Effect of Intrauterine Insemination on Subsequent Pregnancy Outcomes in Couples With Unexplained Pregnancy Loss: A Multicenter, Open-label, Randomized Controlled Trial

Unexplained pregnancy loss remains a major reproductive challenge, and effective management strategies for affected couples are limited. Although intrauterine insemination (IUI) is widely used in reproductive medicine, its effectiveness in improving subsequent pregnancy outcomes among couples with unexplained pregnancy loss has not been well established. This multicenter, open-label, randomized controlled trial aims to evaluate whether IUI improves subsequent pregnancy outcomes compared with natural conception in couples with unexplained pregnancy loss. A total of 558 eligible couples will be enrolled and randomly assigned to either an IUI group or a natural conception group. Participants will be followed to assess reproductive outcomes. The findings of this study are expected to provide high-quality evidence regarding the role of IUI in the management of unexplained pregnancy loss and to inform future clinical practice.

Inclusion Criteria: * Female participants aged 20-37 years. * History of at least one ultrasound-confirmed pregnancy loss (excluding biochemical pregnancy, ectopic pregnancy, and hydatidiform mole), with the most recent pregnancy loss occurring within the previous 12 months. * Desire for pregnancy at the time of enrollment. * Basal follicle-stimulating hormone (FSH) \1.1 ng/mL. * Male partner's semen analysis meeting the criteria for intrauterine insemination (IUI), with a post-processing total progressive motile sperm count ≥5 × 10⁶. * Ability and willingness to provide written informed consent. Exclusion Criteria: * Congenital or acquired uterine structural abnormalities. * Thyroid dysfunction, defined as thyroid-stimulating hormone (TSH) \>4.0 mIU/L. * Positive antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein I antibodies. * Parental chromosomal abnormalities or a history of fetal chromosomal abnormalities in a previous pregnancy. * Participation in another interventional clinical trial during the study period.