Turner Syndrome

 

Detailed information and a list of references can be found in Chapter 2.8 of the FertiPROTEKT book, "Indications and fertility preservation methods for oncological and non-oncological disorders", which can be downloaded free of charge.

Turner syndrome is a genetic disorder (inherited disease) in which there is a loss of an X chromosome or a limitation of its function. Women with Turner syndrome often have smaller stature and malformations of the kidneys, heart and major blood vessels. The latter may be the cause of a life-threatening tear in the aorta (aortic dissection and aortic rupture).

Women with Turner syndrome have a reduced number and quality of oocytes. The consequence of this is that fertility is often very limited at an early stage.  The severity of Turner syndrome depends on the genetic diagnostic findings. Patients, in whom not all cells are affected (mosaic form), have a less pronounced appearance.

 

risks of a pregnancy in turner syndrome patients

Pregnancy in women with Turner syndrome is associated with increased risks for the mother and child. This must be considered when considering fertility preservation.

+ Obstetric risks for mother and child

The risk of life-threatening rupture of the aorta (aortic dissection and aortic rupture) is significantly increased during pregnancy in patients with Turner syndrome. The event itself and the timing cannot be predicted. Risk factors, in addition to high blood pressure which commonly occurs in Turner syndrome, are diseases of the blood vessels and heart. The risk of a woman with Turner syndrome dying in pregnancy as a result of a tear in the aorta is 2%. It is therefore 150 times higher than in healthy pregnant women.

During pregnancy, women with Turner syndrome also have a greatly increased risk of hypertension. Severe complications occur in more than half these cases: pre-eclampsia, eclampsia and HELLP syndrome. The risk of gestational diabetes and an underactive thyroid are also increased.

+ Infant chromosomal abnormalities and miscarriages

In the few cases where women with Turner syndrome become pregnant with their own eggs, there is an increased risk of miscarriage or faulty genes (chromosomal abnormalities). This also applies to women with Turner syndrome who become pregnant with donor eggs. The possibility of prenatal diagnosis should be discussed due to the increased risk.

 

Approach if fertility preservation is considered 

Investigation, risk counselling and monitoring

Every woman with Turner syndrome who is considering a pregnancy should be informed in detail about the risks. This counselling should be carried out by:Jede Frau mit Turner-Syndrom, die eine Schwangerschaft in Betracht zieht, muss eingehend über die Risiken aufgeklärt werden. Diese Aufklärung sollte erfolgen durch:

  • a cardiologist (a specialist in congenital heart disease)
  • a prenatal specialist and obstetrician from a specialized centre
  • a human geneticist.

The patient should be monitored closely for additional risk factors and pre-existing diseases before the final decision about a pregnancy is made. During pregnancy, close monitoring by a team of experts in a specialist centre is necessary.

Estimation of the ovarian reserve

If a pregnancy is possible in principle, the choice of fertility preservation method in Turner syndrome patients depends on the individual ovarian reserve. Factors that indicate the presence of egg cells are shown in the following table. Complex measures such as the freezing of ovarian tissue or eggs should be justified by the simultaneous presence of several of these predictive factors.

+ Predictive factors for the presence of egg cells in turner syndrome patients

  • Mosaic Turner syndrome
  • Normal FSH level
  • Normal AMH level
  • Spontaneous onset of puberty
  • Spontaneous onset of menstrual bleeding (menarche)
  • Normal antral follicle count, AFC

 

Fertility preservation methods

+ egg cell donation with or without surrogacy

For a woman with Turner syndrome, egg cell donation is a way of reducing the risk of faulty genetic material. If she carries the pregnancy herself, the obstetric risk, including cardiovascular risk, remains. In this respect, an egg donation with surrogacy is considered as safer alternative outside Germany in Turner syndrome patients.

Egg donation is prohibited in Germany!

+ Fertility protection in the true sense: freezing of egg cells (oocyte cryopreservation) and ovarian tissue (ovary cryopreservation)

If the patient wishes to retain her own fertility, then her age is considered an important criterion. It enables better assessment of the individual capacity for pregnancy, so that an active approach can be considered, especially in patients from 14 to 16 years of age. Active measures are not usually used before this. On the other hand, it should be considered whether freezing of ovarian tissue in very young girls who still have a favourable egg cell reserve is justifiable and reasonable. After 14 to 16 years of age, more elaborate measures of fertility preservation such as cryopreservation of eggs or ovarian tissue should be carried out, taking into account the AMH value, the cycle regularity and presence of other favourable predictive factors.

Despite the possible solutions, Turner syndrome is not only a difficult situation for fertility preservation in reproductive medicine. Realistically, techniques using own egg cells are possibility, especially for patients with Turner’s mosaisicm. Turner syndrome also means a high risk of illness with potentially life-threatening consequences for a pregnant woman. Therefore it is very important that the patient receives balanced, clear and open information about this complex situation. Turner’s syndrome is considered by the American professional society, ASRM, as a reason to advise against pregnancy and to recommended surrogacy instead.