Embryonic abnormalities at medical termination of pregnancy with mifepristone and misoprostol during first trimester: observational study

Accurate data on the incidence and nature of embryonic and fetal abnormality during the first trimester and of non-viable pregnancy are needed so that women who have experienced miscarriages can be counselled, and abortion and early prenatal diagnostic services can be improved. New medical techniques for abortion in the first trimester¹ enabled us to collect and analyse data on undamaged first trimester pregnancies.

Subjects, methods, and results

Between November 1994 and August 1996, 506 healthy women chose medical termination of their pregnancy before nine weeks’ gestation in the dedicated day care abortion unit of the Liverpool Women’s Hospital. Women attended twice (firstly for oral mifepristone and then for oral misoprostol), and most aborted after receiving misoprostol and while still in the unit. Altogether, 293 passed products of conception in the day care unit (all within six hours of receiving misoprostol); 223 of these had given informed consent to study of the tissues. Women who were ineligible for study included 76 who had passed products of conception after receiving mifepristone but before readmission to the day care unit for misoprostol and a further 127 who passed products after discharge from the day care abortion unit. In only 10 women did the medical termination of pregnancy fail.

All specimens were examined macroscopically on the day of termination and fixed in 4% paraformaldehyde. The embryos that appeared structurally abnormal on macroscopic examination were further examined histologically. Strict criteria were used to distinguish structural abnormality from traumatic damage. Agreement among three investigators (GB, SQ, and ESB) was required before a classification was determined. Two hundred and six specimens containing products of conception were collected and the findings recorded (table 1).

Patients were aged between 16 and 41 (mean 25) years; the incidence of abnormality was evenly spread across all ages. Forty women were students, 41 were unemployed, and 31 were housewives; the rest were employed in the service industry (39), as health professionals (20), in secretarial posts (16), or in other posts (19).

Comment

This study found a potential loss rate for embryos with structural abnormalities or other non-viable conditions of 34%, which is higher than the frequently quoted rate of spontaneous miscarriage for “clinical” pregnancies of 15%.² However, it is difficult to calculate the true rate of spontaneous miscarriage as many women may miscarry at home without seeking medical help.³ We collected tissue from 44% of women, and it is impossible to know whether their abnormality rate reflected that of the whole population; however, if anything, it is likely to represent an underestimation as minor abnormalities might not have been detectable at this stage of pregnancy. Also, abnormal pregnancies might be more susceptible to abortion after mifepristone has been administered and thus to abort before misoprostol ingestion (thereby pre-empting inclusion in our study). We have no reason to believe that mifepristone would itself contribute to the structural changes as abortion occurs within only 72 hours of exposure to the drug, whereas the abnormalities must have occurred much earlier in the gestation. None of the women reported taking any drugs, although recreational drug use may have been a cause of some abnormalities.⁴ We anticipate that the incidence of neural tube defects in a population of planned pregnancies would be significantly reduced by the ingestion of folic acid at the time of conception and for the first 12 weeks of pregnancy.⁵ These findings highlight the importance of encouraging women to take folate supplements around the time of conception and to avoid potential teratogens. In our study, ultrasound examination would have identified the 48 non-viable pregnancies. These women would not have needed a termination of pregnancy if an accurate diagnosis had been made, thus reducing pressure on abortion services and relieving a burden of guilt among the women.

Our findings are unexpected but on balance probably reflect the true loss rate in pregnancies. To our knowledge, this is the first report of detailed studies of embryonic abnormality after early medical termination of pregnancy.

Table.

Abnormalities in 206 embryos studied

Abnormality	No of embryos
None	121
Non-viable pregnancies
Anembryonic; intact gestation sacs	33
Ruptured sac (no embryo present)	15
Resorbing*	15
Structural abnormalities
Neural tube defect:
Open posterior neuropore	5†
Open anterior neuropore	2†
Encephalocele	3†
Abdominal wall defects‡	6†
Facial cleft	3†
Failure of body axis rotation severely disorganised (no somites)	2†
Hydropic	1
Congested	1
TRAP twins (one without a head)	1
Total No of abnormal embryos	39
Total No of potentially non-viable pregnancies	72

TRAP=twin reversed arterial perfusion.  

^*Embryos that were disproportionately small compared with their gestation sac and contained necrotic tissue.  

^†Including some embryos with multiple abnormalities.  

^‡Part of the gastrointestinal tract outside the abdominal wall inconsistent with physiological herniation.