Obstructive Azoospermia Group Research Articles

Reproductive and obstetric outcomes in TESE–ICSI cycles: A comparison between obstructive and non‐obstructive azoospermia

AbstractPurposeComparison of intracytoplasmic sperm injection cycles with testicular sperm extraction in obstructive azoospermia and non‐obstructive azoospermia are limited, and few studies have addressed obstetric and neonatal outcomes.DesignThis study analyzed couples who underwent testicular sperm extraction–intracytoplasmic sperm injection cycles for obstructive azoospermia and non‐obstructive azoospermia to determine whether impaired spermatogenesis in non‐obstructive azoospermia patients would lead to worse reproductive outcomes and higher rates of pregnancy complications and fetal anomalies. This study is a retrospective, single‐center analysis of all testicular sperm cycles performed between January 1, 2001 and December 31, 2020.ResultsA total of 392 couples were considered in the study, leading to 1066 induction cycles, 620 (58.2%) from patients with obstructive azoospermia and 446 (41.8%) from non‐obstructive azoospermia. The cumulative delivery rate did not significantly differ between the two groups (34% vs. 31%; p = 0.326). The miscarriage rate was similar between obstructive azoospermia and non‐obstructive azoospermia patients. Fertilization rate instead showed a statistically significant difference (obstructive azoospermia: 66.1 ± 25.7 vs. non‐obstructive azoospermia: 56.1 ± 27.0; p < 0.001). The overall maternal complication rate in the non‐obstructive azoospermia group was higher (10.7% vs. 18.4%; p = 0.035), but there was no statistical significance for each pathology. There was no statistical difference in gestational age between the two groups for both single and twin pregnancies. Seven cases of congenital defects occurred in the obstructive azoospermia group, while two cases occurred in the non‐obstructive azoospermia group.ConclusionsDespite impaired spermatogenesis in non‐obstructive azoospermia patients, there were no substantial differences in reproductive outcomes compared to patients with obstructive azoospermia, even in terms of obstetric safety and neonatal well‐being.

Global Analysis in Nonobstructive Azoospermic Testis Identifies miRNAs Critical to Spermatogenesis

Introduction. The etiology of male infertility characterized by non-obstructive azoospermia is largely unknown, especially at the molecular level. Identifying dysregulated microRNAs (miRNAs) in male infertility would be useful to achieve a more profound understanding of its pathogenesis. Methods. Small RNA sequencing was performed on the testicular tissues of 10 nonobstructive azoospermic patients with the Sertoli cell only syndrome (SCOS) and 8 obstructive azoospermic individuals with normal spermatogenesis. The expressions of two dysregulated miRNAs were validated by quantitative real-time polymerase chain reaction, confirming the results obtained by sequencing analysis. Bioinformatic analysis was undertaken to identify the main pathways impaired in complete spermatogenic failure. Results. A total of 136 miRNAs were detected to be differentially expressed in the Sertoli cell only syndrome group in comparison with the obstructive azoospermia group. Bioinformatic analysis suggested that the altered miRNAs were substantially involved in pathways related to spermatogenesis. Conclusions. Our study investigates the entire profile of miRNAs with emphasis on the crucial role of miRNAs in idiopathic Sertoli cell only syndrome, suggesting potential targets for employing molecular therapeutic strategies in the treatment of spermatogenic failure.

Leydig Cells in Patients with Non-Obstructive Azoospermia: Do They Really Proliferate?

Background: Non-obstructive azoospermia (NOA) is a form of male infertility caused by disorders of the testicular parenchyma and impaired spermatogenesis. This study aimed to investigate the nature of Leydig cell changes in patients with NOA, especially whether their actual proliferation occurred. Methods: 48 testicular biopsies from infertile patients with NOA and 24 testicular biopsies originating from azoospermic patients suffering from obstructive azoospermia (OA) were included in the study. Leydig cells and their possible proliferative activity were analysed by immunohistochemistry and morphometry (stereology). Results: Unlike in the OA group, Leydig cells in NOA patients were sometimes organised into larger clusters and displayed an abundant cytoplasm/hypertrophy. Moreover, significant fibrosis of the interstitial compartment was demonstrated in some NOA samples, often accompanied by inflammatory cells. Stereological analysis showed no increase/proliferation of Leydig cells; on the contrary, these cells decreased in number in the NOA group. Conclusions: The decrease in the number of Leydig cells can be explained by previous inflammatory changes within the testicular interstitium and consequent interstitial fibrosis. The interstitial fibrosis might have a deteriorating effect on Leydig cells.

Immunohistochemical examination of androgen receptor and estrogen receptor alpha expressions in obstructive and non-obstructive azoospermia

ABSTRACT In this study, the expression of the androgen receptor (AR) and estrogen receptor alpha (ERα) in testicular tissue of male patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) were evaluated by immunohistochemistry. NOA (n = 23) and OA (n = 21) groups were created according to clinical and laboratory archival records. Testicular sperm extraction tissue sections were evaluated according to Johnsen’s tubular biopsy scoring (JTBS) method. ERα and AR immunostaining results were evaluated semiquantitatively. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol were analyzed. Serum FSH and LH concentrations were greater, and testosterone concentrations were lower than the normal values in the NOA group, whereas the OA group revealed normal hormonal values. Serum estradiol concentrations in groups were in the normal range. JTBSs were significantly lower in the NOA group. Decreased AR expression and increased ERα expression were observed in the NOA group compared to the OA group. This suggests that ERα and AR are expressed in Sertoli cells, Leydig cells, and myoid cells and are required for normal testicular function. Decreased expression of the AR and increased expression of ERα in the testis may negatively affect spermatogenesis. Abbreviations: AR: androgen receptor; ER: estrogen receptor; ERα: estrogen receptor alpha; FSH: follicle-stimulating hormone; JTBS: Johnsen’s tubular biopsy scoring; LH: luteinizing hormone; NOA: non-obstructive azoospermia; OA: obstructive azoospermia; TESE: testicular sperm extraction

Gene Alterations and Expression Spectrum of NANOS3 in Nonobstructive Azoospermia.

Nanos3, a zinc finger RNA-binding protein, suppresses the apoptosis in primordial germ cells (PGCs) during migration to gonads and maintains the PGC population. The genetic variations and expression of NANOS3 in patients with non-obstructive azoospermia (NOA) were evaluated in this study. The study included 100 idiopathic infertile men with NOA and 100 fertile men as the as the case and control groups, respectively. NANOS3 gene variations were analyzed using the standard polymerase chain reaction (PCR) and sequencing. For mRNA and protein expression analysis, testicular biopsy specimens from 27 patients including 9 obstructive azoospermia (OA), 9 maturation arrest (MA), and 9 Sertoli cell-only syndromes (SCOS) were collected and evaluated using the real-time PCR technique and immunohistochemistry. Although the evaluation of the 5`UTR regulatory region has shown the significant difference in the numbers of TG repeats in rs11182456 between groups, the odd ratio was not strong enough to consider that as a certain risk factor lead to azoospermia and infertility. Meanwhile, NANOS3 expression at mRNA level had a significant difference among OA, SCOS, and MA groups.

P–032 Assessment of embryonic developmental outcome of direct unequal cleavage in patients with non-obstructive azoospermia and/or obstructive azoospermia

Abstract Study question Does direct unequal cleavage (DC) affect embryonic development after ICSI with testicular sperm (TESE-ICSI) in patients with non-obstructive azoospermia (NOA) and/or obstructive azoospermia (OA)? Summary answer The incidence of DC at the first cleavage (DC1) was extremely high and DC1 negatively affected embryonic development in NOA patients. What is known already It has been reported that the blastocyst development of embryos with direct cleavage (DC) was significantly lower than that without DC, but the clinical pregnancy rate after blastocyst transfer was not different with or without DC. The incidence of DC has been reported to be significantly higher after ICSI with testicular sperm (TESE-ICSI) than ICSI with ejaculated sperm (Ej), but to our knowledge, there are few reports investigating that the embryos with DC after TESE-ICSI affect embryonic development. Study design, size, duration We conducted a retrospective cohort study using time-lapse incubators (Geri, Genea Biomedx, Australia) from September 2018 to November 2020. Of 1033 two-pronuclear (2PN) embryos from TESE-ICSI, 486 and 547 embryos were from OA (35.9±5.5 years) and NOA (33.7±5.2 years), respectively. As an age matched control, we chose 581 embryos from ICSI using Ej (36.5±4.4 years). Participants/materials, setting, methods DC embryos were classified as DC1 (DC at first cleavage), DC2 (DC at second cleavage), and non-DC (without DC). The incidences of DC1 or DC2 and blastocyst development rates were compared among OA, NOA and Ej groups. In TESE-ICSI group, we compared blastocyst development rates with or without DC between good and poor quality embryos on day 3. Good quality embryos were defined as 8 cells with G3 or more by the Veeck’s classification. Main results and the role of chance DC1 incidence was significantly higher in NOA (37.3%) than OA (27.8%) and Ej (22.7%) (P < 0.01), whereas DC2 incidence was not statistically different among three groups; NOA (15.7%), OA (15.0%) and Ej (13.4%). Blastocyst development rates in DC1 were 17.8%, 19.5% and 25.8% for NOA, OA and Ej, respectively, which were significantly lower compared to non-DC in corresponding three groups (65.1%, 67.7%, and 68.5%, respectively, P < 0.01). In TESE-ICSI group, good-quality embryo rate on day 3 was significantly lower in DC1 (34.5%, P < 0.01) than DC2 (60.9%) or non-DC (54.2%). Additionally, blastocyst development rates in DC1 and DC2 were significantly lower than non-DC regardless of embryonic grades on day 3 (35.1%, 51.0%, and 81.6% for good-quality embryos on day 3, 10.1%, 27.0%, and 49.1% for poor-quality embryos on day 3, respectively, P < 0.05). When immotile sperm was used for TESE-ICSI, DC1 incidence was 40.0% (6/15), which did not show statistically differences. When performing single frozen-thawed blastocyst transfers, no pregnancies resulted from either DC1 (n = 13) or DC2 (n = 3) embryos in TESE-ICSI group. Limitations, reasons for caution We had a few data about the pregnancy rates after blastocyst transfers with DC, because embryos with DC were seldom transferred due to those lower priority. Although DC might be influenced by the sperm, we did not analyze the incidence of DC by taking the semen factors into account. Wider implications of the findings: The incidence of DC1 was extremely high and DC1 negatively affected embryonic development in NOA patients. Therefore, it is important to observe embryos using time-lapse incubator in order to recognize embryos with/without pregnancy potential, especially for embryos with DC1 in NOA patients. Trial registration number Not applicable

MRI in the evaluation of the azoospermic male.

PURPOSE We aimed to show the usefulness of magnetic resonance imaging (MRI) in the evaluation of infertile men and its ability to distinguish obstructive from nonobstructive azoospermia. METHODS Between April 2015 and February 2018, 45 azoospermic men underwent scrotal MRI. We evaluated the images with an emphasis on signal characteristics of the testis and morphologic changes typical for obstruction. Testicular volume (TV), apparent diffusion coefficient (ADC) value, T1 and T2 signal ratios (testis/muscle) were measured for every testis. On the basis of histologic results, patients were divided into two groups: obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). RESULTS Testes of patients in the OA group had significantly lower ADC values (mean 0.876±101 ×10-3 mm2/s) than in the NOA group (mean, 1.114±147 ×10-3 mm2/s). TV was significantly higher in patients with OA (median, 17.61 mL; range, 11.1-38.4 mL) than in those with NOA (median, 10.5 mL; range, 5.2-22.2 mL). ROC analysis showed that both TV and ADC values were highly predictive for distinguishing between OA and NOA patients, with an area under the ROC curve of 0.82 and 0.92 respectively. A cutoff value of ≥12.4 mL could distinguish obstructive from nonobstructive azoospermia with a sensitivity of 92% and specificity of 63%, whereas for ADC measurements a cutoff value of ≥0.952 ×10-3 mm2/s exhibited a sensitivity of 81% and specificity of 90% There was no statistically significant difference in T1 and T2 signal ratios between both groups. Abnormalities typical for obstruction of the male reproductive tract (e.g., dilatation of ejaculatory ducts, prostatic or seminal vesicle cysts) were found in 78% of patients (14/18) in the obstructive group. CONCLUSION Scrotal MRI is a very effective tool for the evaluation of azoospermic men and may provide important information facilitating interventional treatment of infertility.

Homo Sapiens (Human) microRNA 187 Expression Is Dysregulated in Testis of Non-obstructive Azoospermic Men

Introduction: MiRNA expression alterations are closely related to growth, proliferation, and cell development. In addition, miR-187 has been found to regulate cellular proliferation. Further, spermatogenesis is a highly complicated process which is regulated through several genes targeted by miRNAs. However, no study has completely addressed the etiology of spermatogenic impairments. Accordingly, the present study examined the expression pattern of Homo sapiens (human) microRNA (hsa-mir-187) in the testicular biopsies of infertile men with non-obstructive azoospermia (NOA) and Sertoli cell-only syndrome (SCOS) subtype in comparison with those with obstructive azoospermia (OA). Methods: Quantitative reverse‐transcription polymerase chain reaction analysis was performed to assess the expression level of hsa-mir-187 using the ΔΔCt method. Results: Our data indicated that hsa-mir-187 was significantly up-regulated in the testis of the SCOS group (P˂ 0.05) in comparison with the OA group. Conclusion: In general, the findings suggest that the differential expression of hsa-mir-187 is linked with male infertility and shed more light on molecular defects that underlie spermatogenic impairments.

Does the FSHB c.‐211G>T polymorphism impact Sertoli cell number and the spermatogenic potential in infertile patients?

A genetic variant within the FSHB gene can deviate FSH action on spermatogenesis. The c.-211G>T FSHB single nucleotide polymorphism impacts FSHB transcription and biosynthesis due to interference with the LHX3 transcription factor binding. This SNP was previously shown to be strongly associated with lowered testicular volume, reduced sperm counts, and decreased FSH levels in patients carrying one or two T-alleles. To determine the impact of the SNP FSHB c.-211G>T on Sertoli cell (SC) number, Sertoli cell workload (SCWL) and thereby spermatogenic potential. Testicular biopsies of 31 azoospermic, homozygous T patients (26 non-obstructive azoospermia (NOA), and five obstructive azoospermia (OA)) were matched to patients with GG genotype. Marker proteins for SC (SOX9), spermatogonia (MAGE A4), and round spermatids (CREM) were used for semi-automatical quantification by immunofluorescence. SCWL (number of germ cells served by one SC) was determined and an unbiased clustering on the patient groups performed. Quantification of SC number in NOA patients did not yield significant differences when stratified by FSHB genotype. SC numbers are also not significantly different between FSHB genotypes for the OA patient group and between NOA and OA groups. SCWL in the NOA patient cohort is significantly reduced when compared to the OA control patients; however, in neither group an effect of the genotype could be observed. The cluster analysis of the whole study cohort yielded two groups only, namely NOA and OA, and no clustering according to the FSHB genotype. The FSHB c.-211G>T polymorphism does not affect SC numbers or SCWL, thereby in principle maintaining the spermatogenic potential. The previously observed clinical phenotype for the FSHB genotype might therefore be caused by a hypo-stimulated spermatogenesis and not due to a decreased SC number.

Pregnancy and Neonatal Outcomes in Azoospermic Men After Intracytoplasmic Sperm Injection Using Testicular Sperm and Donor Sperm.

BackgroundThe safety of intracytoplasmic sperm injection (ICSI) with testicular sperm in azoospermic men has been a concern. We evaluated ICSI outcomes, including neonatal outcomes, in children born using testicular sperm or donor sperm.Material/MethodsNinety-nine males with nonobstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction (micro-TESE) and 126 males with obstructive azoospermia (OA) were included in this study. Sixty-one patients with NOA used donor sperm for ICSI on the day of oocyte retrieval when no spermatozoa were identified by micro-TESE on the day before oocyte retrieval. ICSI outcomes were compared among OA, donor, and NOA groups.ResultsThere was no statistical difference in terms of female partner characteristics among OA, donor, and NOA groups. The normal fertilization rate (P=0.005), high quality embryo rate (P=0.014), implantation rate (P<0.001), clinical pregnancy rate (P=0.015), live birth rate (P=0.043) were significant lower in the NOA group, compared with the donor sperm group. The normal fertilization rate was significant lower in the NOA group than the OA group (P<0.001), but the live birth rate was not significantly lower (P=0.058). The high-quality embryo rate (P=0.014) and implantation rate (P=0.009) were lower in the OA group than the donor group. No differences between groups were observed in our study regarding neonatal parameters of the infants born.ConclusionsThe fertilization and pregnancy outcomes were negatively affected by using testicular sperm from males with NOA. Once a live birth was achieved, there was no difference in neonatal outcomes.

[Impact of multiple morphological anomalies of the flagella on the outcomes of intracytoplasmic sperm injection for males with infertility].

Objective: To evalute the clinical outcomes of intracytoplasmic sperm injection(ICSI) for infertility male with severe asthenospermia induced by multiple morphological anomalies of the flagella (MMAF). Methods: The clinical data of 15 patient with MMAF were retrospectively analyzed, who underwent ICSI treatment using hyponotic swelling test the "live" sperm in the Department of Reproductive Medicine of Yantai Yuhuangding Hospital from January 2011 to December 2016. Another 30 obstructive azoospermia (OA)patients are matched strictly who also accepted ICSI in the same treatment time. The two groups were compared in the couples'age, the body mass index(BMI), the duration of infertility, the retrieved oocytes, the number of ICSI oocytes, and the rates of fertilization, cleavage, transferrable embryos, good embryos, embryos implanted, clinical pregncncy, early abortion, singleton and twins. Results: After 27 cycles of ICSI, all of the MMAF patients achieved clinical pregnancy, including 11 cases of live birth, 2 cases of spontaneous abortion, and 2 cases of pregnancy maintenance. There were no significant difference between MMAF and OA groups in the couples'age and BMI, or the numbers of retrieved oocytes and ICSI oocytes(P>0.05), but the differences in the infertility duration had statistical meaning(P<0.001). No statistical differences were observed among groups in ICSI fertility rate(92.0% vs 91.6%), clesvage rate(95.4% vs 96.5%), high-quality embryonic rate(56.5% vs 57.5%), good blastocyst rate(23/61 vs 35/94), embryo implantation rate(20/48 vs 35/75), early abortion rate(4/19 vs 8/36), clinical pregncncy rate(15/27 vs 28/50), singleton rate (10/13 vs 20/25)and twinning rate(3/13 vs 5/25)(P>0.05). Conclusions: MMAF may not affect ICSI treatment outcomes, but genetic defects can be transmitted through ICSI. The affected couples should be informed of the necessity of prenatal genetic diagnosis before embryo implantation and the inevitable vertical transmission of genetic problems to the offspring.

Distinguishing non-obstructive azoospermia from obstructive azoospermia in Taiwanese patients by hormone profile and testis size

BackgroundAn accurate diagnosis of the etiology of azoospermia is crucial, as sperm retrieval methods differ between patients with non-obstructive azoospermia (NOA) and obstructive azoospermia (OA). The aim of this study was to determine hormone and testes size cutoff values to identify the cause of azoospermia in Taiwanese patients. MethodsThe medical records of azoospermic patients were retrospectively collected from April 2008 to July 2016, including hormone profile, physical examination findings, and testes size. Bilateral testes biopsies or microdissection testicular sperm extraction were performed in all patients for a definite diagnosis. The diagnostic parameters used to distinguish NOA from OA were analyzed using the t-test and receiver operating characteristic curves. ResultsA total of 51 patients with OA and 156 with NOA were included. The mean levels of testosterone (4.5 vs. 3.4 ng/ml) and E2 (26.3 vs. 19.2 pg/ml) were significantly higher in the OA group, whereas the levels of follicular stimulating hormone (FSH) (5.6 vs. 25.4 mIU/ml) and Leutinizing hormone (LH) (3.7 vs. 11.6 mIU/ml) were lower. Receiver operating characteristic curve analysis revealed that FSH and right testis size were the best individual diagnostic predictors. Using a combination of FSH >9.2 mIU/ml and right testis size <15 ml, the positive predictive value for NOA was 99.2% and 81.8% for OA. ConclusionA combination of FSH >9.2 mIU/ml and right testis size <15 ml was a strong predictor of NOA in our Taiwanese patients.

Distribution and number of Cajal-like cells in testis tissue with azoospermia

We investigated the number and distribution of Cajal-like cells in patients with azoospermia. A total of 99 patients with non-obstructive azoospermia were divided into subgroups [19 patientsin hypospermatogenesis group (S1), 40 patients in maturation arrest group (S2), 20 patients in a Sertoli cell-only syndrome (S3), and 20 patients in a testicular atrophy and fibrosis group (S4)], and 20 patients with obstructive azoospermia group (S0). Sections stained with a c-kit antibody were studied by light microscopy to determine the number and distribution of Cajal-like cells in peritubular and perivascular areas of testis. The number of Cajal-like cells were higher in all the non-obstructive groups than in the obstructive group (S0: 2.43 cells/mm2, S1: 3.14 cells/mm2, S2: 4.00 cells/mm2, S3: 4.57 cells/mm2, S4: 3.86 cells/mm2) but statistically significantly different (p<0.05) in the S2 and S3 subgroups only. Distribution of Cajal-like cells were similar in all groups. The number and distribution of Cajal-like cells in non-obstructive groups suggest that these cells may affect spermatogenesis. This cellular type can be responsible for the regulation of cellular motility or spermatogenesis. Electrophysiological and electron microscopic studies are needed to better define morphology and function of Cajal-like cells in the testis, especially totally the normal testis tissue.

Comparison of intracytoplasmic sperm injection with testicular spermatozoa success in infertile men with obstructive and non-obstructive azoospermia; a retrospective analysis

The aim of this study was to compare the outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer between couples with infertility due to male non-obstructive azoospermia (NOA) and obstructive azoospermia (OA). A retrospective analysis of 234 couples with azoospermia who were treated by ICSI and embryo transfer between January 2007 and October 2010 was performed. There were 61 couples in NOA group and 173 couples in OA group. Fertilization rates, pregnancy and clinical pregnancy rates were the main outcome measures. The number of retrieved mature oocytes, injected oocytes, metaphase II (MII) oocytes, two distinct pronuclei oocytes, cleavage embryos and embryos transferred was not significantly different between the groups. The fertilization rate was significantly lower in NOA group when compared to OA group (56.2 vs. 66.7%, respectively; p = 0.013) and the pregnancy rate was significantly lower in NOA group than OA group (36.1 vs. 50.9%, respectively; p = 0.046). The clinical pregnancy rates were not statistically different between the patients with NOA and OA azoospermia groups (24.6 vs. 36.4%, respectively; p = 0.09). This study suggests that ICSI and embryo transfer together with testicular sperm extraction results in statistically significant lower fertilization and pregnancy rates in men with NOA when compared to men with OA.

Histological alterations in Leydig cells and macrophages in azoospermic men.

The study aimed to compare the histological features of Leydig cells and macrophages in the testicular interstitium of obstructive versus nonobstructive azoospermia. Thirty-nine azoospermic men undergoing testicular sperm extraction during intracytoplasmic sperm injection were allocated into obstructive azoospermia group (GI) and nonobstructive azoospermia group (GII) which was subdivided into Sertoli cell-only syndrome (GIIA), germ cell arrest (GIIB) and hypospermatogenesis (GIIC) subgroups. Serum LH, FSH and testosterone levels were measured. Ultrastructural changes and the mean number of CD68-positive cells were estimated in the different groups. In GIIA, Leydig cells' processes came in contact with macrophages and showed smooth endoplasmic reticulum dilatation. In GIIB, Leydig cells showed apoptotic changes. Macrophages were commonly encountered in their vicinity demonstrating large number of lysosomes. In GIIC, Leydig cells showed euchromatic nuclei. Macrophages showed expulsion of their lysosomal contents in the interstitium surrounded by apoptotic bodies. The mean count of total CD68-positive macrophages was higher in cases of obstructive azoospermia with nonsignificant differences compared to nonobstructive azoospermia groups. Significant increase in FSH level was detected in GIIA compared to GI. It is concluded that structural interactions might take place between Leydig cells and macrophages in the interstitial tissue of azoospermic men.

Clinical outcomes and development of children born to couples with obstructive and nonobstructive azoospermia undergoing testicular sperm extraction-intracytoplasmic sperm injection: A comparative study

ObjectiveTo evaluate and compare the clinical outcomes and development of children born between obstructive azoospermia (OA) couples and nonobstructive azoospermia couples (NOA) after testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). Materials and methodsData were collected from infertile couples suffering from azoospermia who underwent TESE and ICSI from January 2001 to December 2009 at Chang Gung Memorial Hospital, Taiwan. A total of 154 ICSI cycles were performed using extracted testicular sperm from men with obstructive azoospermia (67 ICSI cycles) and men with nonobstructive azoospermia (87 ICSI cycles). Retrospective analysis of clinical outcomes and development of children born after TESE-ICSE between obstructive azoospermia couples and nonobstructive azoospermia couples. ResultsThe assisted reproductive technology (ART) result between OA and NOA groups, including age, E2 level on hCG day, number of oocytes retrieved, normal fertilization rate, zygote Grade 1 score distribution, number of top-quality embryos transferred, clinical pregnancy rate per transfer, chemical pregnancy rate per transfer, implantation rate, live birth rate per transfer, and abortion rate per transfer, were all similar. Thirty-one live births resulted from 67 ICSE cycles in the OA group and 33 live births from 87 ICSE cycles in the NOA group. The obstetric and perinatal outcomes were similar between the groups, and children conceived by using ICSI were generally healthy without raised tendency of major birth defect and development impairment. ConclusionIn our study, there were no differences in the fertility rate and clinic pregnancy rate between the OA and NOA groups using TESE-ICSI. Also, the clinical outcomes and development of children were similar between the OA and the NOA groups using TESE-ICSI.

Correlation between leptin content and sperm retrieval in cases of functional azoospermia

IntroductionTesticular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) became the preferable techniques for solving the problem of azoospermic men. Non-invasive techniques are needed to predict sperm retrieval chance before TESE to avoid the psychological and physiological problems that may be developed. AimTo investigate the correlation between serum, seminal and testicular leptin levels and sperm retrieval in functional azoospermic men. MethodsThe study included 61 men classified into 4 groups; normozoospermia (NOR), obstructive azoospermia (OA), positive non-obstructive azoospermia (NOA (+)) and negative non-obstructive azoospermia (NOA (−)). Blood FSH, LH, Prolactin, Free and Total testosterone levels plus serum and seminal leptin levels were measured for all groups. For azoospermic groups, TESE and testicular leptin level were applied. Main outcome measuresBoth OA and NOR groups were used as control groups. The prediction accuracy for FSH and serum, seminal and testicular leptin was compared by receiver operating characteristic (ROC) curve analysis. ResultsThere were no significant differences in serum leptin levels among the four groups. Azoospermic groups showed higher seminal leptin levels than the NOR group. Seminal and Testicular leptin levels of NOA (−) men were significantly increased in comparison with OA and NOA (+) men. There was a significant negative correlation between serum leptin and total testosterone concentrations, and a significant positive correlation between testicular and seminal leptin concentrations. In ROC curve; for differentiation between positive and negative NOA, areas under the curve (AUC) of testicular and seminal leptin were greater than that of serum leptin. The combination of seminal leptin with FSH gave AUC greater than that of FSH alone. ConclusionThere is a role for leptin in spermatogenesis, and seminal leptin can be used as a good assistant marker to increase the prediction accuracy for sperm retrieval in NOA men especially in combination with FSH.

Comparison of ART outcome between non-obstructive azoospermia and obstructive azoospermia: 15 years experiences

ObjectiveThe introduction of ICSI has revolutionized the treatment of severe male infertility. Moreover, ICSI using testicular spermatozoa has been commonly applied in the treatment of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). However, some authors describe similar and high fertilization and pregnancy rates in NOA patients whereas others report lower outcomes in NOA than in OA patients. In this study, we evaluated the differences on ART outcome after ICSI with frozen-thawed testicular spermatozoa between NOA and OA.DesignThis is a retrospective study from 1999 to 2013.Materials and MethodsMultiple testicular biopsy or micro-dissection TESE was performed in NOA patients while simple testicular biopsy was performed in OA patients. ICSI was performed with frozen-thawed testicular spermatozoa from NOA or OA. The ART outcome in the NOA group (4,295 oocytes, 317 cycles) and the OA group (4,187 oocytes, 336 cycles) were compared.ResultsThe wife’s average age and the number of the oocytes retrieved of both groups did not have the significant difference. However, the normal fertilization rate in the NOA group (67.9%) was significantly lower than that in the OA group (77.0%). The average number of embryo transferred was comparable between the two groups. And, the pregnancy rate and the implantation rate did not have the significant difference between the two groups. However, the delivery rate in the NOA group was significantly lower than that in the OA group (32.3% vs 40.8%). The mean birth weight in the NOA group (2953.5±487.9g) was comparable with that in the OA group (2997.3±356.9g). The malformation rate was almost same between the two groups.ConclusionThe normal fertilization rate and the delivery rate in the NOA group were significantly lower than those in the OA group. ObjectiveThe introduction of ICSI has revolutionized the treatment of severe male infertility. Moreover, ICSI using testicular spermatozoa has been commonly applied in the treatment of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). However, some authors describe similar and high fertilization and pregnancy rates in NOA patients whereas others report lower outcomes in NOA than in OA patients. In this study, we evaluated the differences on ART outcome after ICSI with frozen-thawed testicular spermatozoa between NOA and OA. The introduction of ICSI has revolutionized the treatment of severe male infertility. Moreover, ICSI using testicular spermatozoa has been commonly applied in the treatment of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). However, some authors describe similar and high fertilization and pregnancy rates in NOA patients whereas others report lower outcomes in NOA than in OA patients. In this study, we evaluated the differences on ART outcome after ICSI with frozen-thawed testicular spermatozoa between NOA and OA. DesignThis is a retrospective study from 1999 to 2013. This is a retrospective study from 1999 to 2013. Materials and MethodsMultiple testicular biopsy or micro-dissection TESE was performed in NOA patients while simple testicular biopsy was performed in OA patients. ICSI was performed with frozen-thawed testicular spermatozoa from NOA or OA. The ART outcome in the NOA group (4,295 oocytes, 317 cycles) and the OA group (4,187 oocytes, 336 cycles) were compared. Multiple testicular biopsy or micro-dissection TESE was performed in NOA patients while simple testicular biopsy was performed in OA patients. ICSI was performed with frozen-thawed testicular spermatozoa from NOA or OA. The ART outcome in the NOA group (4,295 oocytes, 317 cycles) and the OA group (4,187 oocytes, 336 cycles) were compared. ResultsThe wife’s average age and the number of the oocytes retrieved of both groups did not have the significant difference. However, the normal fertilization rate in the NOA group (67.9%) was significantly lower than that in the OA group (77.0%). The average number of embryo transferred was comparable between the two groups. And, the pregnancy rate and the implantation rate did not have the significant difference between the two groups. However, the delivery rate in the NOA group was significantly lower than that in the OA group (32.3% vs 40.8%). The mean birth weight in the NOA group (2953.5±487.9g) was comparable with that in the OA group (2997.3±356.9g). The malformation rate was almost same between the two groups. The wife’s average age and the number of the oocytes retrieved of both groups did not have the significant difference. However, the normal fertilization rate in the NOA group (67.9%) was significantly lower than that in the OA group (77.0%). The average number of embryo transferred was comparable between the two groups. And, the pregnancy rate and the implantation rate did not have the significant difference between the two groups. However, the delivery rate in the NOA group was significantly lower than that in the OA group (32.3% vs 40.8%). The mean birth weight in the NOA group (2953.5±487.9g) was comparable with that in the OA group (2997.3±356.9g). The malformation rate was almost same between the two groups. ConclusionThe normal fertilization rate and the delivery rate in the NOA group were significantly lower than those in the OA group. The normal fertilization rate and the delivery rate in the NOA group were significantly lower than those in the OA group.

Human zygotes respond to sperm DNA damage by slowing DNA replication

ObjectiveSome authors describe similar and high fertilization and pregnancy rates in non-obstructive azoospermia (NOA) patients whereas others report lower outcomes in NOA than in obstructive azoospermia (OA) patients. Sperm DNA damage is associated with reduced fertilization rates, embryo quality and pregnancy rates and higher rates of spontaneous miscarriage and childhood disease. Meanwhile, mouse zygotes respond to sperm DNA damage through a non-apoptotic mechanism that acts by slowing paternal DNA replication and embryonic development. In this study, we compared the early development of embryos fertilized with NOA and OA spermatozoa by using time-lapse monitoring system.DesignThis is a retrospective study.Materials and MethodsSix oocytes with ICSI using testicular spermatozoa from NOA and 35 oocytes with OA from 2013 to 2014 were used. The exact times for each embryo division and developmental parameters were calculated in hours after ICSI. Time-lapse images of each embryo were retrospectively analyzed by PrimoVision software. The developmental events observed in each embryo were at the time of the visibility of two pronuclei (2PN), syngamy, two cells and four cells. These parameters were compared between the NOA group and the OA group.ResultsThe time of the visibility of 2PN in the NOA group (9.5±1.4 hours) was significantly earlier than that in the OA group (12.1±2.3 hours). However, the time from the visibility of 2PN to the syngamy in the NOA group (13.2±3.4 hours) was significantly longer than that in the OA group (10.6±2.7 hours). The time between the syngamy and the two cells in the NOA group (12.2±1.3 hours) was comparable with that in the OA group (16.6±10.2 hours). The time from the two cells to the four cells in the NOA group (13.5±3.5 hours) was also comparable with that in the OA group (10.0±4.2 hours).ConclusionThe time from the visibility of 2PN to the pronuclear fading (syngamy) after ICSI with testicular spermatozoa from NOA was prolonged compared to that after ICSI with testicular spermatozoa from OA. ObjectiveSome authors describe similar and high fertilization and pregnancy rates in non-obstructive azoospermia (NOA) patients whereas others report lower outcomes in NOA than in obstructive azoospermia (OA) patients. Sperm DNA damage is associated with reduced fertilization rates, embryo quality and pregnancy rates and higher rates of spontaneous miscarriage and childhood disease. Meanwhile, mouse zygotes respond to sperm DNA damage through a non-apoptotic mechanism that acts by slowing paternal DNA replication and embryonic development. In this study, we compared the early development of embryos fertilized with NOA and OA spermatozoa by using time-lapse monitoring system. Some authors describe similar and high fertilization and pregnancy rates in non-obstructive azoospermia (NOA) patients whereas others report lower outcomes in NOA than in obstructive azoospermia (OA) patients. Sperm DNA damage is associated with reduced fertilization rates, embryo quality and pregnancy rates and higher rates of spontaneous miscarriage and childhood disease. Meanwhile, mouse zygotes respond to sperm DNA damage through a non-apoptotic mechanism that acts by slowing paternal DNA replication and embryonic development. In this study, we compared the early development of embryos fertilized with NOA and OA spermatozoa by using time-lapse monitoring system. DesignThis is a retrospective study. This is a retrospective study. Materials and MethodsSix oocytes with ICSI using testicular spermatozoa from NOA and 35 oocytes with OA from 2013 to 2014 were used. The exact times for each embryo division and developmental parameters were calculated in hours after ICSI. Time-lapse images of each embryo were retrospectively analyzed by PrimoVision software. The developmental events observed in each embryo were at the time of the visibility of two pronuclei (2PN), syngamy, two cells and four cells. These parameters were compared between the NOA group and the OA group. Six oocytes with ICSI using testicular spermatozoa from NOA and 35 oocytes with OA from 2013 to 2014 were used. The exact times for each embryo division and developmental parameters were calculated in hours after ICSI. Time-lapse images of each embryo were retrospectively analyzed by PrimoVision software. The developmental events observed in each embryo were at the time of the visibility of two pronuclei (2PN), syngamy, two cells and four cells. These parameters were compared between the NOA group and the OA group. ResultsThe time of the visibility of 2PN in the NOA group (9.5±1.4 hours) was significantly earlier than that in the OA group (12.1±2.3 hours). However, the time from the visibility of 2PN to the syngamy in the NOA group (13.2±3.4 hours) was significantly longer than that in the OA group (10.6±2.7 hours). The time between the syngamy and the two cells in the NOA group (12.2±1.3 hours) was comparable with that in the OA group (16.6±10.2 hours). The time from the two cells to the four cells in the NOA group (13.5±3.5 hours) was also comparable with that in the OA group (10.0±4.2 hours). The time of the visibility of 2PN in the NOA group (9.5±1.4 hours) was significantly earlier than that in the OA group (12.1±2.3 hours). However, the time from the visibility of 2PN to the syngamy in the NOA group (13.2±3.4 hours) was significantly longer than that in the OA group (10.6±2.7 hours). The time between the syngamy and the two cells in the NOA group (12.2±1.3 hours) was comparable with that in the OA group (16.6±10.2 hours). The time from the two cells to the four cells in the NOA group (13.5±3.5 hours) was also comparable with that in the OA group (10.0±4.2 hours). ConclusionThe time from the visibility of 2PN to the pronuclear fading (syngamy) after ICSI with testicular spermatozoa from NOA was prolonged compared to that after ICSI with testicular spermatozoa from OA. The time from the visibility of 2PN to the pronuclear fading (syngamy) after ICSI with testicular spermatozoa from NOA was prolonged compared to that after ICSI with testicular spermatozoa from OA.

Relationships between sperm DNA fragmentation, age of donors and patients and children with psychic disorders

OBJECTIVE: Some authors describe similar and high fertilization and pregnancy rates in non-obstructive azoospermia (NOA) patients whereas others report lower outcomes in NOA than in obstructive azoospermia (OA) patients. Sperm DNA damage is associated with reduced fertilization rates, embryo quality and pregnancy rates and higher rates of spontaneous miscarriage and childhood disease. Meanwhile, mouse zygotes respond to spermDNA damage through a non-apoptoticmechanism that acts by slowing paternal DNA replication and embryonic development. In this study, we compared the early development of embryos fertilized with NOA and OA spermatozoa by using time-lapse monitoring system. DESIGN: This is a retrospective study. MATERIALS AND METHODS: Six oocytes with ICSI using testicular spermatozoa from NOA and 35 oocytes with OA from 2013 to 2014 were used. The exact times for each embryo division and developmental parameters were calculated in hours after ICSI. Time-lapse images of each embryo were retrospectively analyzed by PrimoVision software. The developmental events observed in each embryo were at the time of the visibility of two pronuclei (2PN), syngamy, two cells and four cells. These parameters were compared between the NOA group and the OA group. RESULTS: The time of the visibility of 2PN in the NOA group (9.5 1.4 hours) was significantly earlier than that in the OA group (12.1 2.3 hours). However, the time from the visibility of 2PN to the syngamy in the NOA group (13.2 3.4 hours) was significantly longer than that in the OA group (10.6 2.7 hours). The time between the syngamy and the two cells in the NOA group (12.2 1.3 hours) was comparable with that in the OA group (16.6 10.2 hours). The time from the two cells to the four cells in the NOA group (13.5 3.5 hours) was also comparable with that in the OA group (10.0 4.2 hours). CONCLUSION: The time from the visibility of 2PN to the pronuclear fading (syngamy) after ICSI with testicular spermatozoa from NOAwas prolonged compared to that after ICSI with testicular spermatozoa from OA.