PAULO CESAR SERAFINI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina - Docente
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?(2014) ARAUJO, D. B. de; YAMAKAMI, L. Y. S.; AIKAWA, N. E.; BONFA, E.; VIANA, V. S. T.; PASOTO, S. G.; PEREIRA, R. M. R.; SERAFIN, P. C.; BORBA, E. F.; SILVA, C. A.Objectives: To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE). Method: Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Mullerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed. Results: The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507). Conclusions: The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.
- Clark CA, Laskin CA. Ovarian reserve in antiphospholipid syndrome: the jury is still out. Lupus 2015; 24: 773(2015) YAMAKAMI, L. Y. S.; SERAFINI, P. C.; ARAUJO, D. B. de; BONFA, E.; LEON, E. P.; BARACAT, E. C.; SILVA, C. A.
conferenceObject Luteinized Unruptured Follicle Syndrome in Young Female with Juvenile Idiopathic Arthritis(2017) TOMIOKA, Renato B. B.; FERREIRA, Gabriela R. V.; AIKAWA, Nadia E.; MACIEL, Gustavo A. R.; SERAFINI, Paulo C.; BARACAT, Edmund; CAMPOS, Lucia M. A.; GOLDENSTEIN-SCHAINBERG, Claudia; PEREIRA, Rosa M. R.; BONFA, Eloisa; SILVA, Clovis A.conferenceObject Reduced Ovarian Reserve in Young Juvenile Idiopathic Arthritis Patients(2016) TOMIOKA, Renato B. B.; FERREIRA, Gabriela R. V.; AIKAWA, Nadia E.; MACIEL, Gustavo A. R.; SERAFINI, Paulo C.; BARACAT, Edmund C.; GOLDENSTEIN-SCHAINBERG, Claudia; PEREIRA, Rosa M. R.; BONFA, Eloisa; SILVA, Clovis A.conferenceObject Ovarian Reserve In Women With Primary Antiphospholipid Syndrome(2013) YAMAKAMI, Lucas; SERAFINI, Paulo; ARAUJO, Daniel B.; BONFA, Eloisa; LEON, Elaine P.; BARACAT, Edmund C.; SILVA, Clovis A.- Ovarian reserve in young juvenile idiopathic arthritis patients(2019) FERREIRA, Gabriela R. V.; TOMIOKA, Renato B.; AIKAWA, Nadia E.; LEON, Elaine P.; MACIEL, Gustavo A. R.; SERAFINI, Paulo C.; BARACAT, Edmund C.; GOLDENSTEIN-SCHAINBERG, Claudia; PEREIRA, Rosa M. R.; BONFA, Eloisa; SILVA, Clovis A.Objectives: Juvenile idiopathic arthritis (JIA) occurs during reproductive age, however, there are no systematic data regarding ovarian function in this disease. Methods: Twenty-eight post-pubertal JIA patients and age-matched 28 healthy controls were studied. Complete ovarian function was assessed during the early follicular phase of the menstrual cycle including anti-Mullerian hormone (AMH), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) by ovarian ultrasound, and anti-corpus lutheum antibodies (anti-CoL). Demographic data, menstrual abnormalities, disease parameters and treatment were also evaluated. Results: The mean current age (22.6 +/- 6.59 vs. 22.5 +/- 6.59 years, p = .952) was similar in JIA patients and healthy controls with a higher median menarche age [13(8-16) vs. 12(8-14) years, p = .029]. A lower median AMH levels [2.65(0.47-9.08) vs. 4.83(0.74-17.24) ng/mL, p = .029] with a higher LH [8.44 +/- 4.14 vs. 6.03 +/- 2.80 IU/L, p = .014] and estradiol levels [52.3(25.8-227.4) vs. 38.9(26.2-133.6) pg/mL, p = .008] were observed in JIA compared to control group. Anti-CoL and AFC were similar in both groups (p > .05). Further analysis of JIA patients revealed that current age, disease duration, number of active/limited joints, ESR, CRP, patient/physician VAS, JADAS 71, DAS 28, CHAQ, HAQ, patient/parents PedsQL, PF-SF 36, cumulative glucocorticoid and cumulative methotrexate doses were not correlated with AMH, FSH, estradiol levels or AFC (p > .05). Conclusion: The present study was the first to suggest diminished ovarian reserve, not associated to hypothalamic pituitary gonadal axis, in JIA patients during reproductive age. The impact of this dysfunction in future fertility of these patients needs to be evaluated in prospective studies.
- Lower genital tract infections in young female juvenile idiopathic arthritis patients(2019) V, Gabriela R. Ferreira; TOMIOKA, Renato B.; QUEIROZ, Ligia B.; KOZU, Katia; AIKAWA, Nadia E.; SALLUM, Adriana M. E.; SERAFINI, Paulo; TACLA, Maricy; BARACAT, Edmund C.; PEREIRA, Rosa M. R.; BONFA, Eloisa; SILVA, Clovis A.Background To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. Methods After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. Results The mean current age was similar in JIA patients and controls (23.3 +/- 6.24 vs. 26.1 +/- 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p = 0.206) and biological agent use (p = 0.238) were similar in both JIA groups. Conclusions To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.
- Non-steroidal anti-inflammatory drug induces luteinized unruptured follicle syndrome in young female juvenile idiopathic arthritis patients(2018) TOMIOKA, Renato B.; FERREIRA, Gabriela R. V.; AIKAWA, Nadia E.; MACIEL, Gustavo A. R.; SERAFINI, Paulo C.; SALLUM, Adriana M.; CAMPOS, Lucia M. A.; GOLDESTEIN-SCHAINBERG, Claudia; BONFA, Eloisa; SILVA, Clovis A.To assess prospectively luteinized unruptured follicle (LUF) syndrome in juvenile idiopathic arthritis (JIA) patients with and without non-steroidal anti-inflammatory drugs (NSAIDs) and healthy controls. Twenty-three adolescent and young adult female JIA patients (ILAR criteria) and 11 female healthy subjects were studied by pelvic ultrasound monitoring for follicular development and ovulation in one menstrual cycle. LUF syndrome was prospectively investigated by pelvic ultrasound with a dominant ovarian follicle without signs of follicular rupture, with elevation of serum progesterone in the luteal phase of the menstrual cycle and luteinizing hormone (LH) detected in the urine. Comparison between JIA patients with (n = 8) vs. without NSAIDs (n = 15) and healthy controls (n = 11) revealed that LUF syndrome was significantly higher in the former group (2 (25%) vs. 0% vs. 0%, p = 0.049). These two patients with LUF syndrome had normal menstrual cycles without reduced ovarian reserve, and they were under naproxen 500 mg bid during the menstrual cycle. Disease duration was comparable in JIA with and without NSAIDs [19.8 (4.4-25) vs. 13 (3.1-33) years, p = 0.232]. Further comparison between JIA patients with and without NSAIDs and healthy controls showed similar mean anti-Mullerian hormone levels (p = 0.909), estradiol (p = 0.436), FSH (p = 0.662), LH (p = 0.686), and mean antral follicle count (p = 0.240) and ovarian volume (p = 0.363). No differences were evidenced in three groups regarding Caucasian race, body mass index, duration, and length of menstrual cycles (p > 0.05). This is the first study to identify that JIA patients have a high frequency of LUF without impaired ovarian reserve. Future prospective studies are necessary to determine if chronic/continuous use of NSAIDs in JIA will have an impact in these patients' fertility.
- Ovarian reserve in women with primary antiphospholipid syndrome(2014) YAMAKAMI, L. Y. S.; SERAFINI, P. C.; ARAUJO, D. B. de; BONFA, E.; LEON, E. P.; BARACAT, E. C.; SILVA, C. A.Objective: The objective of this paper is to evaluate ovarian reserve in primary antiphospholipid syndrome (PAPS) women and the association between ovarian reserve tests and clinical and laboratorial parameters, and anti-corpus luteum antibody (anti-CoL). Methods: We screened 85 female patients between 18 to 40 years old with APS. Of these, 67 patients were excluded because of association with other autoimmune diseases (n = 42), contraindication or unwillingness to stop hormonal contraceptive (n = 21), current pregnancy or breastfeeding (n = 3) and previous ovarian surgery (n = 1). Therefore, a cross-sectional study was conducted in 18 PAPS patients and 24 healthy women. They were evaluated at early follicular phase with measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Mullerian hormone (AMH) and sonographic antral follicle count (AFC). Serum measurement of anti-CoL was determined by immunoblot analysis. All analyses were performed after at least six months from the last intake of hormonal contraceptive and resumption of menstruation. Results: The mean age was comparable in PAPS and controls (33.0 +/- 5.0 vs. 30.4 +/- 7.0 years; p = 0.19). Regarding ovarian reserve tests, the frequencies of low AFC (<= 10) (56% vs. 22%, p = 0.04) and very low AFC (<= 5) (37% vs. 9%, p = 0.04) were significantly higher in PAPS patients than controls. Trends of higher frequencies of reduced (< 1.0 ng/ml), low (< 0.5 ng/ml) and negligible (< 0.2 ng/ml) AMH levels were found in PAPS patients (p = 0.08, p = 0.07 and p = 0.07, respectively). FSH, LH and estradiol were similar in patients and controls. There was no association between low ovarian reserve and specific types of antiphospholipid antibodies. Anti-CoL was solely observed in PAPS patients (11% vs. 0%; p = 0.177) and was not related to ovarian reserve tests. Conclusion: Women suffering from PAPS possessed reduced ovarian reserve, with prevalence greater than 50%.
conferenceObject Ovarian Dysfunction In Adult Childhood-Onset Systemic Lupus Erythematosus Patients: A Possible Role Of Methotrexate?(2013) ARAUJO, Daniel B.; YAMAKAMI, Lucas; BONFA, Eloisa; VIANA, Vilma S. T.; PASOTO, Sandra G.; PEREIRA, Rosa M.; SERAFIN, Paulo C.; BORBA, Eduardo F.; SILVA, Clovis A.