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Recurrent Pregnancy Loss April 2001 Welcome This case discussion examines the approach to a couple with the distressing problem of recurrent miscarriage (three or more consecutive miscarriages. A rational approach to investigation together with sensitive and realistic counselling about prognosis are essential to counter the emotional misinformation surrounding this condition. Initial Presentation Janine and Peter are both in their mid-twenties. Since deciding to start a family 18 months ago, Janine has been able to conceive three times. But on each occasion a "missed abortion" was diagnosed and confirmed after dilatation and curettage. Both Janine and Peter have been very well throughout their lives and they have a healthy lifestyle. Janine has a regular 28 day menstrual cycle and her general and pelvic examination is normal. Consultant Comment Although miscarriage is a common complication of pregnancy, occurring in up to 30% of all diagnosed pregnancies, when it recurs it results in major distress, frustration and loss of security for the couple. Clear information about recurrent pregnancy loss and a well organised plan of investigation support are essential. Because of the frequency of miscarriage and because isolated episodes are usually without identifiable cause, it is not recommended that single episodes are investigated. General support and justified optimism about future pregnancy is the best approach. Recurring pregnancy loss is defined when there are three consecutive miscarriages, this occurs in up to 2% of all fertile women. Loss of the pregnancy before 8 weeks of gestation is the commonest type of miscarriage. Very early loss before 6 weeks ("pre-embryonic" or "blighted ovum") may be diagnosed after a transient rise of bHCG and a late period. It is probably due to failed development and limited implantation of the early embryo. Pregnancy loss between 6-8 weeks ("embryonic" or "missed abortion") is usually diagnosed after a suboptimal sequential rise in bHCG and an absence of a fetal heart on vaginal ultrasound after 6 weeks of gestation. It is due to abnormal or failed embryonic development after implantation. After 8 weeks of gestation, a fetal heart is normally visible on ultrasound and 95% of such pregnancies will continue to term. Miscarriage after this time ("fetal loss") may be due to a number of maternal or embryonic abnormalities (see Causes and associations of recurrent pregnancy loss). Our understanding of the causes of recurrent pregnancy loss is improving but many couples will not have an explanation even after extensive investigation. The chance of finding a defined abnormality in Janine and Peter's situation is probably less than 30%. Recent evidence suggests that many early embryonic losses are due to chromosomal abnormalities in the implanting embryo. Single cell biopsies from embryos produced by couples with recurring pregnancy loss have a tenfold greater incidence of aneuploidy (usually monosomy rather than trisomy). This might indicate "premature ageing" of oocytes. Causes (and associations) of recurrent pregnancy loss Pre-embryonic and embryonic: Idiopathic Embryonic chromosomal aneuploidy Luteal phase abnormalities Parental chromosomal abnormality Fetal: Antiphospholipid syndrome Structural uterine abnormalities cervical weakness bicornuate uterus
Bacterial vaginosis Familial thrombophilia Protein S deficiency Protein C deficiency Hyperhomocystinaemia Activated Protein C resistance (Factor V v Leiden mutation)
Janine and Peter were interviewed. Review of Janine's menstrual cycle confirmed that it was less than 35 days in duration and therefore the luteal phase was likely to be normal. Using the Brigham table (Table 1), an optimistic prediction about a future successful pregnancy could be given. They decide that they would like some limited investigations after which they would discuss future management. Results of Investigations Karyotypes - normal for both partners Consultant Comment Embryonic loss occurs more commonly in women who have cycles longer than 35 days. This may imply abnormality in the luteal phase support of an early pregnancy or an intrinsic abnormality in the response of the endometrium to oestrogen and/or progesterone. The antiphospholipid syndrome may be associated with early pregnancy loss, late intrauterine deaths or premature birth. Specific haematological tests for a lupus anticoagulant can be performed, if indicated. Minor uterine abnormalities may co-exist without pregnancy loss. Vaginal ultrasound, hysterography or diagnostic hysteroscopy can detect a bicornuate or subseptate uterus and allow assessment of cervical length and patency. Other tests for vaginal infection and inherited thrombophilia are associated with late pregnancy loss and are not indicated for Janine. Some investigations have suggested endometrial biopsy to identify a hostile population of leucocytes which are present more often in women with recurrent pregnancy loss. At present, this remains an experimental hypothesis. Similarly there is limited evidence that hyperprolactinaemia, endometriosis or immunological incompatibility between partners is of pathophysiological importance in recurring pregnancy loss. It is important to avoid empirical treatments. These couples are desperate and may accept any treatment. Treatment should be evidence based. Janine and Peter were interviewed again and their results were discussed. They decide that they would continue their effort with pregnancy and accept the likelihood that they have experienced a chance repetition of three unrelated miscarriages, most likely due to embryonic genetic abnormalities. They discuss options to support them during the first trimester of their next pregnancy. Consultant Comment bHCG levels increase at a predictable rate with increasing gestational age (Fig 1). Some couples are comforted to know that bHCG is increasing normally in the first few weeks of pregnancy. A reasonable monitoring might be a weekly sample for three weeks after diagnosis followed by a vaginal scan to detect a fetal heart.
Table 1: Predicted probability of a successful pregnancy occurring subsequently following miscarriage:
References Bricker L & Farquharson RG (2000) Recurring miscarriage. The Obstetrician and Gynaecologist 2: 17-23 More Information FMC Social Work Department: Ph 8204 4144  PRINT THIS PAGE
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