To investigate whether treatment with oral corticosteroids and intravenous immunoglobulin (IVIg) improves pregnancy outcomes in women with unexplained recurrent pregnancy loss (RPL) following assisted reproduction technology (ART) treatment.

A randomised, double-blinded, parallel-group, placebo-controlled trial conducted from January 2021 to February 2024.

A single-centre trial at a Danish tertiary clinic for RPL management.

80 women with at least two consecutive early pregnancy losses following ART, age 18–41 years, body mass index below 35, and no identified cause of RPL. Forty participants were allocated to each group, with 37 fulfilling the protocol criteria in each group.

Participants were randomised to receive either a combination of low-dose oral prednisolone starting on the first day of menstruation and IVIg given the first time around the time of embryo transfer; or matching placebo tablets and albumin infusions. Treatment continued until gestational week 8+4 in those who conceived with a total of four infusions.

The primary outcomes were the ongoing pregnancy rate (OPR) defined as a living fetus in gestational week 13 among all randomised participants and in those who conceived after embryo transfer, respectively, based on intention-to-treat (ITT) and per-protocol (PP) analyses. Secondary outcomes included safety outcomes related to pregnancy complications and neonatal health.

OPR was equal to live birth rate. Among all randomised participants (ITT), the OPR was 25.0% in the treatment group and 15.0% in the placebo group (relative risk 1.67; 95% CI 0.67 to 4.15; p=0.26). Among participants without major protocol deviations (PP), OPRs were 21.6% and 16.2%, respectively (relative risk 1.33; 95% CI 0.51 to 3.47; p=0.55). Among participants who became pregnant following embryo transfer, ongoing pregnancy occurred in 83.3% of the treatment group and 42.9% of the placebo group (relative risk 1.94; 95% CI 1.01 to 3.75; p=0.05). No differences in adverse events or neonatal outcomes were observed between the two groups.

The combination of oral corticosteroids and IVIg did not improve overall pregnancy rates in women with RPL after ART. However, among those who achieved pregnancy after embryo transfer, the risk of pregnancy loss appeared reduced. Larger randomised trials are needed to confirm these findings.

ClinicalTrials.Gov: NCT04701034. Registration date: 5 January 2021

EudraCT number: 2020-000256-35; Registration date: 11 November 2020

The North Denmark Region Committee on Health Research Ethics: N-20200066, Registration date: 16 December 2020

The Data Protection Agency: 2020-156; Registration date: 4 November 2020

WHO universal trial number: U1111-1273-8585

Date of first patient’s enrolment: 28 January 2021.