O-110 Mild stimulation is the future in ART
Authors: Nargund G 
Published: June 2023

The World Health Organisation has called for a simple, safe, and effective IVF treatment which could be both affordable and widely accessible. Unfortunately, IVF practice in developed countries seems to be trending in the opposite direction, making ovarian stimulation more intense, complex, expensive, and globally inaccessible, under the pretext of maximising the cumulative live birth rate (LBR) or by offering a ‘package’ of a ‘complete family’ from a single attempt of IVF.

In reality, data from randomised controlled trials (RCTs) has found no difference in fresh cycle as well as cumulative LBRs whether a mild or high stimulation dose is administered. This is because, higher oocyte yield with high ovarian stimulation does not translate into better-quality embryos and this has been demonstrated in systematic reviews and meta-analyses.

There appears to be confusion between stimulation ‘dose’ and ‘response’. Young women with good ovarian reserve are more likely to have a high response to stimulation despite being treated with a dose that falls within the definition of ‘mild stimulation’, whereas aggressive stimulation fails to improve the response in poor responders. A rising cumulative LBR with increasing number of oocytes is attributable to these good responders, but this is disconnected with the intensity of ovarian stimulation.

The euploid embryo yield similarly is related to the number of oocytes and cumulative LBR which are influenced by the woman’s age and ovarian reserve but not the stimulation dose. Both the numbers of aneuploid and euploid embryos rise with increasing oocyte yield, keeping the proportion unchanged.

Advocates of ‘one and done’ approach have shown that only 1 in 5 women can produce the requisite number of oocytes to have more than 1 child. This means, the remaining 80% patients would be subjected to intense stimulation, incurring risks of overstimulation, treatment burden and cost without achieving the goal of ‘completing’ their family. Psychological analysis from a RCT reported a higher incidence of post-treatment depression after Conventional compared to Mild IVF. Even in the era of agonist trigger and ‘freeze all embryos’, OHSS has not been totally eliminated- the World Registry reported around 40 cases of severe OHSS in 10 000 cycles. Clinical complications such as haemorrhage and infection associated with overstimulation could be magnified in low-resource settings with lack of facilities and expertise.

Livebirth rates albeit of key importance cannot be the only index of success. Our commitment should be to make IVF accessible globally by adopting effective stimulation protocols that reduce treatment burden and cost for the patient and improve health outcomes for mother and baby. Only mild stimulation IVF can fulfil this global vision and need as an increasing body of evidence has confirmed that mild stimulation is as successful as conventional stimulation, while being safer and less expensive. Individualised mild stimulation protocols are the smartest way forward in a global setting for all patient groups. It is time to reflect on what is best for our patients and society in the long-term.