Fertility restoration

Infertility not only results in the loss of reproductive function but has numerous psychological sequalae and is associated with significant long-term emotional burden. There is one group of women whose infertility was traditionally believed to be unconditional and absolute: those with absolute uterine factor infertility (AUFI). Whereas not absolute in nature, a major cause of subfertility, is the consequence to the physiological deterioration of ovarian reserve and oocyte quality that is associated with advancing age. This thesis summarises a series of interrelated studies which contribute significantly to the eventual aim of achieving fertility restoration in these groups. Study 1 details extensive analysis of >200 women with AUFI who are interested in potentially undergoing uterine transplantation (UTx), which represents the largest study of its kind globally to date. It highlights important insights into the screening process of women with AUFI who desire to undergo the UTx, including their perceptions toward UTx and alternative options to acquire motherhood. Moreover, comprehensive pre-operative clinical, biochemical, radiological and psychological evaluation of the women selected to proceed with UTx is detailed, to allow comprehensive insight into this cohort. Study 2 demonstrates novel insight into the motivation of women who wish to altruistically donate their uterus and highlights high levels of acceptability after becoming aware of the risks and expected recovery. Despite the significant associated risks and lengthy recovery process, women who donate their uterus expect to gain psychological and emotional benefit by enabling another woman to bear a child themselves. However, despite desire and motivation to donate, the selection criteria currently implemented universally reduce the number of potential donors significantly. Study 3 presents novel data from 186 male to female (M2F) transgender women that clearly highlights a desire to experience physiological experiences that are unique to women, such as menstruation and gestation, as well as potentially having a physiologically functioning transplanted vagina. The findings suggest transgender women believe the potential benefits of UTx outweigh the significant risks with which it is associated and may improve quality of life, happiness and dysphoric symptoms while enhancing feelings of femininity. This chapter also describes a series of feasibility studies including the demonstration of a technique to undertake transgender UTx in the rabbit model. The final study on fertility restoration in AUFI introduces the concept of endometrial transplantation (ETx), including initial pilot studies that helped develop the initial surgical technique, as well as a short-term viability study, in endometrial autotransplantation. This study represents the first ETx trial undertaken globally, and demonstrated gross and microscopic evidence of viable endometrium following endometrial autotransplantation, along with the achievement of clinical pregnancies. Finally, this thesis presents a detailed account of the prospect of elective oocyte cryopreservation, which currently represents an option to restore reproductive potential in women with age related reproductive decline. Novel insight is demonstrated into the perceptions of such women, having undergone the process, including quantitative analysis of how it impacts quality of life. Detailed outcomes of stimulation cycles are also presented, including new perspectives on markers of oocyte yield in such populations and reproductive outcomes including the attainment of livebirths.