Is Letrozole more effective than Clomiphene Citrate at stimulating ovulation in women with PCOS struggling with infertility?

 

INTRODUCTION

1 in 10 women in the UK have PCOS. In short, 1 in 10 women are likely to struggle when trying to conceive. Unable to ovulate due to cystic ovaries. Clomiphene Citrate is currently the 1st line medication given to women with PCOS planning on having a child. But studies have titled their rationale towards Letrozole which may have a higher rate of ovulation and thereby pregnancy in these women. Letrozole is currently used as breast cancer drug, but it is now proving to be used for more than just breast cancer.

 

AIMS

To provide a comprehensive overview on trials that have looked at how Letrozole works better than CC to stimulate ovulation and in result reduce rates of infertility amongst women with PCOS.

 

SEARCH METHOD

[Image of a PRISMA flow diagram]

 

METHODS

The trials included are all RCTs through a database search through SCORUS, PubMed and Cochrane Library. All the trials have the following in common:

• Women were aged 18-40 with diagnosed PCOS

• Ovulation rates were measured with mid-luteal phase progesterone and ultrasound

• Pregnancy confirmed by urine or serum beta-hCG

For a fair comparison, the papers were reduced to RCTs being available in English, available in full-text and providing appropriate methodology and sufficient detail for comparison. Trials not outlining dose or number of cycles were excluded.

 

RESULTS WITH ADDITIONAL DETAIL

Endometrial thickness – 6 out of the 9 trials in the systemic review reported a thicker endometrial thickness in the Letrozole group. Making it more hospitable for implantation.

Progesterone levels – 4 out of 6 trials favoured the Letrozole group- increasing endogenous levels and dominance in more than 8 out 8 weeks.

Observed implantation and oocyte retrieval – Letrozole induced smaller follicles changes to oestrogen levels and increase in FSH.

Smaller FSH rise – Although Letrozole decreased the number of follicles released on monitoring, this allows for a better mono-follicular stimulation.

Shorter FSH exposure – Reduced the number of follicles released with Letrozole allowing for LSF support to allow the maturation of the follicles on ovulation.

Half life of Letrozole is shorter than CC – less time staying in the system for a drug with an action to inhibit ovulation.

Quality of cervical mucous – Due to the longer half-life of CC, there is a higher amount of cervical mucus build up – this alters the motility, migration and aiding of the sperm to the egg. This ultimately can be detrimental to the fertilisation process.

 

CONCLUSION

Although CC remains the first-line medication provided for infertility in hopes of conceiving in women with PCOS, the systemic review has shown that Letrozole is a strong alternative. This is not just reflected in its pharmacological benefits, but also in research which has highlighted higher fertilisation rates in comparison to CC.

 

AUTHORS

Saira Aslam Akhtar, 4th year medical student at the University of Liverpool

Dr Stephanie Woodcock

 

ACKNOWLEDGEMENTS

This work is part of the Research and Scholarship Theme at the University of Liverpool. This work is part of the RS3 project.

 

RESULTS

[Table and bar charts showing comparison data between Letrozole and Clomiphene Citrate across various outcome measures]