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Repeated or late miscarriage When to investigate and what to look
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Repeated or late miscarriage: When to investigate and what to look for
Miscarriage and chance The chance of Table 4: Tests used in miscarriage
THE chance of miscarriage
increases steadily and miscarriage TEST WHY IT IS DONE OR WHAT IT IS LOOKING FOR
strongly with age (table 2). recurring is 1. Women, on presentation, at any time of the ovarian (or menstrual) cycle
Women using no contracep- otherwise higher FBC, blood group and agglutinins, serum General medical health
tion seem to pass from
normal fertility through a
if the woman has creatinine, LFTs
Thyroid function tests Mild hyperthyroidism is more prone to cause infertility and miscarriage than mild
phase when conceptions mis- not previously hypothyroidism
carry, often with normal had a live birth. Antinuclear antibody, anticardiolipin antibody, Screening for the antiphospholipid syndrome, either primary or secondary to SLE
karyotypes, before physio- lupus inhibitor
logical sterility sets in (for Serum gliadin antibodies (IgG, IgA) and Asymptomatic coeliac disease is an occasional (though not unequivocal) cause of
most women about a decade transglutaminase (or endomysial) antibodies unexplained infertility or recurrent miscarriage
before menopause). Fasting plasma glucose Preclinical diabetes; if raised, check fasting plasma insulin and test for PCOS
The chance of miscarriage Serum free testosterone, or free androgen index Screen for PCOS; confirm with day 7-8 vaginal ultrasound (see below)
recurring is otherwise higher Anti-TjA antibody (anti-PP1Pk) Uncommon but well-described cause of up to 13 first trimester miscarriages; a
if the woman has not previ- haemolysin, and not necessarily revealed by a blood group and agglutinin screen
ously had a live birth (table Serum copper and caeruloplasmin Wilson’s disease, a rare copper storage disorder, can present this way in young
3). It is also higher after a products of conception with recurrent miscarriage women
chromosomally normal mis- (preferably all recovered Thrombophilia screen (haematological) Test for protein S, protein C and activated protein C resistance. Not Medicare
carriage than after an aneu- tissue should be sent in rebateable without a history of a thrombotic event
ploid or polyploid miscar- normal saline to the specialist Thrombophilia PCR panel Test for factor V Leiden, MTHFR C677T and A1298C, prothrombin G20210A
riage. Many causes of pathology lab for dissection Karyotype, peripheral blood, both partners Balanced chromosomal translocation in either partner
subfertility also increase the under magnification to
risk of miscarriage when recover trophoblast from Male partner
pregnancy does occur. what will be abundant mater- Karyotype, peripheral blood As above
Most miscarriages happen nal decidua). A specialist lab- Sperm count, preferably with morphology Brings the male partner into the management. Look for a high rate of head or
before 12 weeks. Miscar- oratory can also perform his- assessment using "strict criteria" mid-piece defects. May be necessary to repeat test in acknowledged infertility lab
riages should therefore be tological examination of the Sperm chromatin structure assay Index of sperm head DNA damage (double stranded breaks)
investigated if: placental site, including lym-
■ Two or more miscarriages phocyte immunocytochem- 2. Woman, day 2 of menstrual period or cycle
occur without a live birth istry to identify T cell and Serum FSH, LH, oestradiol (E2) Reduced egg numbers: serum FSH >11 U/L
in a woman younger than NK cell subtypes. PCOS: possible if LH:FSH (U/L) >2:1
30 (recurrent miscar- In either case, E2 >200pmol/L = more severe
riage). Causes of miscarriage In either case, correlate with day 7-8 ultrasound
■ Miscarriage complicates and the tests that can be
infertility, especially in done before the next 3. Woman, day 7-8 of menstrual cycle (or estimated one week before ovulation)
older women. pregnancy Transvaginal ultrasound for uterine abnormalities … Normal endometrium is >5mm thick and echolucent (thick echogenic endometrium
■ A late miscarriage occurs Some tests can be done at means hyperplasia or polyp; thin echogenic, maybe endometritis)
(>14 weeks’ gestation). any time of the ovarian or Look for fibroids distorting the cavity, for uterine septum or bicornuate uterus
If a miscarriage is menstrual cycle, while others … and to characterise the ovaries Follicles present in the ovary indicate the typical egg number achievable: many
inevitable in one of these should be timed carefully. peripheral follicles indicate PCOS; few follicles may indicate premenopause
patients, a karyotype should Table 4 details available Vaginal culture Vaginosis — either Gardnerella vaginalis or other organismal overgrowth with loss
be performed on the fresh tests. of lactobacillus
Hysterosalpingogram Unilateral hydrosalpinx or intrauterine adhesions. Consider test if
■ Previous difficult appendicectomy, other pelvic surgery or presence of
Table 2: Percentage of women experiencing
miscarriage at increasing age antichlamydial antibodies in serum
■ History of diminished periods after an intrauterine procedure
Age Average chance of clinical miscarriage
<20 12%
4. Mid-luteal phase (day 21 of 28-day cycle)
20-24 13%
25-29 14% Serum progesterone Screen for adequacy of ovulation
30-34 16%
5. Premenstrual phase (12 days after ovulation)
35-39 19%
40-42 25% Premenstrual endometrial biopsy Check integrated action of almost two weeks of progesterone on decidualising the
43 plus 50% endometrium
3 Premenstrual endometrial biopsy for Relative prevalence of cytotoxic T cells, uterine NK cells and peripheral NK cells on
Data predominantly from Warburton and Fraser, 1964.
lymphocyte subsets immunocytochemistry
Table 3: Effect of previous miscarriages and births CD = cluster of differentiation KEY
MTHFR C677T and A1298C =
on miscarriage rate Entry level Family practitioners with an interest in miscarriage
loss-of-function polymorphisms of
Chance of next pregnancy Previous No 5,10-methylenetetrahydrofolate
miscarrying baby previous reductase General obstetricians and Reproductive endocrinology and infertility
(average across all ages) baby NK = natural killer cell gynaecologists gynaecologists
After one previous miscarriage 23% 20% PCOS = polycystic ovary
Research interest in miscarriage
syndrome
After two previous miscarriages 28% 44%
Prothrombin G20210A = a gain-of-
After three previous miscarriages 33% 58% function mutation that increases The table is not intended to discourage the interested practitioner from moving deeper into the
4
Source: Jansen (2003). prothrombin production spectrum of testing or interpretation.
Author’s case study
WITH a menstrual cycle that could frustrated her efforts to predict ovu- becoming increasingly painful, her Sophie’s mother had been one of 19.2, which might account for the
vary from 30 to 38 days, it was a lation), Sophie’s partner, Max, read- doctor referred her to a gynaecologist eight children; her father had died cycle irregularity, particularly as
few weeks before Sophie became ily agreed to have a sperm count, for a laparoscopy. The tubes were of a heart attack at 48. They’d had she exercised frequently and inten-
concerned about her missed period. which showed reduced sperm motil- open, the ovaries looked normal and a miscarriage before Sophie’s older sively. There was no tachycardia,
She was just 20. The positive preg- ity but otherwise appeared reason- some endometriosis on the uterosacral sister was born; Sophie’s sister had tremor or lid-lag to suggest thyro-
nancy test caused her and her partner able. ligaments was ablated by diathermy. not put her own fertility to the test toxicosis.
a great deal of anguish but, to their During the next six months, Sophie was prescribed clomiphene, yet. Polycystic ovary syndrome was
relief, she miscarried. Sophie used a saliva-based micro- although earlier measurements of After toying with the notion that excluded as an alternative explana-
The pill not only provided a more scopic “ferning” test she had bought serum progesterone a week after ovu- clomiphene in some circumstances tion for the long cycle (a day-2 serum
planned future as they married, it also at the chemist to detect her preovu- lation on home testing had shown can make miscarriage more likely and FSH was 4U/L, with no increase in
regulated her menstrual cycle and pro- latory oestrogen rise. A visible ferning levels above 35nmol/L, indicative of that ovulatory irregularity itself also the LH:FSH ratio, and the free
vided welcome respite from increas- pattern of her dried saliva alerted her positive, if irregular, ovulation. In the can sometimes produce metabolically androgen index was low). A day-8
ingly troublesome dysmenorrhoea. to start testing for her LH peak with second month after the laparoscopy, or chromosomally defective oocytes, I ultrasound showed abundant folli-
By 24 Sophie’s thoughts had a urine-based kit she bought at the she conceived. However, seven weeks felt these were possible but not con- cles but not in the peripherally dis-
turned to children. When after a year supermarket. from her last menstrual period she vincing explanations and agreed with tributed and similar-sized pattern
nothing had happened (other than a When their efforts continued to be miscarried before an ultrasound had them to do a full workup. typical of PCOS. However, it did
return to irregular periods that again thwarted and her periods were again been scheduled. Clinically Sophie had a BMI of cont’d next page
www.australiandoctor.com.au 22 August 2003 | Australian Doctor | 33
