To characterize the age of ovarian failure in Turner Syndrome (TS) patients by karyotype.
Retrospective cohort study of individuals with TS at an academic university hospital. Subjects were seen in TS Clinic at UNC Hospital between 2014 and 2018. Individuals were analyzed by karyotype category (45X, 45X/46XX mosaicism, miscellaneous) and percentage of 45X cells. Age at follicle-stimulating hormone> 30 was defined as the age at loss of ovarian function.
A total of 79 patients were identified after excluding individuals with unknown ovarian function and those with Y chromosome material. Thirty-eight percent were 45X monosomic, 62% were 45X/46XX mosaic or miscellaneous karyotypes. Fifty-five of 79 (70%) patients had evidence of ovarian failure, median age of failure 11 years (IQR: 4,12). Ovarian failure was more prevalent among individuals with 45X karyotype (100%). The median age of ovarian failure for 45X patients (n=30) was 10 years old, which is significantly younger than other karyotypes (n=49), with a median of 15 years, p<0.01. Linear regression analysis found that 1 percentage point increase in 45X cells in the peripheral karyotype is associated with a 0.09 year decrease in age of ovarian failure (p value=0.01). Only 9% of individuals were referred for fertility counseling.
There is a lower prevalence of ovarian failure among individuals with mosaic TS karyotypes, and referral rate for fertility counseling of patients with TS is low. These findings are in line with published literature. The finding that percentage of 45X cells in peripheral karyotype is associated with earlier age of ovarian failure is novel and warrants further investigation in a larger prospective cohort.
Research funding: None declared.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: This is a retrospective cohort study approved by the University of North Carolina Institutional Review Board (Study No. 18-1568). Primary data for human nor for animals were not collected for this research work.
1. Oktay, K, Bedoschi, G, Berkowitz, K, Bronson, R, Kashani, B, McGovern, P, et al.. Fertility preservation in females with Turner syndrome: a comprehensive review and practical guidelines. J Pediatr Adolesc Gynecol 2016;29:409–16. Search in Google Scholar
2. Zhong, Q, Layman, LC. Genetic considerations in the patient with Turner syndrome—45,X with or without mosaicism. Fertil Steril 2012;98:775–9. Search in Google Scholar
3. Colindres, J. A multidisciplinary approach to puberty and fertility in girls with Turner syndrome. Pediatr Endocrinol Rev 2016;14:33–47. Search in Google Scholar
4. El-Shawarby, SA, Sharif, F, Conway, G, Serhal, P, Davies, M. Oocyte cryopreservation after controlled ovarian hyperstimulation in mosaic Turner syndrome: another fertility preservation option in a dedicated UK clinic. BJOG An Int J Obstet Gynaecol 2009;117:234–7. Search in Google Scholar
5. Huang, JYJ, Tulandi, T, Holzer, H, Lau, NM, MacDonald, S, Tan, SL, et al.. Cryopreservation of ovarian tissue and in vitro matured oocytes in a female with mosaic Turner syndrome: case Report. Hum Reprod 2008;23:336–9. Search in Google Scholar
6. H Gravholt, C, Andersen, NH, Conway, GS, O, Dekkers, Geffner, ME, et al.. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol 2017;177:G1–70. Search in Google Scholar
7. Akira, I, Satoko, O, Goto, M, Tomohiko, M, Nakamura, T, Sachiko, T, et al.. Clinical application of serum anti-Müllerian hormone as an ovarian reserve marker: a review of recent studies. J Obstet Gynaecol Res 2018;44:998–1006. Search in Google Scholar
8. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015;103:e9–17. Search in Google Scholar
9. SAa, L, Aksglaede, L, Anderson, RA, Main, KM, Juul, A, Hagen, CP, et al.. AMH as predictor of premature ovarian insufficiency: a longitudinal study of 120 Turner syndrome patients. J Clin Endocrinol Metab 2015;100:E1030–8. Search in Google Scholar
10. Messina, MF, Aversa, T, Salzano, G, Costanzo, D, Sferlazzas, C, Mirabelli, S, et al.. Inhibin B in adolescents and young adults with Turner syndrome. J Pediatr Endocrinol Metab 2015;28:1209–14. Search in Google Scholar
11. Gravholt, CH, Naeraa, RW, Andersson, A-M, Christiansen, JS, Skakkebaek, NE. Inhibin A and B in adolescents and young adults with Turner’s syndrome and no sign of spontaneous puberty. Hum Reprod Oxf Engl 2002;17:2049–53. Search in Google Scholar
12. Grynberg, M, Bidet, M, Benard, J, Poulain, M, Sonigo, C, Cédrin-Durnerin, I, et al.. Fertility preservation in Turner syndrome. Fertil Steril 2016;105:13–9. Search in Google Scholar
13. Pasquino, AM, Passeri, F, Pucarelli, I, Segni, M, Municchi, G. Spontaneous pubertal development in Turner’s syndrome*. J Clin Endocrinol Metab 1997;82:1810–3. Search in Google Scholar
14. Sutton, EJ, McInerney-Leo, A, Bondy, CA, Gollust, SE, King, D, Biesecker, B. Turner syndrome: four challenges across the lifespan. Am J Med Genet 2005;139A:57–66. Search in Google Scholar
15. Talaulikar, VS, Conway, GS, Pimblett, A, Davies, MC. Outcome of ovarian stimulation for oocyte cryopreservation in women with Turner syndrome. Fertil Steril 2019;111:505–9. Search in Google Scholar
16. Morgan, TL, Kapa, HM, Crerand, CE, Kremen, J, Tishelman, A, Davis, S, et al.. Fertility counseling and preservation discussions for females with Turner syndrome in pediatric centers: practice patterns and predictors. Fertil Steril 2019;112:740-8. https://doi.org/10.1016/j.fertnstert.2019.05.010. Search in Google Scholar
17. Peek, R, Schleedoorn, M, Smeets, D, van de Zande, G, Groenman, F, Braat, D, et al.. Ovarian follicles of young patients with Turner’s syndrome contain normal oocytes but monosomic 45,X granulosa cells. Hum Reprod 2019;34:1686–96. Search in Google Scholar
The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2020-0304).
© 2021 Walter de Gruyter GmbH, Berlin/Boston