The impact of small and asymptomatic intramural and subserosal fibroids on female fertility: a case-control study.

Study question: Do small and asymptomatic intramural and subserosal uterine fibroids affect female fertility?

Summary answer: Small and asymptomatic fibroids that do not encroach the endometrial cavity appear to not markedly affect female fertility.

What is known already: The available evidence on uterine fibroids and fertility is limited. Most information has been obtained in IVF settings by comparing the success in women affected and not affected by fibroids. These studies have shown a detrimental effect of submucosal and possibly intramural fibroids. However, this study design provides information only on embryo implantation, not on female fertility in general.

Study design size duration: A retrospective observational case-control study on 200 women whose partner was diagnosed with severe male infertility and 200 women with unexplained infertility was conducted. If the null hypothesis (that fibroids do not affect fertility) is valid, one would expect a similar prevalence of fibroids in the two study groups. Conversely, if fibroids do impact fertility, one would expect a higher prevalence among women with unexplained infertility. The study was carried out at the Infertility Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico covering a 5-year period between January 2014 and June 2020.

Participants/materials setting methods: We retrospectively recruited women seeking pregnancy whose partner was repeatedly documented to have a sperm concentration below 1 million/ml and matched them by age and study period to a group of women with unexplained infertility. The latter group of women was considered as a case group (infertile subjects), while the former group of women was considered as a control group (reflecting the general female population). Women with fibroids could be included in both study groups; only those with submucosal lesions were excluded.

Main results and the role of chance: Fibroids were diagnosed in 31 women (16%) with unexplained infertility and in 32 women (16%) with severe male factor infertility. The adjusted odds ratio of carrying fibroids in women with unexplained infertility was 0.91 (95% CI: 0.52-1.58). Subgroup analyses according to number, dimension and location of fibroids failed to highlight an increased risk of infertility in any group.

Limitations reasons for caution: This is a retrospective study and some inaccuracies in fibroids detection cannot be ruled out. Moreover, the relatively small sample size hampers robust subgroup analyses. Even though we excluded women with patent causes of infertility, some women with specific causes of infertility could have been included among controls (yet are expected to account for <10% of the group).

Wider implications of the findings: This study suggests that small fibroids that do not encroach the endometrial cavity do not markedly affect female fertility. This information is clinically relevant when counseling infertile women with small fibroids and an otherwise unremarkable diagnostic work-up. Surgery may still be considered but only in selected cases.

Study funding/competing interests: This study was partially funded by Italian Ministry of Health: current research IRCCS. E.S. reports grants from Ferring, grants and personal fees from Merck, and grants and personal fees from Theramex outside the submitted work. All the other authors do not have any competing interest to declare.

Trial registration number: N/A.