1 Department of Obstetrics and Gynaecology, St George's Hospital Medical School, Blackshaw Road, London SW17 0QT, UK and 2 Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Göteborg, Sweden
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Abstract |
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Key words: anembryonic pregnancy/colour Doppler ultrasonography/conservative management/missed abortion/spontaneous miscarriage
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Introduction |
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More recently, it has been proposed that selected cases of spontaneous abortion can be managed using a `watch and wait' or conservative management strategy (Dickey, 1993; Haines et al., 1994
). In a further randomized study, conservative management was used to treat miscarriages at <13 weeks gestation. Inclusion in this study depended on transvaginal ultrasonography showing an anteriorposterior (AP) diameter of the endometrial cavity of 1550 mm. Conservative management was successful in 79% of women, without any increase in complications compared with those who underwent dilatation and curettage (D&C) (Nielsen and Hahlin, 1995
).
We used transvaginal ultrasonography (TVS) and biochemical parameters to evaluate the feasibility of conservative management for first trimester miscarriages. Our study differs in that inclusion was limited to pregnancies with what were thought to be either missed abortions or anembryonic pregnancies. Furthermore, we assessed the value of colour Doppler imaging (CDI) to identify those patients with failing early pregnancies who would be most suitable for conservative management.
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Materials and methods |
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At inclusion, an ultrasound examination including CDI was performed, and blood was taken to assess the full blood count (FBC), serum concentrations of human chorionic gonadotrophin (HCG) and serum progesterone. Patients who were rhesus-negative received anti-D immunoglobulin (125 µg). Paracetamol 1 g in combination with codeine 60 mg was prescribed to alleviate any pain.
The ultrasound examination including CDI, as well as the assessment of serum indices was repeated at intervals of ~1 week, up to 28 days. The intervals were 57, 1214, 2123 and 28 days after inclusion into the study. If the patient had an empty uterus, a further examination with ultrasound including CDI and blood samples was carried out 1214 days after inclusion. If evidence of retained products of conception was found (endometrial cavity AP diameter of >10 mm) at the time of any of the examinations, the options of either continuing with conservative management or undergoing a D&C were given to the patient. If the scan suggested the persistent presence of retained products 28 days after inclusion, the patient was advised to have a D&C. All patients gave written informed consent, and the study protocol was approved by our local Ethics committee.
Subjects
A total of 108 symptomatic patients attending the early pregnancy assessment unit at St George's Hospital, London, UK, were recruited into the study. Pregnancies with an estimated gestation age of <13 weeks from the last menstrual period (LMP) were included. All women included in the study were symptomatic and had reported vaginal bleeding and/or abdominal pain. Inclusion was restricted to those shown by ultrasonography to have either a missed abortion or an anembryonic pregnancy.
Definitions
For the purposes of this study, a missed abortion was defined as the presence of an intrauterine gestation sac containing an embryo of >4.0 mm length, but with no heartbeat. An anembryonic pregnancy was defined as the presence of an empty gestation sac of >20 mm with no visible embryonic structures. Complete miscarriage was defined as having an endometrial cavity thickness of <10 mm and a negative urinary pregnancy test (Clearview, 50 IU/l; Unipath Ltd, Bedford, UK) or serum HCG value of <50 IU/l. The miscarriage was classified as incomplete if the endometrial cavity thickness was >10 mm and/or a gestational sac was present.
Transvaginal ultrasonography and colour Doppler measurements
An Aloka SSD 2000 scanner (Aloka Ltd, Tokyo, Japan) was used for all scans. A vaginal probe incorporating a 5 MHz transducer was used for B-mode and CDI, and for the production of flow velocity waveforms. B mode imaging was used to measure the maximum gestation sac diameter. The presence or absence of an embryo was noted and the crownrump length measured when appropriate. The thickness of the endometrial cavity was the maximum distance across the cavity in the longitudinal plane, including any tissue or clot that might be present. The maximum diameter, side, and morphology (solid or cystic) of the corpus luteum was recorded.
For CDI, the return filter was set at 50 MHz. Uterine arteries were located above the supravaginal portion of the cervix. A pulsed Doppler range gate was placed over each artery in sequence and flow velocity waveforms generated. The resistance index (RI) and pulsatility index (PI) were measured: RI = (A B)/A and PI = (A B)/TAMXV; where A is the peak Doppler shifted frequency, B is the minimum Doppler shifted frequency, and TAMXV the time-average maximum velocity over the cardiac cycle. The angle-corrected peak systolic velocity (PSV cm/s) was also measured. The spiral arteries were recognized by their position at the base of the placenta. This entire area was surveyed by CDI. The power, gain and pulse repetition frequency were adjusted for maximum sensitivity for low velocity blood flow. The lowest velocity signals were gradually filtered out by increasing the pulse repetition frequency, and flow analysis carried out on the highest velocity signals. After positioning the pulsed Doppler range gate, minute adjustments were made to the angle of the probe until the visible and audible signals were considered optimal. The position was considered to be at the optimal angle for the probe at that location. The value with the highest PSV and corresponding TAMXV, PI and RI was recorded. A subjective assessment was made of the presence or absence of blood flow in the presumed intervillous space. In the presence of blood flow, Doppler measurements were taken using the same approach as described above. Finally, the corpus luteum was assessed for size, morphological appearance and the presence of blood flow, the highest velocity of which was recorded.
Outcome measures
The principal outcome measures were the presence or absence of a gestation sac in the uterine cavity, the thickness of the endometrial cavity, and the presence or absence of blood flow in the presumed intervillous space. The frequency of complications was also recorded. Pain was recorded using a linear scale from 1 (little or no pain) to 5 (intolerable pain).
Statistical analysis
The probability of complete spontaneous miscarriage during 1 week of conservative management was estimated by logistic regression analysis. The logistic model was applied in a stepwise manner taking into consideration all diagnostic measures included in Table I. The procedure included a new variable in each step and was stopped when no additional variable contributed significantly to the diagnostic power.
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Results |
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Outcome
By 4 weeks after inclusion, 71 (84%) patients in the conservative management group had undergone a spontaneous complete miscarriage and 14 (16%) had undergone D&C. A breakdown by gestational age and ultrasound characteristics of the miscarriage is shown in Table II. For each gestational age category, the proportion of patients in the expectant management group having a spontaneous complete miscarriage after 1, 2, 3 and 4 weeks after inclusion is shown in Table III
. The chances of the miscarriage resolving were independent of gestational age. After 7 days, 46 (54%) women had undergone a complete miscarriage. Of those women with an incomplete miscarriage, 33 (39%) opted to continue with conservative management and six (7%) for a D&C. The cumulative figures for days 7, 14, 21 and 28 are shown in Figure 1
. The number of women who had undergone a complete miscarriage increased significantly each week up to 28 days.
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Discussion |
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It has therefore been of interest to develop techniques that can be used to select suitable patients for a conservative management strategy. Nielsen et al. (1996) successfully used stepwise logistic regression analysis of five diagnostic variables: serum concentrations of progesterone, CA-125, -fetoprotein and daily changes in serum HCG values and intrauterine diameter to assess the likelihood of spontaneous complete miscarriage occurring. Their results suggested that the outcome in cases of spontaneous miscarriages managed conservatively was associated with the viability of the corpus luteum and trophoblast (as indicated by concentrations of serum HCG and progesterone). However, the inclusion criteria for this study were based on an ultrasound examination that showed `an inevitable or incomplete spontaneous abortion with intrauterine tissue with an AP diameter 1550 mm'. Such criteria must lead to the inclusion of women with only a small amount of decidual tissue, blood clots, or residual villi in the endometrial cavity. This led to criticism of the validity of the study (Ankum and Van der Veen, 1995
). Accordingly our study was restricted to pregnancies where ultrasound had shown the presence of either a missed abortion or anembryonic pregnancy. Even with these criteria, 54% of women underwent a complete miscarriage within 1 week. It is of interest that by 28 days, this number had increased to 84%. Women opting for a conservative management approach can, therefore, be told that prolonging the time of observation is associated with a realistic chance of avoiding surgical intervention. Those women who were followed up longest did not have an increased number of short-term complications. Long-term morbidity, such as posterior fertility, has not been assessed in our study. However, it has been excluded in a previous follow-up study, which showed no difference in mid- and long-term complication between conservative management and D&C (Blohm et al., 1997
). It would seem that the follow-up time of 3 days in the Swedish study (Nielsen and Hahlin, 1995
) was over-restrictive. The acceptability of such long periods of observation will depend very much on the patient population studied; however, we feel that having data that allow the clinician to inform a patient about the likely success of conservative management is likely to increase the number of women opting for this approach. Clearly not all women would find 28 days an acceptable period to wait. Two-thirds will complete the miscarriage within 14 days; perhaps a more acceptable duration for women in our local population. That 11 patients in our study opted for a D&C when a follow-up scan revealed products of conception were still present, may reflect our inability to give sufficient reassurance to these women that complete resolution of their miscarriage could still to be expected.
Our findings in relation to the vascularity of the presumed intervillous space are of both clinical and physiological relevance. We have observed a close relationship between the presence of blood flow in the presumed intervillous space and spontaneous complete abortion occurring within 7 days. Conversely, when blood flow was absent in the region, spontaneous complete miscarriage was unusual. This association was independent of gestational age. This finding can be seen against the background of previous physiological studies. Hustin and Schaaps (1987) used perfused hysterectomy specimens from first trimester pregnancies to show that in early pregnancy, trophoblast plugs occlude the openings of the uteroplacental arteries, and that the intervillous space is avascular. More recently, a study of the vascularity of first trimester pregnancies using transvaginal CDI showed an increase in blood flow within the placenta of complicated, compared with normal intrauterine pregnancies (Jauniaux et al., 1994). An examination of the histological features of the placenta of pregnancies of <12 weeks gestation, which had been shown to have blood flow within the intervillous space using CDI, showed extended dislocation of the trophoblast shell and a massive infiltration of the intervillous space and placental bed by maternal blood. The authors concluded from their study that premature entry of maternal blood into the intervillous space disrupts the maternoembryonic interface, and is probably the final mechanism causing abortion. Our data support these observations. We have shown prospectively that the spontaneous miscarriage of either missed abortions or anembryonic pregnancies is associated with the presence of blood flow in the presumed intervillous space. In contrast, in apparently similar pregnancies that do not resolve spontaneously, blood flow in the presumed intervillous space is usually absent. These data support the view that miscarriage, although not necessarily embryonic demise, follows the breakdown of the normal embryomaternal interface. If blood does not enter the intervillous space, it seems that the trophoblast continues to function, and the spontaneous resolution of a failed early pregnancy does not occur.
In summary, we conclude that conservative management is a feasible strategy for many patients with spontaneous first trimester abortion. This includes both missed abortion and anembryonic pregnancies. Therefore, women can be advised that they can reasonably expect to undergo a complete miscarriage within 28 days from the time of diagnosis of pregnancy failure. Furthermore, in our study the presence of detectable flow within the presumed intervillous space was predictive of spontaneous complete miscarriage. Accordingly, CDI may be used to select those patients most suitable for conservative management.
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Acknowledgments |
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Notes |
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References |
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Submitted on June 25, 1998; accepted on November 24, 1998.