Several autoimmune diseases such as Addison's disease are associated with failing ovarian function, known as premature ovarian insufficiency (POI), which can lead to early menopause and reduced fertility.The underlying cause of POI in these women is considered to be an immunological attack on the ovaries that causes them to not respond to hormonal stimulation from the brain. Hormone replacement effectively counteracts menopausal symptoms, but today there is no treatment to normalize or even improve fertility. As a patient with POI and an autoimmune diagnosis and the desire to become pregnant, you are asked to participate in the study. The aim of this study is to investigate whether immunomodulatory therapy can improve and ideally normalize ovarian function in women of childbearing age with autoimmune disease and proven POI. Patients with a male partner and a desire for children and who respond positively to the first ovarian stimulation will be offered in vitro fertilization (IVF) and will thus be allowed to complete the study. Other participating patients will undergo a total of three ovarian stimulations and treatment with first two infusions of the registered drug rituximab or placebo (inactive agent) and later two additional infusions where all patients receive rituximab. The first two infusions with rituximab or placebo are double-blind, which means that neither you nor the study staff know what you have received. Follow-up takes place up to 12 months after the last infusion.

Inclusion Criteria:

1. The subject has given their written consent to participate in the trial
2. Autoimmune POI (FSH > 25 IU/L) including the presence of oligo/amenorrhea lasting at least 4 months, and elevated FSH levels (FSH > 25 IU/L) confirmed on two separate occasions, with measurements taken at least 4 weeks apart and Addison's disease or ab positivity for 21-hydroxylase or other relevant autoantibodies (SCC, 17-OH, NALP5)
3. 18-38 years of age
4. Body mass index between 19-30
5. Willing to use effective non-hormonal contraceptive (such as intra uterine device (IUD), sexual abstinence, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide) method during the 18-month study period

Exclusion Criteria:

1. Hypersensitivity to rituximab, any of the AxMPs, or any of the excipients (as detailed in the SmPC for the various IMPs)

2. Active, severe infection or JCV positivity

3. Active hepatitis B infection

4. Severe immunosuppression

5. Severe cardiac disease

6. Cancer

7. Benign tumours of the hypothalamus, pituitary, or ovarian pathology

8. Vaginal bleeding of unknown etiology

9. Hormone replacement therapy within four weeks prior study entry

10. Pregnant or lactating women

11. Concurrent treatment with other immunosuppressive drugs

12. Any vaccination within 4 weeks of infusion of study medication

13. Severe psychiatric disorder

14. Any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with rituximab or controlled ovarian hyperstimulation

15. Active thrombolic disorder (contraindicated for Ovirelle)

16. Moderate or severe impairment of kidney or liver function (contraindicated for Orgalutran)

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