July 29, 2015 —Summary of "Continuing Pregnancy After Mifepristone and 'Reversal' of First-Trimester Medical Abortion: a Systematic Review," Daniel Grossman et al., Contraception, June 6, 2015.
"First-trimester medical abortion involves the use of mifepristone followed by misoprostol, generally up to a gestational age of 63 days from last menstrual period," and many women prefer the procedure to surgical abortion because they believe it is "less invasive and more private," according to David Grossman, of Ibis Reproductive Health and the University of California-San Francisco's Bixby Center for Global Reproductive Health, and colleagues.
The researchers noted that lawmakers in Arizona and Arkansas in early 2015 enacted laws requiring physicians to tell "women that if they choose to have a medical abortion and then decide not to complete the abortion, the effect of mifepristone may be reversed with specific treatment"; however, that treatment "is not considered an established practice by the American College of Obstetricians and Gynecologists (ACOG)."
In the study, the researchers reviewed published studies on medication abortion reversal "that documen[t] the proportion of pregnancies continuing after treatment." In addition, Grossman and colleagues wrote that because "the usual care for women seeking to continue pregnancies after ingesting mifepristone is expectant management with fetal surveillance," they also reviewed studies on continuing pregnancies after ingesting only mifepristone.
The researchers reviewed study databases "for reports of pharmacological methods … to reverse the effects of mifepristone prior to administration of misoprostol (or any other prostaglandin) for first-trimester medical abortion." According to the researchers, "[t]he primary outcome was the proportion of women who carried their pregnancies to term after receiving treatment to reverse the effect of mifepristone." For relevant studies, the researchers assessed how many women enrolled and how many pregnancies continued to calculate the overall percentage of continuing pregnancies. The authors also reviewed published studies "that used mifepristone alone during the first trimester of pregnancy to induce abortion" and made the same calculations to determine "the proportion of pregnancies continuing at the time of the follow-up visit after treatment with mifepristone alone."
According to the researchers, only one study met the inclusion criteria on continuing pregnancy following treatment to reverse mifepristone's effects: "a case series by Delgado and Davenport," which involved "seven women who received progesterone treatment after taking mifepristone for medical abortion at 7-11 weeks gestation." Of the participating women, one was "lost to follow-up," four "continued the pregnancy and delivered at term with no apparent congenital malformations" and two "aborted the pregnancy within 3 days of taking mifepristone."
According to Grossman and colleagues, the study did not specify the dosage of mifepristone, while the progesterone regimen -- lasting up to five months -- "varied from progesterone in oil 200 mg intramuscularly daily to twice per week, sometimes followed by oral micronized progesterone, to micronized progesterone administered vaginally." The researchers noted that "in at least five cases, a living embryo was documented prior to initiating progesterone treatment." Further, the Delgado and Davenport study did not specify if any women found to have already aborted were excluded from study participation. Overall, according to Grossman and colleagues, "the proportion of pregnancies continuing after this therapy was 67%" if the patient lost to follow-up was excluded and fell to 57% if that patient's pregnancy was assumed aborted.
Meanwhile, the researchers found 13 articles that met inclusion criteria on continuing pregnancies following the use of mifepristone alone for a first-trimester medication abortion. According to the researchers, "[w]omen were generally assessed 1-2 weeks after mifepristone and those with a continuing pregnancy at that time underwent surgical abortion." Overall, the proportions of continuing pregnancy after taking mifepristone alone ranged from 8% to 46%.
Grossman and colleagues noted that the Delgado and Davenport study on medication abortion reversal "was of poor quality with few details." According to the researchers, the study's limited amount of information means its results cannot be directly compared to studies assessing the rate of continuing pregnancy after mifepristone alone. The researchers wrote that to compare the results, "one must know how many women requested [medication abortion reversal] and were found to already have an embryonic demise or incomplete abortion."
Grossman and colleagues added, "It is reasonable to suppose that women who have an ongoing pregnancy 1-2 days after mifepristone are more likely to have pregnancies that continue to term with no further treatment" and "also possible that some of the continuing pregnancies noted 1-2 weeks after treatment in the studies of mifepristone alone may have aborted if the period of follow-up were longer."
The researchers also noted that while the Delgado and Davenport study did not specify the dosage of mifepristone that women received, it was likely 200 mg, "which is the dosage recommended by ACOG and [the Society of Family Planning] and most often used by providers in the US" Meanwhile, most of the studies assessing the use of mifepristone alone "used a higher dose, and the one study that compared 600 mg to 200 mg found a higher proportion of continuing pregnancies with 200 mg." Further, according to the researchers, "none of the studies of mifepristone alone included women pregnant beyond 56 days, while the report by Delgado and Davenport included women up to 11 weeks gestation." The researchers noted that for medication abortions, the likelihood of continuing pregnancy increases with gestational age.
Meanwhile, Grossman and colleagues wrote that research supporting the use of progesterone in certain types of assisted reproductive technology "or to prevent preterm birth is not directly applicable to the situation after mifepristone treatment." They explained that "[w]omen treated with mifepristone for abortion have normal pregnancies with high progesterone levels, and it is not clear that adding more progesterone would counteract the effect of" mifepristone, which "blocks the progesterone receptor." For example, one study found that the insertion of a "very potent progestin" immediately after ingesting mifepristone "did not reduce the effectiveness of the medical abortion regimen compared to delayed insertion after abortion completion." In addition, the researchers noted that the progesterone treatment assessed in Delgado and Davenport's study was similar to the progesterone treatment used to help prevent preterm labor and "far exceeded the expected duration of action of mifepristone," which at 200 mg dosages is undetectable in humans by 10 weeks. The researchers also wrote that "evidence to date does not suggest an elevated risk of congenital malformations after mifepristone administration alone."
According to the researchers, "[t]he clinical use and new state laws concerning abortion 'reversal' raise serious ethical concerns" because the limited information on such practices "grew out of the anecdotal experiences of physicians who performed experimental treatment on pregnant women, without usual research safeguards." The researchers noted that Delgado and Davenport's study, classified as a "'case report,'" would be better defined as "research," adding that Delgado and Davenport recognized "the report's limitations" and "called for further clinical trials before routine use of their protocol." The researchers wrote, "The new laws in Arizona and Arkansas have now bypassed the research process, in effect making all women who undergo this treatment subjects in an uncontrolled, unmonitored experiment."
Further, the researchers noted that "[p]roviding evidence-based care is part of how physicians meet their beneficence-based obligations to patients, and therefore, it is a moral as well as a clinical mandate to base care on accepted scientific fact." According to Grossman and colleagues, "[t]he new laws compel physicians to say things that may contradict their clinical knowledge and judgment," and "[s]ome physicians will not be able to do so in good conscience; they may feel that suggesting unproven treatment or suggesting that a woman can begin an abortion with uncertainty about her decision contradicts their duty to do no harm."
In addition, the researchers noted that "[w]omen rarely change their minds after beginning a medical abortion," with data showing that "less than 0.004% of women taking mifepristone in the US later chose to continue the pregnancy." The researchers wrote that in the rare instance a woman does wish to continue her pregnancy, she "should be counseled that there is a reasonable chance (10-45%) that the pregnancy will continue."
"We found no credible evidence that using medication after ingestion of mifepristone is better than expectant management in assuring a continuing pregnancy; suggesting otherwise is scientifically untenable," the researchers noted. "In the case of recent Arizona and Arkansas laws, this interference transforms an unproven therapy into law, bases law on methodologically flawed research and in effect turns unethical experimentation on pregnant women into legislative mandate," they wrote, adding, "These features of mifepristone reversal represent an affront to responsible research conduct and to the ethical practice of medicine."