A brief update on the evidence supporting the treatment of infertility in  polycystic ovary syndrome

Michael F Costello; Marie L Misso; Adam Balen; Jacqueline Boyle; Luigi Devoto; Rhonda M Garad; Roger Hart; Louise Johnson; Cailin Jordan; Richard S Legro; Rob J Norman; Lisa Moran; Edgar Mocanu; Jie Qiao; Ray J Rodgers; Luk Rombauts; Eliza C Tassone; Shakila Thangaratinam; Eszter Vanky; Helena J Teede

doi:10.1111/ajo.13051

A brief update on the evidence supporting the treatment of infertility in polycystic ovary syndrome

Costello MF, Misso ML, Balen A, Boyle J, Devoto L, Garad RM, Hart R, Johnson L, Jordan C, Legro RS, Norman RJ, Moran L, Mocanu E, Qiao J, Rodgers RJ, Rombauts L, Tassone EC, Thangaratinam S, Vanky E, Teede HJ

Published December 2019 The Australian & New Zealand Journal of Obstetrics & Gynaecology, 59(6), 867-873

DOI 10.1111/ajo.13051 PMID 31514246

RRM Academy Synopsis

Letrozole had a higher live-birth rate than clomiphene in PCOS

Letrozole led to more live births than clomiphene in randomized trials. The infertility group behind the 2018 guideline wrote this 2019 review. It covered PCOS, now called PMOS (polyendocrine metabolic ovarian syndrome).

Live birth over six cycles: Gonadotrophins, 52 in 100; Clomiphene citrate, 41 in 100. Source: Costello MF et al., 2019, PMID 31514246.

Study at a glance, short review of published trials: Letrozole led to more live births than clomiphene in PMOS. Source: Costello MF et al., 2019, PMID 31514246.

Key Findings

Live birth was higher with letrozole than clomiphene citrate: odds ratio 1.67 (95% CI 1.11–2.49) in one review and 1.79 (95% CI 1.42–2.25) in another.
In a network meta-analysis of eight ovulation induction therapies, letrozole was the only one superior to clomiphene citrate for live birth in WHO Group 2 anovulatory women.
A Dutch randomized trial of 666 anovulatory women with clomiphene citrate failure found live birth in 52% with gonadotrophins and 41% with clomiphene over six cycles (relative risk 1.24; 95% CI 1.05–1.46).
A Cochrane review of lifestyle interventions in PMOS / PCOS located six randomized trials, and none reported live birth.
The guideline located no published randomized trials comparing IVF with ovulation induction treatments or with placebo or no treatment in PMOS / PCOS.

Interpretation

The authors, the guideline's infertility group, wrote a short review of published trials. The network meta-analysis covered women in WHO Group 2 who do not ovulate, a group that includes PMOS / PCOS. The group considers lifestyle change the first-line treatment for women who are overweight or obese. Where no absolute indication for IVF exists, the group says women could be offered it third, after ovulation induction fails. The guideline's own gaps call for larger randomized trials of ovulation induction and lifestyle treatment in PMOS / PCOS.

RRM Context

The authors say PMOS / PCOS has reproductive, metabolic and psychological features. Restorative reproductive medicine starts from that wide picture and checks both partners before treatment. The check shows whether other causes of infertility exist. Ovulation induction targets ovulation itself. IVF goes ahead without finding why ovulation fails.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated.

Aims

This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018.

Materials and Methods

International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages.

Results

Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed.

Conclusion

This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.

Topics

Therapeutics › Ovulation Agents › Aromatase Inhibitors · Clinical Guidelines and Standards › Guidelines by Clinical Area › Fertility and Infertility Guidelines · Infertility › Ovulation Induction › Letrozole

Michael F Costello, Marie L Misso, Adam Balen, Jacqueline Boyle, Luigi Devoto, Rhonda M Garad, Roger Hart, Louise Johnson, Cailin Jordan, Richard S Legro, Rob J Norman, Lisa Moran, Edgar Mocanu, Jie Qiao, Ray J Rodgers, Luk Rombauts, Eliza C Tassone, Shakila Thangaratinam, Eszter Vanky, Helena J Teede

Mike Costello, M Costello, M Misso, A Balen, J Boyle, L Devoto, R Garad, R Hart, L Johnson, C Jordan, Rick Legro, Dick Legro, Rich Legro, R Legro, Robert Norman, R Norman, L Moran, E Mocanu, J Qiao, R Rodgers, L Rombauts, E Tassone, S Thangaratinam, E Vanky, H Teede

PMID 31514246 31514246 DOI 10.1111/ajo.13051 10.1111/ajo.13051 Costello et al. 2019, Costello 2019