the first report of clonidine invivo/invitro effects as a new pharmacological strategy in the infertile women with polycystic ovary syndrome

the first report of clonidine invivo/invitro effects as a new pharmacological strategy in the infertile women with polycystic ovary syndrome

objective:women with polycystic ovary syndrome (pcos) suffer from sympathetic nervous system (sns) hyperactivity. clonidine as the alpha-2 adrenoceptor agonist is widely used for modulation of sns output. study design: this study was designed in two sections: in-vivo / in-vitro and was performed from february 2016 to december 2017. eighty women with pco participated in this randomized clinical trial (in-vivo).

polycystic ovary morphology (pcom) and pregnancy rate were the main outputs which were evaluated by oral dosing of clonidine (0.1 mg) tablet twice a day for two months. a case/control study of cumulus cell culture was another part (in-vitro) of this study. clonidine was added to the culture for two study groups (pco women with drug / without drug) and two control groups (egg donors with drug / without drug), that all of them were candidate for ivf.

ovulation stimulant drugs were administrated for all groups. after the puncture, cumulus cells were collected for treatment by clonidine. results: the pregnancy rate significantly more occurred in the clonidine group (p = 0.002). other results of the clinical trial indicate a significant increase in the total number of antral follicle count (afc) (p = 0.006). the results of the in-vitro assessment in cumulus cell culture showed that in the non-treatment group of pco women, the mrna expression of adr-α1 was higher than the control group (p-value <0.001). in treatment pco group with clonidine, adr-α1 expression decreased (p-value = 0.042) similar mrna expression of adr-α2.

the mrna expression of adr-β2 in pco group was higher than the control (p-value <0.001). the intensity of this effect was adrα1 <adrβ2 <adrα2, respectively. conclusion:the results of afc growth and increased pregnancy rates indicate to the significant role of adrenergic alph2 in pcos, because clonidine as a neuromodulator agonist could effect on the ovarian sns output. therefore, the reduction in gene expression and protein levels by clonidine in cumulus cell culture also confirms the above two findings. these findings can be used in pharmacological treatment and artificial reproduction technology (art).