Reproductive health in Turner syndrome: A narrative review

Abstract

Turner syndrome (TS), a common chromosomal abnormality affecting females, is associated with partial or complete loss of the second sex chromosome. Although the classic karyotype is 45, X, the detection of mosaic TS is increasing. TS is a multisystem disorder with significant endocrine, cardiovascular and reproductive impacts. Accelerated ovarian follicular loss leads to primary amenorrhoea or premature ovarian insufficiency and infertility. Early diagnosis and counselling regarding hormone replacement therapy and future reproductive capacity, including fertility preservation, are essential to improve reproductive outcomes. Pubertal induction or estrogen replacement is usually required to optimise long-term health outcomes; however, initiation may be delayed due to delayed diagnosis. Spontaneous pregnancy occurs in a small number of women; however, many require donor oocytes and assisted reproductive technology to achieve a pregnancy. Pregnancy is a high risk especially when associated with congenital heart disease. Prepregnancy counselling by the multidisciplinary team (MDT) to identify contraindications and optimise pre-existing health issues is essential. Pregnancy management should be led by a maternal-fetal medicine unit with input from the MDT. This review examines reproductive health outcomes in women with TS and how best to manage them to reduce health risks and improve maternal and neonatal outcomes. Key points What's already known:� Reproductive consequences of Turner syndrome include primary amenorrhoea, premature ovarian insufficiency and infertility.� Delayed diagnosis impacts Hormone Replacement Therapy initiation therefore increasing morbidity.� Pregnancy in Turner syndrome, usually requiring assisted reproductive technology, is high risk due to multiple co-morbidities. What's new?� The first report of a live birth using cryopreserved oocytes in a woman with Turner syndrome was published in 2022. This advance highlights the importance of early consideration of fertility preservation options for individuals with Turner syndrome, including cryopreservation of ovarian tissue and prepubertal oocyte freezing.

Unique Challenges of NIPT for Sex Chromosome Aneuploidy

“…Fetal diagnosis for 45,X (or from cord blood prompted by a high-risk NIPT for SCA) opens avenues for earlier intervention. This extends to the recent work and success in both early oocyte freezing and ovarian tissue freezing for future fertility in the 45,X individual without underlying cardiac concerns 8 …”

“…Advances in pubertal induction and hormone replacement have been actively pursued in girls with a prepubertal diagnosis of 45,X. 8 The "typical" phenotype of 45,X is variable and has generally been based on individuals evaluated as children or adults who presented with one of the classic findings. When assessed from a fetal standpoint, even further variability in the phenotype for X chromosome disorders is noted.…”

“…This extends to the recent work and success in both early oocyte freezing and ovarian tissue freezing for future fertility in the 45,X individual without underlying cardiac concerns. 8…”

“…With bilateral ovarian dysgenesis, small stature is expected as well as amenorrhea and infertility. Advances in pubertal induction and hormone replacement have been actively pursued in girls with a prepubertal diagnosis of 45,X 8 . The “typical” phenotype of 45,X is variable and has generally been based on individuals evaluated as children or adults who presented with one of the classic findings.…”

Prenatal screening and diagnosis of sex chromosome conditions: The new normal?

“…One addresses the most common SCAs, 14 and the other focusses specifically on 47,XXY 15 . A third review paper on reproductive outcomes for individuals with Turner syndrome highlights the progress made in reproductive care and provides up to date information for both fertility and prenatal counseling 16 …”