Immunomodulatory Therapy to Restore Ovarian Function and Improve Fertility in Women With Autoimmune Premature Ovarian Insufficiency

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) \-