest that successful

Biopsy at time of Final SA reported with return Final sperm count (in millions Preoperative
Orchidopexy of sperm (time performed) per ml) Testosterone (ng/dL) Paternity

No—Primary spermatocytes 6–11 months A few non-motile spermatozoa No

(MA) on delayed biopsy
No 16 months 22 683
Yes—Primary spermatocytes 16 months 15 650
(MA)
No 3 months A few spermatozoa Yes—IUI (1) and
natural (3)
No 12 months 7.6 417 Yes, IVF/ICSI (2)
and natural (1)
Yes—Primary spermatocytes 21 months 16 No
(MA)
Yes—Primary spermatocytes 10 months 1.6 Yes—IVF/ICSI (1)
(MA)
No 36 months 6.3 537
No 25 months 11.4 343 Yes—Natural (1)
No 8 months A few spermatozoa 483
Yes—SCO 6 months 2
6     | MUNCEY et al.

TA B L E 3 A  Sperm obtained by delayed TESE (N = 10)

Testis
Timing of volume,
Author/ Type of Age at Location delayed Biopsy or TESE at Baseline FSH Right/
Year extraction orchidopexy Right/Left Orchidopexy TESE Orchidopexy elevation Left (ml) Reported yield Paternity

30
Lin et al. TESE 18 Inguinal/ Bilateral 14 years No Yes (30.1 14, 13 A few Yes—with
Inguinal mIU/ml) spermatozoa ICSI

Raman TESE or >20 Bilateral >6 months Yes—6 months prior

et al. 32 multiple (results not
biopsy reported)

Raman TESE or >20 Bilateral >6 months Yes—6 months prior

et al. 32 multiple (results not
biopsy reported)

Raman TESE or >20 Bilateral >6 months Yes—6 months prior

et al. 32 multiple (results not
biopsy reported)

Raman TESE or >20 Bilateral >6 months Yes—6 months prior

et al. 32 multiple (results not
biopsy reported)

Wiser TESE 21
et al.47

Wiser et al. TESE >18

2009

Matsuhita mTESE 29 Inguinal/ Bilateral 10 months Yes—SCO, TESE Yes (23.5 5.4, 4.7 Yes—with
et al. Inguinala  and 7 unsuccessful mIU/ml) ICSI
2013 years

Sangster mTESE 31 Inguinal/ Bilateral Yes—14 Yes—SCO Yes (30.5 6.8, 6.7 1 Vial
et al. 38 Inguinal months mIU/ml)

Sangster mTESE 34 Inguinal/ Bilateral Yes—26 SCO (Right), No (10.0 mIU/ 8.3, 5.4 1 Vial
et al. 38 Inguinal months Spermatogonia ml)
with MA (Left)

Blank cell = not reported.

a
Testicles described to be at the external ring.

restoration of spermatogenesis after bilateral orchidopexy is primar-
ily seen in patients with inguinal UDT. These findings are in agree-
ment with previous studies demonstrating a higher concentration
of spermatozoa and germ cells in undescended testicles anterior to
the external oblique aponeurosis when compared to an abdominal
location.6,21
We found the median time to postoperative identification of
ejaculated spermatozoa was 14 months. Although three cases
demonstrated return in ≤6 months, severe oligospermia was the rule
with counts from minimal spermatozoa up to 2 million/ml. A younger
age at orchidopexy was observed in men who experienced return of
spermatozoa to ejaculate. A normal preoperative testosterone was
documented in all six men who had this reported, with a 40% higher
average testosterone concentration compared with persistently
azoospermic men. Although mean testosterone values were not sig-
nificantly different in these two groups (518 vs. 372, p = 0.061), the
majority of the azoospermic men had levels at or below the median
value of 410 ng/dl (56.0% vs. 16.7%, p = 0.083). While not statis-
tically significant, given the small sample size and risk of type two
error, testosterone could still be considered a potential marker of
successful return of spermatozoa to ejaculate.
Biopsies were inconsistently performed but when reported
demonstrated either MA or SCO. While SCO histology on biopsy
in theory should predict a lower chance of fertility potential, it did
not preclude potential for spermatogenesis. When paternity was
reported, four out of six men were able to father children. In com-
bination, our findings suggest that restoration of spermatozoa to
the ejaculate may occur more commonly following orchidopexy
of inguinal testicles in younger men with normal preoperative
testosterone.
4.2  |  TESE after orchidopexy for bUDT
Hadziselimovic et al. reported that despite successful orchidopexy in
childhood, nearly half of bUDT patients and 13% of unilateral UDT
patients later demonstrated azoospermia.6 Epididymal anomalies are
common in cryptorchid testicles (37–60%), 22,23 but iatrogenic injuries
to the vas deferens and other spermatic cord components during or-
chiopexy are also possible.24 Some have suggested obstruction may
be fully or partially responsible for azoospermia in approximately half
of men undergoing orchiopexy.25 This is somewhat supported by the
MUNCEY et al. |
      7

TA B L E 3 B  Sperm not obtained by delayed TESE (N = 12)

Testis
Timing of volume
Author/ Type of Age at Location delayed Biopsy or TESE at Baseline FSH Right/Left
Year extraction orchidopexy Right/Left Orchidopexy TESE Orchidopexy elevation (ml)

Raman TESE or >20 Bilateral >6 months Yes—6 months

et al.32 multiple prior (results
biopsy not reported)
Raman TESE or >20 Bilateral >6 months Yes—6 months
et al.32 multiple prior (results
biopsy not reported)
Raman TESE or >20 Bilateral >6 months Yes—6 months
et al.32 multiple prior (results
biopsy not reported)
Raman TESE or >20 Bilateral >6 months Yes—6 months
et al.32 multiple prior (results
biopsy not reported)
Raman TESE or >20 Bilateral >6 months Yes—6 months
et al.32 multiple prior (results
biopsy not reported)
Chiba TESE 30 Inguinal/ Bilateral 10 months Yes—SCO (Right/ Yes (23.5 12, 12
et al.17 Inguinal Left), TESE mIU/ml)
unsuccessful
Sangster mTESE 36 Abdominal/ Bilateral 14 months Yes— Yes (21.0 13, 9
et al.38 Abdominal Spermatocytes mIU/ml)
with MA (Right),
Sertoli only
(Left)
Sangster mTESE 23 Abdominal/ Bilateral 16 months Yes—Sertoli only Yes (40.6 8.7, 6
et al.38 Abdominal (Right) mIU/ml)
Sangster mTESE 25 Abdominal/ Unilateral— 10 months Yes—Sertoli only Yes (35.9 8.5, 7.1
et al.38 Inguinal Left (Left) mIU/ml)
Sangster mTESE 36 Inguinal/ Unilateral— 15 months Yes—SCO (Right) Yes (16.2 7.4, 6
et al.38 Abdominal Right mIU/ml)
Sangster mTESE 34 Abdominal/ Bilateral 12 months Yes—SCO (Right), Yes (22.6 8.3, 5.4
et al.38 Abdominal mTESE mIU/ml)
unsuccessful
Barbotin TESE 23 Bilateral
et al.33

Blank cell = not reported.

results of our study, as TESE was successfully performed in 10 of 22
men following adult orchidopexy for bUDT (Table 3a).
By 6–8 months of age, undescended testicles demonstrate ar-
15
rest of gonocyte evolution into adult dark spermatogonia. The
development of adult dark spermatogonia is critical for future
fertility because they serve as a lifelong supply of spermatogonial
stem cells. 26 This gonadal damage could persist or progress in the
post-pubertal patient and may explain why TESE may ultimately fail
in a large percentage of these men.17 Fedder et al. reported a strong
association between a history of cryptorchidism and an inhomoge-
neous histological pattern, with islands of normal testicular tissue
found in testicles otherwise exhibiting SCO. 27 They concluded that
for azoospermic men with a history of cryptorchidism, it may be
particularly relevant to consider multiple TESEs and microsurgery
to obtain spermatozoa from the often isolated islands of normal
testis tissue. Odds of successful conception are additionally aug-
mented by other modern advances in infertility treatment, such as
ICSI. In our review, this technique facilitated half of the successful
paternity cases following adult bilateral orchidopexy. 28–31
The data to set patient expectations for chances of sperm retrieval
after orchidopexy is limited. In their 2003 series, Raman and Schlegel
reported that patients undergoing bilateral orchidopexy after 20 years
of age had a 44% TESE success rate compared with 94% in those
treated before age 10, suggesting age at orchidopexy predicts suc-
cess.32 However, other modern series report the absence of such an
association.33,34 Similarly, some have suggested FSH levels may predict
success of TESE after orchidopexy,33 while reports assessing outcomes
in men with non-obstructive azoospermia generally have suggested it
is unreliable.25,32,35,36 The same is true for testicular volume.32,35–37 A
2018 meta-analysis concluded that neither FSH nor testicular volume
 |
8      MUNCEY et al.

Abdominal bUDT
or
Inguinal bUDT and no
fertility interest

Age <50 y Age > 50 y

1. Surveillance (preferred)
2. Orchiectomy or
orchidopexy with biopsy*
(if unable/unlikely to
Testosterone Assessment follow-up)
Low Normal

1. Orchiectomy 1. Orchidopexy with

(preferred) biopsy* (if feasible)
2. Surveillance 2. Surveillance *Advise very low fertility potential in
abdominal cryptorchid testicles

F I G U R E 2  Suggested pathway for management of bilateral undescended abdominal testicles and men without interest in fertility

alone is predictive of TESE success.37 The number of publications in

our review to report pre-orchidopexy FSH (4 out of 8, median 26.8
mIU/ml) and testis size (eight testicles in four reports, mean volume 8
ml) in TESE patients were few, limiting our ability to make any conclu-
sions regarding their value as predictive tools.
In our review, the only successful instances of sperm extraction
were from TESE procedures performed in delayed fashion after orchi-
dopexy for bUDT. Of note, however, one series reported successful
synchronous mTESE at time of orchidopexy for unilateral undescended
inguinal testis in two men, but this cannot necessarily be extrapolated to
bUDT patients.38 The average time between bilateral orchidopexy and
successful TESE was ~3 years. Promotion of spermatogenesis, possi-
bly stimulated by normalization of testis position and temperature, may
be a prolonged process necessitating provider and patient patience. In
2013, Matsushita et al. described a patient with unsuccessful TESE 10
months after orchidopexy, but who achieved a successful pregnancy
7 years later after mTESE and ICSI.31 Furthermore, our review found
no instance of successful TESE for men with purely abdominal bUDT.
On histological review, only 10% of abdominal testicles had germ cells
identified. Additionally, orchidopexy for an abdominal testis seems
likely to require more stress on the testis and spermatic cord. Success
was achieved in three of four patients when mTESE was performed a
year or more following inguinal orchidopexy. Based on this information,
providers may wish to counsel patients with abdominal bUDT that TESE
is of limited utility and that those undergoing inguinal orchidopexy may
be best served by waiting at least a year before mTESE.
4.3  |  Testis biopsy at time of orchidopexy
Testicular biopsy at the time of adult orchidopexy has been recom-
mended as a screen for malignancy, with multiple specimens ad-
vised by European guidelines.39 The rate of testicular cancer and
incidental germ cell neoplasia in situ (GCNIS) is higher in men with
a history of cryptorchidism than for the general population, with
5–10% of cases appearing in men with a history of undescended
testicles.40,41 However, Ateş et al. evaluated 244 testicles removed
from men with unilateral cryptorchidism and reported one case of
seminoma (0.4%).42 A study of 100 biopsies at the time of adult
orchidopexy found no instances of malignancy.3 Smaller series in-
volving adult cryptorchid men report rates of GCNIS ranging from
2% to 23%.15,43,44 Incidental GCNIS was seldom reported in our
review and not addressed by our analysis, but in light of available
literature, routine tissue sampling in men considering orchidopexy
for improved fertility may afford a risk that outweighs the potential
benefit. Schlegel and Su have reported transient adverse physiologic
effects in testicles up to 6 months after biopsy for sperm retrieval,
and even complete devascularization of the testicle following multi-
ple biopsies.45
In our review, histology taken from cryptorchid testes prior to
orchidopexy failed to reveal spermatids in any case, and most were
without germ cells. Regardless, three men with SCO and four with
MA would later demonstrate spermatogenesis, suggesting adverse
MUNCEY et al.
Inguinal bUDT and interest
in fertility
Orchidopexy
without *If preoperative imaging and serum
tumor markers do not suggest neoplasm
biopsy/TESE*
Semen Analysis
· Can offer at 6 -
12 months
Sperm found
Azoospermia ≥
1 year · Consider
referral for ART
Offer mTESE
F I G U R E 3  Suggested pathway for fertility management in
bilateral undescended inguinal testicles
histology at orchidopexy may not preclude future fertility potential.
Primary spermatocytes represented the highest phase of maturation
identified in any biopsy. Given the potential for testis injury, diagnos-
tic biopsy and/or TESE at time of orchidopexy in men with hopes of
fertility may be undesirable.
4.4  |  Surgical decision-making for adult bUDT
Men with bUDT presenting for infertility should undergo a com-
plete history and physical examination, parallel assessment of
female partners, and laboratory testing for testosterone, FSH, kar-
yotype, and Y chromosome microdeletion.46 Routine assessment
of testis cancer tumor markers has been recommended and may be
considered.47 Magnetic resonance imaging and/or ultrasonography
should be routinely utilized, as some lesions which may necessitate
orchiectomy, such as testis tumors or Müllerian remnants, can be
identified.48,49 We have proposed an algorithm to assist with clini-
cal decision-making following workup for these patients (Figures
2 and 3).
Although bilateral orchiectomy is often recommended and
performed in men with bUDT, 50,51 our review has found tes-
tis preservation may afford adequate endogenous testosterone
production and fertility potential. One study noted an inverse
association with testosterone values and age at orchidopexy, sug-
gesting surgery may prevent deterioration of hormone produc-
tion. 52 Men with inguinal bUDT interested in fathering children
|
      9
should be considered for orchidopexy. An important finding of
this review is that TESE at the time of surgery is unlikely to be
successful and should be omitted. Following scrotal repositioning
of the testicle or testicles, these men should be advised to per-
form self-examination to monitor for development of testicular
masses. A semen analysis at 6 months is reasonable to assess for
presence of spermatozoa, and assisted reproductive techniques
may be considered when feasible and appropriate. If azoospermia
persists beyond a year, mTESE can be considered, while under-
standing that successful commencement or recovery of sper-
matogenesis may take years.
Chances for fertility among men presenting with abdominal
bUDT are exceedingly low. Although this may prompt some to
universally advocate for bilateral orchiectomy in these men, a re-
cent review found that for healthy men > 50 years old, the risk of
death from complications following orchiectomy is higher than
that from a germ cell tumor. 53 For men younger than 50 with ab-
dominal bUDT, considerations include surveillance, orchidopexy,
or orchiectomy. Surveillance protocols should consider imaging
and serial assessments of tumor markers annually. Based upon
the available literature, most men with bUDT have normal base-
line testosterone (89%). Therefore, bilateral orchidopexy may
allow for testicular self-examination and avoidance of lifelong
exogenous testosterone administration. Despite the risks previ-
ously described, it is still felt that men undergoing orchidopexy
or diagnostic laparoscopy for bUDT should undergo testicular
biopsy to assess for malignancy. Following orchidopexy, these
patients should be counseled that despite no documented cases
of spermatogenesis in this population, birth control may still be
necessary and that vasectomy may be ill-advised if spermatic
vessel ligation was performed at time of surgery.
Readers must be cautioned that while this review provides evi-
dence of spermatogenesis commencement after orchidopexy, there
are significant limitations. Given the rarity of this presentation and
subsequent treatment, there is a high likelihood of publication bias
in favor of positive results. There is not agreed upon definition of or-
chidopexy success, and included studies frequently did not describe
the surgical method utilized or surgical outcomes, such as postop-
erative testis location or size, potentially limiting generalizability of
the results. The studies evaluated in this review were all small and
may not be generalizable. Our search strategy was comprehensive
and scrupulous, but we cannot eliminate the possibility of having
overlooked relevant publications. Finally, study variations involving
age at orchidopexy, follow-up protocols, procedural interventions,
and clinical end points, render formation of definitive conclusions
difficult.
5  |  CO N C LU S I O N S
Adult orchidopexy can induce spermatogenesis in men presenting
with inguinal bUDT. In some cases, spermatozoa will subsequently
appear in the ejaculate, whereas others may find success via delayed
 |
10      MUNCEY et al.
mTESE. TESE performed at time of orchidopexy in men with bUDT
is unlikely to afford benefit. Testosterone levels among men pre-
senting with bUDT (inguinal or abdominal) are typically normal, and
the benefits of tissue preservation and avoiding surgical complica-
tions should be weighed against the risk of unidentified and/or un-
treated malignancy among men uninterested in future fertility.
C O N FL I C T O F I N T E R E S T
The authors have no conflict of interest to disclose.
ORCID
Wade Muncey  https://orcid.org/0000-0001-8323-7094
Kyle Scarberry  https://orcid.org/0000-0001-9195-6873
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S U P P O R T I N G I N FO R M AT I O N
Additional supporting information may be found online in the
Supporting Information section.
How to cite this article: Muncey W, Dutta R, Terlecki RP,
Woo LL, Scarberry K. Fertility potential in adult men treated
for uncorrected bilateral cryptorchidism: A systematic
literature review and analysis of case reports. Andrology.
2021;00:1–11. https://doi.org/10.1111/andr.12964