MARCELLO ANTONIO SIGNORELLI COCUZZA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- O ozônio diminui a qualidade do sêmen em pacientes com lúpus eritematoso sistêmico(2016) FARHAT, Juliana; FARHAT, Sylvia Costa Lima; BRAGA, Alfesio Luis Ferreira; COCUZZA, Marcello; BORBA, Eduardo Ferreira; BONFA, Eloisa; SILVA, Clovis ArturObjective: To investigate the deleterious effects of air pollutants exposure in the Sao Paulo metropolitan region on semen quality in systemic lupus erythematosus (SLE). Methods: A seven-years longitudinal repeated-measures panel study was performed at the Laboratory of Experimental Air Pollution and Rheumatology Division. Two semen samples from 28 post-pubertal SLE patients were analyzed. Daily concentrations of air pollutants exposure: PM10, SO2, NO2, ozone, CO, and meteorological variables were evaluated on 90 days before each semen collection dates using generalized estimating equation models. Results: Intravenous cyclophosphamide (IVCYC) and ozone had an association with a decrease in sperm quality of SLE patients. IVCYC was associated with decreases of 64.3 million of spermatozoa/mL (95% CI 39.01-89.65; p = 0.0001) and 149.14 million of spermatozoa/ejaculate (95% CI 81.93-216.38; p = 0.017). With regard to ozone, the most relevant adverse effects were observed from lags 80-88, when the exposure to an interquartile range increase in ozone 9-day moving average concentration led to decreases of 22.9 million of spermatozoa/mL (95% CI 5.8-40.0; p = 0.009) and 70.5 million of spermatozoa/ejaculate (95% CI 12.3-128.7; p = 0.016). Further analysis of 17 patients that never used IVCYC showed association between exposure to ozone (80-88 days) and decrease of 30.0 million of spermatozoa/mL (95% CI 7.0-53.0; p = 0.011) and 79.0 million of spermatozoa/ejaculate (95% CI 2.1-155.9; p = 0.044). Conclusion: Ozone and IVCYC had a consistent adverse effect on semen quality of SLE patients during spermatogenesis. Minimizing exposure to air pollution should be taken into account, especially for patients with chronic systemic inflammatory diseases living in large cities.
- Penile anthropometry in systemic lupus erythematosus patients(2011) VECCHI, A. P.; BORBA, E. F.; BONFA, E.; COCUZZA, M.; PIERI, P.; KIM, C. A.; SILVA, C. A.The aim of this study was to evaluate penile anthropometry in systemic lupus erythematosus (SLE) patients compared with healthy controls and the possible relevant pubertal, clinical, hormonal and treatment factors that could influence penile dimensions. Twenty-five consecutive SLE patients were assessed by urological examination, sexual function, testicular ultrasound, hormones, sperm analysis, genetic analysis, clinical features and treatment. The control group included 25 age-matched healthy males. SLE patients had a lower median penis length and circumference [8 (7.5-10) vs. 10 (8-13) cm, p = 0.0001; 8 (7-10) vs. 10 (7-11) cm, p = 0.001; respectively], lower median testicular volume by right and left Prader [15 (10-25) vs. 20 (12-25) ml, p = 0.003; 15 (10-25) vs. 20 (12-25) ml, p = 0.006; respectively], higher median of follicle-stimulating hormone [5.8 (2.1-25) vs. 3.3 (1.9-9) IU/l, p = 0.002] and lower morning total testosterone levels (28% vs. 0%, p = 0.009) compared with controls. In spite of that, erectile dysfunction was not observed in patients or controls. Analyses of lupus patients revealed that the median penis circumference was lower in patients with disease onset before first ejaculation compared with those with disease onset after first ejaculation [7.8 (7-10) vs. 9.0 (7.5-10) cm, p = 0.026]. No differences were observed in the median penile anthropometry regarding sexual dysfunction (p = 0.610), lower morning total testosterone levels (p = 0.662), oligo/azoospermia (p = 0.705), SLE Disease Activity Index >= 4 (p = 0.562), Systemic Lupus International Collaborating Clinics/ACR Damage Index >= 1 (p = 0.478), prednisone cumulative dose (p = 0.789) and intravenous cyclophosphamide therapy (p = 0.754). Klinefelters syndrome (46XY/47XXY) was diagnosed in one (4%) SLE patient with decreased penile size whereas Y-chromosomal microdeletions was absent in all of them. In conclusion, we have identified reduced penile dimensions in SLE patients with no deleterious effect in erectile function. Disease onset before first ejaculation seems to affect penis development in pre-pubertal lupus. Lupus (2011) 20, 512-518.
- Development of an animal model for endometrial ablation using trichloroacetic acid(2011) COCUZZA, Mariana Amora; COCUZZA, Marcello; MACIEL, Gustavo A. R.; MOTTA, Eduardo Vieira da; CARDOSO, Ana P. T.; SOARES JR., Jose M.; BARACAT, Edmund C.Objective: To develop an animal model of endometrial ablation, and to evaluate the histologic effects of trichloroacetic acid (TCA) in the uterine cavity. Design: Experimental prospective. Setting: Department of gynecology. Patient(s): Thirty female adult rats. Intervention(s): Animals were submitted to injection of TCA in one uterine horn and saline solution in the other. Group 1 was sacrificed the day after the procedure. Group 2 was sacrificed in phase of diestrus. Superficial epithelia of the endometrium, stromal thickness, endometrial glands, and myometrium thickness were compared among the uterine horns of the same rats of group 1. The same evaluation was performed in group 2. Endometrial regeneration was evaluated. Main Outcome Measure(s): Histologic effects. Result(s): In group 1, histologic parameters showed endometrial destruction on TCA injected uterine horn. In group 2, four rats died after the procedure, and six rats had no viable material. In the rest of the group, TCA-injected uterine horns showed endometrial destruction. Superficial epithelia of the endometrium and stromal thickness were similar between TCA uterine horn from groups. However, the number of endometrial glands was higher in group 1. Conclusion(s): The study developed an experimental model for endometrial ablation. TCA acid is a potent agent for endometrial ablation in rat model. No endometrial regeneration was observed after recovery of cycle. (Fertil Steril (R) 2011; 95: 2418-21. (C) 2011 by American Society for Reproductive Medicine.)
- Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men(2016) YAMACAKE, K. G. R.; COCUZZA, M.; TORRICELLI, F. C. M.; TISEO, B. C.; FRATI, R.; FREIRE, G. C.; ANTUNES, A. A.; SROUGI, M.Objectives: To study the impact of obesity, age and varicocele on sexual hormones fof adult and elderly men. Materials and Methods: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. Results: Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. Conclusions: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.
- Gonadal Function and Reproductive System Anatomy in Postpubertal Prune-Belly Syndrome Patients(2020) LOPES, Roberto Iglesias; TAVARES, Alessandro; DENES, Francisco Tibor; COCUZZA, MarcelloOBJECTIVE To gain insight into the causes of infertility in Prune Belly Syndrome (PBS) by evaluating reproductive system anatomy and gonadal function in a cohort of postpubertal PBS patients. METHODS We contacted all PBS patients 14 years old or older treated and followed at our institution. Age at orchiopexy, type of orchiopexy (with or without ligation of gonadal vessels), testicular volumes and positions were evaluated. Pelvic magnetic resonance imaging (to assess prostate size, seminal vesicles, and vas) and hormonal profile were ordered. Sperm analysis and analysis of urine after masturbation were performed after informed consent. RESULTS Fifteen patients were included in this study. Mean age was 19.2 years. Mean age at orchiopexy was 18 months. Fourteen patients (93.3%) had normal and orthotopic testes. Mean testicular volume was 6.9 cc. Eight patients collected semen, 5 of them (62.5%) had spermatozoa in the specimen and motile sperm was found in 4 (50%). Mean hormone levels were LH: 5.3 mg/dL, FSH: 6.9 mg/dL, testosterone 531 mg/dL. Magnetic resonance imaging revealed hypoplastic prostates in 66.6% and unilateral seminal vesicle absence in 66.6%. No vasal abnormality was noted. CONCLUSION Patients with PBS may have normal sexual hormonal levels. Motile spermatozoa were found in half of the patients. Our study highlights a high prevalence of prostate and seminal vesicle abnormalities that may represent an important cause for their infertility. (C) 2020 Elsevier Inc.
- Grade 3 Varicocele in Fertile Men: A Different Entity(2012) COCUZZA, Marcello; ATHAYDE, Kelly S.; ALVARENGA, Conrado; SROUGI, Miguel; HALLAK, JorgePurpose: Although varicocele size has an inverse relationship with baseline semen parameters and a direct relationship with seminal reactive oxygen species in infertile patients, to our knowledge the effect of varicocele grade in fertile men is unknown. We evaluated the impact of varicocele grade on seminal parameters, testicular size and seminal reactive oxygen species in fertile men. Materials and Methods: We prospectively evaluated 194 men from July 2004 to April 2010. Of the men 156 were fertile and classified by presence of varicocele. A total of 38 infertile patients with varicocele as the only identifiable cause of infertility comprised the control group. Physical examination, semen parameters and seminal reactive oxygen species were compared between the groups. Results: Of 156 fertile men 43 (24.3%) had clinical varicocele, which was grade 1 to 3 in 22, 11 and 10, respectively. The remaining 113 men (72.7%) had no varicocele. Infertile men had smaller testes, decreased semen parameters and higher seminal reactive oxygen species than the fertile groups. Testicular size, reactive oxygen species and semen parameters did not differ between fertile men with vs without varicocele. Fertile men with varicocele grade 3 had higher seminal reactive oxygen species than those with lower grade varicocele. As varicocele grade increased, seminal reactive oxygen species increased and sperm concentration decreased. Conclusions: Although fertile men have more efficient defense mechanisms to protect against the consequences of varicocele on testicular function, these mechanisms may not be sufficient in those with varicocele grade 3. Further research is needed to clarify whether they are at increased risk for future infertility.
- Bariatric Surgery Impact on Reproductive Hormones, Semen Analysis, and Sperm DNA Fragmentation in Men with Severe Obesity: Prospective Study(2020) WOOD, Guilherme Jacom Abdulmassih; TISEO, Bruno C.; PALUELLO, Davi V.; MARTIN, Hamilton de; SANTO, Marco Aurelio; NAHAS, William; SROUGI, Miguel; COCUZZA, MarcelloPurpose Growing evidence in the literature suggests that obesity is capable of altering reproductive hormone levels and male fertility. Effects on classic semen parameters and sperm DNA fragmentation (SDF), however, have not been properly established. Additionally, the impact of bariatric surgery (BS) on those parameters is still controversial. Materials and Methods In Phase 1, 42 patients with obesity and 32 fertile controls were submitted to reproductive hormone evaluation, semen analysis, and SDF testing. In Phase 2, patients with obesity were submitted to BS or clinical follow-up and were invited to 6-month revaluation. Results Phase 1: Men with obesity have higher levels of estradiol, LH, and FSH and lower levels of total testosterone (TT) when compared with eutrophic fertile men. Additionally, they present worse semen parameters, with reduction in ejaculated volume and sperm concentration, worse sperm motility and morphology, and higher SDF. Phase 2: 32 patients returned to revaluation. Eighteen were submitted to BS (group S) and 14 were not submitted to any specific therapeutic regimen (group NS). In group S, TT more than doubled after surgery (294.5 to 604 ng/dL,p < 0.0001). Worsening of sperm concentration and total ejaculated sperm count were also noticed, and 2 patients became azoospermic after BS. SDF, however, improved after the procedure. No changes in the variables studied were observed in non-operated patients. Conclusion In this prospective study, we have found that BS results in improvements in reproductive hormone levels and SDF after 6-month follow-up. Sperm concentration, however, reduced after the procedure.
article 10 Citação(ões) na Scopus Testicular adrenal rest tumor in infertile man with congenital adrenal hyperplasia: case report and literature review(2011) MARCHINI, Giovanni Scala; COCUZZA, Marcello; PAGANI, Rodrigo; TORRICELLI, Fabio Cesar; HALLAK, Jorge; SROUGI, MiguelCONTEXT: Synthesis of cortisol and aldosterone is impaired in patients with congenital adrenal hyperplasia (CAH) because of 21-hydroxylase deficiency. Men with CAH have low fertility rates compared with the normal population, and this is related to testicular adrenal rest tumors. Findings of azoospermia in combination with a testicular tumor on ultrasound are likely to have a mechanical cause, especially when in the testicular mediastinum. The preferred treatment method consists of intensive corticoid therapy. However, when the tumor is unresponsive to steroid therapy, surgical treatment should be considered. CASE REPORT: We present the case of a male patient with CAH due to 21-hydroxylase deficiency who presented a testicular tumor and azoospermia. Treatment with low daily corticoid doses had previously been started by an endocrinologist, but after 12 months, no significant change in sperm count was found. Although the adrenocorticotrophic hormone and 17-hydroxyprogesterone levels returned to normal values, the follicle-stimulating hormone (FSH), luteinizing hormone and testosterone levels remained unchanged. Ultrasound examination confirmed that the testicles were small and heterogenous bilaterally, and revealed a mosaic area at the projection of the testis network bilaterally. Magnetic resonance imaging confirmed the finding. Testicular biopsy revealed the presence of preserved spermatogenesis and spermiogenesis in 20% of the seminiferous tubules in the right testicle. The patient underwent testis-sparing tumor resection. After 12 months of follow-up, there was no tumor recurrence but the patient still presented azoospermia and joined an intracytoplasmic sperm injection program.- SARS-CoV-2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services(2021) ESTEVES, Sandro C.; LOMBARDO, Francesco; GARRIDO, Nicolas; ALVAREZ, Juan; ZINI, Armand; COLPI, Giovanni M.; KIRKMAN-BROWN, Jackson; LEWIS, Sheena E. M.; BJORNDAHL, Lars; MAJZOUB, Ahmad; CHO, Chak-Lam; VENDEIRA, Pedro; HALLAK, Jorge; AMAR, Edouard; COCUZZA, Marcello; BENTO, Fabiola C.; FIGUEIRA, Rita C.; SCIORIO, Romualdo; LAURSEN, Rita J.; METWALLEY, Ahmad M.; JINDAL, Sunil K.; PAREKATTIL, Sijo; RAMASAMY, Ranjith; ALVIGGI, Carlo; HUMAIDAN, Peter; YOVICH, John L.; AGARWAL, AshokThe prolonged lockdown of health facilities providing non-urgent gamete cryopreservation-as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS-CoV-2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and propose that the same permissive approach for sperm banking granted for men with cancer is expanded to other groups of vulnerable patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto-immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. In both scenarios, the ""fertility window"" may be transitory; postponing diagnostic semen analysis and sperm banking in these men could compromise the prospects of biological parenthood. Moreover, we provide recommendations on how to continue the provision of andrological services in a considered manner and a safe environment. Our opinion is timely and relevant given the fact that fertility services are currently rated as of low priority in most countries.
- Efficacy of MLPA for detection of Y-chromosome microdeletions in infertile Brazilian patients(2020) FRANCHIM, C. S.; SOARES-JUNIOR, J. M.; SERAFINI, P. C.; MONTELEONE, P. A. A.; COCCUZZA, M. S.; ZANARDO, E. A.; MONTENEGRO, M. M.; DIAS, A. T.; KULIKOWSKI, L. D.; BARACAT, E. C.Purpose Worldwide publications follow the gold standard method-the polymerase chain reaction (PCR)-for detecting Y-chromosome microdeletions; however, markers are frequently variable between the studies. Can we detect the deletions by another molecular method with more genomic coverage? The Y chromosome harbors several different genes responsible for testicular development and spermatogenesis, and its repetitive conformation predisposes it to complex rearrangements that have clinical impact. Our aim was to evaluate a molecular diagnostic method, the Multiplex Ligand Probe-dependent Amplification (MLPA), which is also a valuable ancillary method for the identification of deletions, duplications, and rearrangements in a single and faster reaction, leading to a better comprehension of patients' phenotypes, and should be considered a useful tool for detection of Y chromosome deletions. Methods This is a study of diagnostic accuracy (transversal prospective study) conducted to investigate Y-chromosome deletions in 84 individuals through PCR and MLPA methods. Forty-three infertile men (azoospermic and oligozoospermic) and 41 controls (40 fertile men and 1 normal karyotyped woman) were analyzed by PCR and MLPA techniques. Results We diagnosed seven (7) deletions (16.2%) by PCR and 9 with MLPA (21%). In addition, we found five (5) duplications and a suggestive mosaic. Conclusion Our results demonstrate that MLPA technique is valuable in the investigation of microdeletions and microduplications. Besides deletions, duplications can cause instability of chromosome genes, possibly leading to infertility. Both studied techniques provide an advantageous diagnostic strategy, thus enabling a better genetic counseling.