Turner Syndrome

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Turner syndrome is defined as the presence of characteristics physical features, coupled with complete or partial absence of the second sex chromosome, occurring in 1/2000 to 1/2500 live-born females. The partial loss of the x chromosome is often associated with cell line mosaicism (1). 

The age of diagnosis is highly variable.  The presence of a 45,X0 karyotype is often diagnosed  before the age of 12 months, due to the presence of typical clinical features, but yet around 50% of subjects receive a diagnosis during their adolescence, when they experience primary amenorrhea (2). 

Premature ovarian insufficiency is one of the main concerns for subjects with Turner syndrome. The vast majority (> 90%) are infertile due to gonadal dysfunction caused by germ cell loss during the fetal and early postnatal life (3). This results in streak gonads from childhood with primary amenorrhea. Those who have their menarche are at high risk of premature insufficiency and stop their menstrual function by the age of 30 years in the majority of cases. 

The natural history of this condition leaves with a short but yet present window of time and opportunity for fertility preservation. 

Mature oocyte cryopreservation by vitrification has been documented in numerous postpubertal patient (4-6). Among these cases, only two patients had complete 45,X0 monosomy, while the rest had mosaic Turner syndrome in the karyotype of lymphocytes. Yields of mature oocytes appear to be lower in these patients than in an age-matched population, decreasing the chances of further fertility restoration with this approach. Moreover, this option is limited to postpubertal subjects. Ovarian tissue cryopreservation can be proposed in both women and children with Turner syndrome (7,8). Indeed, recent publications evidenced the presence of early-stage follicles in more than 60% of the ovarian biopsies retrieved in young girls with Turner syndrome.  However, the ovarian follicle pool appears to carry higher rates of morphological abnormalities (9). Karyotyping of ovarian cells in small follicles of from young subjects with mosaic Turner syndrome revealed high levels of aneuploidy in granulosa cells, possibly causing an impairment in follicle development. Nevertheless, the majority of oocytes showed normal X chromosome content, highlighting the opportunity of cryopreserving ovarian tissue with a real potential of restoring fertility (10). 

References:

  1. Bondy C. Turner syndrome: update on current therapies. Expert Rev Endocrinol Metab. 2007 May;2(3):359-366.
  2. Lee MC, Conway GS. Turner’s syndrome: challenges of late diagnosis. Lancet Diabetes Endocrinol. 2014 Apr;2(4):333-338.
  3. Abir R, Oron G, Shufaro Y. Fertility in patients with Turner syndrome. Fertil Steril. 2020 Jul;114(1):73-74.
  4. Oktay K, Bedoschi G. Oocyte cryopreservation for fertility preservation in postpubertal female children at risk for premature ovarian failure due to accelerated follicle loss in Turner syndrome or cancer treatments. J Pediatr Adolesc Gynecol. 2014 Dec;27(6):342-6.
  5. Talaulikar VS, Conway GS, Pimblett A, Davies MC. Outcome of ovarian stimulation for oocyte cryopreservation in women with Turner syndrome. Fertil Steril. 2019 Mar;111(3):505-509.
  6. Vergier J, Bottin P, Saias J, Reynaud R, Guillemain C, Courbiere B. Fertility preservation in Turner syndrome: Karyotype does not predict ovarian response to stimulation. Clin Endocrinol (Oxf). 2019 Nov;91(5):646-651.
  7. Huang JY, Tulandi T, Holzer H, Lau NM, Macdonald S, Tan SL, Chian RC. Cryopreservation of ovarian tissue and in vitro matured oocytes in a female with mosaic Turner syndrome: Case Report. Hum Reprod. 2008 Feb;23(2):336-9. 
  8. Schleedoorn M, van der Velden J, Braat D, Beerendonk I, van Golde R, Peek R, Fleischer K. Turner Fertility trial: PROTOCOL for an observational cohort study to describe the efficacy of ovarian tissue cryopreservation for fertility preservation in females with Turner syndrome. BMJ Open. 2019 Dec 11;9(12):e030855.  
  9. Mamsen LS, Charkiewicz K, Anderson RA, Telfer EE, McLaughlin M, Kelsey TW, et al. Characterization of follicles in girls and young women with Turner syndrome who underwent ovarian tissue cryopreservation. Fertil Steril. 2019 Jun;111(6):1217-1225.e3.
  10. 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 Sep 29;34(9):1686-1696.

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