Immunotherapy with Rituximab May Temporarily Restore Fertility in Autoimmune Premature Ovarian Insufficiency
Key Insights
A proof-of-concept study found that rituximab immunotherapy enabled follicle development in six of ten women with autoimmune premature ovarian insufficiency (search) who previously did not respond to ovarian stimulation.
Three women later gave birth to healthy babies after embryo transfer, with all responders also having autoimmune Addison's disease (search).
The study, led by Karolinska Institutet, was small and uncontrolled; larger randomized trials are now underway to confirm efficacy and safety.
A pilot study from Karolinska Institutet has demonstrated that the immunotherapy drug rituximab may temporarily restore ovarian responsiveness in women with autoimmune premature ovarian insufficiency (search) (POI), enabling egg retrieval and, in three cases, successful pregnancies resulting in healthy births.
The proof-of-concept study, which included twelve women aged 18 to 35 with autoimmune POI, examined whether suppressing the autoimmune process could reactivate residual egg reserves. Two participants withdrew before treatment began. The remaining ten underwent ovarian hormone stimulation before receiving rituximab and again four to six months after treatment.
Treatment Response and Outcomes
Before treatment with rituximab, none of the women responded to ovarian stimulation. After treatment, six out of ten women developed follicles that made it possible to retrieve eggs. In five women, mature eggs could be frozen or fertilised. Three later had embryos transferred, and all three gave birth to healthy babies. For safety reasons, embryo transfer took place no earlier than one year after treatment.
"The results show that in some women there remains an egg reserve that can be activated when the autoimmune process is suppressed," said Professor Angelica Lindén Hirschberg, the study's first author and professor at Karolinska Institutet's Department of Women's and Children's Health.
One serious side effect was reported and was linked to the hormone stimulation rather than the immunotherapy itself.
Autoimmune Link and Addison's Disease
Women with autoimmune POI commonly have other autoimmune diseases. Notably, all six women who responded to the treatment also had autoimmune Addison's disease (search), a condition in which the immune system destroys the adrenal glands. This association may provide clues for identifying which patients are most likely to benefit from the approach.
Study Limitations and Next Steps
The study was a proof-of-concept investigation without a control group and involved a small number of participants, meaning the findings must be interpreted cautiously. "This is a first step. To determine whether the method is effective and safe, larger, randomised studies are required," said Professor Lindén Hirschberg. The research team has now launched such a study.
Clinical Context
Premature ovarian insufficiency (search) affects just over three per cent of women worldwide and occurs when the ovaries stop functioning before the age of 40. The condition significantly reduces fertility and can have several causes, including autoimmune processes and genetics. POI is also linked to long-term health risks caused by oestrogen deficiency, including osteoporosis, an increased risk of cardiovascular disease, cognitive decline and poorer mental and sexual wellbeing.
Hormone replacement therapy can relieve menopausal symptoms and reduce many of these risks, but no treatment has been reliably shown to restore fertility in women with POI. Egg donation was previously the only option for women with the condition who wanted to become pregnant.
Rituximab is an approved and well-established medicine used to treat several autoimmune conditions and cancers.
The study was conducted in collaboration with researchers at Karolinska Institutet, Karolinska University Hospital and the University of Bergen. It was funded by organisations including the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation and Region Stockholm. The researchers reported no conflicts of interest.