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Background: Familial Mediterranean Fever (FMF) is the most common hereditary periodic fever worldwide. Male infertility is a rare complication of FMF; however, some studies have suggested that FMF does not decrease male fertility. The most commonly proposed mechanisms include colchicine use, testicular amyloidosis, and inflammation itself [1]. This is the first study to explore the paternal effects of FMF on pregnancy outcomes and complications.
Objectives: To investigate the effect of FMF on male fertility and the paternal effect of FMF on pregnancy outcomes and complications. To determine the effects of MEFV mutation status and drugs used in the treatment of FMF on these outcomes.
Methods: In this study, 282 adult male patients with FMF were interviewed. Relevant data were collected from archives and interviews. Infertility was defined as failure to conceive after one year of unprotected intercourse.
Results: A total of 180 patients attempted pregnancy and only three (1.7%) could not conceive. Two of them reported that their wives had fertility problems. One of their wives had endometriosis, and the other had leiomyoma uteri. Both had unsuccessful in vitro fertilization (IVF) attempts. The other patient who could not conceive used colchicine while attempting pregnancy. The remaining 177 patients managed to conceive 451 times. These 451 pregnancies resulted in 384 (85.1%) live births, 52 (11.5%) miscarriages, seven (1.6%) abortions, four (0.9%) ectopic pregnancies, three (0.7%) stillbirths and one (0.2%) anembryonic pregnancy. Pregnancy complications and their relationship with the MEFV mutation status and treatment used during conception are shown in Table 1. The presence of the M694V allele was not statistically significant for any parameter. There were 82 (18.8%) non-elective C-sections, 16 (3.5%) preterm births, nine (2.0%) gestational diabetes, five (1.1%) FGR, three (0.7%) gestational hypertensive disorders, one (0.2%) post-term birth and one (0.2%) perinatal asphyxia. There were no statistically significant differences in miscarriage, stillbirth, and preterm birth rates between our patient population and the Turkish population.
Conclusion: The presence of FMF did not lead to a decrease in male fertility. FMF did not have a paternal effect on pregnancy outcomes or complications. Using colchicine during conception led to a significant increase in non-elective cesarean section rates, and not using any drugs during conception led to a significant increase in miscarriage rates. Uncontrolled inflammation may be the underlying mechanism of this increase in miscarriage rates. In patients who stop using colchicine during pregnancy attempts, anti-IL-1 agents can be used to prevent miscarriages.
REFERENCES: [1] Er O, Ugurlu S. Fertilization, reproductive system, and pregnancy in familial Mediterranean fever: Clinical state of art. Mod Rheumatol . Published online July 3, 2023. doi:10.1093/mr/road067.
Pregnancy complications and their relationship with MEFV mutation status and treatment used during conception
| Colchicine only | Colchicine + canakinumab | Sulfasalazine
| No drug | p | M694V allele present | M694V allele not present | p | |
|---|---|---|---|---|---|---|---|---|
| Preterm birth, n (%) | 11 (9.7) | 0 (0) | 0 (0) | 5 (7.7) | 1 | 3 (5.5) | 9 (14.3) | 0.136 |
| Gestational hypertensive disorders, n (%) | 0 (0) | 0 (0) | 0 (0) | 3 (4.6) | 0.07 | 0 (0) | 1 (1.6) | 1 |
| Gestational diabetes, n (%) | 4 (3.5) | 0 (0) | 0 (0) | 5 (7.7) | 0.346 | 3 (5.5) | 3 (4.8) | 1 |
| Non-elective c-section, n (%) | 60 (53.1) | 1 (100) | 0 (0) | 21 (32.3) | 0.031 | 30 (54.5) | 32 (50.8) | 0.71
|
| Fetal growth restriction, n (%) | 3 (2.7) | 0 (0) | 0 (0) | 2 (3.0) | 1 | 1 (1.8) | 1 (1.6) | 1 |
| Perinatal asphyxia, n (%) | 1 (0.9) | 0 (0) | 0 (0) | 0 (0) | 1 | 0 (0) | 0 (0) | 1 |
| Postterm birth, n (%) | 1 (0.9) | 0 (0) | 0 (0) | 0 (0) | 1 | 1 (1.8) | 0 (0) | 0.46 |
| Fetal anomalies, n (%) | 3 (2.7) | 0 (0) | 0 (0) | 0 (0) | 0.567 | 1 (1.8) | 1 (1.6) | 1 |
| Miscarriage, n (%) | 27 (23.9) | 0 (0) | 1 (100) | 24 (36.9) | <.001 | 15 (27.3) | 15 (23.8) | 0.67 |
| Ectopic pregnancy, n (%) | 2 (1.8) | 0 (0) | 0 (0) | 2 (3.0) | 0.555 | 1 (1.8) | 0 (0) | 0.46 |
| Anembryonic pregnancy, n (%) | 1 (0.9) | 0 (0) | 0(0) | 0 (0) | 1 | 0 (0) | 1 (1.6) | 1 |
| Stillbirth, n (%) | 0 (0) | 0 (0) | 0 (0) | 3 (4.6) | 0.07 | 0 (0) | 0 (0) | 1 |
Acknowledgements: NIL.
Disclosure of Interests: None declared.