Friday, November 05, 2004

Just In Case

Regular readers of this blog know that I am unequivocally opposed to politicians [irrespective of party affiliation] making medical decisions for women. So, just in case people you've never met [but might have voted for] decide to no longer permit you to make life and death health decisions, I thought it prudent for us to briefly review the topic of medical termination of pregnancy. A couple of points, before we start:

  • The risk of death/yr from a term pregnancy is 1:10,000, and the risk from an early (before 9 weeks) elective termination is 1:263,000.

  • An elective abortion is not a birth control method, nor should it be used as such [never, ever].


  • Medical termination of pregnancy (MTP) refers to non-surgical methods of terminating a pregnancy. Instead of a surgical procedure, various drugs are used to terminate the pregnancy. The drugs used for MTP end an already established pregnancy, thus they are abortifacients (they cause an abortion). [By contrast, drugs used for birth control prevent a pregnancy and have no effect on an established pregnancy.]

    There are many drugs and regimens used for MTP. Only 3 of these drugs are routinely used for early terminations, meaning pregnancies up to 9 weeks (63 days): misoprostol, mifepristone (RU-486) and methotrexate. [Yes, I know, the drug names sound awfully similar ... not a good idea.]

    An aside: the early MTP drugs are often confused with drugs used for birth control, especially with drugs used for emergency contraception (EC). They are not one and the same--the mechanisms of action involved are completely different. Abortifacients terminate a pregnancy. Birth control prevents it.

    Before we review the individual drugs, there is one very important point you must remember. Although the early pregnancy termination drugs are easy to use and to self-administer, you should only use them under close medical supervision. Why? Because these drugs act on an already established pregnancy. A pregnancy, even an early one, can be associated with potentially deadly complications, like an ectopic.

    This is in contrast to drugs used for EC that act before there is a pregnancy; this makes them safe to use without a prescription, or over-the-counter.

    There are 6 main groups of MTP drugs:

    1. OXYTOCIN

    Oxytocin is a drug that causes uterine contractions and induces labor. High doses of oxytocin are given in small volumes of intravenous fluids.

    2. HYPEROSMOTIC SOLUTIONS

    Hyperosmotic solutions also induce labor. For example, 20-25% saline or 30-40% urea solutions are injected into the amnionic sac (the bag of fluid).

    3. PROSTAGLANDINS AND ANALOGUES

    Prostaglandins are substances naturally produced in the body. They have many actions, including induction of labor. The drugs in this group can be used vaginally, as a shot, into the amnionic sac, and orally (by mouth).

    Misoprostol belongs to this group. The brand name in the U.S. is Cytotec and it is used to induce labor, to treat stomach ulcers, etc.

    4. ANTIPROGESTERONES

    Antiprogesterones are drugs that block the action of the body's hormone progesterone. Progesterone is very important for pregnancy.

    Mifepristone (RU-486), a pill, is a drug in this group. The brand name in the U.S. is Mifeprex.

    An aside. The amount of incorrect information about mifepristone (RU-486) is staggering. Unless you know the actual facts about this drug, it is impossible for you to make an informed medical decisions. Briefly: mifepristone is *not* an abortifacient (an "abortion pill"), it *is* an antiprogesterone. What's the difference? A crucial one: the mechanism of action, the way the drug works. [Important for you to understand this: what people decide to call mifepristone--"the devil's pill" or "the fluffy bunny pill"--is irrelevant. Its mechanism of action is the same, regardless.]

    By definition, an "abortion pill" causes an abortion, meaning it terminates an already established pregnancy. An "abortion pill" has no mechanism by which to prevent a pregnancy from becoming established. A good example is the drug misoprostol. The only mechanism of action of this drug is to induce labor. So, this drug has no way of preventing a pregnancy; it can only terminate one. Misoprostol is an abortifacient.

    Contrast this with the mechanism of action of mifepristone (RU-486). Mifepristone can either block the release of the egg from the ovary, block implantation, or cause the lining of the uterus, together with an implanted egg, to shed. So, this drug can either prevent a pregnancy, or terminate one. Mifepristone is an antiprogesterone. It can be used as birth control, or as an early pregnancy termination drug. [Obviously, the dosage and regimen vary.]

    Back to our discussion. When mifepristone is used for MTP, the dosage/regimen used causes the lining of the uterus, together with the implanted egg, to shed.

    5. PROGESTERONE PRODUCTION BLOCKERS

    Progesterone production blockers, as the name implies, block the production of the hormone progesterone. Progesterone is very important for pregnancy.

    Epostane, a pill, is an agent in this group. The usual dose is 200 mg every 6 hours, for 7 days, and you can take it up to 7 weeks (49 days) from the date of your last normal menstrual period. The rate of successful treatment with epostane is 87% - 90% , and it has a good safety profile. The main side effects are nausea and vomiting. The average length of vaginal bleeding with this regimen is 10.7 days. Once the treatment is complete, usually there is no delay in the resumption of normal periods.

    6. METHOTREXATE

    Methotrexate is a folic acid antagonist, a drug that stops cells from dividing. It comes in the form of a pill, or a shot.

    Remember, only three of the aforementioned drugs--misoprostol, mifepristone (RU-486) and methotrexate--are used for early MTP. [Epostane can also be used, but this is an older regimen, not in common use today.]







    TWO MTP REGIMENS: A COMPARISON TABLE
    RegimenMIFEPRISTONE & MISOPROSTOL

    METHOTREXATE & MISOPROSTOL

    Comments
    How does it work?

    Mifepristone: blocks the action of progesterone, causing the uterine lining to thin and detach.

    Misoprostol: causes uterine contractions that expel the embryo and placental tissue.

    Methotrexate: stops cell division.

    Misoprostol: causes uterine contractions that expel the embryo and placental tissue.

    When does it work?1. Evidence-based: through 9 weeks (63 days) from the last menstrual period (LMP)

    2. FDA-approved: through 7 weeks (49 days) from the LMP

    Once pregnancy is confirmed, through 7 weeks (49 days) from the LMP
    Dose1. Mifepristone 200 mg
    by mouth, followed 1-3 days later by Misoprostol 800 mcg vaginally (self-administered, at home)

    2. Mifepristone 600 mg by mouth, followed 2 days later by Misoprostol 400 mcg by mouth

    Methotrexate 50 mg by mouth or a 50 mg/m2
    shot, followed 3-7 days later by Misoprostol 800 mcg vaginally (self-administered, at home)

    How well does it work?1. ~97%

    2. 92% to 97%

    94% to 96%If the drugs are unsuccessful, surgery is needed to complete the process.
    How many office visits?1. Two

    2. Three

    TwoDepending on the individual case, more visits may be needed.
    Side effectsNausea, vomiting, diarrhea, headache, dizziness, fever or chills, anemia (rare), blood transfusion needed (rarely).

    Nausea, vomiting, diarrhea, headache, fever or chills, stomatitis (rare), anemia (rare), blood transfusion needed (rarely).Bleeding and cramping are expected effects of all termination procedures.
    Expected bleeding~ 13 days

    ~ 10-17 days
    Can it treat an ectopic?Not an effective treatment.

    ~ 90% effective for early, unruptured ectopic (3.5 cm or less, initial beta hCG less than 5,000 mIU/ml).An ectopic pregnancy can be deadly. This is why the supervision of a qualified doctor is imperative.
    Follow-upMust return to confirm termination is complete. If it isn't, surgery is necessary.

    Must return to confirm termination is complete. If it isn't, surgery is necessary.
    U.S. regulatory statusMifepristone--approved for early medical termination.

    Misoprostol--approved for ulcer treatment.

    Both drugs are approved.Worldwide, these drugs have been safely used by millions of women for over 10 years.


    In addition to the established MTP regimens, there have been reports of women using misoprostol by itself, and without medical supervision. While women are most likely to self-administer misoprostol in countries where legal termination is unavailable (e.g., Latin America), evidence suggests that women in the U.S. are also using this regimen. [To be clear: Misoprostol is not usually used as the only drug for early pregnancy termination; nor should it be used without medical supervision.]

    MISOPROSTOL ALONE

    The reported misoprostol-only regimens involve multiple doses, taken at 24-hour intervals. How well the regimen works depends on the time elapsed from the last menstrual period (LMP) and the number of doses. For example, 800 mcg misoprostol administered vaginally up to 49 days from the LMP, is 69.0% effective after one dose, 86.4% effective after two doses, and 91.7% effective after three doses. For the same dose administered vaginally up to 63 days from the LMP, the effectiveness is 78% after one dose, 91% after two doses, and 92% after three doses.

    [Again, please don't use misoprostol on your own; consult with your doctor.]

    Bottom line:

  • MTP is a safe and effective alternative to surgical procedures.

  • MTP allows one to have a termination much earlier, it affords more privacy, and a sense of greater personal control over the experience.



    Williams Obstetrics 21st. ed.

    Stewart FH, Wells ES, Flinn SK, et al. Early Medical Abortion: Issues for Practice. UCSF Center for Reproductive Health Research & Policy: San Francisco, California (2001)





  • 14 Comments:

    At 2:59 AM, Anonymous Anonymous said...

    That was most interesting, and informative. Thank you for taking the time to put this information out there.

    - Deb

     
    At 1:39 PM, Anonymous Samm said...

    This was very informative and well laid out. ta for that

     
    At 11:51 PM, Anonymous Anonymous said...

    Thank you for the information. I have a question & am hoping you can answer. Could any of the drugs, you mentioned, cause aborting of uterus, within a three to four day period?

     
    At 1:17 PM, Anonymous Anonymous said...

    it is interesting but what is the reference literature? I need to use a misoprostol alone regiment to a patient of mine due to inavailability of both methotrexate and mifepriston in my practice.

     
    At 1:25 PM, Anonymous pian said...

    sorry, me again. I need to know is it still imperative to do transvaginal ultrasound to confirm the termination after the dose(s) of misoprostol? forgive me but can I use something less invasive to the patient than TVU such as beta hCG monitoring,either qualitative / quantitave? how many dose can we give as the 800 mcg into the posterior fornix? you only mentioned 3 doses. do you mean that this 3 doses is a course, that can be repeated as necessary?

     
    At 9:26 PM, Blogger ema said...

    pian,

    The misoprostol-only regimen data I used in the post is from the Stewart FH, Wells ES, et al reference.

    For more reading, here's a bit from ARHP, and a PubMed search. In particular, this (review), this, this, this, and this.

    Finally, this is the article to read. It compares several regimens; of interest to you would be Arm 6 [one or two doses of 800 μg pv misoprostol wetted with saline with a 24-h interval (second dose given if intact sac at follow-up on day 2)] and 7 [two doses of 800 μg pv misoprostol wetted with saline with a 24-h interval (all women received second dose). [If you don't have access to Contraception, email me, and I'll cut&paste the article for you.]

    With the proviso that nothing I say is intended as medical advice (sorry for the disclaimer), re U/S f/u, that's the gold standard. Maybe with a good history of passing intact POCs, you could f/u with quantitative BHCG, but you'd have to keep a very close eye on this pt. [I'd be hesitant to skip the U/S.]

    That's one 800 mcg dose pv...wait and see if complete abx at f/u. If not, repeat dose [say q 24], for a maximum of three doses (if necessary) over 3 days.

    Hope this helps.

     
    At 9:30 PM, Blogger ema said...

    Ugh, here's the working ARHP link.

     
    At 5:22 PM, Anonymous Anonymous said...

    thanks alot for the info. I have gained alot cos my friend is scared that she is pregnant and is about just taking anything that comes her way. But with this i can advise her to some extent.thanks again

     
    At 5:38 PM, Blogger amit said...

    thanking u for such a nice information,which everyone must know

     
    At 9:41 PM, Anonymous Anne McGinnis Breen said...

    Mifepristone is Mifeprex and also brand name Corlux for cushings disease. I take a small dose daily to block the regrowth of my recurrent slow growing meningioma brain tumor, which has documented high progesterone receptor levels, it is alot safer than the late aftereffects of brain radiation. I wish its other benefical uses in womens health care were more widely known,instead of totally overlooked because it has such a bad reputation in the media. If you would add some of the other Pub med articles about its safe effective use for meningioma to your blog I would be very grateful. GBYAY Anne McGinnis Breen

     
    At 1:25 PM, Anonymous Anonymous said...

    it is very informative and helpful for people who have unwanted pregnancy..keep initializing

     
    At 10:22 PM, Blogger Anil Philip said...

    We are longing to adopt. Please let us know if you know anyone with an unwanted pregnancy willing to place their baby for adoption http://longingtoadopt.com

     
    At 9:12 PM, Blogger Praveen Dwivedi said...

    my wife took mispristone on the first day and then two 200 mg tablets of misopristol on the second day and then one each after every 12 hours each, but has had no effect at all, can you suggest whayt do we do now.

     
    At 10:57 AM, Anonymous Anonymous said...

    Hello. I don't know if you can help. Yesterday I took 200mg mifepristone and we most deeply regret it. Do you know what will happen if we don't take the second lot of tablets? We are distraught.

     

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