Immunotherapy enabled 3 births in women with early menopause, pilot study finds

A pilot study from Karolinska Institutet has demonstrated that immunotherapy with rituximab can temporarily restore egg maturation in women with autoimmune premature ovarian insufficiency, a condition that typically leads to permanent infertility. Three of ten women treated in the study gave birth to healthy babies, marking the first time immunomodulatory therapy has achieved successful pregnancies in this patient population.

A First in Reproductive Medicine

The study, published June 23 in NEJM Evidence, enrolled ten women with autoimmune POI — a condition in which the immune system attacks the ovaries, causing them to stop functioning prematurely. Before treatment with rituximab, a B-cell depleting monoclonal antibody, none of the women responded to ovarian stimulation. After treatment, six of the ten developed follicles that allowed egg retrieval, and three subsequently gave birth to healthy babies following embryo transfer.miragenews+3

"This is a first step. To determine whether the method is effective and safe, larger, randomised studies are required," said Angelica Lindén Hirschberg, professor at Karolinska Institutet's Department of Women's and Children's Health, who led the research.via.tt+1

How the Treatment Works

POI affects an estimated 3.5 percent of women and currently offers no fertility treatment beyond egg donation. The researchers hypothesized that depleting B cells with rituximab could reverse autoimmune activity against the ovaries, enhancing their responsiveness to gonadotropin stimulation. All responders in the earlier phase of research had autoimmune Addison's disease, suggesting the approach may be most effective in specific autoimmune subtypes.pmc.ncbi.nlm.nih+3

The study was a proof-of-concept trial without a control group, which the authors acknowledge limits the conclusions that can be drawn.miragenews

Larger Randomized Trial Underway

A follow-up randomized, double-blind, placebo-controlled trial is already recruiting patients at multiple sites to determine whether the method is truly effective and safe. That study will include placebo-controlled infusions followed by open-label rituximab treatment for all participants, with follow-up extending 12 months after the final infusion. An accompanying editorial in NEJM Evidence expressed hope the pilot results would lead to a much larger confirmatory trial.evidence.nejm+2