P–504 A randomised controlled trial comparing expectant management or intrauterine-insemination in couples with unexplained subfertility and a poor prognosis for natural conception: the impact on health-related-quality-of-life
Authors: Mol F , Wessel J , Verhoeve H A , Maas J , Bruin J P D , Louwe L , Cantineau A , Mochtar M , Va. Wely M 
Published: August 2021

Abstract

Study question
Is health-related quality of life (HRQoL) in women with unexplained subfertility and a poor prognosis influenced by expectant management or intrauterine insemination with ovarian stimulation?

Summary answer
HRQoL did not differ, except for the relational domain which was lower after expectant management. Anxiety and depression disorders occurred frequently in both groups.

What is known already
In couples with unexplained subfertility and a poor prognosis, IUI with ovarian stimulation (IUI-OS) is a first line treatment. Not much is known about quality of live or depression and anxiety in these couples. The Fertility Quality of Life (FertiQoL) is reliable for assessment within relational and social domains, the Hospital Anxiety and Depression Scale (HADS) is a reliable tool to detect anxiety and depression disorders.

Study design, size, duration
We performed a multicentre RCT in couples with unexplained subfertility with a poor prognosis of conceiving naturally within one year. Women were allocated 1:1 to six months expectant management or to six months IUI-OS. HRQoL was assessed with standard self-administered psychometric measures with established reliability and validity: FertiQol and HADS. We intended to include 1091 couples but after almost 4 years, the study had to stop due to slow inclusion and therefore lack of funding.

Participants/materials, setting, methods
Between June 2017 and September 2020, we recruited 178 women of wich 92 were assigned expectant management and 86 IUI-OS. All women who participated and could read Dutch were eligible for the HRQoL measurements because HRQoL questionnaires in foreign languages were not yet available online. Women completed the questionnaires before randomisation, 3 and 6 months after randomisation. We used mixed model analyses to assess differences between treatment groups and the effect of time.

Main results and the role of chance
One hundred sixty-two women could read Dutch and were invited (162/178 (91%)). Analyzable data of the FertiQol questionnaire were available for 80% (130/162). Compared to women allocated to IUI-OS, women allocated to expectant management had a lower FertiQol score in the relational domain (mean difference –4.3 (95% CI –7.3 to –1.3) but not in the social domain (mean diff van –0.8 (95% CI –4.5 to 2.9).
Data of the HADS questionnaire were available of 156 women (96% (156/162)). Both groups had comparable scores in the Anxiety (mean difference –0.20; 95% CI 0.63; –0.99 to 0.6) and Depressions score (mean difference 0.002; 95% CI –0.67 to 0.67) at all three moments. At baseline, the incidence of an anxiety disorder (definition score 8 or higher) was 19% (30/156) and increased to 30% and 29% at 3 months and 6 months respectively. The incidence of a depression disorder (definition score 8 or higher) was 5% (7/156) and increased to 16% and 18% at 3 months and 6 months respectively. The incidences of anxiety or depression disorders did not differ significantly between expectant management and IUI.

Limitations, reasons for caution
Our randomized controlled trial did not reach the planned sample size. The results are only applicable to women with unexplained subfertility and a poor prognosis and not to all women with unexplained subfertility.
Wider implications of the findings: Although often assumed, IUI-OS does not improve HRQoL compared to expectant management in all domains. IUI might prevent loss of quality of the relationship, but the impact seems small. Future studies should look into the high incidence of anxiety and depression disorders in these women and how to support them.

Trial registration number
Trial register NL5455 (NTR5599)