Removal of small fibroids and polyps in patients with infertility and recurrent miscarriage: The HELP Fertility? RCT

Background: Infertility affects one in six of females globally, with uterine submucous fibroids and endometrial polyps being common findings. The effectiveness of surgical removal to improve fertility remains uncertain. The associated surgical risks and costs highlight the need for more robust research in this area. The HELP Fertility? Study aimed to assess the clinical and cost-effectiveness of hysteroscopic removal of endometrial polyps and submucosal fibroids, compared to no removal, in improving fertility outcomes for participants with infertility or recurrent miscarriage while also evaluating participant experience and longer-term effects. The trial was designed as a multicentre, pragmatic superiority randomised controlled trial with two concurrent trials; one for endometrial polyps and one for submucosal fibroids, with a 9-month feasibility pilot. Participants were randomly assigned 1 : 1 to either receive hysteroscopic resection or no resection. The primary outcome was live birth rate at 15 months. Secondary outcomes included pregnancy rates, procedure details, patient satisfaction and resource use. Results: COVID-19 resulted in significant recruitment challenges, with delays in site set-up and participant enrolment due to pandemic-related healthcare disruptions. The trial was closed early by the National Institute for Health and Care Research-Health Technology Assessment programme following recruitment of 35 participants (19 hysteroscopic resection and 16 no resection) out of a target of 1120. The clinical and cost-effectiveness analyses were severely limited by the small sample size. Clinical pregnancy rates within 15 months of randomisation were 26.5% (5/19) in the hysteroscopic resection group and were 37.5% (6/16) in the no resection group. The live birth rate within 15 months of randomisation (the primary outcome) were 15.8% (3/19) in the hysteroscopic resection group and 18.8% (3/16) in the no resection group: a risk difference of -3.0% (95% confidence intervals -31.1% to 24.2%). No serious adverse events were observed in the follow-up. At the mean, hysteroscopic resection resulted in fewer live births, but increased costs, implying that resection is not cost-effective compared to no resection. However, results were highly uncertain and confidence intervals for incremental costs and the incremental live birth rate spanned zero. At a cost-effectiveness threshold of £20,000 per additional live birth, there is a 10% probability that hysteroscopic resection represents a cost-effective intervention and a 90% probability that no resection is cost-effective. There is a 56% probability that resection is more costly and less effective than no resection. Despite implementing remote training, centralised support and opening 16 National Health Service sites by February 2023, insufficient participants were recruited within planned time frames. The study was ultimately closed as part of the NIHR Research Reset Programme in February 2023. Limitations: With recruitment of 35 participants against a target of 1120 and the follow-up period limited to 15-24 months, the results of this study are limited. Conclusions: The HELP Fertility? Trial faced recruitment challenges, enrolling only 35 participants. Due to the small sample size, researchers could not statistically determine any significant difference in live birth rates between surgical intervention and no resection for small fibroids and polyps. Cost-effectiveness results should be interpreted with caution. Researchers were able to provide valuable insights into clinical research complexities, which include clinician and patient equipoise. Future work: The research highlights several critical considerations for future fertility studies. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128969.