Evaluation of an Updated Gene Panel as a Diagnostic Tool for Both Male and Female Infertility.

In recent years, an increasing number of genes associated with male and female infertility have been identified. The genetics of infertility is no longer limited to the analysis of karyotypes or specific genes, and it is now possible to analyse several dozen infertility genes simultaneously. Here, we present the diagnostic activity over the past two years including 140 patients (63 women and 77 men). Targeted sequencing revealed causative variants in 17 patients, representing an overall diagnostic rate of 12.1%, with prevalence rates in females and males of 11% and 13%, respectively. The gene-disease relationship (GDR) was re-evaluated for genes due to the addition of new patients and/or variants in the actual study. Five genes changed categories: two female genes (MEIOB and TBPL2) moved from limited to moderate; two male genes (SOHLH1 and GALNTL5) moved from no evidence to strong and from limited to moderate; and SEPTIN12, which was unable to classify male infertility, was reclassified as limited. Many infertility genes have yet to be identified. With the increasing integration of genetics in reproductive medicine, the scope of intervention extends to include other family members, in addition to individual patients or couples. Genetic counselling consultations and appropriate staffing will need to be established in fertility centres. Trial registration number: Not applicable.

Ten-year outcomes of patients who developed persistent azoospermia following chemotherapy associated with different oncological diagnoses: A retrospective cohort study from a different perspective.

BACKGROUND: This study evaluated the treatment procedures for chemotherapy (CT)-induced persistent azoospermia and their outcomes from a different perspective. METHODS: In 63 patients (mean age: 30.16 ± 4.91 years) who had undergone CT 11 ± 5 years earlier, the semen volume, gonadotropins level, FSH level, genetics, micro-testicular sperm extraction (m-TESE) result, sperm DNA fragmentation index (SDFI), semen reactive oxidative stress (ROS) rate, duration of embryonic development, and pregnancy and baby take-home rates were examined. The correlations between the ROS rates and the SDFIs, m-TESE results, sperm motility, pathology scores, time-lapses, and baby take-home rates were evaluated. RESULTS: The semen volumes were 3.5 ± 1.1/ml. The FSH level following CT was 17.87 ± 5.80 mIU/ml. A sperm rate of 34.9% was found from the m-TESE result. The mean SDFI and ROS rate were 4 (<15-30>) and 1.29 ± 0.51, respectively. The time-lapse was calculated as 5h. Pregnancy and live birth were achieved at 20.63% and 12.7%, respectively. In the patients with a low ROS (≤1.42) and SDFI (≤15), the m-TESE success rate was high, the FSH value was low, the pathological score and fertilization rate were elevated, the embryonic cleavage period was normal, and the pregnancy and baby take-home rates were high. DISCUSSION: The sperms may be detected using m-TESE in patients who develop persistent azoospermia associated with CT due to different oncological diagnoses. Our study revealed that a low FSH value and normal ejaculatory ROS rates are positive predictive factors of sperm detection before m-TESE. The motility of the sperms detected after m-TESE and normal SDFI rates were found to be positive predictive criteria of high fertilization, good embryonic cleavage, pregnancy, and live birth.

Different group of non-obstructive intermittent azoospermias among non-obstructive azoospermia patients: A ten-year retrospective cohort study with control group.

We have identified patients among non-obstructive azoospermia (NOA) cases in whom spermatozoa could not be detected despite treatment, but intermittent ejaculatory spermatozoon was found in their follow-up. NOA was observed in the retrospective screening at a rate of 15.35% among infertile men (n = 1976/12,871), while non-obstructive intermittent azoospermia (NO-IA) was detected at a rate of 6.8% among NO-IA (n = 135/1976) and 1.1% among all infertile men (n = 135/12,871). Spermatozoon was identified in the form of cryptospermia or extreme oligospermia in 58.13 (13.6-92.3) weeks on average in n = 55/135 patients among NO-IA. Pregnancy and live birth were achieved at a rate of 43.6% (n = 24/55) and 29% (n = 16/55), respectively, in intracytoplasmic sperm injection. NO-IA was composed of a group with no genetic pathological diagnosis, with lower follicle-stimulating hormone, lutenizing hormone and clinical varicocele rates compared with those of NOA (<0.05) and higher testicular volumes and pathological scores (<0.05). A major activity was observed in total testosterone, lutenizing hormone, testicular volumes and the logistic regression of pathological scores (<0.05).

Evaluation from a different perspective of 10-year results of infertile males with Y chromosome AZFc microdeletions compared with a control group.

AZFc microdeletions will be evaluated upon being divided into partial and complete subgroups. The association of deletions with reactive oxidative stress (ROS) and sperm DNA fragmentation (SDFI) and the impact of their coexistence on fertility starting from the pregnancy process until live birth will be presented. Semen analyses, microbiological results, hormones, ROS and sperm TUNEL tests were checked. Preimplantation genetic testing (PGT) was planned for relevant patients. Intracytoplasmic sperm injection (ICSI) was applied. Their embryo fragmentation was monitored via time lapse. Their results were compared with those with no AZF deletion and no other genetic problems. Azoospermia rate was 71.5%, m-TESE success rate was 25%, pregnancy rate was 26% and live child rate was 2.2%. No difference was detected between the partial and total groups in terms of ROS and SDFI rates and no difference was identified with the control group. Better results were obtained in terms of live child rate in patients with partial AZFc and low ROS/SDFI. Spermatozoon was retrieved in AZFc deletions and pregnancy, and live child was identified. No AZFc impact was observed on ROS and SDFI in the results compared with the control groups in terms of their coexistence.

Impact of overactive bladder on retrograde ejaculation

ABSTRACT Purpose: To evaluate the impact of overactive bladder disorder on patients diagnosed with retrograde ejaculation. Materials and Methods: Retrospective analysis of prospective collected database made. Questionnaires conducted in urology polyclinics in five different centers. Main Outcome Measure(s): International Index of Erectile Function - 5 (IIEF - 5), Overactive Bladder 8 - Question Awareness Tool (OAB - V8), urodynamics, semen analysis. The participants of the study were n = 120 patients. There was retrograde ejaculation (RE) in only n = 47 patients (non / minimal symptomatic patients), n = 73 patients had RE and overactive (OAB) complaints (symptomatic patients) and received anticholinergic treatment (trospium), n = 37 control group patients who only had OAB and received an anticholinergic. Results: While no difference was observed in overactive bladder examination and urodynamic values between the non / minimal symptomatic group and the symptomatic group (p > 0.05), sperm was detected and identified as fructose positive in post - ejaculation urine in the symptomatic group. Thus, it was possible to demonstrate the differences between symptomatic patients and non - symptomatic patients. Consequently, following three - month daily treatment with trospium 30 mg 2 x 1 in the control group and the symptomatic group, it was observed that an evident increase was observed in the sperm count and ejaculate volume in the symptomatic group and that no change was observed in the control group (p < 0.05). Conclusion: This clinical study is the first of its kind in terms of revealing the coexistence of RE with OAB upon performing urodynamics and showing that treatment is possible in selected patients.

Impact of overactive bladder on retrograde ejaculation.

PURPOSE: To evaluate the impact of overactive bladder disorder on patients diagnosed with retrograde ejaculation. MATERIALS AND METHODS: Retrospective analysis of prospective collected database made. Questionnaires conducted in urology polyclinics in five different centers. MAIN OUTCOME MEASURE(S): International Index of Erectile Function - 5 (IIEF - 5), Overactive Bladder 8 - Question Awareness Tool (OAB - V8), urodynamics, semen analysis. The participants of the study were n = 120 patients. There was retrograde ejaculation (RE) in only n = 47 patients (non / minimal symptomatic patients), n = 73 patients had RE and overactive (OAB) complaints (symptomatic patients) and received anticholinergic treatment (trospium), n = 37 control group patients who only had OAB and received an anticholinergic. RESULTS: While no difference was observed in overactive bladder examination and urodynamic values between the non / minimal symptomatic group and the symptomatic group (p > 0.05), sperm was detected and identified as fructose positive in post - ejaculation urine in the symptomatic group. Thus, it was possible to demonstrate the differences between symptomatic patients and non - symptomatic patients. Consequently, following three - month daily treatment with trospium 30 mg 2 x 1 in the control group and the symptomatic group, it was observed that an evident increase was observed in the sperm count and ejaculate volume in the symptomatic group and that no change was observed in the control group (p < 0.05). CONCLUSION: This clinical study is the first of its kind in terms of revealing the coexistence of RE with OAB upon performing urodynamics and showing that treatment is possible in selected patients.

Evaluation of sexual function and micro- testicular sperm extraction in men with mosaic Turner syndrome.

Background: Men with mosaic Turner syndrome (TS) having karyotype 45,X/46,XY are infrequently seen. Their sexual function and fertility potential are not well documented. We describe the sexual function and outcomes of sperm extraction in 5 such men who were evaluated between 2008 and 2017. Methods: Five phenotypic men diagnosed to have mosaic TS underwent detailed physical examination, semen analysis and evaluation of follicle-stimulating hormone, luteinizing hormone, prolactin and total testosterone. Blood, testis, oral mucosa and skin fluorescence in situ hybridization (FISH) analyses were done for evaluating the karyotype. Genomic DNA was extracted from peripheral blood for molecular analysis of azoospermic factor (AzF) deletions. Sexual function was assessed using the International Index of Erectile Function-5 (IIEF-5). One patient also underwent micro-testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI). Results: All 5 men had a mosaic 45,X/46,XY genotype and the sex-determining region (SRY) was positive in DYZ1- negative cells. None had a deletion in the AzF a, b or c regions. Sperm was detected in 3 patients through micro-TESE but ICSI could be done in only 1 patient. No embryo development was identified in time lapse (Embryoscope©) follow-up. It was observed that the rate of 46,XY was particularly high in gonadal tissues in the mosaic structure in patients detected to have sperms. Conclusion: Patients with TS having 45,X/46,XY, SRY( + ), with no AzF deletions, and a high percentage of 46,XY in the peripheral blood, especially in gonadal tissues, could have a healthy sexual life and possibly father a child through in vitro fertilization or ICSI upon detection of sperms with micro-TESE.

Comparison of embryo morphokinetics following intracytoplasmic sperm injection in smoker and non-smoker couples: Are the results different?

OBJECTIVE: To assess early embryo development via time-lapse in smokers and non-smokers. METHODS: The retrospective study was conducted at Novafertil IVF centers in Konya, Turkey and comprised oocytes of both smoker and non-smoker couples subjected to in vitro fertilisation / introcytoplasmic sperm injection from 2012 to 2015. Age, basal follicle-stimulating hormone, number of stimulation days, amount of gonadotropin used, number of metaphase II oocytes, number of embryos transferred and pregnancy, abortus and clinical pregnancy rates were noted. The embryos were observed for 72 hours in the time-lapse monitoring system. SPSS 22 was used for data analysis. RESULTS: Of the 257 couples, 132(51.4%) were non-smokers and 125(48.6%) were smokers. A total of 1,414 oocytes were collected from non-smokers and 1,280 oocytes from smokers. There was no significant difference in the age of patients and number of stimulation days between the smoker and non-smoker groups (p>0.05). The number of oocytes, fertilised oocytes, transferred embryos and metaphase II oocytes was significantly less in the smoker group (p<0.05). The rate of pregnancy and ongoing pregnancy was also lower in the smoker group (p<0.05). A difference was observed in time of pronuclei appearance, t8, t9+ cleavage times in time-lapse in the smoker and non-smoker groups (p<0.05). A prolongation was observed in time to pronuclear fading and t2 cleavage times in time-lapse in the non-smoker group (p<0.05). Some chromosomal number and structural defects were identified in pre-implantation genetic in some embryos with prolongation in time-lapse cleavage time in the smoker and non-smoker groups. CONCLUSIONS: The negative impacts of smoking were not observed at each cleavage phase of embryo development in time-lapse.

Body mass index based evaluation of 6-year outcomes after transobturator tension-free vaginal tape for female urinary incontinence.

INTRODUCTION: The long-term results will be presented according to the body mass index (BMI) rates for transobturator tension-free vaginal. METHODS: Three hundred nineteen female patients were evaluated (2008-2014). Their incontinence was classified according to the Stamey classification. The International Consultation on Incontinence Questionnaire-Short form was filled in before and after surgery. The Pelvic Organ Prolapse quantification system was utilized. The Female Sexual Function Index and the International Index of Erectile Functions were asked to be filled in. Their satisfaction level was assessed in the sixth year with the modified Clavien classification system. BMI cut-off points for public health action for the Asian population were adopted in the present study as follows: 18.5-23.0 kg/m2 (normal), 23.1-27.4 kg/m2 (high) and at least 27.5 kg/m2 (obese), respectively. RESULTS: The median success rate on the 12th month was calculated as 81.25% in the follow-ups after TOT; it was observed that the median success rate after 72 months decreased to 79.15%. Significant improvements were observed in the Female Sexual Function Index and the Index of Erectile Dysfunction. The objective cure rates detected according to normal, high and obese BMI rates, respectively, were 93.1%, 75.9% and 81.4%, while the patient satisfaction rates were 83.3%, 81.3% and 83.1%, respectively. CONCLUSIONS: It was observed that the objective and subjective patient satisfaction rates were very good in the long term in all BMI groups. No statistically significant differences were observed in perioperative complication rate, 6-year success rates and patient satisfaction among the three different BMI groups in the long term.

Investigation of Antibacterial Activity and Biofilm Formation of Silicones Coated With Minocycline-Rifampicin, Silver Nitrate, and Nitrofurantoin for Short-term Utilization in In Vitro Urinary System Models.

OBJECTIVE: To analyze antimicrobial activity and biofilm formation on silicones coated with antimicrobial substances in in vivo short-term catheterization simulation using our newly developed in vitro urinary system model and to compare minocycline-rifampin (MR)-, silver nitrate-, and nitrofurantoin (NF)-coated silicone discs. MATERIALS AND METHODS: Silicone discs were exposed to bacterial urine suspension for 168 hours. The antimicrobial activities were assessed in the medium, and the inhibition zone diameters were measured. The weight of the silicones was measured for biofilm growth assessment before and after the experiment, and confocal microscopy images were taken. RESULTS: Although the inhibition zone diameters of silver nitrate silicones were larger than those of pure silicone (PS), MR, and NF silicones, biofilm formation could not be prevented (P < .05). MR and NF silicones were superior to PS in terms of antimicrobial efficacy and prevention of biofilm formation (P < .05). In terms of biofilm prevention, no differences were detected between NF and MR silicones apart from a slightly superior ability of MR silicones to inhibit Escherichia coli (P > .05). Biofilm formation occurred on all silicone discs. CONCLUSION: In short-term urinary catheter utilization, antimicrobial efficacy and biofilm formation prevention were superior in coated silicones, regardless of the type of antibiotic used, compared with the control group (PS). As the study was conducted in an in vitro setting, the findings should be substantiated with in vivo studies on the grounds that different results may be obtained in these settings.

Mandibular osteonecrosis due to bisphosphonate use.

Due to their efficient osteoclastic inhibitor effect in bone metabolism and antiangiogenic activity, bisphosphonates are widely used in many cancer diseases particularly in prostate cancers with bone metastasis, lung cancer, breast cancer and multiple myeloma, as well as in systemic diseases such as osteoporosis, osteopenia, Paget disease and osteogenesis imperfect for the last 13 years. Prostate cancer is a common cancer in males and it is the leading cause of bone metastasis. Mandibular metastasis is rarely encountered during the course of prostate cancer. Mandibular osteonecrosis as well has begun to be observed along with the availability of more efficient and stronger formulations developed following the use of bisphosphonates. Zolendronic acid, which has been used also by our patient, has widely come into practice as a 3(rd) generation bisphosphonate. Because of prostate cancer and widespread bone metastases, our patient has been receiving zolendronic acid with maximum androgen blockage for 4 years. Tomography of the patient, who has undergone intensive treatment because of submandibular abscess, demonstrated extensive osteonecrosis in the fovea sublingual region of the mandible corpus. In large series, although, mandibular osteonecrosis was widely seen due to bisphosphonate use for the metastases of lung and breast cancers, this rate was between 9.6% and 11% for prostate cancer within the series. Although our patient had no mandibular metastasis before, mandibular necrosis was observed due to long-term bisphosphonate use. We are going to present our patient who had this rare complication with his clinical picture.

Migration of endotacker into the bladder 7 years after laparoscopic retroperitoneal Burch application.

Laparoscopy began to be used widely since the second half of 1990s as an alternative to laparotomy or vaginal approaches in incontinence and pelvic diseases in women, based on its claimed better success rates. Injuries were reported in the bladder, gastrointestinal system and the entry of the Verress cannula in early and late laparoscopic applications. De-novo urging, voiding dysfunctions, marked recurrences and surgical inefficiencies were observed in 5-year follow-ups after laparoscopic incontinence surgery. Although tension-free midurethral sling operations replaced open laparoscopic colposuspensions nowadays, laparoscopic colposuspension is still preferred in cases where simultaneous laparoscopic paravaginal repair or sacrocolpopexy is considered or where synthetic graft implantation is contraindicated. Moreover, meshes and endotackers are still frequently used in many laparoscopic applications in various clinics. The migration of the tacker used in mesh fixation in a patient where retroperitoneal laparoscopic Burch was performed 7 years ago due to stress urinary incontinence and the extraction of the ossified tacker from the bladder will be presented.

Evaluation of antimicrobial activities of minocycline and rifampin-impregnated silicone surfaces in an in vitro urinary system model.

OBJECTIVE: To evaluate the antimicrobial activity in urinary catheters and silicones in antibiotic-coated prosthetic urinary systems in order to reduce morbidity and mortality caused by catheter-associated infection. METHODS: The study was initiated in 1993 at Houston, USA and continued in Turkey till 1996. A sterileplastic bag was used as kidney in the in vitro urinary system. Physiological renal jet streams (50 cc/h) were generated with an intravenous metric pump. The temperature was kept at body temperature. The bladder drainage was achieved at the physiological drainage period of 4-6 hours during the 72-hour experiment. Silicone surfaces coated with pure silicone and impregnated with Minocycline-Rifampin were exposed to the urine contaminated with the targeted bacteria in the in vitro urinary model for 72 hours. Antimicrobial activities occurring in the Eosin methylene blue and blood agar media in the infected silicones were assessed. RESULTS: Minocycline-Rifampin silicone surfaces exposed to the urine contaminated with Escherichia coli and Pseudomonas aeruginosa reported reproduction. No reproduction was observed in the culture of Minocycline- Rifampin-impregnated silicone surfaces for Proteus mirabilis.The difference with the control group was regarded as statistically significant for Proteus mirabilis (p < 0.005). Minocycline-Rifampin-coated silicones were closely monitored only for Proteus mirabilis in the in vitro urinary medium. Although inhibition zones (< 10 mm) in the cultures were observed for Minocycline-Rifampin-coated silicones for Escherichia coli and Pseudomonas aeruginosa, but the microbial efficacy was not regarded sufficient. CONCLUSION: There is still need for evidence-based in vivo and in vitro studies where antimicrobial activity is evaluated on the surface of catheters.

Monosymptomatic Persistent Hematospermia due to Rarely Encountered Prostatic Utricle Stones.

We present a young patient who had hematospermia which was unresponsive to repeated medical therapies. In this patient prostatic utricle stones were detected via pelvic and transrectal ultrasonography, the presence of the stones was confirmed by transurethral fenestration, and persistent hematospermia disappeared following surgical excision. Thus, we conclude that prostatic utricle stones might have caused hematospermia in this young patient, who had no additional pathology likely to be responsible for this condition.

Early Morphokinetic Monitoring of Embryos after Intracytoplasmic Sperm Injection with Fresh Ejaculate Sperm in Nonmosaic Klinefelter Syndrome: A Different Presentation.

The patient was diagnosed with nonmosaic 47, XXY Klinefelter Syndrome with the AZF deletion absent and SRY+. The nonmosaic 47, XXY karyotype was confirmed on a skin biopsy chromosomal analysis. Using only ejaculate motile sperms, 11 oocytes underwent ICSI and were placed rapidly in a time lapse (Embryoscope ©) with a specific culture dish. Biopsies were performed on six embryos on the 3rd day, and numerical chromosomal abnormalities were observed using the FISH test before transfer. PGS results were normal in only two embryos with normal morphokinetics in the Embryoscope. For clinical confirmation of pregnancy, ultrasonographic examination was performed during the 7th week of pregnancy, and two gestational sacs and fetal heart beat were observed.

Micropercutaneous nephrolithotomy (microperc) in a two-year-old with the 'all-seeing needle'.

This paper presents the use of the single-step micropercutaneous nephrolithotomy (microperc) procedure for the treatment of a 13-mm renal stone using a 4.85-Fr 'all-seeing needle' in a 2-year-old toddler. In the current literature to date, this is the youngest case. Moreover, the advantages and reliability of this technique in toddler renal stone treatment are also evaluated.

Relapsing idiopathic scrotal calcinosis.

Idiopathic scrotal calcinosis is a rare and benign disease of the scrotum which is described in all age groups. It was initially first defined by Lewinski in 1883. Although many mechanisms have been proposed in the pathogenesis, underlying mechanisms are still controversial at the present time. Currently, the best therapeutic approach is the surgical removal of the scrotum without disrupting its integrity. Although it is indicated in literature that its recurrence is still controversial, we have observed relapse two times in our 41 year-old male patient following surgery at the 19th and 33rd months. We have confirmed recurrence with clinical and pathological assessments. Idiopathic scrotal calcinosis may recur both clinically and pathologically in the long-term follow up. Recurrence should be confirmed with post-surgical long-term follow up in larger series.

Secondary infertility due to use of low-dose finasteride.

Herein, we present an unusual case of secondary infertility after prolonged use of low-dose finasteride for androgenetic alopecia in a 40-year-old man. We detected sperm DNA damage in the patient. Despite such a long-term use, we observed that impairment in semen parameters and sperm DNA fragmentation index regressed after the drug was discontinued. Consequently, pregnancy occurred and resulted in live birth.