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.

Risks for the Foetus

Regardless of whether conception in women with TS is spontaneous or assisted, increased rates of spontaneous abortion and foetal abnormality have been described. In a review of 160 pregnancies in 74 women with TS, 29% resulted in miscarriage, 20% were associated with foetal anomalies such as TS and Down syndrome and 7% resulted in perinatal foetal death.^[3] In a Danish study, 6 (24%) of 25 offspring of TS women had an abnormal karyotype.^[19]

Spontaneous abortion may be due to abnormalities in foetal chromosomes or to an abnormal uterine environment. The uterus may be structurally abnormal (e.g. bicornuate), small due to delayed oestrogen replacement at puberty, or endometrial receptivity may be poor due to long-term hypo-oestrogenism, which should be avoided.^[26–28] In 86 women with TS, 31% were found to have an immature uterus and 20% had not taken regular oestrogen. Uterine size was associated with history of spontaneous puberty, and duration and type of hormone replacement – oestradiol-based regimens were better than oral contraceptive-based regimens.^[28]

Approximately 22–50% of the offspring of TS women have intrauterine growth restriction, low birth weight and prematurity. These may be due to primary factors associated with the TS mother, or iatrogenic factors such as late-onset maternal oestrogen therapy and resultant small uterine size.^[3,29,30]

Anomalies of the X chromosome can be inherited. Women who have X monosomy or structural anomalies of the X chromosome may produce oocytes with the sex chromosome anomaly, resulting in an affected zygote and ensuing spontaneous abortion or offspring with TS.

In view of the risk for foetal anomalies, antenatal diagnostic testing should be offered to all pregnant TS women and the pregnancies should be regarded as high risk.

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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

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Fertility in Turner Syndrome

Risks for the Foetus

Tables

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Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

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