Fertility in Turner Syndrome

Jacqueline K. Hewitt; Yasmin Jayasinghe; David J. Amor; Lynn H. Gillam; Garry L. Warne; Sonia Grover; Margaret R. Zacharin

Disclosures

Clin Endocrinol. 2013;79(5):606-614.

Conclusion

The availability of reproductive technologies promises potential for fertility preservation in young women with TS; however, we await reports addressing whether preserved gametes can lead to the much-wanted safe and successful pregnancies. In the interim, some of these technologies raise new dilemmas for paediatric clinicians. In the majority of girls with TS, there is a narrow window of opportunity to discuss interventions such as cryopreservation of ovarian tissue or oocytes. Families may view this with a degree of urgency. However, ovarian tissue cryopreservation itself remains experimental, no pregnancies have been reported in women with TS, and the risks of pregnancy to the TS mother are great.

While the medical community has made significant gains in reproductive technology, it is clear that greater effort is required to assist counselling of both young women with TS and their families regarding future fertility options. Focus should be on improved coordination between health disciplines, efforts to keep abreast of current reproductive technologies, transparent communication regarding expectations and potential risks of pregnancy, and stringent transition of care to practitioners familiar with the risks involved.

Until evidence of any benefit from earlier intervention exists, we agree with the recommendation that invasive techniques be considered at the age where a child with TS has some understanding of the underlying indication.^[46] At this stage, invasive fertility preservation treatment should be considered only in specialized centres with approved institutional protocols. This could occur via the institutional clinical research or clinical ethics boards, to enable a thorough review of the risks and expected outcomes in each case.

We look forward to further research into outcomes of assisted reproduction in women with TS, particularly for autologous cryopreserved gametes. Of equal importance, we call for further evaluation of the cardiac risks of pregnancy in women with TS, stringent auditing and publication of all pregnancy outcomes, and strategies to address associated morbidity and mortality. Physicians may then be better placed to provide assistance to achieve the much-wanted pregnancies without causing harm.

1 2 3 4 5 6 7 8

Next Section

Disclosure statement
The authors have nothing to declare.

Acknowledgements
JH is supported through a National Health and Medical Research Council Postgraduate Scholarship (APP607439), along with funding from the Royal Australasian College of Physicians and the Australasian Paediatric Endocrine Group. Authors from the Murdoch Childrens Research Institute are supported by the Victorian Government Operational Infrastructure Support Program. The authors would like to thank Dr Patricia Moore for her assistance with the preparation of this manuscript.

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.

IVF, in vitro fertilization.

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 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

processing....

Fertility in Turner Syndrome

Conclusion

Tables

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

Email This

Feedback