Effect of amlodipine on blood flow of preovulatory follicle in polycystic ovarian patients: A Randomized Controlled Trial

Abstract

In the current study, after recruitment of 70 PCOs patients attending the infertility clinic in Ain Shams University Obstetrics and Gynecology medical hospital 9 of them lost for follow up, the patients received 50 mg single morning dose of CC which was given for 5 days starting from the fifth day of menstrual cycle. Ultrasonography, power and color Doppler analysis were performed for all women on day five and day nine of menstrual cycle In the second cycle (wash cycle) the patient did not receive any treatment. In the third cycle Amlodipine 5 mg single early morning dose was added to the CC regimen starting from the fifth day of the cycle daily for five days to be stopped at ninth day of menstrual cycle . Ultrasonography, power and color Doppler analysis were performed for all women on day five and day nine of menstrual cycle in both cycles.Blood samples were collected from each patient on day 21 of menstrual cycle in each cycle to measure progesterone (P) level to confirm or exclude occurrence of ovulation. This study focused on the effect of the vasodilator calcium channel blocker, amlodipine, on preovulatory follicle. Diminished uterine blood flow seems to be one of the principal problems in the pathogenesis of infertility or subfertility in women with PCOs since after treatment ofanovulation by administration of CC in the 1st cycle The cycles of CC plus amlodipine were associated with a higher pregnancy rate when compared to the cycles of CC alone; the difference was, however, statistically not significant [4 (5.7%) vs. 10 (17.5%), respectively, p=0.267; RR 2.47, 95% CI (0.72 to 8.52); number needed to treat = 12. The cycles of CC plus amlodipine were significantly associated with a higher likelihood of presence of at least one mature follicle (≥ 18 mm), when compared to the cycles of CC alone [51 (89.4%) vs. 37 (52.8%), respectively, p<0.001; RR 5.69, 95% CI (2.31 to 14.01); number needed to treat = 3]. The explanation of this is attributed to that the decrease in RI of the ovarian blood flow cause a significant increase in the mean pre-ovulatory follicle blood and thus increase in its mean diameter as compared to the 1st cycle . There were no significant differences between uterine artery Doppler indices PSV, RI or PI measured on day 5, in CC only cycles and CC + amlodipine cycles. The same Doppler indices measured on day 9, however, were significantly higher for PSV and lower for RI and PI in CC + amlodipine cycles, There were no significant differences between ovarian artery Doppler indices PSV, RI or PI measured on day 5, in CC only cycles and CC + amlodipine cycles. The same Doppler indices measured on day 9, however, were significantly higher for PSV and lower for RI and PI inCC + amlodipine cycles

In both CC only cycles and CC + amlodipine cycles, successful biochemical pregnancy was significantly associated with higher endometrial thickness on day 9 and higher midluteal serum progesterone. The mean midluteal serum progesterone in the first cycle was 11.31 ± 10.6ng/ml .During the treatment cycle, the mean midluteal serum progesterone was significantly higher23.2 ± 10.1 (P<0.001)in women of {Amlodipine group} when compared to those of {CC only Group}. Amlodipine could be added to the treatment protocol of polycystic ovarian patients to improve and balance the utero-ovarian blood flow and thus increase the rate of ovulation and the rate of conception. From the results of this study it was concluded that amlodipine has a statistically significant effect on improving uterine, ovarian blood flow, size of pre-ovulatory follicle, midliteal progesterone level and pregnancy outcome when compared with patients who received CC only.