Takeshi Shin

Inflammatory bowel disease in subfertile men and the effect of mesalazine on fertility

Abstract This study aimed to examine the effect of mesalazine on fertility. In this retrospective analysis of 1,225 male subfertile patients, we reviewed the cases of inflammatory bowel disease (IBD) in the medical records and evaluated the prevalence of the disease in our reproduction center. Specifically, we examined IBD patients who ceased mesalazine during male infertility treatment, and compared the seminogram of these patients before and after discontinuation of mesalazine. We also analyzed pregnancy outcome after discontinuation. The prevalence rate of Crohn’s disease and ulcerative colitis in our male infertile patients was 163 per 100,000 men and 490 per 100,000 men, respectively. Seven patients had taken mesalazine and six of them subsequently stopped the medication. The mean values of sperm concentration, sperm motility, percentage of normal formed sperm, semen volume, and total motile sperm count taken before discontinuation increased after discontinuation of mesalazine. Among these parameters, the sperm motility and total motile sperm count were significantly improved (p < 0.05) after discontinuation. Of the six patients who stopped the drug, four achieved pregnancy with their partners, with two of the four men showing significant improvement not only in the percentage of normal shaped sperm but also sperm motility and total motile sperm count. This study provides further insight into the rarely investigated relationship between male fertility and mesalazine.

Spermatogenesis in tumor-bearing testes in germ cell testicular cancer patients

STUDY QUESTION What are the factors that might indicate a greater likelihood of success in oncologic testicular sperm extraction (onco-TESE)? SUMMARY ANSWER Smaller tumor diameter and greater noncancerous testicular tissue width (NCTW) are positive predictors of spermatogenesis in patients with testicular germ cell tumors (TGCTs). WHAT IS KNOWN ALREADY Onco-TESE is a key modality for fertility preservation in cases of inadequate pretreatment sperm collection and azoospermic men with testicular cancer. TGCTs are known to reduce sperm quality such that ∼ 10% of these patients are azoospermic, making surgical TESE at the same time as orchiectomy their only means of fertility preservation. STUDY DESIGN, SIZE, DURATION This study is a retrospective analysis performed in a single university hospital from 2002 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were 102 male patients (104 testes) who underwent inguinal orchiectomy and were diagnosed with a germinoma. In each specimen, the Johnsen Score Count (JSC) in seminiferous tubules at each established distance from the tumor margin (1, 2.5, 5, 7.5, 10 and 12.5 mm) was determined. We analyzed the relations between age, tumor histopathologic type, tumor size (maximum diameter), distance from the tumor, non-tumor tissue width and JSC. MAIN RESULTS AND THE ROLE OF CHANCE The 104 specimens consisted of 78 seminomas and 26 non-seminomatous TGCTs. The mean ± SD JSC was 4.7 ± 2.4 in seminomas and 3.9 ± 2.5 in non-seminomatous germ cell tumors, with no significant difference between the two subtypes. Single regression analysis showed that tumor diameter was significantly negatively correlated with spermatogenesis (RC = -0.422, P < 0.001). Multiple linear regression analysis also showed that tumor diameter had a negative influence on spermatogenesis (RC = -0.437, P < 0.001). The greater the distance the seminiferous tubules from the tumor, the better the preservation of spermatogenesis. Mature spermatozoa were identified in 93.0% of patients with a NCTW ≥ 7.5 mm and in 41.3% of those with NCTW < 7.5 mm (P < 0.001). LIMITATIONS, REASONS FOR CAUTION Study data were obtained retrospectively, which might have affected the quality of data. We were unable to compare spermatogenesis determined using preoperative seminograms with that determined histopathologically. It was not possible to evaluate spermatogenesis in the total volume of noncancerous testicular tissue. WIDER IMPLICATIONS OF THE FINDINGS When Onco-TESE is conducted at sites distant from tumors, the rate of sperm extraction is high and contamination by tumor cells can be prevented. By measuring non-testicular cancerous margin before the operation, the possibility of sperm extraction can be predicted and biopsy of the contralateral testis can be considered based on the results.

Human male infertility and its genetic causes

Infertility affects about 15% of couples who wish to have children and half of these cases are associated with male factors. Genetic causes of azoospermia include chromosomal abnormalities, Y chromosome microdeletions, and specific mutations/deletions of several Y chromosome genes. Many researchers have analyzed genes in the AZF region on the Y chromosome; however, in 2003 the SYCP3 gene on chromosome 12 (12q23) was identified as causing azoospermia by meiotic arrest through a point mutation.

Induction of spermatogenesis by rhFSH for azoospermia due to spermatogenic dysfunction with maturation arrest: five case series

Abstract When sperm cannot be retrieved from the testes of patients with azoospermia due to spermatogenic dysfunction (ASD), there is no rational way for the patient to become a biological father. We investigated the possibility of inducing spermatogenesis in such patients by hormonal therapy with recombinant human follicle-stimulating hormone (rhFSH) alone. Twenty-six ASD patients who could not obtain spermatozoa by microdissection testicular sperm extraction (micro-TESE) were confirmed to have arrested spermatogenesis at the late stage of maturation arrest. They were subsequently treated with 75–150 IU two times/week rhFSH alone for 12 months. The primary endpoint was the appearance of sperm in ejaculate, and we followed the patients to determine the outcome of inseminating their partners. After rhFSH treatment, mature spermatozoa were found in the ejaculate in five of 26 (19.2%) patients, all of whom showed histology of non-uniform type maturation arrest. Intracytoplasmic sperm injection of the mature spermatozoa resulted in two ongoing clinical pregnancies (insemination success rate, 40.0%). Recombinant human follicle-stimulating hormone treatment can be used as an advanced assisted reproductive technology to improve spermatogenesis in some azoospermic patients with maturation arrest of spermatogenesis and is a potential treatment option after unsuccessful micro-TESE.

Transvesicoscopic ureteral reimplantation: Politano–Leadbetter versus Cohen technique

To compare the outcomes of the Politano–Leadbetter and Cohen techniques in laparoscopic pneumovesicum approach for ureteral reimplantation.

Testicular sperm extraction for patients with spinal cord injury‐related anejaculation: A single‐center experience

To present a single‐center experience with testicular sperm extraction and intracytoplasmic sperm injection for fathering biological children in patients with ejaculatory dysfunction as a result of spinal cord injury.

Improvement of seminal quality and sexual function of men with oligoasthenoteratozoospermia syndrome following supplementation with L-arginine and Pycnogenol®

We evaluated the effectiveness of antioxidant co-supplementation therapy using Larginine and Pycnogenol(®) in Japanese men with oligoasthenozoospermia and mild erectile dysfunction (ED). A total of forty-seven adult males with oligoasthenoteratozoospermia syndrome (OAT) were eligible for enrollment. The effectiveness of supplementation with a combination of L-arginine 690 mg and French maritime pine bark extract (Pycnogenol(®)) 60mg for OAT and ED was investigated. The sperm concentration was enhanced significantly after treatment 2 and 4 months (11.79 ± 9.86 to 21.22 ± 28.17 and 20.15 ± 23.99 × 106/ml). Significant improvements in the International Index of Erectile Function (IIEF) were observed in the total score of IIEF (57.69 ± 11.04 to 59.43 ± 12.57) and domain of Orgasmic Function (9.01 ± 1.92 to 9.34 ± 1.66) after 4 months of treatment. L-arginine acts to increase the production of nitric oxide and Pycnogenol(®) activates the endothelial nitric oxide synthase and it is a potent antioxidant and inhibitor of inducible nitric oxide synthase. This study suggests that the combination of Pycnogenol(®) and L-arginine (Edicare(®)) is helpful for infertile men to ameliorate simultaneously quality of sperms as well as erectile functions.

A questionnaire survey on attitude toward sperm cryopreservation among hematologists in Japan

Advances in multimodal treatment have led to dramatic improvement in cancer treatment outcomes. It is now necessary to consider cancer patients’ holistic quality of life. Fertility preservation is the top concern for cancer survivors of reproductive age. Sperm cryopreservation before treatment is recommended for postpubescent men, but many patients lose fertility without having been informed about options for fertility preservation. To determine how sperm cryopreservation is perceived and practiced in Japan, we surveyed hematologists who often treat young males. A questionnaire about sperm cryopreservation was sent to 45 major hematology institutions. A total of 22 institutions responded before the deadline. All institutions but one responded that they felt sperm cryopreservation is necessary. Only 15 institutions responded that they inform patients about sperm cryopreservation, and 12 institutions responded that they perform sperm cryopreservation before chemotherapy. A total of 213 young males started their first course of chemotherapy during the survey period, of whom 61 (28.6%) had their sperm cryopreserved. Although almost all hematologists stated that sperm cryopreservation is necessary for fertility preservation, not all institutions informed patients about it. Our findings indicate that, to promote fertility preservation in Japan, it will be necessary to systematize sperm cryopreservation and build inter-hospital networks.

Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism

Abstract Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34–45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

Nationwide survey of urological specialists regarding male infertility: results from a 2015 questionnaire in Japan

To investigate the incidence, etiology, treatment indications, and outcomes regarding infertile male patients in Japan.