Methylation Analysis of Urinary Sample in Non-Muscle-Invasive Bladder Carcinoma: Frequency and Management of Invalid Result.

BACKGROUND: Numerous studies showed that methylation analysis represents a newly developed urinary marker based on DNA methylation changes in a panel of genomic biomarkers and it could represent a valid tool in terms of the diagnosis and prediction of high-grade urothelial carcinoma recurrences. One of the limits of the use of this new molecular method during a follow-up is represented by the number of invalid tests in routine practice. METHOD: A total of 782 patients with a diagnosis of non-muscle-invasive high-grade carcinoma (NMIBC) was studied. The Bladder EpiCheck test (BE) was performed together with cytology in all cases within 1 year after the end of treatment. In 402 patients, the urinary samples were voided urine (UV), while, in 380 cases, the samples were collected after bladder washing (IU). For all the patients with invalid BE results, a second BE test was performed following the instructions for use that indicated the test should be repeated with a new urinary sample in the case of an invalid result. RESULTS: Analyzing the two different groups (UV and IU), we found the invalid BE results seemed to be not related to urinary samples (p = 0.13 Fisher's exact test), suggesting that the collection method was not relevant in order to reduce the number of invalid tests. CONCLUSIONS: In the follow-up for NMIBC, for patients for whom a BE test is planned, a combined approach of cytology and a methylation test is recommended in order to repeat the BE test with an invalid result only in those cases with a cytological diagnosis of atypical urothelial cells (AUC) suspicious for high-grade urothelial carcinoma (SHGUC) and high-grade urothelial carcinoma (HGUC).

Qualitative evaluation of the Rey-Osterrieth Complex Figure Test in patients with progressive supranuclear palsy.

Objective: In early stages of disease, the differential diagnosis between Parkinson's Disease (PD) and atypical parkinsonism, such as Progressive Supranuclear Palsy (PSP), could be challenging. Growing attention has recently been dedicated to investigating neuropsychological markers of degenerative parkinsonism. The Rey-Osterrieth Complex Figure Test (ROCFT) copy score was hypothesized able to differentiate PSP from PD. However, ROCFT is a drawing test requiring multiple cognitive abilities and it is still unknown which of them assumes an important role in PSP performance. Using a qualitative scoring system, we investigated which cognitive abilities underpin the PSP performance at the ROCFT copy trial. Moreover, we evaluated usefulness of the BQSS scores in discriminating PSP from PD. Methods: Thirty PSP-Richardson's Syndrome (PSP-RS) patients, 30 PD patients, and 30 healthy control (HC) comparable for age, education, and gender were enrolled. All subjects underwent a neuropsychological evaluation; ROCFT copy were evaluated with the 36-Point Score and with the Boston Qualitative Scoring System (BQSS). Results: PSP-RS patients performed worse in ROCFT 36-Point Score and in several BQSS scores compared to other groups. Most suitable scores discriminating PSP-RS from PD were "Perseveration" and "Vertical Expansion" of BQSS. A logistic regression model considering "Perseveration" and "Vertical Expansion" showed a diagnostic accuracy of 83,3% for PSP-RS condition. Conclusion: our findings showed that "Perseveration" and "Vertical Expansion" BQSS scores were useful in discriminating PSP-RS from PD. "Perseveration" and "Vertical Expansion" BQSS scores might be included in the cognitive evaluation along with quantitative scores when PSP diagnosis is considered.

Brain-Derived Neurotrophic Factor (BDNF) and Serotonin Transporter (SERT) in Platelets of Patients with Mild Huntington's Disease: Relationships with Social Cognition Symptoms.

Deficits in social-cognition processing have been identified during early stages of Huntington Disease (HD), attracting interest on their relevance as possible predictors of  neurodegenerative progression. Since the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) and the serotonin (5-HT) transporter (SERT) are known to modulate human adaptive behavior, we appraised these two proteins in mild-HD using blood platelets, with the aim at finding relationships with cognitive/psychosocial skills. Thirteen gene positive and symptomatic patients (9M/4W, HD-stage II, age> 40y) together 11 gender/age matched controls without a concurrent diagnosis of psychiatric disorders, underwent a blood test to determine BDNF storage and membrane-bound SERT in platelets by an ELISA immune-enzyme dosage and [3H]-paroxetine ([3H]-PAR) binding, respectively. Enrolled subjects were concurrently evaluated through a battery of socio-cognitive tests and emotion recognition questionnaires.Results showed greater intra-platelet BDNF (~ +20-22%) in patients versus controls, whereas equilibrium [3H]-PAR binding parameters, maximum density (Bmax) and dissociation constant (KD), did not appreciably vary in the two comparison groups. Cognitive/emotion abilities were found significantly reduced in patients. Additionally, platelet BDNF was unrelated to psycho-cognitive scores, but positively correlated with the illness duration. As well, SERT Bmax was unconnected to HD signs or socio-cognitive scores, whilst KDs negatively correlated with scores for angry voice recognition in both controls and patients. This pilot study suggests that platelet BDNF and SERT do not specifically underlie psychosocial deficits in stage II-HD, while higher BDNF storage in delayed mild symptoms, would derive from compensatory mechanisms. Supplementary investigations are warranted, by also comparing patients in other illness's phases.

A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment.

OBJECTIVE: To design a reproductive treatment algorithm based on the sperm DNA fragmentation (SDF) for couples with unexplained infertility following a poor intrauterine insemination (IUI) outcome. DESIGN: Couples that failed IUI with no apparent reproductive issue in both partners were allocated to diverse reproductive treatments on the basis of SDF. SETTING: Reproductive medical center in an academic setting. PATIENT(S): Over 4 years, couples with an unexpected poor IUI outcome and no apparent female or male partner reproductive issues were recruited. INTERVENTION(S): IUI, IVF, and ICSI were performed in the standard fashion following sperm SDF assays. MAIN OUTCOMES MEASURE(S): Fertilization rate, implantation rate, pregnancy characteristics, and delivery rates. RESULT(S): A total of 354 couples with unexplained infertility and normal semen parameters underwent 1133 IUI cycles. Clinical pregnancy rate (CPR) with IUI at our center in an age-matched cohort is 23.9% while the study cohort had 1.8%. Following SDF assessment, couples with failed IUI attempts but normal SDF (SCSA 9.8 ± 4.6%; TUNEL 11.8 ± 6.2%) underwent IVF with a CPR of 12.7%; those with abnormal SDF underwent ICSI with ejaculated spermatozoa, resulting in a CPR of 18.7%. This group included couples with normal SDF that had failed IVF. Couples with abnormal SDF that failed ICSI with ejaculated spermatozoa achieved a CPR of 31.0% with surgically retrieved spermatozoa. CONCLUSION(S): Couples with unexplained infertility that present with unexpectedly poor IUI outcomes can be funneled into a treatment algorithm guided by the integrity of the sperm genome for higher chances of pregnancy using an alternate method of insemination.

Development of ICSI.

The first conception outside of the human body that led to the birth of Louise Brown was a tremendous accomplishment, which opened the door to the utilization of assisted reproductive techniques globally. This brought the understanding that accomplishing life in a dish required several steps, the most obvious being the timing and characteristics of fertilization. It soon became obvious in the 1980s that the most disappointing phenomenon was unexpected and complete fertilization failure. Among the approaches that were attempted to treat male factor infertility, ICSI surfaced as the technique that brought the ratio of the gametes to 1:1 and was also able to grant consistent fertilization and a higher pregnancy rate. ICSI has now been implemented for a quarter of a century, proving itself as the ultimate technique utilizing ejaculated spermatozoa independent of the semen parameters and is the sole insemination method to be used with surgically retrieved spermatozoa. There are currently various indications for ICSI that are widely adopted, rendering it the most popular insemination method worldwide. The reliability of ICSI ensures its employment in upcoming techniques involving in vitro spermatogenesis and neogametogenesis.

A rationale for biopsying embryos reaching the morula stage on Day 6 in women undergoing preimplantation genetic testing for aneuploidy.

STUDY QUESTION: Is there a benefit to assessing ploidy in delayed embryos reaching the morula stage on Day 6 of development? SUMMARY ANSWER: Day-6 morulae should be considered for biopsy in women <40 years old undergoing preimplantation genetic testing for aneuploidy (PGT-A) because they are associated with acceptable, albeit reduced, euploidy and implantation rates (IRs). WHAT IS KNOWN ALREADY: Embryo development and morphology have been shown to correlate with aneuploidy and pregnancy rates. During PGT-A cycles, embryos are biopsied if they reach the blastocyst stage by Day 5 or 6, whereas slow-developing embryos are typically deselected and discarded. Determining the viability of slow-developing embryos is particularly relevant for women undergoing PGT-A who have diminished ovarian reserve and a relatively low blastocyst yield. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study that was performed at an academic medical center. Patients who underwent IVF with PGT-A were reviewed for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1615 cycles were reviewed. All cycles which involved a biopsy of a cavitating or compacted morula on Day 6 were included (n = 763). PGT-A was performed using array comparative genomic hybridization. The aneuploidy and implantation of morulae were compared to those of blastocysts originating from the same couples. MAIN RESULTS AND THE ROLE OF CHANCE: The study included 763 cycles in which 1260 morulae and 3014 blastocysts were biopsied. Women were divided into four age groups (<35, 35-37, 38-39 and ≥40 years): the prevalence of aneuploidy was consistently lower among blastocysts (40.3, 50.8, 56 and 78.3%, respectively) than among compacted morulae (68.7, 75.5, 88.9 and 98.1%, respectively) and cavitating morulae (57, 66.4, 81 and 91.6%, respectively) throughout the different age groups (P < 0.001). Of note, the majority of compacted morulae (98.1%) and cavitating morulae (91.6%) were aneuploid in women aged ≥40 years. Compacted and cavitating morulae had significantly higher rates of complex aneuploidy, which involves ≥3 chromosomes, compared with blastocysts (P < 0.001). Furthermore, euploid morulae were associated with a significantly lower IR (28.2 versus 54.6%; P = 0.002) and live birth rate (23.1 versus 55.0%; P = 0.001) compared to euploid blastocysts. LIMITATIONS REASONS FOR CAUTION: This study confirms that Day-6 morulae should not be discarded in young women undergoing PGT-A. However, a potential drawback of biopsying embryos at the morula stage is the inability to distinguish between inner cell mass and trophectoderm cell origin. The sample size of euploid morula transfer cycles in this study was limited. Thus, a larger cohort would be beneficial to validate the reassuring live birth and spontaneous abortion rates reported here. Furthermore, the reproducibility of our findings should be determined at different centers. WIDER IMPLICATIONS OF THE FINDINGS: Although Day-6 morulae are associated with higher aneuploidy rates and lower IRs compared to blastocysts, they still yielded successful pregnancies. Therefore, testing Day-6 morulae should be considered, especially for women <40 years old who are undergoing PGT-A with a small cohort of available blastocysts for biopsy. STUDY FUNDING/COMPETING INTEREST(S): The authors have nothing to disclose. They received no specific funding for this work. TRIAL REGISTRATION NUMBER: N/A.

Intracytoplasmic sperm injection: state of the art in humans.

Among infertile couples, 25% involve both male and female factors, while male factor alone accounts for another 25% due to oligo-, astheno-, teratozoospermia, a combination of the three, or even a complete absence of sperm cells in the ejaculate and can lead to a poor prognosis even with the help of assisted reproductive technology (ART). Intracytoplasmic sperm injection (ICSI) has been with us now for a quarter of a century and in spite of the controversy generated since its inception, it remains in the forefront of the techniques utilized in ART. The development of ICSI in 1992 has drastically decreased the impact of male factor, resulting in millions of pregnancies worldwide for couples who, without ICSI, would have had little chance of having their own biological child. This review focuses on the state of the art of ICSI regarding utility of bioassays that evaluate male factor infertility beyond the standard semen analysis and describes the current application and advances in regard to ICSI, particularly the genetic and epigenetic characteristics of spermatozoa and their impact on reproductive outcome.

Antipsychotic drugs in Huntington's disease.

INTRODUCTION: The aim of this review is to overview the pharmacological features of neuroleptics experienced in the treatment of Huntington's disease (HD) symptoms. Despite a large number of case reports, randomized controlled trials (RCT) and drug comparison studies are lacking. Areas covered: After evaluating current guidelines and clinical unmet needs we searched PubMed for the term 'Huntington's disease' cross referenced with the terms 'Antipsychotic drugs' 'Neuroleptic drugs' and single drug specific names. Expert commentary: In clinical practice antipsychotics represent the first choice in the management of chorea in the presence of psychiatric symptoms, when poor compliance is suspected or when there is an increased risk of adverse events due to tetrabenazine. Antipsychotics are considered valid strategies, with the second generation preferred to reduce extrapyramidal adverse events, however they may cause more metabolic side effects. In the future 'dopamine stabilizers', such as pridopidine, could replace antipsychotics modulating dopamine transmission.

Surgical excision of Essure® devices with ESHRE Class IIb uterine malformation: sequential hysteroscopic-laparoscopic approach to the septate uterus.

OBJECTIVE: While contraindications to Essure® placement have been provided by the manufacturer, there is no consensus on how best to remove these contraceptive devices. Here, we describe a non-hysterectomy removal of Essure® for a patient with a septate uterus (ESHRE Class IIb uterine malformation). CLINICAL CASE: A 35yr old G4 P2 presented for removal of Essure® implants after three years of gradually increasing pelvic pain, weight gain, headache, dizziness, lower extremity paresthesia, and fatigue which followed hysteroscopic sterilization (HS). Prior to HS, the patient was in good general health. She did not smoke and had never had a miscarriage. HS was performed under general anesthesia in October 2012. HSG obtained three months later, confirmed bilateral tubal occlusion but revealed an abnormal uterine cavity. A repeat HSG in 2015 showed minimal device migration, no contrast dye spill and a deeply bifid uterine cavity. At our center laparoscopic cornual dissection and bilateral partial tubal resection achieved removal of both devices intact and the patient was discharged three hours after surgery. Her postoperative recovery was uneventful. CONCLUSION: The presence of a Müllerian anomaly is a relative contraindication to the Essure® procedure. This is the first reported description of successful removal of Essure® coils in the setting of an ESHRE Class IIb uterine anomaly, and underscores the importance of careful patient selection, accurate pre-operative imaging and a conservative technique which renders hysterectomy unnecessary.

Gene expression of INPP5F as an independent prognostic marker in fludarabine-based therapy of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease-related and patient-related factors have been shown to influence the course of the disease. The aim of this study was to identify novel biomarkers of significant clinical relevance. Pretreatment CD19-separated lymphocytes (n=237; discovery set) and peripheral blood mononuclear cells (n=92; validation set) from the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide alone, underwent gene expression profiling. By using Cox regression survival analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase F (INPP5F) as a prognostic factor for progression-free survival (P<0.001; hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.35-1.98) and overall survival (P<0.001; HR, 1.47; 95% CI, 1.18-1.84), regardless of adjusting for known prognostic factors. These findings were confirmed on the validation set, suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic biomarker for fludarabine-based therapy in CLL.

Diagnostic value of cytological analysis of tumours and tumour-like lesions of the oral cavity in dogs and cats: a prospective study on 114 cases.

Neoplastic or non-neoplastic masses are common findings in the oral cavity of cats and dogs. The aim of this prospective study was to compare the results of cytological examinations of lesions of the oral cavity following fine-needle aspiration (FNA), fine-needle insertion (FNI), and impression smear (IS) with histopathological results being considered as the diagnostic gold standard. In total, 85 dogs and 29 cats were included in the study. Cases were included when histology and cytology (FNA, FNI, and/or IS) were available from the same lesion; κ-agreement and accuracy between cytological and histopathological results were calculated. Eighteen cytological specimens were excluded, with a retrieval rate of 84.2%. Of the 96 samples analysed, FNA, FNI, and IS were available from 80, 76, and 73 animals, respectively. Overall, 60/67 (89.6%) and 21/29 (72.4%) lesions were neoplastic in dogs and cats, respectively, with the remaining being non-neoplastic. For all lesions, κ-values obtained by FNA, FNI, and IS were in dogs 0.83 (95% confidence interval [CI]: 0.77-0.90), 0.87 (95% CI: 0.81-0.93) and 0.75 (95% CI: 0.67-0.84), respectively, and in cats 0.92 (95% CI: 0.87-0.96), 0.92 (95% CI: 0.88-0.97) and 0.86 (95% CI: 0.79-0.92), respectively. The diagnostic accuracies of FNA, FNI, and IS in dogs with neoplasia were 98.2%, 98.1%, and 91.8%, respectively, and in cats with neoplasia were 95.6%, 95.6% and 95.8%, respectively. In conclusion, the high agreement with histopathology suggests that cytological examinations by FNI, FNA, and IS are all appropriate methods to correctly diagnose lesions of the oral cavity in dogs and cats.

Pneumonia associated with Salmonella spp. infection in a cat receiving cyclosporine.

Salmonellosis is uncommon in cats, usually affects the gastrointestinal tract or skin, and can be fatal. This report describes a domestic shorthair cat with severe pneumonia caused by Salmonella spp. without accompanying gastrointestinal or skin manifestations, in which previous administration of cyclosporine may have played a permissive role in its development. Clinical and laboratory findings as well as follow-up are described from diagnosis until complete recovery. This unusual presentation serves to alert practitioners to consider Salmonella spp. as a possible cause of lung disease in cats, especially if immunocompromised.

Thermochemotherapy for non-muscle-invasive bladder cancer: is there a chance to avoid early cystectomy?.

OBJECTIVES: Non-muscle-invasive bladder cancer is characterized by a high recurrence rate after primary transurethral resection. In case of bacillus Calmette-Guérin-refractory neoplasms, cystectomy is the gold standard. In this study the effects of thermochemotherapy with mitomycin C were evaluated in high-risk bladder cancer nonresponders to previous therapy. PATIENTS AND METHODS: Between January 2006 and December 2009, 30 patients were enrolled with recurrent stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder cancer refractory to chemotherapy or immunotherapy and so becoming suitable for radical cystectomy. All patients underwent endovesical thermochemotherapy: 16 patients underwent a prophylactic scheme and 14 patients underwent an ablative scheme. RESULTS: All the patients completed the study. The mean follow-up for all the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were disease free and 17 patients (56.70%) had recurrence. In the prophylactic group, 7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor recurrence; no progression was observed. In the ablative group, 3 patients (17, 64%) had progression to muscle-invasive disease. Side effects were generally mild. CONCLUSIONS: Thermochemotherapy could be considered an additional tool in patients refractory to intravesical therapies before considering early cystectomy.

Value of current chemotherapy and surgery in advanced and metastatic bladder cancer.

The aim of the present paper was to review findings from the most relevant studies and to evaluate the value of current chemotherapy and surgery in advanced unresectable and metastatic bladder cancer. Studies were identified by searching the MEDLINE® and PubMed® databases up to 2011 using both medical subject heading (Mesh) and a free text strategy with the name of the known individual chemotherapeutic drug and the following key words: 'muscle-invasive bladder cancer', 'chemotherapeutics agents', and 'surgery in advanced bladder cancer'. At the end of our literature research we selected 141 articles complying with the aim of the review. The results showed that it has been many years since the MVAC (methotrexate, vinblastine, adriamycin, cisplatin) regimen was first developed. The use of cisplatin-based combination chemotherapy is associated with significant toxicity and produces long-term survival in only approximately 15-20% of patients. Gemcitabine + cisplatin represents the gold standard in the treatment of metastatic bladder cancer. In conclusion, the optimal approach in the management of advanced urothelial cancer continues to evolve. Further progress relies on the expansion of research into tumor biology and an understanding of the underlying molecular 'fingerprints' that can be used to enhance diagnostic and therapeutic strategies. Cisplatin-based therapy has had the best track record thus far.

Paclitaxel-hyaluronic acid for intravesical therapy of bacillus Calmette-Guérin refractory carcinoma in situ of the bladder: results of a phase I study.

PURPOSE: Carcinoma in situ represents high grade anaplasia of the bladder mucosa. Intravesical immunotherapy with bacillus Calmette-Guérin is the gold standard treatment for patients with carcinoma in situ. Patients with carcinoma in situ refractory to bacillus Calmette-Guérin are candidates for major surgery such as radical cystectomy. We identified the maximum tolerated dose and the recommended dose, and evaluated the safety profile of paclitaxel-hyaluronic acid bioconjugate given by intravesical instillation to patients with carcinoma in situ refractory to bacillus Calmette-Guérin. MATERIALS AND METHODS: A total of 16 patients with carcinoma in situ refractory to bacillus Calmette-Guérin were enrolled in a phase I, open label, single institution study. A minimum of 3 eligible patients were included per dose level. Paclitaxel-hyaluronic acid solution (ONCOFID-P-B™) was administered for 6 consecutive weeks. The primary objective was to identify the maximum tolerated dose and the recommended dose. As secondary objectives the safety profile of ONCOFID-P-B, the pharmacokinetic profile after each instillation and the tumor response were also evaluated. RESULTS: No dose limiting toxicity occurred at any drug level evaluated. The plasma levels of the study drug were always below the lower limit of quantification at all tested doses after each instillation. A total of 11 adverse events were reported by 7 patients and 9 (60%) showed complete treatment response. CONCLUSIONS: Intravesical instillation of ONCOFID-P-B for carcinoma in situ refractory to bacillus Calmette-Guérin showed minimal toxicity and no systemic absorption in the first human intravesical clinical trial to our knowledge. Finally, satisfactory response rates were observed.

Rehabilitative treatment in peripheral artery disease: protocol application and follow-up.

AIM: Peripheral arterial disease (PAD) is a chronic figure suitable to be treated at the II stage to prevent the extreme developments both of the critical limb ischemia and the amputation, as well. The aim of this study was to establish a rehabilitation program (pharmacological and physical) focused not only on the improvement of the flow but also on the metabolic rebalancing in the claudicant limb. METHODS: The study enrolled 222 patients, (125 non-diabetics and 97 diabetics): 54 II A and 168 II B stage; 172 patients (131 II B and 41 II A; 104 non-diabetics and 68 diabetics) were submitted to iv. L-propionil carnytine (Lpc) and physical training on treadmill or exercise bike and 50 patients to iv. therapy alone. Instrumental (Rheoscreen, Oximetry, ABI, walking distance measurement) and clinical checks (questionnaire - Appendix 1) were performed at days: T0, T45,T 90,T180, T230 and during the follow up stated at T 90,T180,T360 from T 230 (end of DH). RESULTS: A significant increasing of the walking distance has been reached in the group undergoing the rehabilitation program. Treadmill: non-diabetics +261.48% at 0% and +122.53% at slope 10% (T230) further increasing to +502.31% at 0% and +289.42% at slope 10% (T360); diabetics: + 158.49% at T0 and + 98.26% at slope 10% (T230) further increased to +287.74% at 0% and +197.39% at 10% (T360) in comparison with the group which had only iv. Lpc : non-diabetics +141.63% at 0% and +104.08% at slope 10% (T230) further increased to +202.064% at 0% and +155.10% at slope 10% (T360); diabetics: +109.124% at T0 and +100% at slop 10% (T230) further increased to +171.08% at 0% and +140% at 10% (T360) . Exercise bike: non-diabetics: +170.27% at T230 in comparison T0 increased to +305.4% at T360; diabetics: +166.66 at T230 reaching +288.88% at T 360. CONCLUSION: Our rehabilitative program gives not only good results at the end of the treatment but mainly stable, with the chance to reach further improving of both walking distance and quality of life, particularly in those patients which observe constantly the physical training.

[Sport, infertility and erectile dysfunction]. / Sport, sterilità e disfunzione erettile.

In the last decades a growing interest has been dedicated to prevention, diagnosis and therapy of male genital pathologies, such as varicocele, infertility and erectile dysfunction in the population involved in sport activities. High incidence (up to 30%) of varicocele has been reported in a population of athletes and up to 60-80% in the subgroup of body-builders. The incidence of varicocele specifically increases with hours of training, in a linear model. Controversial data come from literature about the effects of physical activity on fertility, with prevalence of trials demonstrating worsening of seminal parameters. Furthermore, it has been demonstrated that physical stress in healthy male athletes can interfere with LH levels. Bicycling is one of the major risk factors for erectile dysfunction, with incidence of 13-24%. This is due to the prolonged compression of perineal arteries leading to reduced chronic penile perfusion. Bioengineering studies have been the basis for industry to produce specifically shaped saddles that significantly reduce and minimize compressive effects. Finally, high frequency of lower urinary tract symptoms (LUTS) in cyclists has been related to increased incidence of erectile dysfunction in comparison with normal population.

Human blastocyst culture in IVF: current laboratory applications in reproductive medicine practice.

For fertility patients undergoing in vitro fertilization (IVF), blastocyst culture brings a number of potential advantages over laboratory techniques leading to traditional cleavage-stage embryo transfer. Because day 2-3 embryos normally should transit the oviduct only, their direct exposure to an intrauterine microenvironment is physiologically inappropriate. This mismatch is obviated by blastocyst transfer. Moreover, the nutritional milieu inside the fallopian tube is not the same as within the endometrial compartment, a feature possibly antagonistic to implantation when a day 2-3 embryo is placed directly within the uterus. Delaying transfer to day 5-6 may also improve reproductive outcome by reducing risk of embryo expulsion, given increased myometrial pulsatility measured at day 2-3. However, rigid reliance on a blastocyst culture approach will more often result in treatment cancellation due to embryo loss (no transfer), or having fewer embryos for cryopreservation. The development of sequential media to support embryos in extended in vitro culture was a significant laboratory refinement, since it enabled direct observation of embryos to improve transfer selection bias. This approach, in tandem with blastocyst cryopreservation, leads to fewer embryos being transferred and reducing multiple gestation rate. This review discusses key features of human blastocyst culture and its application in clinical reproductive medicine practice.