O-227 First successful ovary allotransplants to Turner’s syndrome patients requiring immunosuppression
Authors: Silber S  J , Goldsmith S 
Published: July 2024

Abstract

Study question
To determine whether we can safely and successfully transplant an ovary tissue allograft from a non-identical donor to her Turner’s syndrome sister.

Summary answer
We report the first successful cases (with pregnancy) of ovarian tissue allotransplantation to Turners syndrome women using a safe immunosuppression protocol.

What is known already
Young women with Turner’s have been unable to have children without the use of donor egg IVF, but many Turner’s women would like to have normal hormonal function and to become pregnant naturally. Frozen ovarian cortex tissue can be successfully auto-transplanted back to women with ovarian failure and result in normal pregnancy and live birth with a success rate of 41-76%. This has never been accomplished between a non-identical donor to her Turner syndrome sister. Added benefits are hormonal function obviates the need for hormone replacement, and pregnancy can occur naturally rather than with donor egg IVF.

Study design, size, duration
1.) 20 year-old woman with non-mosaic XO Turner’s, no menses, and AMH (Anti-Mullerian hormone) of 0.015 ng/mL, whose 22 year-old sister had two children, normal menses, and an AMH of 4.97. They were HLA identical but ABO incompatible. 2.) A 21 year-old woman with non-mosaic XO Turner’s, no menses and AMH of 0.015 whose 28 year old sister had 2 children, normal menses, and AMH of 2.92. They were ABO compatible, but one HLA mismatch.

Participants/materials, setting, methods
The left ovary of the donor was removed and dissected. One third of the cortex was transplanted to the right streak ovary of the recipient and the remaining two-thirds were cryopreserved. The immunosuppression protocol consisted of methylprednisolone the morning of surgery along with anti- thymocyte globulin, and for maintenance, tacrolimus 3 mg orally BID with a target trough of 5-10 ng/mL, azathioprine 100 mg orally, and prednisone only 5 mg po daily.

Main results and the role of chance
By 168 days post-op the first Turner’s recipient was menstruating and ovulating normally with no sign of rejection. Her AMH began to rise at 168 days from 0.05 to 0.35ng/mL by 223 days, typical for a successful ovary cortical graft, and her FSH varied from 4.5 to 8.5 mIU/mL. By one year her uterus grew from infantile to that of a normal adult and she became spontaneously pregnant 10 months later and delivered a healthy baby. The donor FSH was 6.8 mIU/mL, unchanged from pre-op, she continued menstruating normally, and became spontaneously pregnant with her third child (despite having an IUD in place) by six months post op. The second Turner’s syndrome began menstruating monthly at 4 months post-op, and her AMH rose to 0.25 mg/mL as her FSH dropped to 5.3 mIU/mL. At the time of this writing she is 6.5 months post-op and continues to menstruate and ovulate normally.

Limitations, reasons for caution
There are only the first two cases and therefore at this stage, the conclusions are only a proof of concept.

Wider implications of the findings
We have demonstrated successful ovarian tissue transplantation with spontaneous pregnancy to Turner’s syndrome females using a safe immunosuppression protocol. The fact that ABO incompatibility did not cause rejection indicates that an ovary tissue graft can survive on diffusion alone. Furthermore, HLA mismatch does not preclude success with this immunosuppression protocol.

Trial registration number
not applicable