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Turner syndrome and Fertility

Clare Boothroyd


Queensland Endocrine Group 3 August 2012



Turner syndrome

Spontaneous conception and fetal outcome

Oocyte donation

Risks of pregnancy – mother, obstetric outcomes

Assessing and preserving fertility


Ovarian cortex cryopreservation

Oocyte storage

Embryo storage

Disclosures and Acknowledgements

Gratuities from Merck Serono, MSD and Ramsay Health

Medical Director and shareholder of Assisted Conception Australia

Thanks to Seema Mohiuddin, CREI trainee, IVF Australia who shared slides and literature review

Spontaneous conception in TS

Spontaneous conception lifelong:

<5%( Hovatta 1999 )

40% (Bryman Fertil Steril Jun 2011)

8% (Birkebaek Clinical Genetics, Jan. 2002)

Bryman, Sweden, large number of 45X0/46XX


Spontaneous puberty in TS

8-10% 45XO have spontaneous puberty

16% in Italian series of TS – 40% if 45XO/46XX mosaic (Pasquino J Clin Endocrinol Metab 1997)

Oocyte reserve in TS

Accelerated atresia in utero

Reduced total number at birth

Ongoing accelerated atresia

Spontaneous puberty in TS

8-10% 45XO have spontaneous puberty

16% in Italian series of TS – 40% if 45XO/46XX mosaic (Pasquino J Clin Endocrinol Metab 1997)

This group have higher initial oocyte reserve and/or reduced rate of atresia and therefore chance of spontaneous conception and option of fertility preservation

Spontaneous conception and fetal outcome

Dewhurst 1978 J Med Genetics

Elsheikh et al 2002 Endocrine Reviews


Clinical recommendations

“Never say never”

Contraception if absolutely no wish for pregnancy

Estimate chance according to spontaneous menstrual function and karyotype

0.5% to 40%

High chance of miscarriage, chromosomal abnormality and reduced chance of normal baby but normal babies are born spontaneously to women with TS ~40%

Turner syndrome and Oocyte donation

Oocyte donation

Commonest means of achieving a pregnancy with TS

First reported in Melbourne (Lutjen et al Nature 1984)

Chance of success relates primarily to age of oocyte donor

Usually known donor, related family member or friend, undergoes IVF cycle, occasionally altruistic donation

500 babies per year born by this method in ANZ

No legislation in Queensland


Reproductive outcome and risks to TS mother having a pregnancy

Miscarriage after oocyte donation

Reported as high as 40% in mid 90s (Press Fertil Steril 1995, Yaron Fertil Steril 1996, Khastgir Hum Reprod 1997)

Hypothesised that uterine hypoplasia, bicornuate uteri ?related to GH deficiency

Recent reports not validated high miscarriage rate


Obstetric outcome in 93 pregnancies in women with TS using donated oocytes


Obstetric outcome in 101 pregnancies in women with TS using donated oocytes


Recommendations from Practice Committee of the ASRM -Fertil Steril 2008

Risk of aortic root dissection and rupture 2% in pregnancy and risk of death ?100 fold.

Cardiology consultation and screening at initial diagnosis and yearly cardiac assessment and BP.

MRI if cardiac echo abnormal or aortic root not well visualised.

Cardiology consultation if any abnormality detected


Contraindications to pregnancy in TS

1.Aortic root dilatation >4cm, any significant abnormality on echocardiography.   ASRM-2008

2.H/o aortic surgery or aortic dissection, aortic dilatation with the largest aortic diameter above 25mm/m2 or 35mm, coarctation of aorta, uncontrolled HTN despite treatment and portal HTN with oesophageal varicose veins- French College of O&G, Cabanese et al 2010.



Recommendations for Turner syndrome women prior to pregnancy (ASRM 2008)

Counselling regarding the risks with pregnancy

Preconception cardiac screening and regular cardiac evaluation at intervals.

Turner syndrome- relative contraindication for pregnancy/Absolute contraindication with positive cardiac evaluation.

Single embryo transfer

Clinical recommendations

Cardiac assessment mandatory before use of donated oocytes

Information : all deaths reported in women with coarctation, aortic root dilatation, some before pregnancy, some during or immediately after pregnancy

Assessment of glucose tolerance and hypothyroidism also mandatory and should be treated

Early pregnancy desirable (“reproductive life plan”)



Assessment of fertility and preservation of fertility in TS

Anti Mullerian Hormone (AMH)

Parallels the number of antral and preantral follicles in the ovary

Can be taken at any time of the menstrual cycle including during oral contraceptive use

?Prob need some FSH ie lower in hypogonadotrophic hypogonadism and COC use

Not currently funded by Medicare

Very useful investigation in fertility assessment

Predicts the number of follicles from an IVF cycle

Inferior to maternal age in predicting live birth



Ovarian cortex cryopreservation

Developed as research, fertility preservation for women about to undertake chemotherapy

~20 babies born worldwide to women having autotransplantation of cryopreserved ovary after successful treatment for malignancy

Ovarian cortex cryopreservation

Variable techniques

Donnez et al, two laparoscopies one week apart with minced thawed cortex inserted to vascular peritoneal pocket in pelvic side wall (Demeesteere Hum Reprod 2006)

Allograft of ovary from monozygous twin 46XX to 45XO, live birth age 37 Donnez Fert Ster 2011

Clinical recommendations
Ovarian cortex cryopreservation

Still research

Appropriate to consider in some girls with TS

spontaneous puberty

?falling AMH

able to understand pros and cons

able to understand uncertainty

HREC involvement

Other options for fertility

Mother cryopreservation of oocytes 1-3% chance of live birth (if mother aged <34)

Parental cryopreservation of embryos 16-20% chance of live birth

Uterine surrogacy arrangements



Conclusion Should TS women be offered ART ?

Increased risk of death from AD

But absolute risk is low particularly after appropriate cardiac screening

Oocyte donation is successful treatment

Majority of pregnancies if managed as high risk will have good maternal and neonatal outcome


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