SUN-156 - Reversal of Autoimmune Premature Ovarian Insufficiency by Low Dose Triple Immunosuppression; Report of Two Cases

Background
Premature Ovarian Insufficiency (POI) is the cessation of menses due to ovarian failure in females before the age of 40. In 20-30% of cases, it is autoimmune in nature and frequently associates other autoimmune endocrinopathies, commonly thyroid disease. To date no treatment had been authorized to restore fertility in affected females. We hereby report our experience with two cases in whom low dose triple immunosuppression was successful in recovering ovarian function.
Subjects
Two young ladies with autoimmune thyroid disease and POI were referred to our clinic for endocrine assessment. Both were below the age of 30 with amenorrhea of more than 4 months and FSH>25 mIU/ml (measured on two occasions separated by more than one month apart). Patient 1, aged 27, was first seen in November 2019 and had Graves’ Disease while Patient 2, aged 23, presented to our clinic in March 2023 and had Hashimoto Thyroiditis. They were keen to restore their capacity to conceive, and were thus offered a course of immunosuppression, based on the presence of anti-thyroid antibodies. The risks and benefits of immunosuppression were explained in detail and they both accepted. The immunosuppressive regimen was initially started by Prednisolone (0.25 mg/kg/day), Azathioprine (2 mg/kg/day) and Cyclosporin A (2 mg/kg/day).
Results
Menstrual cycles were resumed by the third month of treatment in both cases. Patient 1 demonstrated improvement in FSH level (from 27 to 13 mIU/mL) and in the following month conceived spontaneously. Immunosuppression was discontinued before 8 weeks of gestation and the pregnancy was completed uneventfully. She delivered a full-term healthy baby. Patient 2 maintained regular cycles with normalization of FSH level (from 57 to 6.3 mIU/mL) and improvement of AMH (from 0.94 to 1.53 ng/mL). She was able to perform two sessions of Ova collection and cryopreservation. Over 3 months of treatment in patient 1, and 32 months in patient 2, the treatment was well tolerated; blood counts, liver and kidney functions remained unaffected. Patient 1 weaned her baby after 6 months then developed amenorrhea and thyrotoxicosis again one year later. This time she opted not to receive immunosuppression, and went into menopause at age 30 years (FSH 43 mIU/mL). Patient 2 opted to continue immunosuppression till she gets married hoping to conceive naturally. As of November 2025, she still receives Prednisolone 5 mg/day, azathioprine 50 mg /day and cyclosporin A 25 mg twice daily and enjoys regular cycles with no reported or observed side effects, and her latest AMH measures 1.59 ng/ml.
Conclusion
We conclude that POI as part of autoimmune endocrinopathy, can be managed with prudent immunosuppression with the aim of salvaging ovarian function. Early diagnosis in the presence of viable ovarian reserve is necessary for the success of the treatment. To this end, low dose triple immunosuppression was safe and effective.

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