 |
 |
 |
|
 |
|||
 |
 |
||
| |
|
|
|
| |
|
|
|
| |
|||
| |
|
||
| |
|
|
|
 |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Premature Ovarian Failure April 2002 Initial Presentation Mary who is 35 years old, consulted her general practitioner because of post-pill amenorrhoea. Her menstruation had commenced at the age of 14 and had been regular until she commenced the pill at age 20. Over the next 10 years, she experienced regular withdrawal bleeding on the pill and her periods returned during several breaks off the pill. Six months ago she and her partner Alex decided to start a family, but after stopping the pill, Mary became amenorrhoeic. She has been irritable, stressed and had some trouble sleeping, which she has attributed to work pressures. She exercises at the gym twice a week, has a normal diet and is of normal weight. Initial investigations are as follows:
Consultant Comment Mary's history and her investigations suggest premature ovarian failure which has evolved whilst she has been taking the pill and which has now become evident since cessation of the pill. Ovarian failure can be due to a number of causes (see table 1), but once serum FSH is raised, the number of oocytes remaining in the ovary is markedly reduced, probably to less than 1,000. A raised serum FSH also indicates a higher prevalence of chromosomal aberrations in these remaining oocytes which will reduce fertilisation and embryo development. Ovarian failure can be intermittent over one or two years with hormone levels returning to normal as a cohort of oocytes develop. Occasional pregnancies may occur spontaneously. If surviving oocytes are protected from high levels of FSH by reinstituting the pill, they may develop in a coordinated way by ceasing the pill. Mary's doctor arranged for some further blood tests for her and a semen analysis was ordered for Alex. Despite the poor prognosis for fertility, the coupled decided that they would like to pursue the options available and were referred for further advice. Further investigations
Consultant Comment The raised serum TSH and thyroid autoantibodies suggest an underlying autoimmune thyroiditis causing reduced thyroid reserve. Since this may progress to hypothyroidism, a replacement dosage of thyroxine should be prescribed. The relevance of this finding is that autoimmune oophoritis may be associated with other autoimmune conditions and therefore represents a possible cause of ovarian failure. A family history of early menopause or infertility occurs in up to 30% of cases and specific chromosomal abnormalities have been described involving the X chromosome including variant forms of Turner's syndrome and the Fragile X syndrome. Visible chromosome abnormalities are reported in 5-30% of cases, including deletions, translocations, inversions in the X-chromosome and XXX karyotype. The Fragile X syndrome is the most common inherited cause of intellectual disability, affecting 1 in 4,000 males in the community. Approximately 1 in 300 women are carriers for this condition which increases the risk of premature ovarian failure by 20 fold. Identification of this abnormality is important to other members of the family. If they carry this abnormality then they are also at risk of premature ovarian failure and of having a child affected by Fragile X Syndrome. The sperm test is of marginal quality (low count). The result needs repeating and a clearer attempt to establish a cause (see Newsletter 2). Alex requires proper clinical examination. If the abnormalities are consistent then ICSI may be preferred to IVF. If Alex and Mary are to proceed with assisted reproduction then a volunteer egg donor will be required. Occasionally such donors volunteer spontaneously, but more usually a close relative or friend agrees to assist. Clearly, there are important ethical and social issues involved and both the donating and recipient couples require individual counselling sessions. Other requirements of a potential donor are: Age less than 35 years Non-commercial arrangement Does not involve intergenerational donation from a close relative (ie daughter, niece, mother aunt) Free of known genetic disease Clear consent from all individuals involved Agreement to be known as a donor to the children To have completed own family As in all assisted reproduction, treatment cannot be given if there are significant reservations about potential harm that may be imposed on the child to be born (SA Reproductive Technology Act 1988). Following further extensive discussions and consideration of the options available, Mary and Alex decided to proceed with an overseas adoption. Mary was commenced on hormone replacement treatment with combined oestrogen and progesterone and a program of medical surveillance was instituted. Causes of premature ovarian failure Chromosomal X associated Turner's syndrome Turner's mosaic Fragile X syndrome Other X linked conditions Non-X chromosomes Autoimmune oophoritis Drugs and radiation Cyclophosphamide Chemotherapy Galactosaemia Idiopathic  PRINT THIS PAGE
|
