Immunotherapy may temporarily restore fertility in premature menopause

Immunotherapy may temporarily restore fertility in women with autoimmune premature ovarian insufficiency, a pilot study suggests.

Three of the 10 women who received treatment later gave birth to healthy babies.

Premature ovarian insufficiency, or POI, 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.

Researchers at Karolinska Institutet examined whether immunotherapy could make the ovaries temporarily responsive to hormonal stimulation in women with POI caused by autoimmunity.

The study included 12 women aged between 18 and 35 with autoimmune POI.

Two withdrew before treatment began. The remaining 10 underwent ovarian hormone stimulation before receiving rituximab and again four to six months after treatment.

Rituximab is an approved and well-established medicine used to treat several autoimmune conditions and cancers.

None of the women responded to ovarian stimulation before receiving the drug.

After treatment, six developed follicles that made it possible to retrieve eggs in response to ovarian stimulation.

Follicles are small sacs within the ovaries where eggs develop.

Professor Angelica Lindén Hirschberg, the study’s first author and a professor at Karolinska Institutet’s Department of Women’s and Children’s Health, said: “The results show that in some women there remains an egg reserve that can be activated when the autoimmune process is suppressed.”

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, the embryo transfers took place no earlier than one year after treatment.

One serious side effect was reported and was linked to the hormone stimulation rather than the immunotherapy.

Women with autoimmune POI commonly have other autoimmune diseases.

All six women who responded to the treatment also had autoimmune Addison’s disease, a condition in which the immune system destroys the adrenal glands.

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.

A proof-of-concept study is an early investigation designed to assess whether an approach could work before it is tested more widely.

Professor Lindén Hirschberg said: “This is a first step. To determine whether the method is effective and safe, larger, randomised studies are required.”

The research team has launched a larger randomised study.

The work was carried out by 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.

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.