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.

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

Purpose: To investigate the incidence, etiology, treatment indications, and outcomes regarding infertile male patients in Japan. Methods: Between April, 2014 and March, 2015, the authors contacted 47 clinical specialists in male infertility who had been certified by the Japan Society for Reproductive Medicine. The participating clinicians were sent a questionnaire regarding information on their infertile patients, according to etiology and the number and success rates of male infertility operations that had been performed in their practice. Results: Thirty-nine specialists returned the questionnaire and provided information regarding 7268 patients. The etiology of infertility included testicular factors, sexual disorders, and seminal tract obstruction. During the study year, the clinicians performed varicocelectomies, testicular sperm extractions (TESEs), and re-anastomoses of the seminal tract. The rate of successful varicocelectomies was >70%. The sperm retrieval rates with conventional TESE and microdissection TESE were 98.3% and 34.0%, respectively, while the patency rates with vasovasostomy and epididymovasostomy were 81.8% and 61.0%, respectively. Conclusion: Surgical outcomes for infertile male patients are favorable and can be of great clinical benefit for infertile couples. To achieve this, urologists should work in collaboration with gynecological specialists in order to optimize the treatment of both partners.

Significant changes of T2 value in the peripheral zone and seminal vesicles after ejaculation.

OBJECTIVES: To analyse the quantitative changes of the prostate and seminal vesicles (SV) on magnetic resonance imaging (MRI) after ejaculation. METHODS: Ten healthy young males were enrolled for T2-weighted and T2 mapping MRI before and after two consecutive ejaculations. T2 values of the peripheral zone (PZ) and the central gland (CG) at the midgland of the prostate were compared before and after ejaculation, respectively. T2 values of the PZ at the apex and base were also compared before and after, respectively. Pre- and post-ejaculation SV volumes were compared. The Wilcoxon's signed rank test with Bonferroni adjustment was used for comparison. RESULTS: After ejaculation, T2 values of the PZ significantly decreased (mean, 119±20 vs. 105±21, p=0.002) while those of the CG did not significantly change at the midgland. At the apex, T2 values of the PZ also decreased significantly (mean, 114±9 vs. 94±7, p=0.002). On the other hand, T2 values of the PZ did not change at the base. SV volumes were significantly reduced after ejaculation (mean, 11.1±7.7mL vs. 7.2±6.7mL, p=0.002). CONCLUSIONS: Ejaculation decreases T2 values of the PZ at the midgland and apex, and reduces SV volumes. Abstinence periods should be considered in evaluating the prostate and SV on MRI. KEY POINTS: • T2 values decrease after ejaculation in the apical-mid peripheral zone. • Ejaculation does not affect T2 values of the central gland. • Volume of the seminal vesicles decreases after ejaculation. • An abstinence period should be considered before pelvic MRI in men.

Human male infertility and its genetic causes.

Background: 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. Methods: We mainly describe the SYCP3 and PLK4 genes that we have studied in our laboratory, and add comments on other genes associated with human male infertility. Results: Up to now, The 17 genes causing male infertility by their mutation have been reported in human. Conclusions: Infertility caused by nonobstructive azoospermia (NOA) is very important in the field of assisted reproductive technology. Even with the aid of chromosomal analysis, ultrasonography of the testis, and detailed endocrinology, only MD-TESE can confirm the presence of immature spermatozoa in the testes. We strongly hope that these studies help clinics avoid ineffective MD-TESE procedures.

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.

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

OBJECTIVES: 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. METHODS: Testicular sperm extraction was carried out in 52 male patients with ejaculatory dysfunction as a result of spinal cord injury. We investigated sperm retrieval rates and pregnancy rates from medical records. Data on age, testicular volume, hormonal status (luteinizing hormone, follicle stimulating hormone and testosterone), and time since spinal cord injury were obtained and analyzed to detect potential associations with the presence of spermatogenesis. RESULTS: Testicular sperm retrieval was achieved in 42 of 52 patients (80.7%). Intracytoplasmic sperm injection was carried out for 37 patients, and pregnancy was achieved in 32 (86.5%). The take-home baby rate was 70.2%. In the group with successful sperm extraction, testicular volume was significantly greater, time from spinal cord injury to extraction was significantly shorter, and serum luteinizing hormone and follicle-stimulating hormone levels were significantly lower. Serum follicle-stimulating hormone levels had the strongest association with feasibility of sperm retrieval by testicular sperm extraction. Furthermore, the sperm retrieval rates of patients injured within the preceding 12 years were significantly better than those injured longer before treatment (P = 0.045). CONCLUSIONS: Testicular sperm extraction and intracytoplasmic sperm injection seem to provide favorable results for patients with ejaculatory dysfunction as a result of spinal cord injury. However, early testicular sperm extraction is recommended, because sperm retrieval becomes more difficult with time from spinal cord injury.

Infertility in men with inflammatory bowel disease.

Inflammatory bowel disease (IBD) predominantly affects young adults. Fertility-related issues are therefore important in the management of patients with IBD. However, relatively modest attention has been paid to reproductive issues faced by men with IBD. To investigate the effects of IBD and its treatment on male fertility, we reviewed the current literature using a systematic search for published studies. A PubMed search were performed using the main search terms "IBD AND male infertility", "Crohn's disease AND male infertility", "ulcerative colitis AND male infertility". References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, smoking, medications, and surgery may cause infertility in men with IBD. In surgery such as proctocolectomy with ileal pouch-anal anastomosis, rectal incision seems to be associated with sexual dysfunction. Of the medications used for IBD, sulfasalazine reversibly reduces male fertility. No other medications appear to affect male fertility significantly, although small studies suggested some adverse effects. There are limited data on the effects of drugs for IBD on male fertility and pregnancy outcomes; however, patients should be informed of the possible effects of paternal drug exposure. This review provides information on fertility-related issues in men with IBD and discusses treatment options.

Microdissection testicular sperm extraction in Japanese patients with persistent azoospermia after chemotherapy.

BACKGROUND: Combinations of surgery, radiation therapy, and chemotherapy can achieve high remission rates in patients with cancer, but these treatments can have damaging effects on spermatogenesis. In particular, cytotoxic chemotherapy may lead to irreversible spermatogenic dysfunction. Microdissection testicular sperm extraction (micro-TESE) is the only method that can address infertility in cancer survivors with persistent postchemotherapy azoospermia. METHODS: We included 66 Japanese patients with postchemotherapy azoospermia who underwent micro-TESE for sperm retrieval in this analysis. Age, oncology data, hormone profiles, and outcomes of micro-TESE and subsequent intracytoplasmic sperm injections (ICSIs) were reviewed. RESULTS: The common disease in our patients was testicular cancer (21 patients), followed by acute lymphoblastic leukemia and Hodgkin's lymphoma (nine patients). In this cohort of 66 patients, sperm was successfully retrieved in 31 patients (47 %), and clinical pregnancy occurred in 23 cases (35 %). The live birth rate was 27 %. No significant differences in sperm retrieval, clinical pregnancy, and live birth rates were seen between testicular cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, or sarcoma cases. Multiple logistic regression analysis showed that the chance of retrieving sperm during micro-TESE could not be predicted by any variable. CONCLUSIONS: Cryopreservation of sperm should be offered before any gonadotoxic chemotherapy takes place. However, micro-TESE and subsequent ICSI could be effective treatment options for patients with persistent postchemotherapy azoospermia whose sperm were not frozen before therapy. Our results suggest that micro-TESE-ICSI could benefit 27 % of such Japanese patients.

[Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

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.

[SUCCESSFUL INGUINAL ORCHIECTOMY IN A PATIENT WITH A PAINFUL METASTATIC SPERMATIC CORD TUMOR: A CASE REPORT].

A 71-year-old man was referred to our department due to inflammation in the right scrotum. A tumor in the right spermatic cord was suspected on palpation, and abdominal computed tomography revealed a 4-cm mass in the tail of the pancreas and a low-density lesion in the liver segment 6. In addition, the patient's serum level of CA19-9 was high, at 135.7 U/mi. We referred the patient to our institution's Department of Gastroenterology, where he was diagnosed as having a liver metastasis from pancreatic cancer. Despite three courses of gemcitabine and erlotinib combination therapy for pancreatic cancer, his serum level of CA19-9 increased to 744.0 U/m, indicating no response to chemotherapy. Because uncontrollable pain developed in the right scrotum and right inguinal area during the course of treatment, inguinal orchiectomy was performed for pain management and pathological diagnosis. Careful examination revealed a hard, whitish tumor occupying the right spermatic cord and extending from the epididymis to the internal inguinal ring. Because a palpable mass in the peritoneum near the internal inguinal ring was detected, part of the peritoneum was resected concurrently. Pathological findings were remarkable with spermatic cord metastasis and peritoneal dissemination from pancreatic cancer. Pain subsided postoperatively and no analgesics were needed. Pancreatic cancer accompanied by spermatic cord metastasis and peritoneal dissemination is extremely rare. Surgical resection in the present case provided effective treatment of the intractable pain due to spermatic cord metastasis. To the best of our knowledge, this is only the 14th case reported in Japan of spermatic cord metastasis from pancreatic cancer as a primary cancer.

[Fertility in testicular cancer patients].

Testicular cancer(TC)is the most common and curable cancer affecting men of reproductive age. Successful treatment approaches have resulted in longer life expectancy in TC survivors. The most frequently used treatment for TC is a combination of inguinal orchiectomy, and either radiotherapy or cisplatin-based chemotherapy. In many TC patients, sperm quality is already abnormal and there may even be a lack of viable spermatozoa at the time of diagnosis. Therefore, the effect of cancer treatment on fertility is a potentially significant issue. Fertility preservation in these men has become essential and needs to be discussed prior to the start of cancer treatment. The only currently established fertility preservation method is the cryopreservation of sperm before therapy. For most patients seeking cryopreservation, the semen sample is collected via masturbation. If the patient is unable to ejaculate for any reason, other techniques such as vibratory stimulation and electroejaculation can be performed. In azoospermic or severely oligozoospermic patients, testicular sperm extraction at the time of the inguinal orchiectomy is a useful technique for obtaining spermatozoa before cytotoxic therapy. We herein present an overview of the current topics on fertility in TC patients, including the effects of surgery, chemotherapy, and radiation therapy. We also describe the strategy for fertility preservation in these patients.

Transvesicoscopic ureteral reimplantation: Politano-Leadbetter versus Cohen technique.

OBJECTIVES: To compare the outcomes of the Politano-Leadbetter and Cohen techniques in laparoscopic pneumovesicum approach for ureteral reimplantation. METHODS: We retrospectively reviewed the medical records of 24 patients who underwent transvesicoscopic ureteral reimplantation during the period from 2007 to 2014. The patients were treated with either the Cohen or Politano-Leadbetter technique. Operative duration, duration of hospital stay, and success and complication rates were compared. RESULTS: Operative duration was 1 h longer for the Politano-Leadbetter technique than for the Cohen technique (P < 0.05). Foley catheters were removed 2-3 days after the procedures. The mean hospital stay was 3.6 days. Reflux completely resolved in 21 patients (35 ureters, 94.6%), but not in two patients (2 ureters). There was no difference in the success rate or durations of catheterization or hospital stay between patients treated with the Politano-Leadbetter technique and those treated with the Cohen technique. CONCLUSIONS: The Politano-Leadbetter and Cohen techniques are both reliable for transvesicoscopic ureteral reimplantation. Despite a longer operative time, because of the higher surgical complexity, the Politano-Leadbetter ureteral reimplantation offers important physiological advantages over other techniques.

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

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.

Mature Testicular Teratoma with Positive Estrogen Receptor Beta Expression in a Transgendered Individual on Cross-Sex Hormonal Therapy: A Case Report.

Estrogen exposure has been linked to a risk of testicular germ cell cancers, although predominantly in animal studies. In the human testis, estrogen receptor beta (ER-ß) mediates the physiological action of estrogen. We describe a case of a 30-year-old transgender woman (male-to-female [MtF]) with gender dysphoria who developed a mature testicular teratoma with positive estrogen receptor beta expression while receiving cross-sex hormonal therapy with estradiol and progesterone. Although the presence of hormone receptors does not always imply that hormones have played a role in the development of the tumor, a contribution of exposure to exogenous estrogen in this case cannot be ruled out.

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

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.

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

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.

[Acute abducens nerve palsy following prostatitis due to prostate biopsy].

This is a case of repeated acute abducens nerve palsy following prostatitis due to prostate biopsy. A 64-year-old man came to our hospital because of high prostate specific antigen (PSA; 25 ng/ml) on routine medical examination. Transrectal prostate needle biopsy revealed atypical small acinar proliferations in two cores taken from the apex of the prostate. One day after biopsy, the patient presented with chills and a fever. Prostatitis due to prostate biopsy was diagnosed, and hydration and intravenous antibiotics were administered. Although he showed signs of improvement, seven days after biopsy, he complained of double vision in the left gaze. Upon referral to the neurology, head MRI and CSF examination showed no particular abnormality. He was thus diagnosed with post-infection abducens nerve palsy and treated with steroid therapy. His symptoms gradually ameliorated. One year after biopsy, his PSA level was still high, although follow-up prostate biopsy was benign. One day after follow-up biopsy, he presented again with chills and a fever. He was retreated with hydration and intravenous antibiotics. Six days after follow-up biopsy, he complained of double vision in the left gaze as in the previous year. With the diagnosis of post-infection abducens nerve palsy, he was retreated with steroid therapy.