The first report of clonidine in vivo/ in vitro effects on infertile women with polycystic ovary syndrome (in vivo/ in vitro study)

Abstract

The sympathetic nervous system (SNS) is hyperactive in women with polycystic ovary syndrome (PCOS). This study was designed in two sections: in vivo/in vitro with clonidine as the alpha-2 adrenoceptor (ADR-α₂) agonist for modulating this hyperactivity. Eighty women with PCO participated in this randomised clinical trial (in vivo). A clonidine (0.1 mg) tablet was given twice a day for two months. Polycystic ovary morphology (PCOM) and pregnancy rate were the main outcome measurements. In the candidates for in vitro fertilisation (IVF), clonidine was added to the culture medium during IVF for two study groups (PCO-clonidine/PCO-without) and two control groups (egg donors-clonidine/egg donors-without). Our results showed that the pregnancy rate significantly was higher in the study group (p = .002). The mRNA expression of ADR-α₁ and ADR-β₂ in PCO was higher than control group (p value <.001). But ADR-α₁ expression in PCO-clonidine group decreased (p value = .042), the same as ADR-α₂ expression. The intensity of this effect showed a pattern for ADR-α₁<ADR-β₂<ADR-α₂. Increase of antral follicle count (AFC) growth and pregnancy rate indicate the significant role of ADR-α₂ in PCOS. Clonidine reduced gene expression and protein levels, confirming the above results. These results would aid in pharmacological treatments, as well as assisted reproductive technologies (ARTs).Impact StatementWhat is already known on this subject? In women with PCOS, sympathetic nerve activity is higher than in healthy women. Clonidine is widely used as an alpha-2 presynaptic adrenoceptor (autoreceptor) agonist to modulate the output of the sympathetic nervous system (SNS). Our in vivo/in vitro results showed that the optimal dose of clonidine can increase the oocyte maturity and pregnancy rate in PCO women. This finding was also confirmed by the results in cumulus cell culture.What do the results of this study add? The results of administration of 0.2 mg of clonidine (in vivo) for oocyte maturation and pregnancy rate confirms the in vitro response in the cumulus cell culture of PCO women's follicle.What are the implications of these findings for clinical practice and/or further research? These findings can be used in pharmacological treatment of anovulation and assisted reproductive technology (ART).

Keywords: ADR-α1/2 gene expression; ADR-β2 gene expression; clonidine; cumulus cell; polycystic ovary syndrome (PCOS).