O-094 Management of subfertility in women with PCOS: expectations, problems and solutions
Authors: Norman R J , Costello M 
Published: June 2023

Polycystic ovarian syndrome (PCOS) is a common cause of subfertility particularly when anovulation is present. In this circumstance efforts are made to induce ovulation through lifestyle modification, medication, or a combination of both. Other patients with PCOS may be ovulatory but require IVF/ICSI for other causes, including male factor or tubal infertility. In all cases, attention needs to be placed on the underlying metabolic, psychological, and reproductive features that may complicate treatment and subsequent pregnancy. Pregnancy itself has a higher chance of complications and these can be reduced by adequate preconception evaluation and intervention.

Recently, the international evidence-based guideline for evaluation and treatment of PCOS has been updated (1) and the infertility section subjected to a literature integrity check to exclude publications that did not meet the highest criteria for incorporation into clinical management. A recent individual patient data meta-analysis has also clarified the relative efficacy of fertility treatments (2). The following conclusions are recommended;

1. Letrozole is the first line drug of choice for ovulation induction based on its efficacy and lower multiple pregnancy rate

2. Clomiphene is an effective drug particularly given a long experience of use and its lower cost

3. Metformin may be valuable for some patients particularly if glucose intolerance is present

4. A combination of clomiphene and metformin may be effective, particularly in overweight individuals

5. Gonadotrophins are an effective treatment in experienced clinics which the resources to undergo adequate monitoring

6. Laparoscopic ovarian surgery may assist some patients and is associated with a lower multiple pregnancy rate and may have long term benefits

7. IVF may be safely conducted with appropriate safeguards to reduce ovarian hyperstimulation syndrome in those where ovulation induction has failed.

It should be noted that some of these drugs are “off-label” in many countries and are not recommended in several healthcare systems.There are several areas where further information may lead to altered and improved practice:

1. IVF as a first line therapy may be more effective and allow better control of multiple pregnancy rates.

2. In vitro maturation (IVM) with IVF/ICSI shows increasing success with no or minimal FSH use (3).

3. Bariatric surgery is more readily available and may lead to significant weight loss related ovulation.

4. Newer GLP1 receptor agonists show dramatic weight loss and are being evaluated in PCOS.

5. First line gonadotrophin treatment has been advocated by some proponents.

6. Higher dose and longer use of standard oral agents may help in ovulation induction resistant patients.

7. Inositol and myoinositol are being evaluated as safe, low cost, over the counter alternatives.

8. Alternatives to hCG are available for ovulation induction in oral and IVF cycles.

9. Promising pharmacogenomic approaches may allow individualisation of treatment.

While the genomic and environmental aetiology of PCOS remains uncertain, the increasing emphasis on evaluation and assessment of effective therapies for subfertility is advancing rapidly.

References

1. https://www.monash.edu/__data/assets/pdf_file/0004/1412644/PCOS_Evidence-Based-Guidelines_20181009.pdf

2. Wang R et al Hum Reprod Update. 2019 Nov 5;25(6):717-732.

3. Vuong LN Hum Reprod. 2020 Nov 1;35(11):2537-2547.