Fertility in Turner Syndrome

Abstract and Introduction

Abstract

There is increasing interest in fertility and use of assisted reproductive technologies for women with Turner syndrome (TS). Current parenting options include adoption, surrogacy, and spontaneous and assisted reproduction. For women with TS, specific risks of pregnancy include higher than usual rates of spontaneous abortion, foetal anomaly, maternal morbidity and mortality. Heterologous fertility assistance using oocytes from related or unrelated donors is an established technique for women with TS. Homologous fertility preservation includes cryopreservation of the patient's own gametes prior to the progressive ovarian atresia known to occur: preserving either mature oocytes or ovarian tissue containing primordial follicles. Mature oocyte cryopreservation requires ovarian stimulation and can be performed only in postpubertal individuals, when few women with TS have viable oocytes. Ovarian tissue cryopreservation, however, can be performed in younger girls prior to ovarian atresia – over 30 pregnancies have resulted using this technique, however, none in women with TS. We recommend consideration of homologous fertility preservation techniques in children only within specialized centres, with informed consent using protocols approved by a research or clinical ethics board. It is essential that further research is performed to improve maternal and foetal outcomes for women with TS.

Introduction

Advances in reproductive medicine increasingly offer the possibility of childbearing to women who have declining ovarian function. These new techniques are being considered for young women who have Turner syndrome (TS), in whom accelerated oocyte atresia usually leads to ovarian failure before childbearing age. While patients' expectations rise with technical advances, there are associated issues regarding safety and ethical use in a younger TS population. In adult women with TS, pregnancy is associated with increased risk of maternal mortality, foetal loss, foetal congenital abnormality and abnormal karyotype.^[1–3] Success rates are low for many invasive reproductive techniques, and newer technologies such as ovarian cryopreservation are presently considered experimental.

Specialists involved in the care of individuals with TS face a range of important considerations. Adult reproductive endocrinologists involved in fertility assistance have relatively recently begun to appreciate the mortality risk to the TS mother that pregnancy may entail.^[2,4] Assisted reproduction techniques possible in children prior to the decline of ovarian reserve, such as ovarian tissue cryopreservation, require paediatric surgery. Ethical challenges relating to consent and beneficence thus arise for the paediatric endocrinologist and gynaecologist. During any pregnancy that eventuates, obstetricians and cardiologists must be prepared for life-threatening complications.

These concerns must be balanced against the fact that TS women report infertility to be one of the greatest challenges they face.^[5] Young women and their parents are often intensely interested in future fertility options. While women with TS enjoy a good quality of life, infertility is significantly associated with poor self-esteem and psychosocial adjustment, and demands discussion with empathy and sensitivity.^[6] A review of 276 women with TS in the US found that 9·1% chose to adopt children and 3·2% had spontaneous or assisted pregnancies; however, 87·7% of this cohort had no children.^[7]

This clinical practice update will discuss fertility in TS, pregnancy risks, the reproductive technologies in current use, and associated ethical issues. It will not cover parenting choices such as adoption and surrogacy, but recommends that these need to be considered in view of the pregnancy risks and fertility outcomes in TS (Table 1).

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

Abstract and Introduction

Abstract

Introduction

Tables

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

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