First author : SOTSKIY P
Revue: Clin Exp Rheum
Reference: Clin Exp Rheumatol. 2024 Sep 19. doi: 10.55563/clinexprheumatol/9yc77f. Online ahead of print.PMID: 39360377
Lien vers pubmed: https://pubmed.ncbi.nlm.nih.gov/39360377/
Introduction:
Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. Previous studies have shown a clear correlation between patients' genotype and the clinical severity of FMF. However, no specific study has explored a direct correlation between the patient’s genotype and the reproductive system.
This study aimed to compare reproductive disorders in homozygous and heterozygous female FMF patients with healthy controls.
FMF can be accompanied by abnormalities in women’s reproductive function through the following mechanisms:
Acute peritonitis, which can lead to peritoneal adhesions and obstruction of the fallopian tubes, resulting in mechanical infertility.
Peritonitis during an acute FMF attack in a pregnant woman can cause uterine contractions, leading to miscarriage or preterm labor.
Inflammatory amyloidosis may theoretically thicken the ova, resulting in difficulty for sperm penetration.
Patients and Methods:
The study included 249 women with reproductive disorders at a gynecology center of the National Center for Medical Genetics and Primary Health Care in Yerevan, Armenia. FMF diagnosis was confirmed using the Tel-Hashomer criteria along with genetic analysis of the 12 most common MEFV mutations: E148Q, P369S, F479L, M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H. A severity score was calculated for each FMF patient.
The women were divided into three groups:
Group 1: 40 FMF women with two identical MEFV mutations (homozygous).
Group 2: 47 FMF women with a single MEFV variant (heterozygous).
Group 3: A control group of women with reproductive problems but no other systemic disease, particularly FMF.
All patients were recruited, gave informed consent, and were examined in the same gynecology clinic for reproductive issues. Reproductive problems assessed included menstrual dysfunctions, primary and secondary infertility, endometrial hyperplasia, spontaneous miscarriages, ectopic pregnancies, and preterm deliveries.
Results:
As expected, homozygous patients had more severe FMF, with the M694V/M694V genotype found in 75% of these patients, followed by M680I/M680I and V726A/V726A. The most common genotypes in heterozygous patients were M694V/-, M680I/-, V726A/-, and E148Q/-.
Primary infertility was significantly higher in homozygous patients (79.4%) compared to heterozygous patients (38.5%). The primary cause of infertility in FMF patients was tubal-peritoneal. Adhesions in the pelvic, peritubal, and periovarian regions were more common in FMF patients than in controls. Sterility was 1.54 times more frequent in homozygous patients than in heterozygous and control groups.
Causes of infertility in the control group included endometriosis, uterine fibroids, and adenomyosis.
Homozygous FMF patients had a higher rate of spontaneous miscarriages and lower pregnancy rates compared to heterozygous patients.
Live birth rates were higher in heterozygous patients.
Non-adherence or inadequate treatment with colchicine was associated with higher infertility rates, with 38.2% of homozygous and 84.6% of heterozygous patients receiving insufficient treatment.
Delayed use of colchicine due to late diagnosis of FMF or irregular use also contributed to infertility problems.
In conclusion, the severity of FMF, genotype, and adherence to colchicine treatment impact pregnancy outcomes and reproductive health.
In practice, this study highlights the need to improve patient education on strict adherence to colchicine treatment.
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