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Ϯ The authors consider that these authors should be regarded as joint first authors.
Jitske Eliveld
Footnotes
Ϯ The authors consider that these authors should be regarded as joint first authors.
Affiliations
Amsterdam UMC location University of Amsterdam, Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam, The Netherlands.Amsterdam Reproduction and Development, Amsterdam, The Netherlands.
Amsterdam UMC location University of Amsterdam, Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam, The Netherlands.Amsterdam Reproduction and Development, Amsterdam, The Netherlands.
Amsterdam UMC location University of Amsterdam, Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam, The Netherlands.Amsterdam Reproduction and Development, Amsterdam, The Netherlands.
Amsterdam UMC location University of Amsterdam Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam, The Netherlands.Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands.
Amsterdam UMC location University of Amsterdam, Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam, The Netherlands.Amsterdam Reproduction and Development, Amsterdam, The Netherlands.
What is the risk of hypogonadism in men with obstructive azoospermia, non-obstructive azoospermia (NOA) or Klinefelter syndrome after testicular sperm extraction (TESE)?
Design
This prospective longitudinal cohort study was carried out between 2007 and 2015.
Results
Around 36% of men with Klinefelter syndrome, 4% of men with obstructive azoospermia and 3% of men with NOA needed testosterone replacement therapy (TRT). Klinefelter syndrome was strongly associated with TRT while no association was found between obstructive azoospermia or NOA and TRT. Irrespective of the pre-operative diagnosis, a higher testosterone concentration before TESE was associated with a lower chance of needing TRT.
Conclusions
Men with obstructive azoospermia or NOA have a similar moderate risk of clinical hypogonadism after TESE, while this risk is much larger for men with Klinefelter syndrome. The risk of clinical hypogonadism is lower when testosterone concentrations are high before TESE.
Testicular sperm extraction (TESE) has become a standard procedure for azoospermic men who wish to achieve biological fatherhood. Intracytoplasmic sperm injection (ICSI) with testicular spermatozoa results in live birth rates of 20–45% per cycle (
Reproductive outcomes, including neonatal data, following sperm injection in men with obstructive and nonobstructive azoospermia: case series and systematic review.
). However, data on safety, especially on the risk of hypogonadism, are limited, and this is worrying in view of the wide acceptance of this invasive procedure.
Previous studies regarding the risk of hypogonadism after TESE have generally been limited to mean serum testosterone levels and have shown inconsistent findings, with a reduction of serum testosterone concentrations after TESE (
Microdissection testicular sperm extraction in men with nonobstructive azoospermia: Experience of King Saud University Medical City, Riyadh, Saudi Arabia.
Testosterone levels among non-obstructive azoospermic patients 2 years after failed bilateral microdissection testicular sperm extraction: a nested case-cohort study.
Serial follow-up study of serum testosterone and antisperm antibodies in patients with non-obstructive azoospermia after conventional or microdissection testicular sperm extraction.
). A previous meta-regression analysis revealed a transient decrease in serum testosterone concentrations after TESE in men with non-obstructive azoospermia (NOA) and men with Klinefelter syndrome, with a significant decrease in mean testosterone concentrations 6 months after TESE (
Although this decrease in mean testosterone concentrations provides information on the overall effect of TESE on testosterone concentrations, the proportion of men suffering from hypogonadism (i.e. low testosterone combined with symptoms and/or signs) and therefore in need of testosterone replacement therapy (TRT) after TESE – which is clinically more relevant – has still not been adequately studied. According to the European Association of Urology guideline, the diagnosis of hypogonadism should be based on the presence of persistent symptoms (
), while other studies have focused only on testosterone concentrations.
The aim of this study was therefore to assess the risk of hypogonadism after TESE in men with obstructive azoospermia, NOA or Klinefelter syndrome. To do this it examined the percentage of men in each diagnostic category who were in need of TRT (i.e. men with diagnosed hypogonadism) after TESE because of symptoms of hypogonadism.
Material and methods
Study design and study population
This prospective cohort study included men diagnosed with obstructive azoospermia, NOA or Klinefelter syndrome who underwent a TESE procedure in Amsterdam UMC location AMC from June 2007 up to August 2015. Obstructive azoospermia was diagnosed when there was evidence of an obstruction, Klinefelter syndrome was diagnosed using karyotyping, and NOA was diagnosed when there was no proof of either an obstruction or a Klinefelter syndrome karyotype. Men with obstructive azoospermia were included after an unsuccessful microsurgical epididymal sperm aspiration (MESA), i.e. in cases where no epididymal spermatozoa were found.
Study exclusions were as follows: transwomen (transgender male-to-females); men receiving TRT or human chorionic gonadotrophin stimulation at the time of their initial assessment or less than 3 months before the TESE procedure; men in whom a previous – diagnostic or therapeutic – testicular biopsy had been taken less than 1 year before TESE; and men for whom no pre- or post-TESE testosterone concentrations were available or whose testosterone concentration had not been measured between 08:00 hours and 11:00 hours as recommended (
). Men receiving TRT after TESE or having a second TESE were not excluded when there were available testosterone data from before and at least once after the first TESE but before TRT initiation or the second TESE procedure; however, the data after the start of treatment or the second TESE were excluded from the analyses. Therefore, pre-TESE serum testosterone concentrations and at least one post-TESE testosterone concentration were available for all the men included in this study. In this way paired analyses could be carried out at the individual level instead of having analyses of mean testosterone concentrations.
Ethical approval
The Dutch Central Committee on Research involving Human Subjects (CCMO) approved the research protocol for this study (NL12408.000.06, 18 October 2006), in which the primary outcome was the behavioural, cognitive and motor performance and physical development of children born after TESE–ICSI. The safety of TESE related to the testosterone concentrations of the men undergoing TESE was a secondary outcome (
Behavioral, cognitive, and motor performance and physical development of five-year-old children who were born after intracytoplasmic sperm injection with the use of testicular sperm.
). All the men included in this cohort gave written informed consent for surgery and follow-up.
TESE
Before TESE, scrotal ultrasonography was performed to measure the testicular volume. The TESE procedure was performed by one urologist-andrologist (A.M.) under local anaesthesia, or very occasionally general anaesthesia. After disinfection, the scrotal skin and tunica vaginalis were opened. Under visualization using a surgical microscope, a longitudinal incision was made in the tunica albuginea and the testicular parenchyma was examined for dilated, opaque tubules. If all the seminiferous tubules appeared to have the same diameter, a representative biopsy was taken from several segments of the testis. If the seminiferous tubules of interest were clustered focally, these specific tubules were harvested. If only very thin tubules were seen, a deeper and more extensive exploration was performed. Depending on the initial size of the testis, the biopsy had a size of 100–500 µl. The first sample from the biopsy procedure was processed for the retrieval of spermatozoa, and a second smaller biopsy was taken for histopathological examination to assess spermatogenesis and rule out germ cell cancer neoplasia in situ. The participants were discharged on the day of surgery.
Endocrine measurements
The participants underwent blood sampling before and approximately 6 and 12 months after the TESE procedure, to measure the baseline total testosterone and LH concentrations. All hormone assessments were performed at the Endocrine Laboratory of Amsterdam UMC. Total testosterone was measured using an in-house radio-immunoassay (RIA) until 4 March 2013 and thereafter with an in-house liquid chromatography–tandem mass spectrometry (LC-MS/MS) method with an interassay variation of less than 7.5% (
). LH concentrations were measured with an automated immunoassay (Immulite Siemens Diagnostics, Germany) until 4 March 2008 and thereafter with an automated immunoassay (Cobas Roche Diagnostics, the Netherlands) with interassay variations of less than 3.5% and less than 6.5%, respectively.
To make the total testosterone data of the RIA method comparable to the LC-MS/MS results, the Passing and Bablok regression belonging to the method comparison was applied. This resulted in the formula: LC-MS/MS = 0.94*RIA – 0.41 (nmol/l) to correct the data from the RIA method. The European Association of Urology guideline recommends that testosterone assays should be validated on reference ranges by the laboratory measuring the samples (
Establishing normal values of total testosterone in adult healthy men by the use of four immunometric methods and liquid chromatography-mass spectrometry.
). Therefore, the lower limit of the reference interval determined specifically for the LC-MS/MS technique, 9 nmol/l, was used as a threshold for hypogonadism.
For LH data the concentrations measured using the Immulite assay compared with the Cobas assay were recalculated using the following formula: Cobas = 1.14*Immulite + 0.01 (U/l), based on the Passing and Bablok regression analysis of the method comparison.
Data extraction
The following information was extracted from the patient records: past medical history, clinical type of azoospermia, age, TRT, testicular volume, unilateral or bilateral TESE, concentration and motility of the testicular spermatozoa, histology of the testicular biopsy and whether a second TESE was performed. In addition, individual information was extracted on total testosterone concentrations before and after TESE, LH concentrations and testis volume before TESE, together with the date and time of blood withdrawal. As blood withdrawal was not always performed at exactly 6 and 12 months after TESE, the information was extracted on all testosterone concentrations after TESE up to 18 months. As a recovery of the decreased testosterone concentrations after TESE was seen 18 months after TESE, it was believed that an effect on testosterone concentrations would be captured within this time frame (
For men with acquired low testosterone concentrations after TESE, below the 9 nmol/l threshold concentration of hypogonadism, or men who started TRT after TESE, information was extracted on clinical symptoms of hypogonadism including decreased libido, depressed mood, decreased energy and erectile dysfunction (
To compare baseline characteristics in men diagnosed with obstructive azoospermia, NOA or Klinefelter syndrome, one-way analysis of variance was used, in combination with a Tukey post-hoc test for numerical data or a chi-squared test for categorical data with Bonferroni adjusted post-hoc pairwise z-tests. Normal distribution was determined by histogram evaluation. Because of the heterogeneity of follow-up time, the effect of TESE on testosterone concentrations was assessed over time using mixed-models analyses. To assess any association of the type of azoospermia and testosterone concentrations before TESE with TRT after TESE, odds ratios (OR) with 95% confidence intervals (CI) were calculated using logistic regression analysis. IBM SPSS Statistics 25 (IBM Corp, USA) was used to perform these statistical analyses. A P-value <0.05 was considered significant. Fractional-polynomial plots to explore the changes in testosterone concentrations over time were generated with STATA 14.2 (Stata Statistical Software: Release 14; StataCorp, USA).
This manuscript is reported according to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement (
A total of 725 men undergoing TESE at Amsterdam UMC location AMC were recruited. Exclusions from this study were mainly due to the lack of available testosterone concentrations or medical history (Supplementary Figure 1). Finally, 53 men with obstructive azoospermia, 177 men with NOA and 11 men with Klinefelter syndrome were eligible for inclusion in the study.
The baseline pre-operative characteristics, TESE procedure and outcome and histology are summarized in Table 1. Men with NOA or Klinefelter syndrome were younger and had a lower testicular volume and less frequent findings of spermatozoa with TESE compared with those with obstructive azoospermia. In men with Klinefelter syndrome, a second biopsy in the contralateral testis was performed more often than in men with obstructive azoospermia or NOA. Histology, where conclusive, varied from mainly normal in men with obstructive azoospermia to Sertoli-cell-only and mixed phenotypes in men with NOA or Klinefelter syndrome.
Table 1Baseline characteristics of the study population
Calculated based on the testicular volume of both testicles in individual men. Men with a testicular volume measured only in one testicle were excluded from this calculation.
Data are presented as mean ± SD (n data available) or n (%) (n data available); all percentages were calculated from the total diagnosis cohort.
a Calculated based on the testicular volume of both testicles in individual men. Men with a testicular volume measured only in one testicle were excluded from this calculation.
b Maximum P-value resolution possible.ANOVA, analysis of variance; KS, Klinefelter syndrome; na, not applicable; NOA, non-obstructive azoospermia; OA, obstructive azoospermia.
Endocrine characteristics of men with obstructive azoospermia, NOA or Klinefelter syndrome undergoing TESE
The endocrine characteristics of the three groups are described in Table 2. Before TESE, men with NOA or Klinefelter syndrome had lower testosterone concentrations and higher LH concentrations than men with obstructive azoospermia. In men with Klinefelter syndrome a higher percentage had testosterone concentrations below the threshold of 9 nmol/l compared with men with obstructive azoospermia.
Table 2Endocrine characteristics of men with OA, NOA and KS before and after TESE
Parameter
OA (n = 53)
NOA (n = 177)
KS (n = 11)
P-value ANOVA/chi-squared
Outcome post-hoc
Before TESE
Testosterone (nmol/l)
17.35 ± 5.3
(53)
14.67 ± 4.6
(177)
12.10 ± 5.8
(11)
<0.001
OA vs NOA 0.001 OA vs KS 0.003 NOA vs KS 0.199
LH (IU/l)
4.41 ± 2.3
(46)
8.56 ± 4.3
(150)
16.76 ± 5.9
(7)
<0.001
OA vs NOA <0.001 OA vs KS <0.001 NOA vs KS <0.001
Cases of low testosterone (<9 nmol/l)
0 (0%)
(53)
14 (8%)
(177)
3 (27%)
(11)
0.004
OA vs NOA 0.044 OA vs KS <0.05 NOA vs KS 0.065
After TESE
Mean difference in testosterone (nmol/l), ≤4 months
–0.66 ± 2.7
(10)
+0.68 ± 3.7
(30)
–2.24 ± 2.2
(6)
na
na
Mean difference in testosterone (nmol/l), 5–8 months
–1.84 ± 5.1
(35)
–0.52 ± 4.1
(125)
–0.58 ± 6.2
(3)
na
na
Mean difference in testosterone (nmol/l), 9–12 months
–2.05 ± 4.6
(28)
–0.54 ± 3.2
(82)
–1.08 ± 1.8
(2)
na
na
Mean difference in testosterone (nmol/l), >12 months
Could not be calculated due to the low number of measurements in this group. ANOVA, analysis of variance; KS, Klinefelter syndrome; na, not applicable; NOA, non-obstructive azoospermia; OA, obstructive azoospermia; TESE, testicular sperm extraction.
(1)
na
na
Cases of new-onset low testosterone (<9 nmol/l)
6 (11%)
(53)
17 (10%)
(163)
1 (13%)
(8)
na
na
Spontaneous recovery
2/6
5/17
0/1
Data are presented as mean ± SD (n data available), or n (%) (n data available).
Only testosterone and LH are included; these were measured between 08:00 hours and 11:00 hours.
a Could not be calculated due to the low number of measurements in this group.ANOVA, analysis of variance; KS, Klinefelter syndrome; na, not applicable; NOA, non-obstructive azoospermia; OA, obstructive azoospermia; TESE, testicular sperm extraction.
After TESE, most of the follow-up data concerning testosterone were available between 5 and 12 months (Table 2). Because the follow-up time was not restricted to exactly 6 and 12 months, all follow-up data up to 80 weeks were included (Figure 1 A-C). Compared with men with obstructive azoospermia, men with NOA showed a similar pattern of individual testosterone concentrations over time, while the decrease in testosterone concentrations started earlier and was steeper in men with Klinefelter syndrome (Figure 1 A–C). This negative effect on individual serum testosterone concentrations over time was significant only in men with obstructive azoospermia (P = 0.003) and not in men with NOA (P = 0.088) or Klinefelter syndrome (P = 0.716).
Figure 1Testosterone deviation after testicular sperm extraction (TESE) over time. The average change, with 95% confidence intervals, in testosterone concentrations after TESE in men with obstructive azoospermia (OA; A), with non-obstructive azoospermia (NOA; B) or with Klinefelter syndrome (KS; C). Mixed-model analysis was performed, and the P-values are shown. Change in testosterone concentrations in the subgroup of men with new-onset low testosterone concentrations for individual men with obstructive azoospermia (D), non-obstructive azoospermia (E) or Klinefelter syndrome (F).
Six men (11%) with obstructive azoospermia, 17 men (10%) with NOA and one man (13%) with Klinefelter syndrome had new-onset low testosterone concentrations (Table 2). Of these, two men with obstructive azoospermia and five men with NOA showed a spontaneous recovery of testosterone concentrations to normal within their individual follow-up, up to 80 weeks (Figure 1D–F).
Symptoms of hypogonadism after TESE
Two men with obstructive azoospermia (3.8%), six men with NOA (3.3%) and four men with Klinefelter syndrome (36%) started TRT because they experienced clinical symptoms of hypogonadism after TESE (Table 3). The reported clinical symptoms of hypogonadism were decreased energy (n = 5), lower libido (n = 4), decreased muscle strength (n = 2), erectile dysfunction (n = 2), depressed mood (n = 1) and/or increase in weight (n = 1). The baseline characteristics of these men are described in Supplementary Table 1. There seems to be no relationship with age and bilateral biopsy as this is comparable to the whole of the study populations described in Table 1. In all three groups (OA/NOA/KS) testicular volume is observed to be smaller than in the various study populations described in Table 1.
Table 3Men taking TRT and their symptoms of hypogonadism after TESE
TRT was offered at between 1 and 15 months (average 8 months) after TESE. Klinefelter syndrome was strongly associated with the requirement for TRT (Klinefelter syndrome versus NOA: OR 16.3, 95% CI 3.71–71.1) whereas no association was found between obstructive azoospermia or NOA and TRT (obstructive azoospermia versus NOA: OR 1.12, 95% CI 0.22–5.71) (Figure 2). In view of the small number of participants, however, this result should be considered with care.
Figure 2Association between testosterone replacement therapy (TRT) and type of azoospermia.
In all the participants, irrespective of the diagnosis, a higher testosterone concentration before TESE was associated with a lower chance of needing TRT (OR 0.66, 95% CI 0.52–0.83). Of the 12 men who started TRT, five had new-onset low testosterone concentrations after TESE (one man with obstructive azoospermia, three men with NOA and one man with Klinefelter syndrome). Other men with a new onset of low testosterone did not have symptoms and therefore did not receive TRT. Another five of the 12 men had no new-onset low testosterone but already had low testosterone concentrations (<9 nmol/l) both before and after TESE (two men with NOA and three men with Klinefelter syndrome). One man with obstructive azoospermia and one man with NOA receiving TRT had borderline testosterone concentrations after TESE of 9.8 and 9.5 nmol/l, respectively.
Discussion
Men with Klinefelter syndrome have a higher chance of needing TRT after TESE compared with men with obstructive azoospermia or NOA. Around 36% of men with Klinefelter syndrome, 4% of men with obstructive azoospermia and 3% of men with NOA needed TRT due to symptoms including decreased energy, lower libido, decreased muscle strength and erectile dysfunction. Testosterone concentrations before TESE predicted the risk of hypogonadism after TESE, where higher testosterone concentrations before TESE were associated with lower chances of needing TRT.
The strength of the current study is that the need for TRT after TESE was assessed in a large population of men with azoospermia according to their clinical diagnosis, i.e. obstructive azoospermia, NOA or Klinefelter syndrome. Some limitations also warrant discussion. First, the sample size was relatively small for men with Klinefelter syndrome. This was partly because Dutch law before 2010 prevented men with Klinefelter syndrome from undergoing TESE. In view of the small sample size, the results should be interpreted prudently.
Second, although this study reports on the largest cohort ever published based on the number of men with available data after TESE, a power analysis was not performed before the study as the testosterone concentration over time was a secondary outcome of the original research protocol (NL12408.000.06). The primary outcome measures were the behavioural, cognitive and motor performance and physical development at birth to 5 years of age of the children born after TESE–ICSI (
Behavioral, cognitive, and motor performance and physical development of five-year-old children who were born after intracytoplasmic sperm injection with the use of testicular sperm.
). Furthermore, a high number of men (n = 245) had to be excluded because no follow-up data on testosterone concentrations were available. This might have led to a selection bias that then could lead to an overestimation of men with low testosterone concentrations. However, as the decrease in testosterone concentrations in men with NOA or with Klinefelter syndrome was no bigger than reported in previous studies, the authors believe that this bias has not occurred.
Third, the study did not systematically monitor symptoms of hypogonadism in the cohort included, but only assessed these symptoms in men starting TRT and men with new-onset low testosterone concentrations after TESE as a required hallmark of hypogonadism. This would have caused bias if the participants did not report their symptoms to their treating clinician. This selection bias might cause an underestimation of men suffering from symptoms linked to hypogonadism after TESE.
Regarding men with NOA, there was a lower risk of the need of TRT (3.4%) compared with a previous study that reported an incidence of 20% (
). This discrepancy might be explained by several differences in study set-up. First, the current study assessed men starting TRT while the previous study assessed erectile dysfunction. It might be that in the current cohort there were more men suffering from erectile dysfunction who did not start TRT for whatever reason. Second, the high occurrence of a new onset of erectile dysfunction was seen 6 months after TESE whereas there was a follow-up of 20 months. As a spontaneous recovery of testosterone concentrations occurred in the cohort over time, the symptoms might have recovered. Third, there was a higher sperm retrieval in the current cohort (51%) compared with that study (40%), perhaps indicative of slightly different populations.
In the current study, there was a significant effect of TESE on testosterone over time in men with obstructive azoospermia, but not in men with NOA or Klinefelter syndrome. Men with obstructive azoospermia have never previously been studied as a separate group, and therefore these data cannot be compared with those of previous studies. In men with obstructive azoospermia, MESA was performed before TESE in the same operation. However, because MESA is performed in the epididymis, where no Leydig cells are located, the authors do not consider this to be a confounder, and it therefore does not explain the difference in the effect of TESE on testosterone concentrations over time.
The outcome for men with NOA and Klinefelter syndrome is contradictory to the results of the authors’ previous meta-analysis in which testosterone concentrations after TESE in men with NOA or Klinefelter syndrome were significantly decreased (
Testosterone levels among non-obstructive azoospermic patients 2 years after failed bilateral microdissection testicular sperm extraction: a nested case-cohort study.
). Unlike the meta-analysis, this study did not analyse mean serum testosterone concentrations but used individual changes in testosterone concentrations over time for the paired analyses. Herndon and colleagues studied a selected group of men with NOA, in whom no spermatozoa were found during TESE; the current study did not, however, make this selection, which could explain the discrepancies in the testosterone data.
A difference in surgical technique might affect the outcome in terms of the risk of hypogonadism. From the literature it is known that conventional TESE has a higher or comparable risk in terms of the decrease in testosterone concentrations compared with microdissection TESE (
Serial follow-up study of serum testosterone and antisperm antibodies in patients with non-obstructive azoospermia after conventional or microdissection testicular sperm extraction.
). Furthermore it might be important whether the surgery is performed unilaterally or bilaterally. A difference in outcome due to surgical techniques might, however, also be explained by the selection of patients. One could expect that a less extensive exploration of tubules is needed in men with obstructive azoospermia with normal testicular volumes compared with men with a smaller testicular volume. The current reported a lower testicular volume in the men who had started TRT after TESE compared with the study population (Supplementary Table 1 and Table 1). This lower volume might influence the surgical technique used, which might subsequently influence the outcome. On the other hand, the damage caused by a biopsy in a smaller testis will be relatively larger and therefore the effect on testosterone concentrations might be greater regardless of the surgical technique used.
Next to testicular volume, the higher risk of men with Klinefelter syndrome needing TRT may be explained by their lower testosterone concentrations at baseline (Table 2). Testicular biopsy must have a larger impact in these men with low baseline testosterone concentrations than in men with obstructive azoospermia or NOA (Table 1). Due to this, a non-significant decrease in testosterone can still lead to clinical symptoms in these men. On the other hand, a significant decrease in testosterone concentrations in men with obstructive azoospermia will not lead to hypogonadism in the majority of these men because testosterone concentrations are in the normal to high range at baseline. Furthermore, it should be noted men with Klinefelter syndrome already have a risk of hypogonadism due to a progressive deterioration of testicular tissue. For this reason the effect of TESE might be bigger in this group of men and needs further exploration.
In contrast to the similar percentage of men with a new onset of low testosterone concentrations after TESE for obstructive azoospermia, NOA or Klinefelter syndrome (Table 2), there was a higher risk of hypogonadism for men with Klinefelter syndrome based on the number of men starting TRT after TESE. This points to the importance of analysing these men separately for research purposes but, even more importantly, when counselling men scheduled for TESE. In addition to the pre-TESE diagnosis of azoospermia, testicular histology might also be related to hypogonadism. A different trend in testosterone concentrations before and after TESE in men with maturation arrest and Sertoli-cell-only syndrome compared with hypospermatogenesis has already been shown (
). The current group of men with diagnosed hypogonadism was too small to draw any conclusions on this topic.
Conclusions
Men with obstructive azoospermia and NOA have a similar and moderate risk of clinical hypogonadism after TESE, while this risk is much higher for men with Klinefelter syndrome. The risk of clinical symptoms of hypogonadism is lower when testosterone concentrations are high before TESE. These data will contribute to a better counselling of men scheduled for TESE on the expected magnitude of the risk for hypogonadism.
Acknowledgements
The authors would like to thank Mohamed Jaddioui, MB BS, Mick Uijldert, MSc and Niels van der Weide, MSc, for their help in data collection.
Funding
This research was funded by Amsterdam UMC.
Author contributions
Study conception and design was performed by A.M.M.v.P., F.v/d.V., S.R., A.M., M.v.W., J.E. and I.v/d.B. Data collection was performed by I.v/d.B, A.M., A.T.S. and A.C.H. and the data analysis was carried out by M.v.W., I.v/d.B and J.E. J.E., I.v/d.B, M.v.W., A.M., A.C.H., S.R., F.v/d.V. and A.M.M.v.P. were involved in the interpretation of the data. Article drafting was performed by J.E. and I.v/d.B., where all other authors contributed in the critical discussion and revising this article. All authors approved the final version.
Declaration
The authors report no financial or commercial conflicts of interest.
Microdissection testicular sperm extraction in men with nonobstructive azoospermia: Experience of King Saud University Medical City, Riyadh, Saudi Arabia.
Reproductive outcomes, including neonatal data, following sperm injection in men with obstructive and nonobstructive azoospermia: case series and systematic review.
Testosterone levels among non-obstructive azoospermic patients 2 years after failed bilateral microdissection testicular sperm extraction: a nested case-cohort study.
Serial follow-up study of serum testosterone and antisperm antibodies in patients with non-obstructive azoospermia after conventional or microdissection testicular sperm extraction.
Behavioral, cognitive, and motor performance and physical development of five-year-old children who were born after intracytoplasmic sperm injection with the use of testicular sperm.
Establishing normal values of total testosterone in adult healthy men by the use of four immunometric methods and liquid chromatography-mass spectrometry.
Jitske Eliveld graduated from the University of Amsterdam (UvA), the Netherlands, after which she focused her research on reproductive medicine. She obtained her PhD (UvA) in the field of male reproduction, with special attention to stem cells, Leydig cells and testosterone production. She is currently working as a clinical embryologist in training
Key message
Men with Klinefelter syndrome have a higher risk of hypogonadism after testicular sperm extraction (TESE) than men with obstructive or non-obstructive azoospermia. High testosterone levels before TESE decrease the chance of hypogonadism after TESE. These findings contribute to a better counselling of men scheduled for TESE.
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