Cancer drug may improve IVF success rates in women with low ovarian reserve

A clinical study has shown that the aromatase inhibitor letrozole can enhance ovarian response, embryo quality and live birth outcomes in women with diminished ovarian reserve who undergo in vitro fertilisation

Researchers have reported that the addition of letrozole, a drug widely used in breast cancer treatment, to a standard in vitro fertilisation protocol has improved live birth outcomes in women who show a poor response to ovarian stimulation. The findings have addressed a persistent clinical challenge in reproductive medicine, where conventional hormone regimens often fail to yield sufficient viable oocytes in this patient group.

The study, conducted at Dongguan Maternal and Child Healthcare Hospital, Guangdong, China, evaluated 176 women aged between 35 and 42 who had been classified as poor ovarian responders on the basis of diminished ovarian reserve. This group represents a particularly difficult cohort in assisted reproduction, as age-related decline in ovarian function and reduced follicular reserve can limit both the quantity and quality of oocytes retrieved during treatment cycles.

In standard in vitro fertilisation, clinicians aim to stimulate the ovaries with exogenous hormones to induce the development of multiple follicles, thereby increasing the number of oocytes available for fertilisation. However, in women with reduced ovarian reserve, even high-dose gonadotropin regimens often fail to elicit an adequate response. Escalation of hormone dosage has not consistently improved outcomes and has introduced additional financial burden and risk of adverse effects, prompting ongoing efforts to refine stimulation strategies.

Letrozole, an aromatase inhibitor, exerts its effect by blocking the enzymatic conversion of androgens into oestrogen. This mechanism leads to a reduction in circulating oestrogen levels and a compensatory increase in endogenous follicle-stimulating hormone secretion, which can enhance follicular recruitment. The present study has explored whether incorporation of letrozole into a gonadotropin-releasing hormone antagonist protocol could optimise ovarian response in poor responders.

The investigators reported that women who received letrozole in combination with the standard protocol required significantly less exogenous hormone medication and completed the stimulation phase approximately two days earlier than those who received the standard regimen alone. These findings suggest a more efficient stimulation process, with potential implications for both patient burden and treatment cost.

Crucially, the addition of letrozole has been associated with improvements in key embryological parameters. Women in the letrozole group produced a higher proportion of mature oocytes suitable for fertilisation, as well as a greater number of high-quality embryos. These laboratory outcomes translated into clinically meaningful differences in success rates. The live birth rate reached 23.7 per cent in the letrozole group, compared with 11 per cent in the control group, indicating a more than twofold increase. Statistical analysis showed that patients who received letrozole were 2.6 times more likely to achieve a live birth.

Age-stratified analysis has further clarified the differential benefit within this cohort. Among women aged 35 to 38, the clinical pregnancy rate reached 60 per cent and the live birth rate 44 per cent. In contrast, women aged 39 to 42 achieved rates of 25.5 per cent and 13.7 per cent respectively. These findings underscore the continued influence of age on reproductive potential, even within a population defined by poor ovarian reserve.

“Even though we find that letrozole improves the overall outcomes, younger patients with poor ovarian reserve stand to benefit the most,” the authors stated.

The authors have emphasised that further validation is required before widespread adoption. They have called for larger, multicentre randomised controlled trials to confirm the reproducibility of these findings across more diverse populations and clinical settings. Such studies would also need to assess long-term safety, cost-effectiveness and optimisation of dosing regimens.

If corroborated, the integration of letrozole into established stimulation protocols could represent a clinically meaningful refinement in the management of poor ovarian responders. By reducing reliance on high-dose gonadotropins while improving both embryological and live birth outcomes, this approach has the potential to offer a more efficient and accessible pathway through assisted reproduction for a group of patients that has traditionally faced limited success.

For further reading please visit: 10.1097/RD9.0000000000000155