Objective
Our objective was assessment of fetopathological examination after termination of pregnancy (TOP) for fetal anomalies with normal karyotype <17 weeks of gestation.
Study Design
This was a multicenter retrospective study. Records of TOP for fetal anomalies with normal karyotype were analyzed. Primary outcomes were modifications of genetic counseling and management of next subsequent pregnancies. Medical TOPs were compared with surgical TOPs.
Results
In all, 59 pregnancies were included (30 aspirations, 29 inductions). Fetopathological examination modified genetic counseling for 22 patients: 62% for the medical induction group vs 13% in the vacuum aspiration group ( P < .001). Management of subsequent pregnancies was modified in 17% in the medical induction group vs 3% in the aspiration group ( P = .06).
Conclusion
Fetopathological examination for early TOP with normal karyotype is relevant, especially when an intact fetus is examined. Thanks to it, genetic counseling is often modified, as is management of the next pregnancy. Medical procedures should be preferred to surgical procedures.
In most countries the first ultrasound screening during pregnancy is performed between 11-14 weeks of gestation (WG). Thanks to progress in ultrasound, more fetal malformations that used to be diagnosed later are now detected during this first trimester, such as cephalic pole malformations, bone anomalies, hygromas, anomalies of the anterior wall, and others, including multiple malformations. In France, when such anomalies are suspected, the patient is referred to a prenatal diagnosis center. When severe malformations are confirmed by an experienced sonographer, termination of pregnancy (TOP) can be requested by the parents and accepted by the prenatal diagnosis center, according to French law. In the case of fetal malformations related to an abnormal karyotype, vacuum aspiration is proposed. However, when the fetal karyotype is normal, medical induction is usually recommended so that an intact fetus is available for fetopathological examination. Some patients though ask for vacuum aspiration because the procedure is believed to be simpler. Although autopsy is known to offer a real benefit after 18 WG, its value for genetic counseling and management of the next pregnancy has never been studied for earlier TOP. Is there a difference in autopsy quality between aspiration and induction? To answer this question we carried out a retrospective multicenter study.
Materials and Methods
This retrospective study concerning the period from January 2006 through December 2008 was carried out in 2 prenatal centers in Paris (Port-Royal Saint-Vincent de Paul Hospital and Robert Debré Hospital). The aim of the study was to assess the value of fetopathological examination in early TOP. Does it complement ultrasound examination, and modify genetic counseling and management of the next pregnancy? Does the method used for TOP change the value of the autopsy and the risk incurred by patients?
To answer these questions, we retrieved from the prenatal diagnosis center registers all medical records of pregnancies that ended in TOP <17 WG. We excluded TOPs performed because of an abnormal karyotype, a genetic abnormality already known in the family (eg, sickle cell anemia, hemophilia, myopathy, metabolic disease), or a maternal indication (eg, cancer, psychiatric or cardiac reasons). In both last groups (genetic disorders and maternal diseases) the early scans were normal.
All patients underwent first ultrasound screening between 11-14 WG. All malformations were suspected during this screening. Gestational age was calculated using the crown-rump length. All reports on fetal ultrasound examinations, laboratory tests, and fetal samples were pooled. All data concerning management of TOP and postabortum were studied. The detailed fetopathological reports were analyzed, as were genetic records. Data were then analyzed by a board of experienced practitioners including a sonographer, a fetopathologist, a geneticist, and an obstetrician.
The primary outcomes were to determine the effects of fetopathological examination on genetic counseling and on management of the next pregnancy. Fetopathological data were considered uninformative when the fetus was so fragmented that organs could not be identified. Secondary outcomes were to know whether fetopathology identifies malformations missed by ultrasound, to review major and minor maternal complications, and to analyze the duration of hospital stay.
Patients chose the method for TOP after medical counseling. They were offered both options, but medical induction was recommended.
In the case of vacuum aspiration, the patient received 200 mg of mifepristone orally 2 days before the surgical aspiration. On the day of TOP, the patient was admitted early in the morning and received 400 μg of misoprostol vaginally at least 2 hours before the aspiration, which was performed under general anesthesia in the operating room. Cervical dilatation was increased mechanically to a diameter of 12 mm using Hegar dilators. Evacuation was done with a cannula connected to a suction pipe under ultrasound guidance.
In the case of medical induction, the patient received 200 mg of mifepristone orally 2 days before the induction. She was admitted the evening before the induction. Laminaria were used in 1 center (Robert Debré Hospital). Early in the morning the patient was taken to the delivery room and given 400 μg misoprostol vaginally every 3 hours under epidural anesthesia.
The fetopathological examinations were carried out according to standardized protocols that were the same in both centers. With the patient’s consent, the fetus or vacuum aspiration products, in a fresh state, were sent to the laboratory as rapidly as possible. The vacuum aspiration products were washed, and then fixed overnight in 4% formol. The macroscopic examination consisted of separating different elements (decidua, placenta, cord, fragments, and fetal organs). For the identifiable elements, we carried out a morphological examination, took digitized pictures and radiographs (Faxitron cabinet x-ray system-Faxitron series; Faxitron Bioptics, Lincolnshire, IL), and performed a histologic examination.
The autopsy protocol for a whole fetus involved routine radiological examination followed by standardized x-rays (whole body, face, profiles). The macroscopic examination concerned the face, limbs and extremities, and anterior abdominal wall. All organs were then dissected. Samples of the brain, muscles, and ribs were collected routinely; the marrow and eyes were studied depending on the context. These organs were examined histologically. Macroscopic and histologic examinations of the extraembryonic structures, placenta, and membranes were routine.
TOP was divided into 5 groups according to indication: anomalies of the cephalic pole, bone anomalies, hygromas, anomalies of the anterior wall, and others, including multiple malformations.
Results were analyzed using the χ 2 test.
Results
During the 36 months of the study, there were 22,386 deliveries in the 2 centers and 247 patients underwent TOP <17 WG. This corresponds to 29% of all TOP (n = 848) during this period. In all, 188 patients were excluded from the study: 18 who had undergone TOP for maternal medical reasons, 38 because of a genetic disease in the family, and 132 for an abnormal karyotype. Most fetuses with an abnormal karyotype had trisomy 21 (n = 59) or trisomy 18 (n = 40).
Fifty-nine pregnancies were included ( Figure 1 ) . All fetuses had a normal karyotype and isolated or multiple anomalies detected by ultrasonography and of sufficient severity for the prenatal diagnosis center to agree to the parents’ request for TOP, in accordance with French law.
Thirty patients underwent vacuum aspiration (average gestational age 13.5 WG) and 29 medical induction (average gestational age 15.3 WG). Indications and methods for TOP are shown in Table 1 .
| Indication | Vacuum aspiration (n = 30) | Medical abortion (n = 29) | Total (n = 59) |
|---|---|---|---|
| Anomalies of cephalic pole | 12 | 12 | 24 |
| Bone anomalies | 5 | 5 | 10 |
| Hygroma | 6 | 4 | 10 |
| Anomalies of anterior wall | 3 | 5 | 8 |
| Multiple malformations or others | 4 | 3 | 7 |
The fetopathological examinations were uninformative in 23 of 59 cases (39%): 22 vacuum aspiration products were too fragmented to be analyzed; 1 fetus with a hygroma was examined 2 days after medical induction, the state of desiccation was advanced, cutaneous edema could not be found and the rest of the findings were normal. Thirty-six examinations were informative: 8 vacuum aspirations and 28 medical inductions. Figures 2 and 3 show examples of fetopathological examination after vacuum aspiration and medical induction, respectively.
The results are shown in Table 2 .
| Method used | Not informative | Informative | Superior to ultrasonography | Modification of genetic counseling | Modification of management of subsequent pregnancies |
|---|---|---|---|---|---|
| Vacuum aspiration (n = 30) | 22 | 8 | 6 | 4 | 1 |
| Medical abortion (n = 29) | 1 | 28 a | 19 | 18 a | 5 b |
| Total (n = 59) | 23 | 36 | 25 | 22 | 6 |
Of the 36 informative examinations, 25 (42%) autopsies revealed more pathological details than ultrasonography (19 [65%] in the medical induction group vs 6 [20%] in the vacuum aspiration group). In 22 (37%) patients, these new details affected genetic counseling (18 [62%] in the medical induction group and only 4 [13%] in the vacuum aspiration group). Autopsy after medical induction significantly improved genetic counseling compared with aspiration ( P < .0001). Management of the next pregnancy was modified for 6 patients, ie, 5 (17%) in the medical induction group vs 1 (3%) in the vacuum aspiration group ( P = .06). These 6 cases are detailed in Table 3 . Details of the 22 cases in which fetopathological examination affected genetic counseling are available in the Appendix ( Supplementary Tables 1-5 ).
