BACKGROUND Factor affecting sperm retrieval rate (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in patients with non-obstructive azoospermia (NOA) have not been systematically evaluated. In addition, although micro-TESE (mTESE) has been advocated as the gold standard for sperm retrieval in men with NOA, its superiority over conventional TESE (cTESE) remains conflicting. OBJECTIVE AND RATIONALE The objective was to perform a meta-analysis of the currently available studies comparing the techniques of sperm retrieval and to identify clinical and biochemical factors predicting SRR in men with NOA. In addition, PRs and live birth rates (LBRs), as derived from subjects with NOA post-ICSI, were also analysed as secondary outcomes. SEARCH METHODS An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR derived from cTESE or mTESE in patients with NOA and their specific determinants were included. Data derived from genetic causes of NOA or testicular sperm aspiration were excluded. OUTCOMES Out of 1236 studies, 117 studies met the inclusion criteria for this study, enrolling 21 404 patients with a mean age (± SD) of 35.0 ± 2.7 years. cTESE and mTESE were used in 56 and 43 studies, respectively. In addition, 10 studies used a mixed approach and 8 studies compared cTESE with mTESE approach. Overall, a SRR per TESE procedure of 47[45;49]% (mean percentage [95% CI]) was found. No differences were observed when mTESE was compared to cTESE (46[43;49]% for cTESE versus 46[42;49]% for mTESE). Meta-regression analysis demonstrated that SRR per cycle was independent of age and hormonal parameters at enrolment. However, the SRR increased as a function of testis volume. In particular, by applying ROC curve analysis, a mean testis volume higher than 12.5 ml predicted SRR >60% with an accuracy of 86.2% ± 0.01. In addition, SRR decreased as a function of the number of Klinefelter’s syndrome cases included (S = −0.02[−0.04;−0.01]; P < 0.01. I = 0.12[−0.05;0.29]; P = 0.16). Information on fertility outcomes after ICSI was available in 42 studies. Overall, a total of 1096 biochemical pregnancies were reported (cumulative PR = 29[25;32]% per ICSI cycle). A similar rate was observed when LBR was analysed (569 live births with a cumulative LBR = 24[20;28]% per ICSI cycle). No influence of male and female age, mean testis volume or hormonal parameters on both PR and LBR per ICSI cycle was observed. Finally, a higher PR per ICSI cycle was observed when the use of fresh sperm was compared to cryopreserved sperm (PR = 35[30;40]%, versus 20[13;29]% respectively): however, this result was not confirmed when cumulative LBR per ICSI cycle was analysed (LBR = 30[20;41]% for fresh versus 20[12;31]% for cryopreserved sperm). WIDER IMPLICATIONS This analysis shows that cTESE/mTESE in subjects with NOA results in SRRs of up to 50%, with no differences when cTESE was compared to mTESE. Retrieved sperms resulted in a LBR of up to 28% ICSI cycle. Although no difference between techniques was found, to conclusively clarify if one technique is superior to the other, there is a need for a sufficiently powered and well-designed randomized controlled trial to compare mTESE to cTESE in men with NOA.

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Background The microRNA‐371a‐3p (miR‐371a‐3p) has been reported to be an informative liquid biopsy (serum and plasma) molecular biomarker for both diagnosis and follow‐up of patients with a malignant (testicular) germ cell tumor ((T)GCT). It is expressed in all histological cancer elements, with the exception of mature teratoma. However, normal testis, semen, and serum of males with a disrupted testicular integrity without a TGCT may contain miR‐371a‐3p levels above threshold, of which the cellular origin is unknown. Objectives Therefore, a series of relevant tissues (frozen and formalin‐fixed paraffin‐embedded (FFPE), when available) from the complete male urogenital tract (i.e., kidney to urethra and testis to urethra) and semen was investigated for miR‐371a‐3p levels using targeted quantitative RT‐PCR (qRT‐PCR). Materials and methods In total, semen of males with normospermia (n = 11) and oligospermia (n = 3) was investigated, as well as 88 samples derived from 32 different patients. The samples represented one set of tissues related to the entire male urogenital tract (11 anatomical locations), three sets for 10 locations, and four sets for six locations. Results All testis parenchyma (n = 17) cases showed low miR‐371a‐3p levels. Eight out of 14 (57%) semen samples showed detectable miR‐371a‐3p levels, irrespective of the amount of motile spermatozoa, but related to sperm concentration and matched Johnsen score (Spearman's rho correlation coefficient 0.849 and 0.871, p = 0.000, respectively). In all other tissues investigated, miR‐371a‐3p could not be detected. Discussion This study demonstrates that the miR‐371a‐3p in healthy adult males is solely derived from the germ cell compartment. Conclusions The observation is important in the context of applying miR‐371a‐3p as molecular liquid biopsy biomarker for diagnosis and follow‐up of patients with malignant (T)GCT. Moreover, miR‐371a‐3p might be an informative seminal biomarker for testicular germ cell composition.

Testicular sperm is increasingly used during in vitro fertilization treatment. Testicular sperm has the ability to fertilize the oocyte after intracytoplasmic sperm injection (ICSI), but they have not undergone maturation during epididymal transport. Testicular sperm differs from ejaculated sperm in terms of chromatin maturity, incidence of DNA damage and RNA content. It is not fully understood what the biological impact is of using testicular sperm, on fertilization, preimplantation embryo development and post-implantation development. Our goal was to investigate differences in human preimplantation embryo development after ICSI using testicular sperm (TESE-ICSI) and ejaculated sperm. We used time-lapse embryo culture to study these possible differences. Embryos (n = 639) originating from 208 couples undergoing TESE-ICSI treatment were studied and compared to embryos (n = 866) originating from 243 couples undergoing ICSI treatment with ejaculated sperm. Using statistical analysis with linear mixed models, we observed that pronuclei appeared 0.55 hours earlier in TESE-ICSI embryos, after which the pronuclear stage lasted 0.55 hours longer. Also, significantly more TESE-ICSI embryos showed direct unequal cleavage from the 1-cell stage to the 3-cell stage. TESE-ICSI embryos proceeded faster through the cleavage divisions to the 5- and the 6-cell stage, but this effect disappeared when we adjusted our model for maternal factors. In conclusion, sperm origin affects embryo development during the first embryonic cell cycle, but not developmental kinetics to the 8-cell stage. Our results provide insight into the biological differences between testicular and ejaculated sperm and their impact during human fertilization.

The aim of this study was to compare sperm DNA damage between men with a history of congenital undescended testis (UDT) and men with a history of acquired UDT. A long-term follow-up study of men with previous UDT was performed. Fifty men with congenital UDT who had undergone orchiopexy at childhood age, 49 men with acquired UDT after a 'wait-and-see'-protocol (e.g. awaiting spontaneous descent until puberty and perform an orchiopexy in case of non-decent), and 22 healthy proven fertile men were included. The DNA fragmentation index (DFI) using sperm chromatin structure assay (SCSA) was used to express the level of sperm DNA damage. Decreased fertility potential was considered if DFI was above 30%. Sperm DNA damage was not statistically different between cases of congenital and acquired UDT. DFI was significantly more often >30% in the complete group of men with congenital UDT (9/50; 18%) and in the subgroup with bilateral congenital UDT (3/7; 43%) in comparison with the controls (none) (p-value 0.049 and 0.01, respectively). Age at orchiopexy in congenital UDT had no statistical effect on DNA damage. In men with acquired UDT, DFI did not statistically differ between those having undergone orchiopexy and those experiencing spontaneous descent. This study supports the hypothesis that UDT is a spectrum representing both congenital UDT and acquired UDT. Sperm DNA damage at adult age is not influenced by age at orchiopexy in congenital UDT cases and by orchiopexy or spontaneous descent in acquired UDT cases.

Samenvatting Semencryopreservatie is een algemeen geaccepteerde methode om kinderwens in de toekomst mogelijk te maken voor mannen die door gonadotoxische chemoof radiotherapeutische behandeling onvruchtbaar dreigen te worden. In een retrospectief onderzoek in een cohort van 604 mannen met een maligne testistumor, toonden wij aan dat bij een op de zes patiënten semencryopreservatie niet mogelijk of suboptimaal was in verband met azoöspermie, aspermie of cryptozoöspermie. Bij deze patiënten kan testiculaire sperma-extractie (TESE) een alternatieve methode van fertiliteitspreservatie zijn. TESE kan tijdens de radicale orchiëctomie plaatsvinden uit niet-aangedaan testisparenchym dat naast de testistumor is gelegen, of uit de contralaterale testis. In dit artikel dragen wij argumenten aan voor semencryopreservatie bij patiënten met testistumoren vóór de radicale orchiëctomie. fertility in men with cancer that enables couples to embark on assisted reproduction. In 604 patients with testicular cancer, we retrospectively showed that sperm cryopreservation was unsuccessful in one out of six patients because of azoospermia, aspermia or cryptozospermia. In these patients, testicular sperm extraction (TESE) can be an alternative sperm preservation method. TESE can be performed during radical orchiectomy in normal testicular parenchyma adjacent to the testicular tumor or in the contralateral testis. We provide arguments for sperm preservation strategies in patients with testicular cancer before radical orchiectomy. Keywords sperm cryopreservation · testicular cancer · azoospermia · TESE · male infertility IntroductieSemencryopreservatie is een algemeen geaccepteerde methode om kinderwens in de toekomst mogelijk te maken voor mannen die onvruchtbaar dreigen te worden [1]. Semencryopreservatie wordt doorgaans aangeboden voor de aanvang van gonadotoxische chemo-of radiotherapeutische behandelingen.In het Erasmus MC wordt sinds 1983 semencryopreservatie aangeboden bij oncologische patiënten. Wij toonden eerder aan dat bij 7,5 % van de verwezen patiënten een azoöspermie wordt geconstateerd, waardoor semencryopreservatie niet mogelijk is [2]. De zaadkwaliteit bij cryopreservatie is significant lager bij mannen met een testiscarcinoom dan bij mannen met andere maligniteiten [2]. Pre-existente verminderde fertiliteit bij mannen met maligne kiemceltumoren zijn, net als cryptorchisme, testiculaire microcalcificaties en testisatrofie, geassocieerd met de

Literature concerning corporotomy location in multicomponent inflatable penile prosthetic surgery via a penoscrotal approach is scarce if not nonexistent. Aim of our study was to report practices in low-, moderate-, and high-volume penile implant centers regarding corporotomy location and evaluate its potential impact on intraoperative and short-term postoperative complications. Data from 18 (13 European and 5 American) implant centers were collected retrospectively between September 1st, 2018 and August 31st, 2019. Variables included: intraoperative proximal and distal corpus cavernosum length measurement, total corporal length measurement, total penile implant cylinder length, and length of rear tip extenders. Eight hundred and nine virgin penile implant cases were included in the analysis. Mean age of participants was 61.5 ± 9.6 years old. In total, 299 AMS 700™ (Boston Scientific, USA) and 510 Coloplast Titan® (Minneapolis, MN USA) devices were implanted. The mean proximal/distal corporal measurement ratio during corporotomy was 0.93 ± 0.29 while no statistical difference was found among low-, moderate-, and high-volume penile implant centers. A statistically significant correlation between lower proximal/distal measurement ratio and higher age (p = 0.0013), lower BMI (p < 0.0001), lower use of rear tip extenders (RTE) (p = 0.04), lower RTE length (p < 0.0001), and absence of diabetes (p = 0.0004) was reported. In a 3-month follow up period, 49 complications and 37 revision procedures were reported. This is the first study reporting the current practices regarding corporotomy location during IPP placement in a multicenter cohort, particularly when including such a high number of patients. Nevertheless, the retrospective design and the short follow up period limits the study outcomes. Corporotomy location during penoscrotal IPP implantation does not correlate with intraoperative or short-term postoperative complication rates. Future studies with longer follow up are needed in order to evaluate the association of corporotomy location with long-term complications.

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