The impact of immunomodulating drugs on ovarian reserve in multiple sclerosis patients

Abstract

OBJECTIVE: To determine the impact of immunomodulating drugs on ovarian reserve in patients with multiple sclerosis (MS). DESIGN: Prospective controlled clinical study. MATERIALS AND METHODS: Thirteen normally menstruating MS patients using immunomodulating drugs and 15 age-matched healthy controls were included in the study. Subjects were examined on cycle day 2-5 of a menstrual cycle with transvaginal ultrasound to evaluate ovarian volume, antral follicle count (AFC) and ovarian stromal artery flow by Doppler. On the same day, blood was drawn for determining follicle stimulating hormone (FSH) and estradiol (E2) levels. RESULTS: MS patients and controls were comparable with regard to body mass index and age at study inclusion. FSH and E2 levels and ovarian volumes did not show any significant differences between the two groups, but mean number of total antral follicles (2-10 mm) was significantly lower in MS patients than in controls (7.7±4.04 vs 11.4±4.5) (table-1).Table 1Results of ovarian reserve tests in MS patients using immunomodulating therapiesMS patients (n=13)Control (n=15)p valueAge±SD34.62±5.1732.27±5.87NSBMI25.59±3.9324.04±4.09NSFSH (mIU/mL)8.60±3.507.72±1.69NSE2 (pg/mL)54.14±35.741.67±23.02NSTotal AFC (2-10 mm)7.73±4.0411.40±4.50.03Ovarian volume (cm3)6.67±3.136.98±1.97NSRI.49±.10.43±.08NSPI.85±.23.73±.19NSS/D2.14±.561.85±.35NSPSV10.43±3.4414.423±3.37.01∗BMI: Body mass index. FSH: Follicle stimulating hormone. E2: Estradiol. AFC: Antral follicle count.RI: Resistance index. PI: Pulsatility index. S/D: Systolic/diastolic ratio. PSV: Peak systolic velocity. Open table in a new tab BMI: Body mass index. FSH: Follicle stimulating hormone. E2: Estradiol. AFC: Antral follicle count.RI: Resistance index. PI: Pulsatility index. S/D: Systolic/diastolic ratio. PSV: Peak systolic velocity. The mean ovarian stromal artery resistance index, pulsatility index and systolic/diastolic ratio of MS patients were higher than of the control group, but the difference did not reach statistical significance. The only statistically significant difference in Doppler indices was lower mean peak systolic velocity (PSV) in MS patients. CONCLUSIONS: We found a significant decrease in mean AFC and PSV of ovarian stromal arteries in patients with MS using immunomodulating drugs. These findings support that MS patients using immunomodulating drugs may have a diminished ovarian reserve and fertility. The diminishment maybe related to altered ovarian blood flow but further research will be needed to prove this hypothesis. In the mean time, patients undergoing treatment with immunomodulators should be informed about the possible gonadotoxic effects of these therapies.