A Review of Second- and Third-line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome.

Michael F Costello,Cailin Jordan,Christos A Venetis,Hayden Homer,Roger Hart,Helena J Teede,William L Ledger,Eszter Vanky,Jie Qiao,Edgar Mocanu,Rhonda M Garad,Luk Rombauts,Louise Johnson

doi:10.3390/medsci7070075

Abstract

In clomiphene-citrate-resistant anovulatory women with polycystic ovary syndrome (PCOS) and no other infertility factors, either metformin combined with clomiphene citrate or gonadotrophins could be used as a second-line pharmacological therapy, although gonadotrophins are more effective. Gonadotrophins could also be used as a second-line pharmacological therapy in anovulatory women with PCOS and clomiphene-citrate-failure. Laparoscopic ovarian surgery can also be used as a second-line therapy for ovulation induction in anovulatory women with clomiphene-citrate-resistant PCOS and no other infertility factors. The usefulness of letrozole as a second-line pharmacological treatment for ovulation induction in clomiphene-citrate-resistant women with PCOS requires further research. In terms of improving fertility, both pharmacological anti-obesity agents and bariatric surgery should be considered an experimental therapy in anovulatory women with PCOS and no other infertility factors. Where first- or second-line ovulation induction therapies have failed, in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) could be offered as a third-line therapy in women with PCOS in the absence of an absolute indication for IVF/ICSI. For women with PCOS undergoing IVF/ICSI treatment, the gonadotropin-releasing hormone (GnRH) antagonist protocol is preferred and an elective frozen embryo transfer strategy could be considered. In assisted conception units with sufficient expertise, in-vitro maturation (IVM) of oocytes could be offered to women with PCOS.

Highlights

Polycystic ovary syndrome (PCOS), with a prevalence of between 8% and 13%, depending on the population studied and definitions used, is the most common endocrinopathy affecting reproductive-aged women
Metformin combined with clomiphene citrate could be used as second-line pharmacological therapy in anovulatory women with polycystic ovary syndrome (PCOS) and no other infertility factors, as it is superior to clomiphene citrate alone in clomiphene-citrate-resistant women
Ovulation induction with gonadotrophins began in the 1960s and there is a large body of observational evidence supporting the use of gonadotrophin ovulation induction in clomiphene citrate resistant or clomiphene-citrate-failure PCOS women, with the use of the low dose step-up protocol with typical starting doses of follicle-stimulating hormone (FSH) 50–75 IU being recommended in order to reduce the risk of multiple pregnancy and ovarian hyperstimulation syndrome [21]

Summary

Introduction

Polycystic ovary syndrome (PCOS), with a prevalence of between 8% and 13%, depending on the population studied and definitions used, is the most common endocrinopathy affecting reproductive-aged women. First-line pharmacological treatment for infertile women with PCOS may include letrozole, clomiphene citrate, metformin, clomiphene citrate combined with metformin and gonadotrophins, of which letrozole is considered the first-line therapy [6,7]. The aim of this narrative review is to provide a summary and brief update of the best available and most current research evidence that evaluates the second- and third-line treatment of PCOS-related infertility and which has informed the recommendations in the assessment and treatment of infertility section of the International Evidence-Based Guideline on PCOS [6,7]. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across the quality of evidence (QOE) [8]

Background

Evidence

Summary

Gonadotrophins versus Other Ovulation Induction Therapies

Findings

10. Conclusions