Papers

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

BMJ 1998; 316 doi: https://doi.org/10.1136/bmj.316.7146.1712 (Published 06 June 1998) Cite this as: BMJ 1998;316:1712
  1. G Blanch, senior registrar (SQuenby{at}liv.ac.uk)a,
  2. S Quenby, lecturera,
  3. E S Ballantyne, research fellowa,
  4. C M Gosden, professor of medical geneticsa,
  5. J P Neilson, professor of obstetrics and gynaecologya,
  6. K Holland, sisterb
  1. aDepartment of Obstetrics and Gynaecology, University of Liverpool, Liverpool L69 3BX,
  2. bDay Care Abortion Unit, Liverpool Women's Hospital, Liverpool
  1. Correspondence to: Dr Blanch
  • Accepted 22 December 1997

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).

Abnormalities in 206 embryos studied

AbnormalityNo of embryos
None121
Non-viable pregnancies
Anembryonic; intact gestation sacs33
Ruptured sac (no embryo present)15
Resorbing*15
Structural abnormalities
Neural tube defect:
   Open posterior neuropore5
   Open anterior neuropore2
   Encephalocele3
Abdominal wall defects6
Facial cleft3
Failure of body axis rotation severely disorganised (no somites)2
Hydropic1
Congested1
TRAP twins (one without a head)1
Total No of abnormal embryos39
Total No of potentially non-viable pregnancies72
  • 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.

Abnormalities in 206 embryos studied

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.

Acknowledgments

We thank Mr G M Kidd, consultant in charge of the day care abortion services for his support and for his permission to examine the fetal material.

Contributors: GB and SQ initiated and coordinated the formulation of the primary study hypothesis; discussed core ideas; and participated in the collection and examination of specimens, the analysis and interpretation of data, and the writing of the paper. GB and SQ will also act as guarantors for the paper. ESB discussed core ideas and participated in the collection and examination of specimens. KH participated in the collection and examination of specimens. CMG discussed the core ideas. JPN agreed the funding for the project, discussed core ideas, and contributed to drafts of the manuscript.

Funding: ESB was supported as a clinical research fellow by the British Brain and Spine Foundation.

Conflict of interest: None.

References

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