Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome? A multicenter study and systematic review of the literature

Abstract

STUDY QUESTION Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome (TS)? SUMMARY ANSWER The oocyte cryopreservation strategy is not well adapted for all TS women as their combination of high basal FSH with low basal AMH and low percentage of 46,XX cells in the karyotype significantly reduces the chances of freezing sufficient mature oocytes for fertility preservation. WHAT IS KNOWN ALREADY An oocyte cryopreservation strategy requiring numerous stimulation cycles is needed to preserve fertility in TS women, to compensate for the low ovarian response, the possible oocyte genetic alterations, the reduced endometrial receptivity, and the increased rate of miscarriage, observed in this specific population. The validation of reliable predictive biomarkers of ovarian response to hormonal stimulation in TS patients is necessary to help practitioners and patients choose the best-personalized fertility preservation strategy. STUDY DESIGN, SIZE, DURATION A retrospective bicentric study was performed from 1 January 2011 to 1 January 2023. Clinical and biological data from all TS women who have received from ovarian stimulation for fertility preservation were collected. A systematic review of the current literature on oocyte retrieval outcomes after ovarian stimulation in TS women was also performed (PROSPERO registration number: CRD42022362352). PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 14 TS women who had undergone ovarian stimulation for fertility preservation were included, representing the largest cohort of TS patients published to date (n = 14 patients, 24 cycles). The systematic review of the literature identified 34 additional TS patients with 47 oocyte retrieval outcomes after ovarian stimulation in 14 publications (n = 48 patients, n = 71 cycles in total). MAIN RESULTS AND THE ROLE OF CHANCE The number of cryopreserved mature oocytes on the first cycle for TS patients was low (4.0 ± 3.7). Oocyte accumulation was systematically proposed to increase fertility potential and was accepted by 50% (7/14) of patients (2.4 ± 0.5 cycles), leading to an improved total number of 10.9 ± 7.2 cryopreserved mature oocytes per patient. In the group who refused the oocyte accumulation strategy, only one patient exceeded the threshold of 10 mature cryopreserved oocytes. In contrast, 57.1% (4/7) and 42.9% (3/7) of patients who have underwent the oocyte accumulation strategy reached the threshold of 10 and 15 mature cryopreserved oocytes, respectively (OR = 8 (0.6; 107.0), P = 0.12; OR= 11 (0.5; 282.1), P = 0.13). By analyzing all the data published to date and combining it with our data (n = 48 patients, n = 71 cycles), low basal FSH and high AMH concentrations as well as a higher percentage of 46,XX cells in the karyotype were significantly associated with a higher number of cryopreserved oocytes after the first cycle. Moreover, the combination of low basal FSH concentration (<5.9 IU/l), high AMH concentration (>1.13 ng/ml), and the presence of 46,XX cells (>1%) was significantly predictive of obtaining at least six cryopreserved oocytes in the first cycle, representing objective criteria for identifying patients with real chances of preserving an adequate fertility potential by oocyte cryopreservation. LIMITATIONS, REASONS FOR CAUTION Our results should be analyzed with caution, as the optimal oocyte number needed for successful live birth in TS patients is still unknown due to the low number of reports their oocyte use in the literature to date. WIDER IMPLICATIONS OF THE FINDINGS TS patients should benefit from relevant clinical evaluation, genetic counseling and psychological support to make an informed choice regarding their fertility preservation technique, as numerous stimulation cycles would be necessary to preserve a high number of oocytes. STUDY FUNDING/COMPETING INTEREST(S) This research received no external funding. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

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

“…The median number of vitrified oocytes in the first stimulation cycle in women with TS is in line with other studies that reported a mean/median of 4-9 vitrified oocytes per cycle [13][14][15]. Compared to women who cryopreserve oocytes before the start of an oncological treatment (mean 9.5 ± 6.1 oocytes per cycle), the number of vitrified oocytes per cycle is generally lower in women with TS due to the accelerated loss of follicles at a young age [2,18].…”

“…Our results are largely consistent with previous studies that have reported on vitrification outcomes in women with TS [13][14][15]. The majority of ovarian stimulations and oocyte retrievals were performed safely, as complications only occurred after 3/69 punctures.…”

“…The majority of ovarian stimulations and oocyte retrievals were performed safely, as complications only occurred after 3/69 punctures. Similar to other studies, the mean age of women during the first stimulation cycle was 21 years [13,14]. In contrast with the study conducted by Martel et al, the number of cancelations prior to oocyte retrieval due to poor response in our group was small.…”

“…Vitrification of mature oocytes is, therefore, the most applied treatment for women with TS to preserve their fertility, but also has limitations [9,11]. Firstly, the majority of women with TS have a low ovarian reserve, and, therefore, a lower oocyte yield at oocyte retrieval is to be expected [12,13]. Secondly, the higher risk of miscarriages in women with TS necessitates more vitrified oocytes to be stored for an ongoing pregnancy compared to women in the general population [5].…”

“…Publications on vitrification of oocytes and subsequent reproductive outcomes in young girls and women with TS are currently scarce. In past years, approximately 50 cases have been reported concerning the outcomes of oocyte vitrification in girls and women with TS [13][14][15]. So far, only one case has been published, describing a woman with 45,X/46,XX TS who became pregnant by using her own vitrified oocytes [16].…”