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2002 Selected Articles

Early Pregnancy Termination:
A More Personalized And Private Approach

Herbert P. Brown, MD, FACOG

Late first-trimester aspiration at 7 to 12 weeks after the last menstrual period (LMP), the most frequent method of pregnancy termination, has an excellent record of safety and efficacy.¹ However, in the minds of some women, the prospect of this surgery and waiting for it to be performed produces fear, anxiety. and feelings of loss of control. The new medical alternative represented by mifepristone promises to restore to women a measure of self-control over their reproduction. The recommended interval for its use is from the time pregnancy is confirmed up to 49 days post-LMP (ie, the end of the seventh postmenstrual week). Additionally, faced with the present shortage of clinicians willing to perform pregnancy termination, the ease of providing a medical regimen promises to help make the service more widely available and to promote easier access for women in need.

Lastly, the new regimens represent a major public health advance by bringing pregnant women to medical attention early in gestation. Not only would unwanted pregnancies be terminated earlier and more safely, but anomalies such as molar, ectopic, and anembryonic ("blighted ovum") pregnancies could be detected and treated in a more timely manner. With early therapy comes the potential to further reduce complications in an already safe setting. Moreover, early prenatal care could be initiated in normal pregnancies where a patient changes her mind or where there are complicating medical concerns.

Medical abortion regimens should not be confused with emergency contraception. The so-called "morning-after pill" is a contraceptive taken within 72 hours after intercourse to prevent unintended pregnancy. It does not work if a woman is already pregnant, and it does not cause abortion.

In the late 1990s, technologic advances occurred that allowed for very early surgical abortion, ie, at less than 7 weeks post-LMP, or when pregnancy becomes detectable on home urine testing (Table 1). This paper reviews the principles of early medical and surgical abortion to update practitioners on this rapidly evolving area of women’s reproductive health management.

MEDICAL REGIMENS

The discovery of a selective, nontoxic, progesterone-receptor blocker by Baulieu in 1980 made early, nonsurgical pregnancy termination a reality.² Mifepristone (MFP, Mifeprex^®, RU-486) has been studied extensively for 12 years in France, the United Kingdom, and several other countries.^2,3 Research proceeded in the United States but was hampered for a decade by antiabortion activists;^4,5 eventually, the US Food and Drug Administration (FDA) approved MFP in September 2000 as safe and effective for pregnancy termination up to 49 days post-LMP (Table 2). Regimens including MFP now represent the standard treatment for early medical abortion. The drug does not act directly on the fetus,⁶ but rather blocks the ability of progesterone to provide endometrial support for early pregnancy, as well as causing uterine contractions and cervical ripening. As a result, the uterus is no longer able to sustain the pregnancy.

Frustration over the nonavailability of MFP in this country during the 1990s led to a search for alternative medications that were available here. Methotrexate (MTX) has been in clinical use in the United States for more than 44 years. Encouraged by the safety of the drug in the treatment of ectopic pregnancy⁷ and other nongynecologic conditions, American researchers undertook clinical trials using MTX as an abortifacient.⁸ This antimetabolite (an antifol) interferes with the activity of rapidly dividing cells, primarily of the cytotrophoblast, but also of the decidua. It can affect the fetus, but usually only at dosages beyond those used for abortion (chemotherapy range). The drug is inexpensive and widely available. Regimens including MTX have proved to be clinically safe and effective, and may become an alternative to MFP. However, MTX has not yet been approved by the FDA for this indication.

Used alone, neither MFP nor MTX induces myometrial contractions strong enough to evacuate the uterine contents efficiently. However, the addition of potent prostaglandins to MFP in the late 1980s in Europe was accompanied by severe, occasionally dangerous side effects.⁹ Three myocardial infarctions, one fatal, occurred in women over age 35 who smoked and were given sulprostone after MFP. Switching to other prostaglandins, including misoprostol (MSP, Cytotec^®) eliminated these risks. Researchers in Europe and the United States found this prostaglandin E₁ analog, to be safe and effective, significantly reducing the incidence of side effects. It is commonly used to protect the gastric mucosa in cases of chronic nonsteroidal anti-inflammatory drug (NSAID) ingestion, and is widely available, inexpensive, and chemically stable at room temperature. The drug can produce nausea, vomiting, headache, and/or diarrhea, but to a substantially lesser degree than other therapeutic prostaglandins. Misoprostol has been used exclusively in the US clinical trials of MFP.

Additionally, even though formulated for oral use, MSP may be administered vaginally. This increases its efficacy, especially if the clinician chooses to use the regimen later than the recommended protocol, ie, at 49 to 63 days post-LMP.⁵ Clinical trials have shown nearly equal efficacy (92% to 95%, with some reports as high as 98%) when MFP or MTX is used in combination with MSP.^5,8 An unanticipated finding in the clinical trials was that, while MTX is effective against ectopic pregnancy, MFP is not. Also, in the rare event of a continuing pregnancy, there is a possibility of teratogenesis associated with the use of MTX and of MSP.¹⁰ So far, there have been no reports of congenital abnormalities due to MFP exposure when used alone in continuing pregnancies. Furthermore, there have been no findings of impaired future fertility attributable to either of the medical regimens.

Advantages

Medical abortion regimens have proved safe and effective in extensive clinical trials, both in the United States and worldwide. They allow the patient more control over the termination process, which closely mimics a spontaneous miscarriage, giving it a more "natural" feel. In addition to affording a degree of privacy that is not possible in a surgical setting, medical abortion provides an alternative for women who fear surgery and avoids the need for sedative and narcotic medications. Most internists and OB/GYNs are familiar and comfortable with the use of MTX, which has the added benefit of treating a possible early ectopic pregnancy that has not yet been diagnosed. Furthermore, MFP and MTX are suitable for use in most primary care office settings, and need not be restricted to experienced surgical providers.

Disadvantages

One of the main disadvantages of medical abortion is the time to completion, which is slow compared with surgery. Patients should expect the MFP-MSP regimen to require a minimum of 72 hours, and the MTX-MSP protocol to take up to 3 weeks to complete the termination. By contrast, surgical abortion is usually accomplished in less than 30 minutes. Cramping and associated discomforts such as headache, nausea, and diarrhea may persist for 1 to 2 days after taking MSP, compared with postoperative cramping of 24 hours or less. The medical regimens are most efficacious during the first 49 days post-LMP (package labeling for MSP) with the failure rate increasing gradually with time thereafter, so that the patient must accept the unlikely but possible need (2% to 5%) for surgical completion.^4,5,8,14 Medical regimens require multiple visits to confirm termination, raising the issue of patient compliance. In the event of continuing pregnancy, the use of MTX and MSP (alone or in combination) have the potential for teratogenesis. There is also the rare possibility (less than 0.5%) of hemorrhage sufficient to require blood transfusion; although low, this incidence is still higher than that associated with surgical abortion.¹⁴

EARLY SURGICAL TERMINATION

Early surgical abortion is an aspiration procedure performed at 4 to 7 weeks post-LMP. From the time of a positive pregnancy test, this procedure can be undertaken as soon as the gestational sac is visible on ultrasonography. Manual vacuum aspiration (MVA) dates back to the late 1960s, when it was used for "menstrual extraction", in essence, a large-scale endometrial biopsy. The procedure was essentially abandoned for early termination in the United States because of a higher failure rate than modern machine suction techniques (30% to 50% versus 98% to 99%). Additionally, a major epidemiologic study (JPSA) suggested that complications of surgical abortions followed a J-shaped curve, with the lowest incidence between 7 and 9 weeks post-LMP, and increased rates before and after that period.^1,11

In the mid to late 1990s, technologic advances revived MVA as a realistic approach to early pregnancy termination. One innovation was the radioimmunoassay for serum b-hCG, providing a reliable, noninvasive method for determining the viability or persistence of trophoblastic tissue. A concurrent development was the advent of vaginal ultrasonography, allowing for precise localization of an early or persistent gestational sac. Finally, it was established that meticulous examination of the aspirated tissue with magnification was necessary to both ensure completion of the procedure and confirm evacuation of the gestational sac. If early experience is confirmed, MVA could have a renaissance in the United States.¹²

Indeed, MVA is preferable to machine suction for early pregnancy termination. Even though both procedures involve identical amounts of vacuum, MVA disrupts the integrity of the aspirated tissue much less, permitting easier identification of the gestational sac to avoid continuing pregnancy, the main problem with menstrual extraction. By the same token, the absence of a gestational sac post-MVA suggests the possibility of ectopic pregnancy, a diagnosis of personal and public health importance.

Advantages

The MVA procedure provides a rapid, minimally invasive method for terminating pregnancy in a single visit; in some cases, it is not even necessary to dilate the cervix. It is well-suited for use at 4 to 6 weeks post-LMP. Operative discomfort can usually be controlled by local nerve blocks. Postoperative cramping generally lasts for 1 to 2 days, and responds well to NSAIDs or codeine-based analgesics. Serious complications are very rare, as is failure to terminate the pregnancy. The procedure is easy for the office-based clinician to master, and the equipment is neither expensive nor extensive. As for long-term sequelae, experience with MVA and other suction procedures has shown no impairment of future fertility.¹²

Disadvantages

Early surgical termination requires the patient to go to the physician’s office or a clinic, and subjects her to the same type of potentially vulnerable intraoperative exposure and discomfort as do procedures performed later in pregnancy; in this respect, it provides less privacy than medical regimens. In addition, it is essential to ensure meticulous tissue evaluation. The timing of both medical and surgical abortion regimens is summarized in Table 3.

FUTURE PROSPECTS

Although the current medical regimens have proved safe and effective in extensive clinical trials, they are still evolving with regard to drug dosage and timing. And while the FDA has limited its approval of MFP to 49 days, both MFP and MTX are clearly effective beyond that time (Table 4). However, the useful duration and appropriate clinical settings remain to be established. Other medical regimens using tamoxifen with MSP, and MSP alone, show promise in small trials, and require further study.^13,14 Additionally, newer, more selective progesterone-receptor blockers are in development that may be more clinically effective.¹⁵

Table 4. Evidence-based Alternatives to FDA Approved MFP-MSP Regimen Alternative Benefit Source MSP, 200 mg Efficacy comparable to MSP, 600 mg Kahn JG, Becker BJ, MacIsaac L, et al.The efficacy of medical abortion: a meta-analysis. Contraception. 2000;61 (1):29-40. Vaginal administration of MSP Lower rates of incomplete abortion, gastrointestinal side effects, continuing pregnancy. More rapid expulsion of conceptus el-Rafaey H, Rajasekar D, Abdalla M, et al. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol.N Engl J Med. 1995;332(15)983-987. Home use of MSP Safe, effective, and acceptable to patients Schaff EA, Stadalius LS, Eisinger SH, Franks P. Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. J Fam Pract. 1997;44(4):353-360. Flexibility in day of MSP use Equal efficacy whether used 24, 48, or 72 hr after MFP Schaff EA, Fielding SL, Westhoff C, et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: a randomized trial. JAMA. 2000;284(15):1948-1953. Flexibility in initial follow-up evaluation Follow-up before 14 days using ultrasonography Schaff EA, Fielding SL, Eisinger SH, et al. Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days. Contraception. 2000;61(1):41-46. MTX-MSP regimens Equal efficacy to MFP regimens up to 49 days gestation Pymar HC, Creinin MD. Alternatives to mifepristone regimens for medical abortion. Am J Obstet Gynecol. 2000;1 83(2 Suppl):S54-S64 [review].

If wider use of MVA for early surgical abortion confirms the findings to date, primary care clinicians equipped for vaginal ultrasonography could provide early medical or surgical abortion without the burden of significant equipment purchase or long surgical experience. Interested physicians can contact the National Abortion Federation at 202-667-5881 or www.earlyoptions.org for information about training in early abortion regimens and procedures.

CONCLUSION

In the United States today, 50% of all pregnancies are unintended, and 50% of these end in abortion.¹⁶ Until this public health problem can be controlled through behavior modification and more successful use of contraception, there will be a continued need for abortion services. Now that the FDA has approved MFP, both medical and surgical approaches to early pregnancy termination can enter routine clinical use. As a result, the patient will have more choices and personal control with regard to pregnancy management. Also, the widespread use of medical regimens and MVA will enable both generalist and specialist primary care physicians to provide these much-needed services without great equipment expense, more clinic space, or long surgical training. Thus, more providers would become available to improve access by US women to these services

J. Kell Williams, MD, is director, Division of Gynecology, and Anna Parsons, MD, is director, Image-Based Gynecology, both in the Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa.

REFERENCES

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3. Peyron R, Aubeny E, Targosz V, et al. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Engl J Med. 1993;328(21):
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7. Stovall TG, Ling FW, Gray LA. Single dose methotrexate for treatment of ectopic pregnancy. Obstet Gynecol. 1991;77 (5):754-757.
8. Creinin MD, Darney PD. Methotrexate and misoprostol for early abortion. Contraception. 1993;48(4):339-348.
9. A death associated with mifepristone/sulprostone [Notice Board]. Lancet. 1991;337:969.
10. Fonseca W, Alencar AJ, Mota FS, Coelho HL. Misoprostol and congenital malformations. Lancet. 1991;338(8758):356.
11. Tietze C, Lewit S. Legal abortions: early medical complications. An interim report of the joint program for the study of abortion. J Reprod Med. 1972;8(4):193-204.
12. Maclsaac L, Darney PD. Early surgical abortion: an alternative to and backup for medical abortion. Am J Obstet Gynecol. 2000;183(2 Suppl):S76-S83.
13. Mishell DR, Jain JK, Byrne JD, Lacarra MDC. A medical method of early pregnancy termination using tamoxifen and misoprostol. Contraception. 1998;58(1):1-6.
14. Creinin MD, Aubeny E. Medical abortion in early pregnancy. In Paul M, Lichtenberg ES, Borgata L, et al, eds. A Clinician’s Guide to Medical and Surgical Abortion. New York: Churchill-Livingstone; 1999;91-106.
15. Personal communication with PN Rao, PhD, Southwest Foundation for Biomedical Research, San Antonio, Tex.
16. Henshaw SK. Unintended Pregnancy in the United States. Fam Plann Perspect. 1998;30(1):24-29, 46.

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