Lucas Yugo Shiguehara Yamakami

Autoimmune primary ovarian insufficiency

Primary ovarian insufficiency (POI) is defined as sustained amenorrhea, increased follicle-stimulating hormone and low estrogen levels, whereas diminished ovarian reserve (DOR) is characterized as regular menses and alterations of ovarian reserve tests. POI of autoimmune origin may be associated with adrenal autoimmunity, non-adrenal autoimmunity or isolated. This autoimmune disease is characterized by serum ovarian, adrenocortical or steroidogenic cell autoantibodies. POI of adrenal autoimmune origin is the most frequent type observed in 60-80% of patients. Clinically, amenorrhea is the hallmark of POI, however before menstruation stops completely, irregular cycles occur. Infertility, hot flushes, vaginal atrophy, and dyspareunia are also common. Autoimmune oophoritis is characterized by mononuclear inflammatory cell infiltrate in the theca cells of growing follicles, with early stage follicles without lymphocytic infiltration. This infiltrate includes plasma, B and T-cells. A novel classification criterion for autoimmune POI/DOR is proposed subdividing in three distinct categories (possible, probable and confirmed) according to autoantibodies, autoimmune disease and ovarian histology. Unfortunately, up to date guidelines for the treatment of autoimmune oophoritis are not available. Strategies to POI treatment include hormone replacement and infertility therapy. Assisted conception with donated oocytes has been proven to achieve pregnancy by intra cytoplasmic sperm injection in POI women.

Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?

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-Müllerian 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.

Ovarian reserve in women with primary antiphospholipid syndrome

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-Müllerian 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%.

Cystadenoma of the seminal vesicle

Primary tumors of the seminal vesicle are extremely rare. Among them, there is a spectrum of tumors derived from both epithelium and stroma and so classified as epithelial-stromal tumors. Herein, we report a case of a cystadenoma in a 49-year-old asymptomatic man, detected in a routine ultrasonography for liver disease follow-up. The digital rectal examination detected a large mass anterior to rectum and posterior to bladder. Computed tomography scan and magnetic resonance imaging showed a normal prostate and a 9.0 cm cystic tumor, replacing the left seminal vesicle. The gross appearance and microscopic aspect was compatible with cystadenoma of seminal vesicle. Patients postoperative recovery was uneventful. He is currently alive, 3 years after the diagnosis, with no signs of recurrence.

Reduced Ovarian Reserve in Patients with Takayasu Arteritis

Objective. To assess ovarian reserve markers in patients with Takayasu arteritis (TA). Methods. Twenty patients with TA and 24 healthy controls were evaluated for ovarian reserve by follicle-stimulating hormone, luteinizing hormone, and estradiol, and antral follicle count (AFC). Anti-Müllerian hormone (AMH) was measured by ELISA using 2 different kits. Demographical data, menstrual abnormalities, disease variables, and treatment were also analyzed. Results. The median current age was similar in patients with TA and controls (31.2 ± 6.1 vs 30.4 ± 6.9 yrs, p = 0.69). The frequencies of decreased levels of AMH in patients with TA were identical using both kits and higher when compared to controls (50% vs 17%, p = 0.02; 50% vs 19%, p = 0.048). A positive correlation was observed between the 2 kits in patients with TA (r = +0.93, p < 0.0001) and in healthy controls (r = +0.93, p < 0.0001). The apparent lower AFC (11 vs 16, p = 0.13) and the higher frequency of low AFC (41% vs 22%, p = 0.29) in TA compared to controls did not reach statistical significance. Other hormones were similar in both groups (p > 0.05). Further evaluation of patients with TA with low AMH levels (< 1.0 ng/ml) versus normal AMH levels (> 1.0 ng/ml) revealed that the frequency of current disease activity (p = 1.0) and the median of erythrocyte sedimentation rate (p = 0.6), C-reactive protein (p = 0.4), prednisone cumulative dose (p = 0.8), and methotrexate cumulative dose (p = 0.8) were comparable in both groups. Cyclophosphamide use was reported in only 1 patient with reduced ovarian reserve, whereas none of the remaining patients received gonadotoxic drugs. Conclusion. To the best of our knowledge, our present study was the first to suggest that patients with TA may have diminished ovarian reserve.

Resultados maternos e perinatais em pacientes com disfunção sistólica grave

OBJECTIVE: The objective of this study was to evaluate maternal and fetal outcome in patients with severe left ventricle systolic dysfunction followed in a terciary-care hospital. METHODS: We retrospectively evaluated 12 pregnant women with severe systolic dysfunction, defined as a ejection fraction <40%. Follow-up data included functional class evaluation, ocurrency of cardiac and obstetric events, labor data and neonatal outcome. Cardiac events were defined as new onset of arrhythmias, stroke, pulmonary thrombosis, pulmonary edema, cardiac arrest, and death. RESULTS: The mean ejection fraction was 28,9±6,47%. Four patients were in the NYHA class III, and 8 in class I or II on presentation. Ten patients had deteriorated during pregnancy. The most common cardiac event was pulmonary edema (3 patients). Three of the four patients with class III on presentation had a good evolution during pregnancy, and the other one had preterm delivery due to worsening symptons. There were 2 vaginal espontaneous deliveries and 10 cesarean sections. Small-for-gestational-age birthweigth ocurred in 10 pregnancies. There was no maternal or neonatal death. CONCLUSIONS: Pregnancy in patients with severe left ventricle systolic dysfunction increases the risk of maternal complications and compromises fetal growth. It is important to follow this women in a tertiary-care hospital.

Clark CA, Laskin CA. Ovarian reserve in antiphospholipid syndrome: the jury is still out. Lupus 2015; 24: 773

Sir, We appreciate the letter to the editor, including comments and suggestions made by Clark and Laskin regarding our article: Ovarian reserve in women with primary antiphospholipid syndrome (PAPS). The possibility that Gen II anti-Müllerian hormone (AMH) kit measurements used in our study resulted in potentially false high or low levels is a concern that we were not aware of before the acceptance of our paper. Subsequently, we performed four ovarian reserve studies in systemic lupus erythematosus, Takayasu arteritis, Behçet’s disease and dermatomyositis using an additional kit (AMH Gen II enzyme-linked immunosorbent assay (ELISA) versus US AMH/MIS AnshLabs ELISA). The comparable results obtained with high correlation (r> 0.9) between the two AMH kits minimized the possibility of instability in terms of AMH Gen II ELISA values reported in our PAPS paper. Nevertheless, we agree that that restricted inclusion and exclusion criteria resulted in a limited sample size precluding a definitive conclusion about the prevalence of reduced ovarian reserve in PAPS patients and therefore our conclusion should be toned down.

FRI0461 Subclinical Ovarian Dysfunction in Takayasu Arteritis Patients

Background Takayasu arteritis (TA) is a rare idiopathic systemic chronic vasculitis that involves large arteries. This disease occurs mainly in female gender during the reproductive age and ovarian reserve and future fertility are major topic of interest. Aging, surgery and hypothalamic-pituitary-gonad axis dysfunction have been found to influence the quantity and quality of primordial follicles in ovaries and, ultimately, the ovarian reserve. Other conditions such as autoimmune oophoritis and immunosuppressive drugs, particularly cyclophosphamide, may also result in diminished ovarian reserve. Female TA patients are susceptible to these factors but there is no systematic study assessing this ovary abnormality in these patients. Objectives To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in TA patients. Methods We have screened 52 consecutive female patients with TA. All patients aged between 18 and 45 years and fulfilled the American College of Rheumatology classification criteria. Exclusion criteria were: current pregnancy, hypothalamus-pituitary-gonadal axis dysfunction, use of hormonal contraceptive in the last six months, gynecological surgery, gynecological cancer, presence of an additional autoimmune disease, did not agree to participate in this study and incomplete gonadal evaluation. Thirty-two were excluded: use of hormonal contraceptive (n=15), did not agree to participate (n=7), incomplete assessment (n=4), presence of granulomatosis with polyangiitis (n=2), current pregnancy (n=2), hyperprolactinemia (n=1) and current treatment for gynecological cancer (n=1). Therefore, a cross sectional study was conducted in 20 patients with TA and 24 healthy controls according to the same exclusion criteria. Anti-CoL (immunoblot) and ovarian reserve were assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Müllerian hormone (AMH), and antral follicle count (AFC). Demographical data, menstrual abnormalities, disease parameters and treatment were also analyzed. Results The median current age was similar in TA patients and controls (31.2±6.1 vs. 30.4±6.9 years, p=0.69). The frequency of decreased levels of AMH (50% vs. 17%, p=0.02) and the median of AMH (0.7 vs. 2.7ng/mL, p=0.008) were significantly reduced in TA patients compared to controls without significant menstrual abnormalities with regard to the median of flow duration (p=0.25) and cycle length (p=0.85). The other hormones and AFC were similar to controls (p>0.05). Anti-CoL was solely observed in TA patients (5% vs. 0%, p=0.45). Further evaluation of TA patients with low AMH levels (<1.0 ng/mL) versus normal AMH levels (>1.0 ng/mL) revealed that the frequency of disease activity (p=1.0) and the median of ESR (p=0.6), CRP (p=0.4), prednisone cumulative dose (p=0.8) and methotrexate cumulative dose (p=0.8) were comparable in both groups. Cyclophosphamide use was reported in only one patient with reduced ovarian reserve, whereas none of the remaining patients received gonadotoxic drug. Conclusions Therefore, the present study demonstrated for the first time a high prevalence of diminished ovarian reserve in TA patients reinforcing fertility counseling. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1484

PReS-FINAL-2289: Ovarian dysfunction in adult childhood-onset lupus patients: a possible role of methotrexate?

Reduction of ovarian reserve has been observed in childhood-onset SLE (c-SLE) and adult SLE populations, and most of them were limited to follicle stimulating hormone (FSH) levels and few recent reports included antral follicle count (AFC) and/or anti-Mullerian hormone (AMH) levels. In addition, the contribution of diminished follicle ovarian pool using anti-corpus luteum antibodies (anti-CoL) was not available in pediatric lupus population.