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 Statement

• What 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-α_1/2 gene expression
• ADR-β₂ gene expression
• cumulus cell
• polycystic ovary syndrome (PCOS)
• clonidine

Author contributions

Farideh Zafari Zangeneh: protocol/project development determining of the dose of clonidine for treatment in animal and clinical trials, data collection or management, writing – review.

Samad Muhammadnejad, determination of clonidine dose.

Mohammad Mehdi Naghizadeh, data analysis.

Mina Jafarabadi, infertility fellowship.

Maryam Sarmast Shoushtari, writing – review, editor.

Masoumeh Masoumi, coordinator for patients with IVF centre.

Disclosure statement

The authors declare no conflict of interests.

Additional information

Funding

This study was supported by funding of the Research Council of Tehran University of Medical Sciences; Tehran, Iran which supported this study by a Grant Publication No. 39-30274 revised 2015.