Fertility in Turner Syndrome

Ethical Considerations

The primary ethical question raised by these techniques is whether to offer intervention for fertility preservation during childhood/adolescence, and if so, which intervention, and at what stage.

Homologous IVF techniques such as ovarian tissue cryopreservation and oocyte preservation may improve the psychosocial well-being of women with TS, by increasing the chance of having a child with their own genetic complement. Offering these interventions in adolescence promotes autonomy by increasing the range of future options.^[55,76] Considerations against include concern that techniques associated with low success rates may produce false hope and later psychosocial harm; concern that risks associated with invasive retrieval of tissue are not outweighed by benefits that can reasonably be expected; concern that the offer of intervention may not actually promote autonomy, where the child with TS is not competent to make her own decision and her future choices are not represented by her parents; and concern that the young person may not comprehend maternal and foetal risks associated with any pregnancy which may ensue. In the case of ovarian tissue cryopreservation, there is a further risk of reduction in fertility by removing potentially viable tissue. Physicians must first do no harm.

If assisted reproduction is offered to young patients who have TS, consideration is required to whether this should be offered to all, or only to those where the probability of success lies above a minimum level. If there is virtually no chance of viable ovarian tissue existing based on clinical and biochemical grounds, then it would be unethical to offer intervention to preserve this tissue, which would be futile and could cause harm.

There are potential legal issues for parents and clinicians regarding the decision to remove and preserve gonadal tissue (with the inherent surgical risk and potential risk of reduction in viable gonadal tissue), on behalf of a child who is unable to consent, rendering a parent or clinician negligent. Reasons for each decision should be articulated and documented. Where tissue is removed from a minor with parental consent, the legalities of who 'owns' the tissue need to be clarified.

Table 1. Parenting options for women with Turner syndrome
Adoption	Parenting of a child who cannot be cared for by their biological parents.
Surrogacy	Planned pregnancy which is carried by another female on behalf of the woman with TS. Gametes used can be donated or the patient's own.
Heterologous IVF	Use of donated gametes to create an embryo for implantation in a pregnancy carried by the woman with TS.
Homologous IVF	Use of the patient's own gametes to create an embryo for implantation in a pregnancy carried by the woman with TS.

Table 2. Recommended contraindications to pregnancy in women with Turner syndrome
History of aortic surgery or aortic dissection
Coarctation of the aorta
Aortic size index >2·5 cm/m² or maximal aortic diameter 3·5 cm
Uncontrolled hypertension despite treatment
Portal hypertension with oesophageal varicose veins
Other major cardiac anomaly

Table 3. Assisted reproduction techniques for women with Turner syndrome
Technique	Method	Advantages	Disadvantages	Success rate
Heterologous IVF
Ovum donation and IVF-embryo transfer	Receipt of oocytes from a healthy donor, followed by IVF and fresh or frozen-thawed embryo transfer.	Rate of pregnancy loss and karyotypic abnormalities in offspring reduced. No need for invasive procedures in the child.	The TS mother is not the biological mother.	Established in adult women with TS. Pregnancy rate 17–40% per embryo transfer.
Oocyte donation and cryopreservation	If ovum donation from a relative is performed for a child, the oocytes are cryopreserved until the appropriate time for IVF and embryo transfer.	As above. Maintenance of familial genetic lineage.	Donor must have good ovarian function. Parentage confusion in resultant offspring. Risk of donor coercion.	Mother to daughter oocyte donation and preservation is being performed; however, there are no reported pregnancies in TS.
Homologous IVF
IVF and embryo transfer	Ovarian stimulation, collection of oocytes, then IVF and embryo transfer (fresh or frozen-thawed embryos).		Requires maturation of ovarian follicles. Requires sperm from partner or donor. Not appropriate in children.	An established IVF procedure for the general adult population. Most healthy embryos survive the process. A small number of pregnancies have been reported in women with TS.
Oocyte cryopreservation	Ovarian stimulation, collection of mature oocytes transvaginally and vitrification or slow freezing of oocytes.	Does not require sperm. Does not require surgery.	Requires maturation of ovarian follicles. Requires some physical and psychological maturity. May require a general anaesthetic for oocyte retrieval in adolescents. Not appropriate in prepubertal children.	Over 1000 births have been reported in the general adult population. Case reports exist of oocyte collection in young adolescents and women with TS, no pregnancies reported.
Ovarian tissue cryopreservation	Laparoscopic collection of ovarian tissue containing immature ovarian follicles, which is then cryopreserved. Some reports of in vitro maturation of follicles prior to vitrification.	Ovarian stimulation is not required preoperatively. No lower age limit.	Requires surgery. High rates of loss of oocytes in vitrification and thawing. In vitro maturation of follicles difficult.	More than thirty reported births in adult women. Experimental, but established precedent in children undergoing cancer treatment. No pregnancies in TS.

Table 3. Assisted reproduction techniques for women with Turner syndrome

Technique

Method

Advantages

Disadvantages

Success rate

Heterologous IVF

Ovum donation and IVF-embryo transfer

Receipt of oocytes from a healthy donor, followed by IVF and fresh or frozen-thawed embryo transfer.

Rate of pregnancy loss and karyotypic abnormalities in offspring reduced.
No need for invasive procedures in the child.

The TS mother is not the biological mother.

Established in adult women with TS. Pregnancy rate 17–40% per embryo transfer.

Oocyte donation and cryopreservation

If ovum donation from a relative is performed for a child, the oocytes are cryopreserved until the appropriate time for IVF and embryo transfer.

As above.
Maintenance of familial genetic lineage.

Donor must have good ovarian function.
Parentage confusion in resultant offspring.
Risk of donor coercion.

Mother to daughter oocyte donation and preservation is being performed; however, there are no reported pregnancies in TS.

Homologous IVF

IVF and embryo transfer

Ovarian stimulation, collection of oocytes, then IVF and embryo transfer (fresh or frozen-thawed embryos).

Requires maturation of ovarian follicles.
Requires sperm from partner or donor.
Not appropriate in children.

An established IVF procedure for the general adult population.
Most healthy embryos survive the process.
A small number of pregnancies have been reported in women with TS.

Oocyte cryopreservation

Ovarian stimulation, collection of mature oocytes transvaginally and vitrification or slow freezing of oocytes.

Does not require sperm.
Does not require surgery.

Requires maturation of ovarian follicles.
Requires some physical and psychological maturity.
May require a general anaesthetic for oocyte retrieval in adolescents.
Not appropriate in prepubertal children.

Over 1000 births have been reported in the general adult population.
Case reports exist of oocyte collection in young adolescents and women with TS, no pregnancies reported.

Ovarian tissue cryopreservation

Laparoscopic collection of ovarian tissue containing immature ovarian follicles, which is then cryopreserved.
Some reports of in vitro maturation of follicles prior to vitrification.

Ovarian stimulation is not required preoperatively.
No lower age limit.

Requires surgery.
High rates of loss of oocytes in vitrification and thawing.
In vitro maturation of follicles difficult.

More than thirty reported births in adult women.
Experimental, but established precedent in children undergoing cancer treatment.
No pregnancies in TS.

Table 4. Recommended criteria for consideration of ovarian cryopreservation in children and adolescents with Turner syndrome
Age 14 years and above
Spontaneous pubertal commencement
FSH <40 IU/l
AMH measurable
Normal cardiac status
Informed consent obtained from child and family: including counselling regarding mortality risk, foetal risk and absence of current success using this technology
Institutional clinical or research ethics approval, including criteria for follow-up

Fertility in Turner Syndrome

Ethical Considerations

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