Luteinized unruptured follicle syndrome increased by inactive disease and selective cyclooxygenase 2 inhibitors in women with inflammatory arthropathies

Abstract

Objective. Administration of nonsteroidal antiinflammatory drugs (NSAIDs) may impair fertility. The occurrence of the luteinized unruptured follicle (LUF) syndrome was assessed in women with inflammatory arthropathies exposed to NSAIDs and compared to that in nonexposed women. Methods. Fourteen patients with inflammatory rheumatic disease, 29 women with noninflammatory musculoskeletal conditions, and 449 women not exposed to NSAIDs were studied by intravaginal ultrasound monitoring for follicular development and ovulation in 1 or more menstrual cycles. Disease activity was assessed in inflammatory rheumatic disease. Results. In 59 monitored cycles of patients with continuous NSAID exposure, 35.6% of LUF syndromes occurred compared to 3.4% of LUF syndromes in untreated women (P < 0.001). Etoricoxib was responsible for 75% of LUF syndromes in patients exposed continuously, whereas diclofenac generated 15% of LUF syndromes. An ibuprofen dosage of 1,600 mg/day did not induce LUF syndrome either at continuous periovulatory or discontinuous exposure. Interestingly, the frequency of LUF syndrome was 46.2% in patients with inactive inflammatory disease compared to 15% in patients with active disease (P ‫؍‬ 0.023). Etoricoxib generated LUF syndrome in 94.2% of the cases with inactive disease versus 28.6% in patients with active disease (P ‫؍‬ 0.003). Conclusion. NSAIDs increased the risk of the LUF syndrome, particularly in patients with inactive disease. The selective cyclooxygenase 2 (COX-2) inhibitor etoricoxib was a more potent inductor of LUF syndrome than nonselective COX inhibitors. Continuous periovulatory exposure to NSAIDs should be avoided when planning a pregnancy in patients with rheumatic diseases.

The effect of RA and medication on female fertility

“…Inhibition of follicle rupture requires high anti-inflammatory doses of NSAIDs, and selective inhibitors of COX-2 are more potent than non selective inhibitors. 5 However, active rheumatic dis ease might actually reduce the occur rence of LUF syndrome, as shown in a study that compared exposure to NSAIDs in patients with active and inactive rheumatic dis ease. 5 The effect of cortico steroids on fertility is com plex and includes both facilita tory and inhibitory effects on reproduction.…”

“…5 However, active rheumatic dis ease might actually reduce the occur rence of LUF syndrome, as shown in a study that compared exposure to NSAIDs in patients with active and inactive rheumatic dis ease. 5 The effect of cortico steroids on fertility is com plex and includes both facilita tory and inhibitory effects on reproduction. 6 Theoretic ally, cortico steroids act in several ways: by disturbing the hypothalamic-pituitary-ovarian axis; by inhibiting phos pholipase A2 enzymes '' Can subfertility in female patients with rheumatoid arthritis (RA) be prevented?…”

Pregnancy implications for systemic lupus erythematosus and the antiphospholipid syndrome

“…Protection of ovarian function can be provided by treatment with gonadotropin-releasing hormone analogues [126]. Women should be informed that NSAIDs may inhibit ovulation, therefore they should stop them at day 8 of the menstrual cycle when they want to conceive [127].…”

Role of Ultrasound in the Assessment of Female Infertility

“…Micu et al conducted a prospective study which showed that women receiving nonsteroidal antiinflammatory drugs (NSAIDs) for rheumatic disease had a greater incidence of the LUF syndrome as compared to nonexposed women (35.6 vs 3.4%). 16 Etoricoxib, a COX2 inhibitor, was found to have the most potent effect (75% of all LUF cases) while diclofenac was less significant (15%). Interestingly, there was a much higher frequency of LUF syndrome in patients with inactive rheumatic disease compared with active disease.…”

“…Interestingly, there was a much higher frequency of LUF syndrome in patients with inactive rheumatic disease compared with active disease. 16 There is an association between LUF syndrome and unexplained infertility, chronic pelvic infections and endometriosis.…”