Evaluation of efficacy and safety profile of tadalafil 5 mg daily dose in the tablet form versus oral dispersible film in men with mild-to-moderate erectile dysfunction: a comparative placebo-controlled study.

PURPOSE: We aimed to compare the efficacy, safety, and compliance of tadalafil 5 mg daily dose in the tablet form versus oral dispersible film (ODF) in men with mild-to-moderate erectile dysfunction (ED). METHODS: One hundred thirty-five randomized patients were equally divided into three groups according to age where each group included forty-five patients. Within each group, 15 patients received oral tadalafil 5 mg, 15 patients received ODF tadalafil 5 mg and 15 patients received a placebo once daily for 1 month. All participants were assessed by the validated Arabic version of the international index of erectile function (ArIIEF-5) at baseline and after 1 month. Also, the efficacy of different forms of tadalafil 5 mg was assessed by responding affirmatively to a questionnaire. RESULTS: Patients aged > 25 to < 40 years and 40-55 years and > 55 years showed a statistically significant improvement of ArIIEF-5 scores after tadalafil 5 mg tablet and ODF tadalafil 5 mg compared to placebo ODF (23 ± 1.4; 22.7 ± 0.9; 20 ± 0.9; 20.4 ± 1.3; 20.2 ± 1.2; 16.6 ± 1.2; 18.5 ± 1.7; 19.6 ± 1.4; 16.3 ± 1.4; p < 0.001, respectively). Three patients (> 25 to < 40 years) who received tadalafil 5 mg tablet showed muscle and back pain. Gastrointestinal (GIT) upset (eight patients) followed by headache (seven patients) were the main side effects reported in patients (40-55 years) who received tadalafil 5 mg tablet. While GIT upset was the main side effect reported in patients (> 55 years) who received tadalafil 5 mg tablet. CONCLUSION: ODF tadalafil 5 mg is an effective, tolerable, and safe formulation that can be used in patients with mild-to-moderate ED.

Mutational analysis of Aurora kinase C gene in Egyptian patients with macrozoospermia.

Macrozoospermia is a rare syndrome. The key marker of the disease is a high percentage of spermatozoa with abnormal phenotypes namely enlarged head and multiple tails. The presence of at least 70% of spermatozoa with a large head is usually associated with Aurora kinase C gene (AURKC) mutations. We sought to assess AURKC as a potential genetic actor of macrozoospermia in a sample of infertile Egyptian men. We recruited 30 patients and conducted a clinical examination, semen analysis, and DNA sequencing and RFLP for AURKC. We diagnosed 17 patients with characteristic macrozoospermia and classified them into eight severe and nine mild cases. We detected genetic variants of AURKC in five patients (29.4%): Three patients with severe macrozoospermia had c.144delC mutations in exon 3 (37.5% of the severe), and two mild cases had c.1157G>A polymorphism in the 3' UTR (22.2% of the mild). A successful intracytoplasmic sperm injection (ICSI) was achieved only with a severe macrozoospermia patient without apparent AURKC mutation. The present study is the first report to link macrozoospermia and AURKC mutations in Egypt. The study recommends macrozoospermia patients to perform AURKC gene analysis and attempt ICSI, even those with a high percentage of large head spermatozoa.

Increased insulin resistance in men with unexplained infertility.

This prospective case-control study aimed to test the presence of insulin resistance (IR) in men with unexplained infertility. We included two groups: the study group including 160 infertile men with unexplained oligozoospermia (sperm count <10 × 106/ml) and normal hormonal profile, and the control group of 79 men with proven fertility within the preceding year. A fasting blood test measured IR, FSH, LH, total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides. Insulin level was significantly higher in the study group (13.67 ± 10.44) compared with the control group (5.46 ± 3.15), P < 0.0001, and IR was significantly higher in the study group, P < 0.0001. FSH was significantly (P < 0.0001) higher in the study group (4.71 ± 2.57) than the control group (3.15 ± 1.92). LH was significantly higher in the study group (4.98 ± 2.41) compared with the control group (3.15 ± 1.12), P < 0.0001. Total cholesterol was significantly higher in the study group (198.29 ± 37.52) than the control group (182.45 ± 35.92), P < 0.05. In conclusion, IR in men with unexplained infertility may be a cause of reproductive and metabolic abnormalities. The benefit of insulin-sensitizing agents for these patients should be tested.

Does the outcome of ICSI in cases of obstructive azoospermia depend on the origin of the retrieved spermatozoa or the cause of obstruction? A comparative analysis.

OBJECTIVE: To compare the outcomes of intracytoplasmic sperm injection (ICSI) for men with obstructive azoospermia and normal spermatogenesis, according to the use of epididymal or testicular spermatozoa and the cause of obstruction. DESIGN: Retrospective study. SETTING: Private infertility center. PATIENT(S): A detailed chart review of a cohort of 1,121 men with obstructive azoospermia who underwent intracytoplamic sperm injection (ICSI) was performed. INTERVENTION(S): Patients were grouped according to the origin of spermatozoa: epididymal (n=331) or testicular (n=790). They were further classified into two subgroups according to the cause of obstruction: congenital bilateral absence of vas deferens (CBAVD; n=434), and other causes of obstruction (n=687). MAIN OUTCOME MEASURE(S): Fertilization, clinical pregnancy, and miscarriage rates. RESULT(S): Fertilization (64.2% vs. 68.0%), clinical pregnancy (42.3% vs. 43.2%), and miscarriage (17.6% vs. 18.4%) rates did not differ between epididymal spermatozoa and testicular spermatozoa, respectively. Fertilization, clinical pregnancy, and miscarriage rates were also similar in the patients with CBAVD or due to other causes of obstruction. CONCLUSION(S): The source of sperm used for ICSI in cases of obstructive azoospermia and the etiology of the obstruction do not affect the outcome in terms of fertilization, pregnancy, or miscarriage rates.

Effect of high environmental temperature on semen parameters among fertile men.

OBJECTIVE: To evaluate the effect of high environmental occupational temperature on semen parameters of fertile men. DESIGN: Prospective. SETTING: Steel-casting plant. PATIENT(S): Ninety fertile workers exposed to a high temperature compared with 40 fertile workers working under ordinary conditions as control subjects. INTERVENTION(S): Measurement of scrotal temperature by invagination thermometry, air temperature, relative humidity by aspirated psychrometer, radiant heat by globe thermometer, air velocity by light vane anemometer, and semen analysis. MAIN OUTCOME MEASURE(S): Scrotal temperature and semen analysis. RESULT(S): Nonsignificant difference was found between the two groups regarding their scrotal temperature. Also, nonsignificant differences were demonstrated regarding semen analysis parameters being in the normozoospermic range. CONCLUSION(S): Under high environmental temperature, semen parameters were within normozoospermic levels owing to body acclimatization mechanisms.

Length of androgen receptor-CAG repeats in fertile and infertile Egyptian men.

Androgens play key roles in spermatogenesis, and they exert their effect via the androgen receptor (AR). The AR gene has a repetitive DNA sequence in exon 1 that encodes a polyglutamine tract. Instability in the glutamine (CAG) repeat unit length is polymorphic across ethnic groups. Previous studies of the relationship between the repeat unit length and male infertility have been contradictory. To establish the range of wild-type alleles in Egyptian men, we determined the range of repeat lengths in a population of normally fertile, ethnically selected Egyptian men. We also investigated the association between trinucleotide repeat length within the AR gene and male factor infertility in a population of ethnically selected Egyptian infertile men, who were compared with fertile, ethnic group-matched and age-matched controls. The study included 129 clinically selected infertile Egyptian men who were scheduled for intracytoplasmic sperm injection and 52 ethnically matched fertile controls. The experimental population was grouped according to sperm counts ranging from nonobstructive azoospermia to normozoospermia. The CAG repeat N-terminal domain region of the AR gene was amplified in peripheral blood DNA, and allele size was determined by fragment analysis. Allele size and single-nucleotide polymorphism and mutation rates were determined by sequencing individual amplified alleles. The mean CAG repeat length in the azoospermia group was 18.55 +/- 2.0; in the severe oligozoospermia group it was 18.21 +/- 3.42; in the oligozoospermia group it was 18.27 +/- 2.93; and in the infertile with normal sperm count group it was 17.72 +/- 2.0. In the control group, the mean CAG repeat length was 18.18 +/- 3.63. No significant correlation was found between CAG repeat length and the risk of male factor infertility in an ethnically defined population of Egyptian men. However, a significant and positive correlation between CAG repeat length and serum testosterone concentration was demonstrated. This suggests the involvement of epigenetic regulation linked to this region.

Electrical activation of oocytes after intracytoplasmic sperm injection: a controlled randomized study.

OBJECTIVE: To evaluate the electrical activation of oocytes in patients with previously failed or limited fertilization after intracytoplasmic sperm injection (ICSI) and in patients with possible failure of fertilization. DESIGN: Prospective randomized study. SETTING: A private IVF center in Egypt. PATIENT(S): Two hundred forty-six patients with severe oligoasthenospermia or nonobstructive azoospermia with total teratospermia or totally immotile spermatozoa were selected for the study. Patients who previously had total failure or limited fertilization after ICSI also were included. INTERVENTION(S): Sibling oocytes were randomly divided after ICSI into two groups: the study group (n = 1,640) was subjected to electroactivation, and the control group (n = 1,435), to no electroactivation. Electroactivation was performed by using a double-square direct-current pulse. Embryo transfer was performed with the best available embryos. MAIN OUTCOME MEASURE(S): Fertilization rate, degeneration rate, and pregnancy outcome. RESULT(S): Two hundred forty-one ICSI cycles were included in the study. The fertilization rate was statistically significantly higher in the electroactivated group as compared with in the control group (68% vs 60%, odds ratio = 1.397, 95% confidence interval = 1.197 to 1.629). The oocyte degeneration rate was not statistically significantly different between the two groups (5.9% vs 4.9%, odds ratio = 0.96, 95% confidence interval = 0.73 to 1.26). In total, 112 clinical pregnancies resulted (pregnancy rate = 46.5%). Total fertilization failure occurred in 5 cycles in the control group, and none failed in the study group. CONCLUSION(S): Oocyte electroactivation after ICSI significantly improved the fertilization rate in severe oligoasthenoteratospermia and nonobstructive azoospermia.

Semen parameters in men with spinal cord injury: changes and aetiology.

AIM: To assess the changes in semen parameters in men with spinal cord injury (SCI) and the possible causes of these changes. METHODS: The study included 45 subjects with SCI. Semen retrieval was done by masturbation (2), vigorous prostatic massage (n = 13), penile vibratory stimulation (n = 13) or electroejaculation (n = 17). RESULTS: The semen of men with SCI showed normal volume (2.3 +/- 1.9 mL) and sperm count (85.0 X 10(6) +/- 83.8 X 10(6)/mL) with decreased motility (11.6% +/- 0.1%), vitality (18.5% +/- 5.2%) and normal forms (17.5% +/- 3.4%), and pus cells has been increased (6.0 X 10(6) +/- 8.2 X 10(6)/mL). Total (13.4 +/- 9.9 vs. 7.1 +/- 6.8) and progressive (4.4 +/- 3.9 vs.2.2 +/- 2.1) motility were significantly higher in subjects with lower scrotal temperatures. There was no statistical significant difference between electroejaculation and penile vibratory stimulation groups as regards any of the semen parameters. Subjects'age, infrequent ejaculation, injury duration and hormonal profile showed no significant effect on semen parameters. CONCLUSION: The defining characteristics of the seminogram in men with SCI are normal volume and count with decreased sperm motility, vitality and normal forms, and the increased number of pus cells. The most acceptable cause of the deterioration of semen is elevated scrotal temperature.

Testosterone therapy can enhance erectile function response to sildenafil in patients with PADAM: a pilot study.

INTRODUCTION: Recent studies suggest a direct relationship between free testosterone and cavernous vasodilatation. Some men with erectile dysfunction (ED) associated with PADAM (partial androgen deficiency in aging men) might possibly benefit from testosterone undecanoate therapy (TRT). OBJECTIVES: To determine the efficacy of testosterone undecanoate in facilitating the erectile response and patient satisfaction with sildenafil in men 40-70 years old with PADAM symptoms. DESIGN AND METHODS: Prospective study including 40 patients recruited after a sildenafil therapeutic trial. Total testosterone and sex hormone binding globulin (SHBG) were measured to calculate the free androgen index. Prostate specific antigen (PSA) was measured and repeated 2 months after treatment. A rating score was used for PADAM symptoms, and the 5-point abbreviated version of the International Index of Erectile Function (IIEF-5) to assess erectile function. Men failing to respond to sildenafil were randomized into two groups receiving sildenafil plus continuous TRT (group 1ST), and TRT (group 1T) alone. Men partially responding to sildenafil were randomized into two groups receiving sildenafil plus continuous TRT for 2 months (group 2ST), or sildenafil alone (group 2S). Treatment efficacy was assessed by analysis of between-group differences. RESULTS: Groups 1T, 2S, and 2ST showed significant improvement in PADAM scores (P<0.05, Wilcoxon matched pairs test). Patients receiving both sildenafil plus continuous TRT (groups 1ST and 2ST) showed significant improvement in IIEF-5 scores (P<0.5, paired t-test). No significant changes in serum levels of PSA were detected (paired t-test). CONCLUSIONS: We conclude that TRT appears to be beneficial and safe in facilitating the erectile response and patient satisfaction with sildenafil in men with PADAM symptoms. Androgen supplementation should be carried out cautiously with careful monitoring to avoid possible adverse effects.

Percutaneous aspiration biopsy using an intravenous catheter for testicular sperm retrieval in patients with obstructive azoospermia.

Testicular needle aspiration has been proposed as a simple alternative to open biopsy for the diagnosis and treatment of azoospermia. This study describes a new modification of needle aspiration biopsy using an ordinary intravenous catheter to retrieve testicular spermatozoa from patients with obstructive azoospermia, and compares it to the classical fine-needle aspiration (FNA) method. The study included 86 consecutive patients with obstructive azoospermia. Thirty-one patients underwent FNA using butterfly needles (G21 or G23) and a 20 ml syringe. For the remaining 55 patients, an i.v. catheter (G14 or G16) was used instead of the butterfly needle. When testicular tissue was seen in the aspirate, the catheter was clamped and removed from the testis. If, after a maximum of three punctures, insufficient spermatozoa were retrieved, an open biopsy was carried out. Successful sperm retrieval was achieved in 54 out of 55 patients (98.1%) using an i.v. catheter, compared with 16 out of 31 patients (51.6%) using FNA (P < 0.05). Enough aspirated tissue was obtained for cryopreservation of spermatozoa in all 54 patients using the i.v. catheter, compared with 6/16 (37.5%) of the patients undergoing classical FNA. No significant complications were reported. In conclusion, the use of an i.v. catheter for testicular aspiration biopsy significantly improved sperm retrieval compared with FNA in obstructive azoospermia, and allowed for cryopreservation of excess tissue. The procedure is simple and inexpensive, however regular follow up and testing of possible adverse consequences of this method is indicated to establish its safety.

Selection of individual testicular tubules from biopsied testicular tissue with a stereomicroscope improves sperm retrieval rate.

The present study describes a new modification for testicular sperm extraction (TESE) with an intraoperative surgical loop, coupled with stereomicroscopic dissection in the laboratory, to identify sperm-containing tubules. The study included 116 consecutive patients with nonobstructive azoospermia (NOA) undergoing TESE and intracytoplasmic sperm injection. After dissection of testicular tissue under the stereomicroscope, patients were separated into 2 groups according to tubular diameter. In the first group (n = 72), all tubules were of the same diameter. In the second group (n = 44), tubules with variable diameters could be identified. In such cases, 1-2 of the most distended and opaque seminiferous tubules were selected and minced alone, then examined for the presence of spermatozoa. The rest of the testicular tissue suspension was minced and examined separately. In 11 (25%) cases, retrieved spermatozoa were found in the isolated distended tubules only. In 21 (47.7%) cases, spermatozoa were found in both the isolated distended tubules and the rest of the specimen. In 2 cases, spermatozoa were found only in the whole sample, not in the isolated tubules. In the remaining 10 cases, spermatozoa were not found in either the whole sample or the isolated tubules. The sperm recovery rate in the isolated tubules was significantly higher than that of the rest of the specimen (72.7% vs 52%, chi(2) = 3.93, P <.05), and larger numbers of spermatozoa could be easily retrieved in a shorter period of time. In conclusion, the selection and isolation of the most dilated and opaque seminiferous tubules by using the surgical loop, coupled with laboratory stereoscopic dissection, improves sperm retrieval for men with NOA. It is possible that surgical-loops TESE coupled with stereomicroscope may offer superior sperm retrieval when compared with conventional TESE and may also offer reduced operative time when compared with microdissection TESE.

Intracytoplasmic spermatid injection can result in the delivery of normal offspring.

Almost one-third of all patients with nonobstructive azoospermia undergoing testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) have cancelled cycles due to failure to find spermatozoa. For these patients, every attempt should be made to rescue the cycles by searching for spermatids. In this retrospective study, we report our experience in using elongating (stage Sb2) and elongated (stage Sc and Sd1) spermatids for ICSI. The study included 488 consecutive ICSI and TESE cycles performed for 452 patients with nonobstructive azoospermia. In 179 (36.7%) cycles, neither spermatozoa nor mature spermatids (stage Sd2) suitable for injection were found. After an extensive search only Sb2, Sc, and Sd1 spermatids were found in 22 of these 179 cycles (12.3%). These spermatids were used for injection of retrieved oocytes. The fertilization rate was 33.2%, and 19 patients (86.4%) reached the embryo transfer stage. In 6 cycles a chemical pregnancy occurred, and 3 clinical pregnancies were established, resulting in the delivery of 3 healthy boys with normal karyotypes. When normal living spermatozoa or mature spermatids (stage Sd2) cannot be found during TESE, late spermatids (stage Sb2, Sc, and Sd1) can be used successfully and result in the delivery of healthy offspring.

The use of clomiphene citrate/human menopausal gonadotrophins in conjunction with GnRH antagonist in an IVF/ICSI program is not a cost effective protocol.

OBJECTIVE: To evaluate the cost effectiveness of a clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/GnRH antagonist protocol versus a long-acting GnRH agonist/hMG protocol. PARTICIPANTS AND METHODS: One hundred eighty nine couples having their first trial of ICSI for male factor infertility were divided into two groups. Group I (no = 33) received CC 100-150 mg/day for five days starting from day 2 of the cycle and 150 IU of hMG/day on days 6-10. GnRH antagonist (Centrorelix) 0.25 mg/day was started when the leading follicle reached 16 mm in the absence of an LH surge. Group II (no = 156) received 0.1 mg Deacapeptyl/day as our standard long protocol. RESULTS: Clinical pregnancy was observed in 8 out of the 33 cases in group I (24%) while in group II, 92 out of 156 achieved clinical pregnancy (59%), the difference was statistically significant (P = 0.019). The cost of medications/cycle was estimated to be 1110+/-492 E.P in group I, while it was 1928+/-456 E.P. in group II. However, the total cost per pregnancy was 19653 EP in group I and 10047 EP in group II. CONCLUSION: The use of the clomid/hMG/antagonist protocol is not a cost effective strategy and should not be recommended in IVF-ICSI cycles.