The local effects of ovarian diathermy in an ovine model of polycystic ovary syndrome.

Fiona Connolly,Michael T Rae,W Colin Duncan,Mairead Butler,Alan S Mcneilly,Alexander L Klibanov,Vassilis Sboros

doi:10.1371/journal.pone.0111280

Abstract

In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30–100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles.

Highlights

Polycystic ovary syndrome (PCOS), the most prevalent endocrine disorder in women of reproductive age [1,2], is the leading cause of anovulatory related infertility [2,3]
clomifene citrate (CC) is successful at inducing ovulation in approximately 50–80% of cases, pregnancy rates are suboptimal
We used the paradigm of prenatal androgenisation from day 30 to day 100 of gestation in sheep to create offspring who develop a robust PCOSlike condition. We studied these offspring in the second breeding season when the anovulatory PCOS-like phenotype is fully established [13,14,15,16,17,18,19]

Summary

Introduction

Polycystic ovary syndrome (PCOS), the most prevalent endocrine disorder in women of reproductive age [1,2], is the leading cause of anovulatory related infertility [2,3]. CC is successful at inducing ovulation in approximately 50–80% of cases, pregnancy rates are suboptimal. This is thought to arise due to the anti-estrogenic effects of CC on the endometrium and luteinising hormone surge [4,5]. It has been reported that follicle stimulating hormone therapy results in higher pregnancy rates than CC treatment [7,8]. Such treatment is expensive, requires enhanced monitoring to reduce ovarian hyperstimulation and multiple pregnancy rates and it is not available in all secondary care settings.

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Results

Conclusion