Reproductive Outcomes of Women with Turner Syndrome Undergoing Oocyte Vitrification: A Retrospective Multicenter Cohort Study

Abstract

Background: Turner syndrome (TS) is accompanied with premature ovarian insufficiency. Oocyte vitrification is an established method to preserve fertility. However, data on the oocyte yield in women with TS who vitrify their oocytes and the return rate to utilize the oocytes are scarce.

Methods: Retrospective multicenter cohort study. Data was collected from medical records of women with TS who started oocyte vitrification between 2010 and 2021.

Results: Thirty-three women were included. The median cumulative number of vitrified oocytes was 20 per woman. Complications occurred in 4% of the cycles. Significant correlations were found between the cumulative number of vitrified oocytes and AMH (r = 0.54 and p < 0.01), AFC (r = 0.49 and p < 0.01), percentage of 46,XX cells (r = 0.49 and p < 0.01), and FSH (r = -0.65 and p < 0.01). Spontaneous (n = 8) and IVF (n = 2) pregnancies occurred in 10 women ± three years after vitrification. So far, none of the women have returned to utilize their vitrified oocytes.

Conclusions: Oocyte vitrification is a feasible fertility preservation option for women with TS, particularly in those with 46,XX cell lines or sufficient ovarian reserve. Multiple stimulation cycles are recommended to reach an adequate number of vitrified oocytes for pregnancy. It is too early to draw conclusions about the utilization of vitrified oocytes in women with TS.

Keywords: Turner syndrome; fertility preservation; oocyte vitrification; pregnancy.

Figure 1

Overview of ovarian stimulation cycles and oocyte retrieval in 33 women with TS. LP = long protocol, using GnRH agonist with recombinant FSH or human menopausal gonadotropin or urofollitropin. SP = short protocol, using GnRH antagonist with recombinant FSH or human menopausal gonadotropin or urofollitropin. FU = flare up protocol, using GnRH agonist with recombinant FSH or human menopausal gonadotropin or urofollitropin. LH = luteinizing hormone.

Figure 2

AMH levels and number of vitrified oocytes. Baseline AMH levels and the number of vitrified oocytes after the first stimulation cycle (A) and cumulative number of vitrified oocytes (B) of 26 women with TS are presented. In most women, AMH < 1 µg/L corresponded with ≤5 vitrified oocytes in the first cycle and <10 vitrified oocytes in total. The number of vitrified oocytes varied widely in women with an AMH ≥1 µg/L. Green dots represent women with a 46,XX cell line, blue dots represent women with structural aberrations, and orange dots represent women with 45,X/47,XXX karyotype. Stimulations that were cancelled are indicated with *.

Figure 3

Number of vitrified oocytes per stimulation cycle and karyotype. An overview of 75 stimulation cycles of 33 women with TS is presented. Dark blue bars represent the number of vitrified oocytes after the first cycle, light blue bars after the second cycle, grey bar after the third cycle, and black bars after the fourth cycle. X indicates that no oocytes were vitrified.

Figure 4

Cumulative number of vitrified oocytes and percentage of 46,XX cells. An overview of the total number of vitrified oocytes of 33 women with TS and the percentage of 46,XX cells in lymphocytes or buccal cells are presented. Mainly women with >20% 46,XX cells had cumulatively ≥20 vitrified oocytes. Remarkably, some patients without 46,XX cell line were able to vitrify ≥20 oocytes. Green dots represent women with a 46,XX cell line, blue dots represent women with structural aberrations, and orange dots represent women with 45,X/47,XXX karyotype. Percentages of 46,XX cell line in buccal cells are indicated with *.