Fertility in Turner Syndrome

Assisted Reproduction

Assisted reproduction techniques have offered women with TS the opportunity for childbearing, with varying rates of complications and success [Table 3, and reviewed in Ref.^[43]]. In a Swedish cohort of 482 women with TS, 12% achieved pregnancy, of which 40% were spontaneous, 60% with assisted reproduction and of these 53% used oocyte donation.^[17] In 276 women in the US, 1·4% achieved pregnancy with assisted reproduction, all with oocyte donation.^[7]

Heterologous in Vitro Fertilization (Oocyte Donation)

Oocyte donation from either related or nonrelated women was until recently the only reproductive option for women with TS who experience ovarian failure, with this technique showing some success. While initial pregnancy rates (determined by human chorionic gonadotropin level) may be comparable with the rest of the population utilizing in vitro fertilization (IVF) technologies, successful clinical pregnancy rates (visualization of a gestation sac) are lower than for women who undergo oocyte donation for other reasons: 17–40% vs 73%.^{[27,29–31,44,45]} A review of 23 women with TS following ovum donation in Belgium reported a miscarriage rate of 44% and take home baby rate of 18% per transfer.^[30] In a Swedish cohort of 30 women following oocyte donation, 26% of clinical pregnancies ended in miscarriage, much lower than the miscarriage rate of 45% using the patient's own gametes.^[17] Donated oocytes can also be cryopreserved for future use using the methods which will be described for homologous IVF.

Heterologous ovarian tissue transplantation is a method which has not yet been reported in women with TS; however, it has shown success in providing fertility to approximately 30 women worldwide.^[43]

Homologous in Vitro Fertilization (Patient's Own Gametes)

Patients with TS are often counselled against homologous IVF due to poor success rates and risk of chromosomal aberrations in the offspring.^[3] Most adult women with TS already have established ovarian failure with a high serum follicle stimulating hormone (FSH) level at the time they wish to start a family, although this does not indicate absolute absence of viable follicles.^[46]

Types of homologous IVF include oocyte collection for immediate IVF and embryo transfer, or various methods of fertility preservation (cryopreservation of individual mature oocytes, cryopreservation of ovarian tissue containing immature primordial follicles, or cryopreservation of embryos) for possible future use in an individual with actual or expected decline in ovarian function. While immediate IVF and embryo transfer has been used successfully in TS, harvesting of oocytes or ovarian tissue for storage in girls and women with TS remains experimental, despite an increasing body of literature.^[17,47]

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

Assisted Reproduction

Heterologous in Vitro Fertilization (Oocyte Donation)

Homologous in Vitro Fertilization (Patient's Own Gametes)

Tables

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

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