Infertility Causes and Pregnancy Outcome in Patients With Familial Mediterranean Fever (FMF) and Controls

2020 ◽  
pp. jrheum.200574
Author(s):  
Pavel Olegovich Sotskiy ◽  
Olga Leontevna Sotskaya ◽  
Hasmik Sureni Hayrapetyan ◽  
Tamara Fadei Sarkisian ◽  
Anna Rafaelovna Yeghiazaryan ◽  
...  

Objective Recurrent attacks of peritonitis of Familial Mediterranean fever (FMF), may lead to peritoneal adhesions and fallopian tube obstruction. Colchicine - the treatment of choice for FMF - may disturb cell division. Secondary amyloidosis - a complication of untreated FMF - may involve the testes and ovaries. Thus, FMF and colchicine may potentially affect fertility and pregnancy in FMF patients. The aims of the study are to evaluate the causes of infertility and pregnancy outcome in FMF patients and to compare them with two groups: non-FMF patients with peritoneal female genital tuberculosis (FGTB) and normal healthy control. Methods This is a retrospective study in which FMF patients with reproductive disorders were recruited from the National Center of Medical Genetics and Primary Health Care in Yerevan, Armenia. The FGTB patients and the normal control patients with reproductive problems were recruited successively from a large gynecology clinic in Yerevan. Genetic analyses for FMF were performed using ViennaLab Diagnostics GmbH Strip Assay. Results The FMF group (211 patients) resembles the FGTB group (127 patients) regarding etiologies of infertility. However, in vitro fertilization (IVF) success rate and pregnancy outcome were comparable between the FMF patients and the control group (167patients). Infertility in FMF patients was clearly associated with a more severe disease and a lack of adequate colchicine treatment. Conclusion Colchicine medication and controlled FMF disease do not adversely affect the reproductive system and pregnancy outcome. However, a lack of an appropriate colchicine treatment may cause infertility and poor pregnancy outcome.

2019 ◽  
Vol 47 (5) ◽  
pp. 2056-2066
Author(s):  
Xinrong Wang ◽  
Wenjuan Wang ◽  
Qinglan Qu ◽  
Ning Zhang ◽  
Cuifang Hao ◽  
...  

Objective This retrospective study was conducted to explore causes of unsynchronized follicular maturation (UFM) and analyze the effects of large follicle puncture on embryo quality and pregnancy outcome. Methods Clinical features and controlled ovulation hyperstimulation (COH) were compared between the puncture group (n = 48) and the control group (n = 2545). We analyzed the COH process with in vitro fertilization during fresh cycle embryo transfer with different clinical pregnancy outcomes. We compared clinical characteristics and COH process of patients in the clinical pregnancy (n = 774) and non-clinical pregnancy (n = 527) groups. Finally, factors related to pregnancy outcomes were analyzed using multivariate logistic regression analysis. Results Age, level of estradiol on down-regulation day, and initial gonadotropin dose were significantly higher in the puncture group than in the control group. We detected significant differences in age, infertility, and body mass index (BMI) between the clinical and non-clinical pregnancy groups. Age, BMI, and endometrial thickness on the day of human chorionic gonadotropin administration were the independent factors influencing pregnancy outcome. Conclusions Patient’s age and level of anti-Müllerian hormone were the main factors causing UFM in patients undergoing COH. Large follicle puncture had no significant effect on pregnancy outcome.


2013 ◽  
Vol 12 (4) ◽  
pp. 370-377
Author(s):  
AK Daoud ◽  
WH Rajab ◽  
KM Alawneh ◽  
MA Nizar Harfiel

Rationale: We wanted to study the effects of Familial Mediterranean Fever (FMF) genetic mutations in Northern Jordan population and in vitro Colchicine treatment on the peripheral blood mononuclear cells (PBMN) production of IL-6 as a marker of disease activity. Methods: - 17 FMF patients and 9 controls were studied. (4 patients had exon 10 mutations only (M680I and V726A), 5 patients had exon 2 mutations (R202Q and E148Q) only and 8 patients with both exon mutations (compound homozygous or heterozygous M694V and R202Q). PBMN cells were incubated with Lipopolysaccharide at 100ng/ml or colchicine 10 ng/ml alone or both. Results: The results showed higher IL-6 levels in the FMF group than control for all treatment modalities, (108.97 vs. 56.49 ng/ml for unstimulated cells) with the highest levels when both exons are involved. Exon 10 mutations were associated with a higher IL-6 level than exon 2 mutations only. Exon 2 mutations alone also were associated with a higher than control IL-6 levels suggesting that it is not a polymorphism phenomenon and is involved in the pathogenesis. In vitro Colchicine treatment caused an increase in the production of IL-6 - although not as high as with LPS - for all groups. Conclusions: Mutations occurring in exon 10 are more significant than mutations occurring in exon 2, although both are contributing to the disease. However colchicine was associated with a paradoxical increase in IL-6 levels. This observation needs confirmation with different colchicine levels in the culture medium and warrants thinking about its exact mechanism of action. DOI: http://dx.doi.org/10.3329/bjms.v12i4.16659Bangladesh Journal of Medical Science Vol. 12 No. 04 October ’13 Page 370-377


2021 ◽  
Author(s):  
Esra Nagehan Akyol Onder ◽  
Pelin Ertan

Abstract Background Familial Mediterranean fever (FMF) is the most seen monogenic periodic fever syndrome characterised by bouts of fever and serositis. It is known that subclinical inflammation (SI) can persist in the symptom-free period and lead to amyloidosis even under colchicine treatment. This study aimed to evaluate the role of the fibrinogen-to-albumin ratio (FAR) in FMF and its correlation with SI. Material and Methods A total of 112 patients with FMF and 78 controls were enrolled in this retrospective study. Demographic, laboratory and genetic data were obtained from the hospital records. Results The FAR values of the FMF cases were significantly higher than the control group (p<0.001). In the FMF group, the patients with SI had higher FAR values than those without SI (p<0.001). FAR was positively correlated with SI (r=0.413, p<0.001). The receiver operating characteristic curve analysis showed that FAR had a higher area under the curve value than albumin and fibrinogen. Conclusion Detecting SI in patients with FMF is crucial in preventing amyloidosis, the most devastating complication of FMF. FAR is a simple, inexpensive, easily obtained indicator which can be used for reflecting SI in FMF.


2016 ◽  
pp. 137-139
Author(s):  
K.P. Golovatyuk ◽  

The objective: was to investigate the levels of cytokines IL-4 and IL-17 in serum and conditioned medium cultures of blood mononuclear cells (MNC) and evaluation association between their products and miscarriage, which occurred in IVF cycles. Patients and methods. We observed 240 patients with recurrent miscarriage, came in IVF cycles, and 100 apparently healthy fertile women in the control group. The concentrations of IL-4 and IL-17 in serum and conditioned medium of MNC cultures were determined. Results. The levels of IL-4 in the serum and conditioned medium in spontaneous and stimulated mitogen secretion was not significantly different from those in the control group, whereas IL-17 levels were higher than those in the control group serum, in conditioned media of stimulated and non-stimulated MNCs. Conclusion. Disregulation of activity of circulating blood mononuclear cells in women with recurrent miscarriage that followed IVF, is accompanied by increased secretion of IL-17 and almost constant production of IL-4 on the back of high stimulation index of production of these cytokines. Key words: in vitro fertilization, miscarriage, interleukin-4, interleukin-17, serum stimulated and non-stimulated mononuclear blood.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.3-1228
Author(s):  
M. E. Tezcan ◽  
N. Şen ◽  
M. Yilmaz ◽  
Ö. Volkan ◽  
E. Tükel ◽  
...  

Background:Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients.Objectives:One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF)1. This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities.Methods:We enrolled 158 FMF patients who fulfilled modifiedTel-HashomerDiagnosisCriteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities arehypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant.Results:Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups.Table.Features of mild and severe FMF groupsMild (n=135)Severe (n=23)pGender (M/F)47/8811/120.23Age36.4±11.336.5±14.30.68Smoking (%)38 (28.1)5 (21.7)0.52BMI (kg/m2)24.3±9.224.0±8.90.34Disease duration (year)7.7±11.38.6±14.30.09Amyloidosis (%)2 (1.4)3 (13.0)0.02Exon 10 homozygote (%)35 (25.9)9 (39.1)0.19Colchicine dosage (mg/day)1.2±0.41.4±0.50.02ISSF scores0.7 ±0.73.4±0.5<0.001Co-morbidity (%)25 (18.5)9 (39.1)0.02Conclusion:In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly.References:[1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016;75:1051-6.[2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014;13:388-90.Acknowledgments:NoneDisclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1808.2-1809
Author(s):  
D. Karatas ◽  
Z. Öztürk ◽  
D. Cekic ◽  
Z. Yuertsever ◽  
Ü. Erkorkmaz ◽  
...  

Background:Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent attacks of fever, peritonitis, pleuritis, arthritis, and skin eruption (1). It is shown by studies that chronic diseases like diabetes mellitus, chronic heart disease, hypertension which other than inflammatory – rheumatologic disease increase depression and anxiety (2). There are a few studies evaluating depression and anxiety in FMF patients, and these results are conflicting (3,4).Objectives:To assess the frequency of depression and anxiety in patients with Familial Mediterranean Fever (FMF)Methods:In this study, 77 FMF patients aged 18 and over who were followed up in Sakarya University Education and Research Hospital, Department of Rheumatology, and 78 healthy volunteers aged 18 and over as thecontrol group. Beck depression scale and Beck anxiety scale were used to depression and anxiety, respectively. Beck’sdepression scale was evaluated as 9 and below normal, 10-16 mild depression, 17-29 moderate depression, 30-63 severe depression. Beck anxiety scale was evaluated as 0-8 normal, 8-15 mild anxiety, 16-25 moderate anxiety, 26 and above severe anxiety.FMF disease severity was determined by Pras scoring.Results:The study group, comprised 77 diagnosed with FMF with a meanage of 37.18 and a control group comprised of 78 healthy controls (C) with a meanage of 35.32 (p=0,058). İn studygroup (P) %63.6, control group (C) %53.8 as female. %36.4 of thestudy group(C), %46.2 of the control group are male. (p=0,216). The prevalence of depression was significantly higher in FMF patients compared to the control group (in order P;C: normal %24,7; %47,4, mild depression: %40.3; %26.9, moderate depression %26; %19.2, severe depression %11.7; %6.4 p<0.015). Similarly in depression results; the prevalence of anxiety was significantly higher in FMF patients compared to the control group (in order P;C normal %23,4; %57.7, mild anxiety %26; %20.5, moderate anxiety %26; %15.4, severe anxiety %24.4; %6.4 p<0,001). Depression status was not correlated with FMF disease severity (p=0.645). A correlation was found between FMF severity and anxiety which it is which was found statistically significant (p=0.005).There was no relationship between erythrocyte sedimentation rate and C-reactive protein with depression and anxiety.Conclusion:Both anxiety and depression frequency are increased in FMF patients compared to healthy controls.References:[1]Livneh A, Langevitz P, Zemer D et al. (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40 (10), 1879–85.[2]Alonso J, Ferrer M, Gandek B, Ware JE Jr, Aaronson NK, Mosconi P, Rasmussen NK, Bullinger M, Fukuhara S, Kaasa S, Leplège A, IQOLA Project Group (2004) Health-related quality of life associated with chronic conditions in eight countries: results from the International Quality of Life Assessment (IQOLA) Project. Qual Life Res 13:283–298[3]Makay B, Emiroglu N, Unsal E (2010) Depression andanxiety in children and adolescents with familial Mediterranean fever. Clin Rheumatol 29, 375–9.[4]Giese A, Ornek A, Kilic L, Kurucay M, Sendur S. N., Lainka E, Henning B. F. Anxiety and depression in adult patients with familialMediterranean fever: a study comparing patients living in Germany and Turkey. International Journal of Rheumatic Diseases 2017; 20: 2093–2100Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1784.1-1784
Author(s):  
R. Dos Santos Sobrín ◽  
M. Martí Masanet ◽  
B. Lopez-Montesinos ◽  
L. Lacruz Pérez ◽  
I. Calvo

Background:Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder caused mostly by mutations in MEFV gene. Its inheritance is autosomal recessive and is the most frequent periodic fever syndrome. First-line treatment is based in colchicine use, so biologics (anti-IL-1) are reserved for refractory cases1, 2.Objectives:To account for clinic and treatment features of patients with FMF in a specialized center as opposed to non-referent centers.Methods:This study was developed in the Pediatric Rheumatology Service in Hospital Universitario y Politécnico La Fe de Valencia. Demographic, clinic and treatment data were collected from patients diagnosed of FMF since January 2004 to September 2019.Results:106 patients met last FMF criteria3. 55% had a pathogenic mutation in genetic analysis. 52% were female. Before 10 years old, 71% of patients had the diagnosis (51% before 4 years old). Arthralgia/myalgia (73%), periodic fever (62%) and abdominal pain (54%) were the most common symptoms. Systemic Juvenile Idiopathic Arthritis (JIA, 6), other forms of JIA (9) and vasculitis (10) were the most prevalent comorbidities. When talking about treatment, 76,4% received Colchicine (60,5% with good response), 22,6% needed a classical disease modifying antirheumatic drug (mostly Methotrexate) and 22 patients got biologic treatment (73% anti-IL-1).Conclusion:When analyzing this case-review, JIA has a strong association with our patients, so it could explain severe disease activity and more articular involvement. This could be an illustration to the higher use of Methotrexate. Also, the most relevant symptom was arthralgia while fever is the most frequent in literature. Likewise, age of diagnosis has been earlier than other case-series (this would be more frequent in other autoinflammatory syndromes, as literature relates)1, 2, 4.References:[1]Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. (2019).[2]Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644-651.[3]Sag E, Demirel D, Demir S, et al. Performance of the new “Eurofever/PRINTO classification criteria” in FMF patients. Semin Arthritis Rheum. 2019;19:30369-5.[4]Rozenbaum M, Rosner I. Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial Mediterranean fever (FMF). Clin Exp Rheumatol. 2004;22:S75-8.Disclosure of Interests:Raquel Dos Santos Sobrín: None declared, Miguel Martí Masanet: None declared, B Lopez-Montesinos: None declared, Lucía Lacruz Pérez: None declared, Inmaculada Calvo Grant/research support from: Bristol-Myers Squibb, Clementia, GlaxoSmithKline, Hoffman-La Roche, Merck Sharpe & Dohme, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, GlaxoSmithKline, Hoffman-La Roche, Novartis


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