Compound heterozygous KCTD19 variants in a man with isolated nonobstructive azoospermia.

Case: A 40-year-old Japanese man with nonobstructive azoospermia (NOA) was found to carry rare variants in KCTD19, a newly identified causative gene for spermatogenic failure. This patient was identified through mutation screening of KCTD19 in 97 men with etiology-unknown isolated NOA. Outcome: The patient had two heterozygous variants in KCTD19 that affect consensus sequences of splice-donor sites [c.300+2T>A and c.2667C>T (p.E889E)]. Both variants were predicted to cause exon skipping. Long-read sequencing confirmed the compound heterozygosity of the variants. The patient exhibited small testes and a mildly elevated level of follicle-stimulating hormone but no other phenotypic abnormalities. Testicular histology showed borderline findings between spermatocyte maturation arrest and severe hypospermatogenesis. Conclusion: These results provide evidence that biallelic loss-of-function variants of KCTD19 represent rare causes of isolated NOA.

Testicular seminoma in transverse testicular ectopia.

Introduction: Transverse testicular ectopia is a rare anomaly in which both testes descend toward the same side of the hemiscrotum. Case presentation: A 35-year-old man presented with right inguinal enlargement. Computed tomography showed a normal testis in the right hemiscrotum and a 58 mm heterogeneous mass in the right inguinal area. No testis was observed in the left hemiscrotum. The vascular structures extended from the right inguinal mass to the left renal vein. Consequently, the left testicular tumor was diagnosed as transverse testicular ectopia, and a left orchiectomy was performed. The histological diagnosis was seminoma stage pT2. Furthermore, left para-aortic lymph node metastasis developed 10 months postoperatively. A complete response was obtained after systemic chemotherapy. Conclusion: Awareness of seminomas in transverse testicular ectopia could facilitate appropriate diagnosis and treatment. Furthermore, the location of the lymph node metastasis indicated that the ectopic testis could have originated from the left side.

Isodicentric Y Chromosome with Multiple Breakpoints in the Pseudoautosomal Region 1.

INTRODUCTION: Isodicentric Y chromosomes are relatively common structural variants of the human genome. The underlying mechanism of isodicentric Y chromosomes with short arm breakpoints [idic(Yq)] remains to be clarified. CASE PRESENTATION: We encountered a Japanese man with azoospermia and mild short stature. G-banding and array-based comparative genomic hybridization indicated that his karyotype was 45,X/46,X,idic(Y)(qter→p11.32::p11.32→qter) with a ∼1.8 Mb terminal deletion. Whole-genome sequencing suggested that the Y chromosome had four breakpoints in a ∼7 kb region of the pseudoautosomal region 1 (PAR1). CONCLUSION: This case was assumed to have an idic(Yq) resulting from multiple DNA double-strand breaks in PAR1. This rearrangement may have been facilitated by the PAR1-specific chromatin architecture. The clinical features of the patient can be ascribed to SHOX haploinsufficiency and the presence of a 45,X cell line, although copy-number gains of some Yq genes and the size reduction of PAR1 may also contribute to his spermatogenic failure.

Systematic molecular analyses for 115 karyotypically normal men with isolated non-obstructive azoospermia.

STUDY QUESTION: Do copy-number variations (CNVs) in the azoospermia factor (AZF) regions and monogenic mutations play a major role in the development of isolated (non-syndromic) non-obstructive azoospermia (NOA) in Japanese men with a normal 46, XY karyotype? SUMMARY ANSWER: Deleterious CNVs in the AZF regions and damaging sequence variants in eight genes likely constitute at least 8% and approximately 8% of the genetic causes, respectively, while variants in other genes play only a minor role. WHAT IS KNOWN ALREADY: Sex chromosomal abnormalities, AZF-linked microdeletions, and monogenic mutations have been implicated in isolated NOA. More than 160 genes have been reported as causative/susceptibility/candidate genes for NOA. STUDY DESIGN, SIZE, DURATION: Systematic molecular analyses were conducted for 115 patients with isolated NOA and a normal 46, XY karyotype, who visited our hospital between 2017 and 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 115 unrelated Japanese patients. AZF-linked CNVs were examined using sequence-tagged PCR and multiplex ligation-dependent probe amplification, and nucleotide variants were screened using whole exome sequencing (WES). An optimized sequence kernel association test (SKAT-O), a gene-based association study using WES data, was performed to identify novel disease-associated genes in the genome. The results were compared to those of previous studies and our in-house control data. MAIN RESULTS AND THE ROLE OF CHANCE: Thirteen types of AZF-linked CNVs, including the hitherto unreported gr/gr triplication and partial AZFb deletion, were identified in 63 (54.8%) cases. When the gr/gr deletion, a common polymorphism in Japan, was excluded from data analyses, the total frequency of CNVs was 23/75 (30.7%). This frequency is higher than that of the reference data in Japan and China (11.1% and 14.7%, respectively). Known NOA-causative AZF-linked CNVs were found in nine (7.8%) cases. Rare damaging variants in known causative genes (DMRT1, PLK4, SYCP2, TEX11, and USP26) and hemizygous/multiple-heterozygous damaging variants in known spermatogenesis-associated genes (TAF7L, DNAH2, and DNAH17) were identified in nine cases (7.8% in total). Some patients carried rare damaging variants in multiple genes. SKAT-O detected no genes whose rare damaging variants were significantly accumulated in the patient group. LIMITATIONS, REASONS FOR CAUTION: The number of participants was relatively small, and the clinical information of each patient was fragmentary. Moreover, the pathogenicity of identified variants was assessed only by in silico analyses. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that various AZF-linked CNVs are present in more than half of Japanese NOA patients. These results broadened the structural variations of AZF-linked CNVs, which should be considered for the molecular diagnosis of spermatogenic failure. Furthermore, the results of this study highlight the etiological heterogeneity and possible oligogenicity of isolated NOA. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Grants from the Japan Society for the Promotion of Science (21K19283 and 21H0246), the Japan Agency for Medical Research and Development (22ek0109464h0003), the National Center for Child Health and Development, the Canon Foundation, the Japan Endocrine Society, and the Takeda Science Foundation. The results of this study were based on samples and patient data obtained from the International Center for Reproductive Medicine, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Robot-assisted radical prostatectomy using the novel hinotoriTM surgical robot system: initial experience and operation learning curve at a single institution.

Background: The hinotoriTM surgical robot system (HSRS) is the first made-in-Japan robotic system used for radical prostatectomy. Here, we report initial results and describe our learning curve (skill development) implementing robot-assisted radical prostatectomy using HSRS (h-RARP). Methods: Between November 2021 and December 2022, 97 patients who underwent h-RARP at our institution were enrolled in this study. We retrospectively evaluated the surgical outcomes of the initial cases using h-RARP, comparing those of RARP using da Vinci surgical robot system (d-RARP) in our institution. Furthermore, the learning curves of two surgeons with the highest number of h-RARP were analyzed. Patients treated by each surgeon were categorized into two groups: 1-15 cases (earlier group) and >15 cases (later group). Preoperative patient characteristics, operation parameters, and complication rates were compared between the two groups. Results: In terms of surgical outcome, h-RARP was comparable to d-RARP. The procedures performed by the HSRS were successfully completed in all cases. There was no complication of grade 3 or higher. Comparing the two surgeons, surgeon 1, who had performed 40 d-RARP procedures, had time using robot system of the later group that was significantly shorter than that of the earlier group. However, for surgeon 2 with more than 100 d-RARP procedures, there was no statistically significant difference in time using robot system between groups. Other parameters showed no difference between earlier and later groups for the two surgeons. Conclusions: Our results show that surgical outcomes of h-RARP are comparable to those of d-RARP during the initial experience of clinical application. In addition, the surgeons' learning curves for the total RARP experience suggest that the experience of d-RARP can carry over to performance using the novel HSRS.

Two tumor types in a unilateral testis in a patient with severe oligozoospermia and a history of cryptorchidism surgery: A case report.

Testicular cancer, the most common cancer among young male adults, is associated with infertility. A 38-year-old male patient was admitted to Dokkyo Medical University Saitama Medical Center, Japan, with infertility associated with severe oligozoospermia. Scrotal ultrasonography revealed two distinct tumors in the left testis: A mass with abundant blood flow on the cranial side and a mass with poor blood flow on the caudal side. Additional analysis revealed mild elevation of intact human chorionic gonadotropin (hCG) levels (tumor marker level assessment), high testosterone and low luteinizing hormone and follicle-stimulating hormone levels (hormonal level assessment) and severe oligoasthenozoospermia (semen assessment). The preoperative diagnosis was left-sided testicular cancer and severe oligoasthenozoospermia and the patient underwent left high orchiectomy and oncological testicular sperm extraction. Based on the pathological assessment, the cranial tumor was diagnosed as a seminoma with syncytiotrophoblastic cells, whereas the caudal tumor had only scar tissue with germ cell neoplasia in situ in the adjacent parenchyma. Following surgery, intact hCG and hormone levels of the patient were normalized, and the semen parameters (semen volume, sperm density, and motility) improved dramatically. To the best of our knowledge, the present case is the first report of two types of testicular tumor in a unilateral testis in a patient with a history of cryptorchidism surgery. The present case demonstrated that scrotal ultrasonography should be performed in patients with abnormal semen results to rule out testicular tumors.

A Case Report of Successful Kidney Transplantation in a Patient With Chronic Myelogenous Leukemia (CML) Who Has Been in Remission for 15 Years on Imatinib.

For chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal disease into a manageable chronic disease with a close-to-normal life expectancy. Active malignancy is an absolute contraindication to kidney transplantation. However, it is controversial whether kidney transplantation can be safely performed in patients with a history of CML who are in remission. We describe the clinical course of a 64-year-old male patient with chronic kidney disease from diabetic nephropathy (DMN) who underwent living donor kidney transplantation. The patient was diagnosed with CML 15 years ago and promptly achieved cytogenetic and molecular biological remission after starting imatinib. After that, he continued imatinib treatment for 15 years and was in remission, but his chronic kidney disease from DMN gradually worsened. A preemptive living donor kidney transplant was performed in July 2020. Imatinib for CML was discontinued because the patient maintained deep molecular remission (DMR) of major molecular response for more than 15 years before kidney transplantation. After kidney transplantation, the transplanted kidney function remained good at approximate serum creatinine levels of 1.1 mg/dL without histopathologic rejection, and the 3 monthly BCR-ABL1 measurement results were negative and are in progress. Thus, he continues to maintain treatment-free remission status without imatinib for 26 months after renal transplantation. In conclusion, this result suggests that CML with long-lasting DMR on imatinib therapy can be considered an inactive malignancy and therefore a relative indication for kidney transplantation.

A regressed germ cell tumor discovered secondary to azoospermia.

Introduction: Regressed germ cell tumors are a rare disease commonly diagnosed with metastatic symptoms without local symptoms in the testis. Case presentation: A 33-year-old man with azoospermia was referred to our hospital. His right testis was slightly swollen, and ultrasonography revealed hypoechogenicity of the right testis with decreased blood flow. Right high orchiectomy was performed. Pathologically, the seminiferous tubules were absent or highly atrophied with vitrification degeneration; however, no neoplastic lesion was confirmed. One-month post-surgery, the patient noticed a mass in the left supraclavicular fossa, of which a biopsy revealed seminoma. The patient was diagnosed with a regressed germ cell tumor and underwent systemic chemotherapy. Conclusion: We reported the first case of a regressed germ cell tumor discovered due to complaints of azoospermia.

[INSURANCE COVERAGE FOR INFERTILITY TREATMENT SINCE APRIL 2022: HOW MALE INFERTILITY TREATMENT HAS CHANGED IN INSURANCE MEDICAL INSTITUTION -FROM THE QUESTIONNAIRE FOR JAPAN SOCIETY FOR REPRODUCTIVE MEDICINE MALE INFERTILITY SPECIAL INTEREST GROUP (SIG)].

(Introduction) Beginning in April of 2022, infertility services-including assisted reproductive technologies and examinations and treatments for male infertility-were covered by health insurance in Japan. Although these changes are expected to bolster birth rates in Japan, increased numbers of patients and surgeries are anticipated, particularly following reductions in patient visits caused by COVID-19. (Materials and methods) We surveyed 13 members of the Male Infertility Special Interest Group of the Japanese Society for Reproductive Medicine using Microsoft Forms. Respondents were asked about the number of new male infertility patients and surgeries at their respective facilities before the COVID-19 pandemic, after the first wave, after the sixth wave, and after the insurance changes to cover treatments for male infertility. Respondents were also asked to describe challenges in meeting the demand created by these insurance coverage changes. (Results) Patients and surgeries (varicocelectomy and testicular sperm extraction) declined markedly after the first wave of COVID-19 but gradually recovered after the sixth wave. However, once male infertility-related services were covered by insurance in Japan, respondents observed a marked increase in new patients and surgeries compared to pre-COVID-19. The most frequently reported problem was that sperm cryopreservation was not covered by insurance. (Conclusions) This survey should be readministered after additional time has passed to capture longer-term changes following changes to insurance coverage in Japan. We anticipate the responses to the survey will reflect ongoing challenges associated with changes in insurance coverage for male infertility-related services.

Preoperative testosterone and follicle stimulating hormone levels are important predictors for sperm retrieval by microdissection testicular sperm extraction in non-mosaic Klinefelter syndrome.

This study aimed to assess outcomes of microdissection testicular sperm extraction (MD-TESE) and identify predictors for sperm retrieval (SR) in patients with non-mosaic Klinefelter syndrome (NM-KFS). We retrospectively evaluated 37 patients with NM-KFS who underwent MD-TESE. Data of age at operation, body mass index (BMI), testicular volume, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), preoperative and postoperative testosterone levels with reduction ratio between the two values, and FSH/preoperative testosterone ratio were analysed. These patients were divided into two groups according to success or failure of SR: the successful and failure groups. Factors related to SR were evaluated by statistical analyses using the Mann-Whitney U test and logistic regression modelling. Regarding these factors, the cut-off level was specified using the receiver operating characteristics (ROC) curve. Moreover, the percentage of SR at that level was assessed. A simple scoring model was developed based on the multivariate analysis. Fourteen patients underwent successful SR, whereas 23 experienced failure SR. Statistical analysis found preoperative testosterone and FSH levels to be significant factors associated with SR. On the ROC curve, the cut-off levels for preoperative testosterone and FSH were 2.34 ng/ml and 33.2 mIU/ml respectively. A new scoring model was developed, consisting of preoperative testosterone (≥2.34 ng/ml) and FSH (≤33.2 mIU/ml). The sperm retrieval rates (SRRs) were clearly discriminated by stratification according to the scoring model. The SRR of the cases of scores of 2, 1 and 0 were 87.5%, 31.6% and 10% respectively. At our hospital, the SRR of MD-TESE in patients with NM-KFS was 37.8%. The patients with high testosterone and low FSH levels tended to demonstrate successful SR.

Evaluation of the sperm DNA fragmentation index in infertile Japanese men by in-house flow cytometric analysis.

Semen analysis has long been used to evaluate male fertility. Recently, several sperm function tests have been developed. Of those, the sperm DNA fragmentation index (DFI), which describes the status of the sperm DNA, is thought to be a suitable parameter for evaluating male fertility. However, there have been no large-scale studies on the sperm DFI of Japanese men. Therefore, we investigated the feasibility of using an in-house flow cytometry-based sperm DFI analysis based on the sperm DNA fragmentation test of sperm chromatin structure assay (SCSA) to assess male fertility in Japan. This study enrolled 743 infertile and 20 fertile Japanese men. To evaluate reproducibility, inter- and intraobserver precision was analyzed. A receiver operating characteristic curve analysis was used to set a cutoff value for the sperm DFI to identify men who could father children by timed intercourse or intrauterine insemination. The variability of the sperm DFI among fertile volunteers was determined. The relationship between semen parameters and the sperm DFI was assessed by Spearman's rho test. A precision analysis revealed good reproducibility of the sperm DFI. The cutoff value of sperm DNA fragmentation in infertile men was 24.0%. Semen volume had no relationship with the sperm DFI. Sperm concentration, sperm motility, total motile sperm count, and percentage of normal-shaped sperm were significantly and negatively correlated with the sperm DFI. The median sperm DFI was smaller in fertile volunteers (7.7%) than that in infertile men (19.4%). Sperm DNA fragmentation analysis can be used to assess sperm functions that cannot be evaluated by ordinary semen analysis.

Seminal oxidation-reduction potential and sperm DNA fragmentation index increase among infertile men with varicocele.

Varicocele is a common cause of male infertility. It is reported that low sperm concentration, motility and morphology are indicative of increased sperm DNA fragmentation index (DFI) in men with varicocele. Although research has been conducted into the relationship between varicocele and DFI, little is known about seminal oxidation-reduction potential (ORP) in varicocele patients. We assessed the relationship between varicocele with seminal ORP and sperm DFI in both fertile and infertile men. This prospective case-control study compared the findings from infertile men with varicocele to those of men with normal spermatogenesis without varicocele. Semen samples were collected and assessed using the WHO (2010) guidelines. ORP was measured (mV) and normalized to sperm concentration (mV/106 sperm/mL). DFI was measured using the sperm chromatin structure assay (SCSA) method. For group comparisons, only samples with a concentration >1 × 106 sperm/mL were included. Infertile men with varicocele had significantly lower mean sperm concentration, motility and total sperm count. Conversely, infertile men with varicocele had a significantly higher mean serum FSH level, and higher ORP and DFI values than fertile controls. ORP was higher in patients with varicocele and positively correlated with DFI (p < 0.01). ORP and DFI showed significant negative correlations with semen parameters (sperm concentration, motility and total sperm count) in infertile men with a varicocele.

Status of online sperm donation and sperm bank in Japan.

Facilities worldwide offering donor sperm insemination face sperm donor shortages. There are also known dangers of online information about sperm donation and using donated sperm to conceive without the involvement of medical professionals. Therefore, the authors investigated 140 Web sites retrieved by common Japanese search engines using sperm donation-related keywords. The authors assessed them according to criteria, but most were deemed unsafe (96.4%). Ultimately, 2 personal and 3 company Web sites provided adequate information. However, the personal Web sites lacked representative individual information and the company Web sites had issues including high costs, overseas location of facilities performing insemination, and possible non-Japanese origin of donated sperm.

Does mirabegron deteriorate spermatogenesis? A lesson from spinal cord injury cases.

OBJECTIVES: To evaluate whether the long-term usage of mirabegron, which was reported to have potential side effects on male reproductive organs in animal studies, was harmful to spermatogenesis in human testis. METHODS: Thirty consecutive patients with spinal cord injury (20-48 years old) who performed clean intermittent catheterization were involved in this study. Ten patients were treated with mirabegron (50 mg/d) for more than 2 years and refrained from using an antimuscarinic agent due to the side effects of constipation and dry mouth. Twenty patients were treated with neither anticholinergic agents nor mirabegron. All underwent conventional testicular sperm extraction. The sperm recovery rate and histopathologic findings of the retrieved testicular tissue were compared between both groups. RESULTS: We found no difference in the sperm recovery rate (P = .083) between both groups. Spinal cord injury patients treated with mirabegron had better spermatogenesis than those not treated with mirabegron (P < .05). CONCLUSIONS: From these data, we conclude that the therapeutic dose of mirabegron had no harmful effect on spermatogenesis in spinal cord injury patients of reproductive age.

SRY-Positive 46, XX Testicular Disorder of Sexual Development With Leydig Cell Tumor.

The risk of a gonadal tumor is high in testicular disorder of sexual development (DSD) with the Y chromosome, but cases of DSD without the Y chromosome are extremely rare. We reported a gonadal tumor in a phenotypically male individual with 46, XX testicular DSD. A testicular tumor was incidentally found in a 32-year-old phenotypic male who was presented to the hospital with male infertility. A diagnosis of 46, XX testicular DSD was made by the presentation of karyotype analysis of 46, XX with the sex-determining region of the Y chromosome (SRY) positive and gonadal tissue without female gonads. Surgery was performed due to a gradually growing tumor. The partial orchidectomy was performed with the diagnosis of a benign Leydig cell tumor in frozen biopsy.

Testicular volume in non-obstructive azoospermia with a history of bilateral cryptorchidism may predict successful sperm retrieval by testicular sperm extraction.

PURPOSE: Cryptorchidism is one of the most common causes of non-obstructive azoospermia (NOA) in adulthood. Even if early orchidopexy is performed to preserve fertility potential, some patients still suffer from azoospermia. Fertility potential is significantly lower in bilateral than unilateral cryptorchidism. The aims of this study were to identify clinical parameters that predict the likely success of sperm recovery by microscopic testicular sperm extraction (micro-TESE) and also the likely outcome of intracytoplasmic sperm injection using sperm from NOA patients who submitted to bilateral orchidopexy. METHODS: Fifty-two NOA patients with a history of bilateral cryptorchidism underwent micro-TESE. The following clinical parameters were evaluated as predictive factors for successful sperm recovery: age at micro-TESE; age at orchidopexy; period from orchidopexy to micro-TESE; luteinizing hormone (LH); follicle-stimulating hormone (FSH); testosterone; average testicular volume; and body mass index. RESULTS: In the successful sperm retrieval group, average testicular volume was significantly greater, while serum LH and FSH, and body mass index were significantly lower. In a multivariate analysis, average testicular volume was positively correlated with successful sperm recovery. CONCLUSION: Our results indicate that testicular volume in NOA patients with bilateral cryptorchidism is a predictor for successful sperm recovery.

The Diagnostic Accuracy of Testicular Torsion by Doctors on Duty Using Sonographic Evaluation with Color Doppler.

As testicular torsion is a medical emergency, it requires quick diagnosis and treatment. Color Doppler ultrasound (CDUS) is useful for the diagnosis of testicular torsion. An accurate diagnosis can be difficult when CDUS indicates the preservation of blood flow in the testis. We examined the accuracy of testicular torsion diagnosis in patients with acute scrotum made by doctors on duty using CDUS. The subjects included 26 patients who visited our department between January 2016 and June 2018 presenting with acute scrotal pain. Patients were placed into one of three groups based on testicular blood flow evaluated by CDUS. The first group had no testicular blood flow, the second had diminished blood flow, and the last group had normal or increased blood flow. Patients were also diagnosed through scrotal exploration. Finally, patients were further divided into two groups identified by CDUS frequency utilized during diagnosis (12 MHz groups and ≤8 MHz groups), and the diagnostic accuracy of the two groups was compared. Characterizing torsion by either the absence of or diminished, testicular blood flow in the CDUS evaluation, the sensitivity and specificity of the CDUS performed by doctors on duty accounted for 69.2% and 53.8%, respectively. No improvement in diagnostic accuracy was evident despite the usage of a 12-MHz ultrasonic transducer. In this study, the sensitivity of CDUS performed by doctors on duty was about 70%, suggesting that scrotal exploration should be performed promptly even if testicular blood flow is observed and testicular torsion is suspected from medical history and body findings.

Comparison between semen parameters in specimens collected early in the morning and in the evening.

The majority of facilities in Japan that offer artificial insemination as part of assisted reproduction programs currently perform semen collection in the early morning. The total motile sperm count of the semen used in intrauterine insemination is an important factor in achieving successful fertilization and subsequent childbirth. The present study was initiated to determine whether semen parameters varied with the time of day at which the semen sample was collected. The study subjects were 20 fertile males and 20 infertile males with abnormal seminograms who attended our Reproduction Center. Semen was collected early in the morning (morning collection group) and in the evening (evening collection group) from the same subjects, and total motile sperm count was assessed as the primary outcome measure. As secondary outcome measures, semen volume, sperm concentration, sperm motility and total sperm count were assessed. A sexual abstinence period of 3 days was set for all participants. The semen samples were analyzed using CASA CEROS, a sperm motility analysis system, and the data from the morning and evening collection groups were compared using a Wilcoxon signed rank test. We found that the fertile males had a significantly higher total motile sperm count and total sperm count in the evening collection group than in the morning collection group. In contrast, the male infertility patients showed no significant difference in total sperm count between the two collection times; however, the total motile sperm count was significantly higher in the evening collection group than the morning collection group. Our analyses indicate that total motile sperm count in ejaculated semen is significantly higher after evening collection than after morning collection. From a male side perspective, we suggest that successful intrauterine insemination might be easier to achieve using semen collected in the evening than in the early morning.Abbreviations: IUI: intrauterine insemination; OAT: oligoasthenoteratozoospermia; TSC: total sperm count; TMSC: total motile sperm count.