Higher Pregnancy Success Rates in Patients with Diminished Ovarian Reserve < 40 Years When Initially Treated by Intrauterine Insemination with Mild Ovarian Stimulation Compared to In Vitro Fertilization Alone: A Pilot Study

For women with idiopathic diminished ovarian reserve (DOR), direct start with IVF has been suggested to potentially shorten the time to pregnancy. Others however prefer intra-uterine insemination with ovarian stimulation (IUI + OS) due to the expected low response in IVF. In this pilot study, we determined the effect of these two strategies in women with DOR < 40 years. From a retrospective cohort, we included 135 women that met the diagnostic criteria of DOR. Patients were randomly referred to two different outpatient clinics in the Netherlands between 2012-2018 because of subfertility. Primary outcome was clinical pregnancy; secondary outcomes included ongoing pregnancies, live births, time to pregnancy and pregnancy-related complications. An instrumental variable analysis was used to assess the average effect of treatment with IUI + OS followed by IVF (protocol A) compared to IVF alone (protocol B) and correct for (unknown) confounders. Treatment protocol A was performed in 72.6% patients in Centre 1 and 30.6% in Centre 2. In Centre 1 61.6% (45/73) women had a clinical pregnancy compared to 41.9% (26/62) in Centre 2 (difference 19.7% (95% CI 3.1%-36.3%), p = 0.02). Early miscarriage occurred in 24% of the women in Centre 1 in comparison to 45% of the women in Centre 2. There were no significant differences in pregnancy-related complications. This pilot study suggests that women < 40 with DOR, if treated with IUI + OS followed by IVF, have higher estimated cumulative clinical pregnancy success, with a trend towards higher ongoing pregnancies and live births, in comparison to women treated with IVF alone.