Ovarian tissue transplantation

Since the first live birth after transplantation of frozen-thawed ovarian tissue in 2004 (1), the number of children born worldwide using this technique has shown a slow but steady increase, becoming exponential over the past few years (2,3). 

Ovarian tissue can be transplanted to orthotopic sites, namely the pelvic cavity (back to the medulla of the ovaries or a specially created peritoneal window on the broad ligament or abdominal wall), or heterotopic sites, namely outside the pelvic cavity (subcutaneously in forearm or abdominally under rectus muscle) (4,5). Of all techniques, orthotopic transplantation has proved to be the most effective in terms of both endocrine and fertility outcomes. Part of the cryopreserved ovarian tissue is transplanted back to the pelvis, finding a well vascularized grafting site, by laparoscopy or minilaparotomy (6-8). 

Ovarian endocrine function resumes in around 90% of subjects. The mean interval between transplantation and the first menstruation is 4-5 months, which is consistent with the folliculogenesis time frame for primordial follicles to develop to the antral stage. The lifespan of further ovarian activity can be very disparate and depends on a number of factors: patient age, interpatient variability in the ovarian reserve, and exposure to gonadotoxic treatments before cryopreservation. In more than 50% of patients, it lasts for more than 5 years, showing a strong correlation with patient age at the time of tissue freezing (8).

In a recently published study of 285 transplanted patients, conception rates were similar in women conceiving naturally (40%) and through IVF (36%). Live birth rates were slightly lower in the IVF group (spontaneous: 30% vs IVF: 21%), while miscarriage rates appeared to be slightly higher (spontaneous: 10% vs IVF: 18%) (8). This difference in pregnancy chances in favor of spontaneous conception may be due to the significant decline in the ovarian follicle reserve in transplanted ovarian tissue. Indeed, women undergoing IVF after ovarian tissue transplantation show high empty follicle rates and responses to ovarian stimulation similar to poor responders (9). 

References:

1. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, Martinez-Madrid B, van Langendonckt A. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004 Oct 16-22;364(9443):1405-10.
2. Donnez J, Dolmans MM. Fertility Preservation in Women. N Engl J Med. 2017 Oct 26;377(17):1657-1665.
3. Gellert SE, Pors SE, Kristensen SG, Bay-Bjørn AM, Ernst E, Yding Andersen C. Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort. J Assist Reprod Genet. 2018 Apr;35(4):561-570.
4. Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Orthotopic and heterotopic ovarian tissue transplantation. Hum Reprod Update. 2009 Nov-Dec;15(6):649-65.
5. Gook D, Hale L, Polyakov A, Manley T, Rozen G, Stern K. Experience with transplantation of human cryopreserved ovarian tissue to a sub-peritoneal abdominal site. Hum Reprod. 2021 Aug 18;36(9):2473-2483.
6. von Wolff M, Andersen CY, Woodruff TK, Nawroth F. FertiPROTEKT, Oncofertility Consortium and the Danish Fertility-Preservation Networks – What Can We Learn From Their Experiences? Clin Med Insights Reprod Health. 2019 Apr 30;13:1179558119845865.
7. Shapira M, Dolmans MM, Silber S, Meirow D. Evaluation of ovarian tissue transplantation: results from three clinical centers. Fertil Steril 2020;114:388–97.
8. Dolmans MM, von Wolff M, Poirot C, Diaz-Garcia C, Cacciottola L, Boissel N, Liebenthron J, Pellicer A, Donnez J, Andersen CY. Transplantation of cryopreserved ovarian tissue in a series of 285 women: a review of five leading European centers. Fertil Steril. 2021 May;115(5):1102-1115.
9. Andersen ST, Pors SE, Poulsen LC, Colmorn LB, Macklon KT, Ernst E, et al. Ovarian stimulation and assisted reproductive technology outcomes in women transplanted with cryopreserved ovarian tissue: a systematic review. Fertil Steril 2019;112:908e21.