Misoprostol and Mifepristone for Medical Pregnancy Termination

Misoprostol and Mifepristone for Medical Pregnancy Termination

Misoprostol and Mifepristone for Medical Pregnancy Termination

A Practical and Secure Choice

Introduction

Unsafe abortion continues to be a severe health issue worldwide. Fifty-sixFor example,  percent, or 3.6 million, of the 6.4 million abortions carried out in India in 2002 and 2003 were unsafe (Abortion Assessment Project I, 2004). The most common procedure in obstetrics and gynecology is induced abortion, which is thought to be performed in 46 million abortions annually worldwide. (1) Mifepristone and prostaglandin were initially used for Medical Abortion in 1988 and are currently recognized in 31 nations. Since the invention of this procedure, research has concentrated chiefly on enhancing its effectiveness and identifying the best prostaglandin analog type, dose, and administration route. Finding the smallest effective dose of Mifepristone required to cause an abortion has also been the topic of numerous investigations. The comparatively high cost of Mifepristone has been a significant factor in dosage reduction. You can better comprehend the development and issues surrounding Medical Abortion with the aid of this pamphlet.

Changes in Medical Abortion

It's not a novel idea to use medications to induce abortion. In the past, women have ingested a staggering variety of drugs, tablets, decoctions, and other ingredients, including papaya, abrus precatorius, etc., to cause an abortion, according to historical records. However, most of these medications have been found to be either harmful to the health and/or even the women's lives or ineffectual as an abortifacient. The general public now believes that pharmaceutical abortion may not be very effective due to this. This is a blatantly false perception; throughout counseling, it should be underlined how safe and effective current medications are.

Identifying prostaglandins

This was a crucial milestone in the creation of safer procedures. Prostaglandin was injected intra-amniotically during the early studies. These techniques, meanwhile, could only be used to induce abortions in the second trimester. Very rapidly, a prostaglandin that could be applied vaginally was created, and it worked well in the first trimester of pregnancy. However, the disadvantages of the prostaglandin analogs that were then in use, such as the pain they caused and their gastrointestinal side effects, were significant barriers to their widespread usage. However, in addition to the issues mentioned above, myocardial infarction caused by sulprostone-induced coronary spasm and the drawbacks of gemeprost (which is unstable at room temperature, difficult to store and transport, expensive, and only available in a select few countries) led to their replacement by the safer medication Misoprostol.

Misoprostol

A synthetic prostaglandin E 1 is Misoprostol. Misoprostol causes the uterus to contract and the cervix to efface (soften). Additionally, it prevents human gastric acid secretion.

The way Misoprostol works

Misoprostol interacts with specific receptors on myometrial cells to trigger myometrial contractions. Through this interaction, calcium concentrations are altered, which starts muscular contraction. In addition, Misoprostol causes the uterus to contract and the cervix to soften, which leads to the ejection of the uterine contents. This is accomplished via interacting with prostaglandin receptors.

Misoprostol's oral and vaginal pharmacokinetics

The biologically active form of Misoprostol, free acid, which is also responsible for its clinical action, is extensively absorbed and easily digested. Following oral delivery, the plasma Misoprostol levels rose quickly, peaked at 30 minutes, then promptly decreased by 120 minutes before remaining low. Contrarily, following vaginal administration, the plasma concentration progressively rose, reaching its peak after 70–80 minutes, and then gradually decreased, becoming detectable after 6 hours. Because vaginal Misoprostol was in the bloodstream for a more extended time than oral Misoprostol, it stimulated the uterus for a more extended time than oral Misoprostol. However, a more significant dose of Misoprostol was needed when used alone for Medical Abortion, which resulted in substantial gastrointestinal side effects such as cramping, nausea, vomiting, and diarrhea.

The Spiral of Change (Discovery of Mifepristone)

Mifepristone's Mode of Action

Mifepristone is an anti-progesterone medication that suppresses progesterone's function and causes pregnancy termination. Mifepristone competes with progesterone for binding sites on progesterone receptors, which causes it to have anti-progestational effects. As a result, pregnancy is terminated due to inhibiting endogenous or exogenous progesterone action. Mifepristone dosages of 1 mg/kg or more have been demonstrated to counteract progesterone's effects on women's endometrium and myometrium. In addition, progesterone-dependent genes are down-regulated due to the receptor-Mifepristone complex, which also causes decidual necrosis and the separation of the fetus' products. When taken alone, Mifepristone had a maximum efficiency of 80%, which was discovered to be insufficient for use as an abortifacient medication in ordinary clinical practice. The fourth innovation was the revelation that Mifepristone improved the pregnant myometrium's sensitivity to prostaglandins, allowing for administering a lower dose of prostaglandin. This prompted the creation of a dual therapy that included Misoprostol and Mifepristone. Mifepristone is used to separate the pregnancy, and Misoprostol is used to expel it, to put it very simply.

Permission for Medical Abortion

The first country to legalize Medical Abortion was France in 1988, then the UK (1991), and Sweden (1992). (1992). In India, Medical Abortion was legalized in 2002. The MTP act permits medication abortions up to 49 days after conception. For this to happen, the provider must fully comply with the MTP act, including filling out Form C and the MTP registry.

Up to 49-day regime

Day 1: 200 mg orally of Mifepristone Anti-D to Rh-negative patient after injection Day 3: Misoprostol 400 mg orally or vaginally on day three. Day 14: Follow-up visit to determine whether abortion was successfully completed, ideally clinically or by ultrasound if necessary. The Drug Controller Authority of India has approved the use of the Combipack of Mifepristone & Misoprostol for up to 63 days after LMP.

49 to a 63-day regime

Day 1: Mifepristone 200 mg orally. Inj. Anti-D to the patient with Rh negativity. Day 3: Misoprostol 800, preferably vaginally but also sublingually or buccally. Day 14: Clinical evaluation follow-up appointment. According to the MTP Act, a registered medical practitioner (as defined in the act) may prescribe medical techniques for termination of pregnancy for up to seven weeks if they have access to a location authorized by the government under Section 4 (b) and Rule 5 of the MTP Rules. RMP must have a certificate from the owner of the assigned location stating as much. In addition to the regimen above, the following regimens are also used.

1. 2000 US FDA authorized regime:

The dosage is permitted for gestations lasting up to 49 days. Day 1: 600 mg of Mifepristone orally Day 3: 400 mg orally of Misoprostol Day 14: Follow-up appointment to determine whether the abortion has been successfully completed clinically, through ultrasonography, or by observing a significant drop in serum beta-hCG levels. If a viable pregnancy is found at this time by ultrasonography, surgical termination is advised since the pregnancy could continue and there is a chance of a fetal abnormality.

2. The Royal College of Obstetrics and Gynecology (RCOG) and the World Health Organization both suggest this regimen (WHO)

The program is advised for gestations lasting up to 63 days. Day 1: 200 mg orally of Mifepristone Day 3: Misoprostol 800? vaginally If abortion has not occurred 4 hours after Misoprostol administration in women between the ages of 49 and 63, the second dosage of 400 mcg of Misoprostol may be given orally or vaginally. Day 14: Follow-up appointment to determine whether the abortion has been successfully completed clinically, through ultrasonography, or by observing a significant drop in serum beta-hCG levels. Surgical termination is advised if a viable pregnancy is discovered at follow-up since the pregnancy could continue and there is a chance of a fetal abnormality.

Counseling

It might be accurate to state that counseling significantly influences how patients see pharmacological abortion. Counseling needs to be appropriate, nonjudgmental, and private. The following conversational topics should be covered at a minimum, and any doubts the patient may have should be clarified. Up to 10 to 14 days may pass between periods of bleeding. Usually, it mimics a heavy, protracted menstrual cycle. The patient should tell the doctor immediately if she notices significant bleeding or starts passing clots. On rare occasions, the patient may observe the fetal products during ejection. You ought to tell her that. Typically, these appear as pinkish lumps. Again, she should be informed that this is normal and part of the procedure. The process usually requires three visits. In the unlikely event that a medical procedure fails, any retained fetal material, Surgical completion of the abortion can be necessary if there is considerable bleeding. To avoid another unintended pregnancy after an abortion, contraception is essential.

Confirmation of Termination of Pregnancy

Following the administration of Mifepristone, patients should be scheduled for and attend a follow-up appointment to ensure that the pregnancy has been fully terminated and to gauge the severity of bleeding. Vaginal bleeding is not proof that a pregnancy has ended. Clinical examination or an ultrasonographic scan can both verify termination. However, a lack of bleeding after treatment typically denotes failure. Therefore, surgical termination should be used to treat failed Medical Abortions. It is crucial to emphasize that ultrasound should never be viewed as a necessary step in the overall medication abortion process. Instead, it is a tool that the clinician must employ as directed.

The success of these Regimens

Actual drug failure is characterized as the existence of heart activity two weeks after the delivery of Mifepristone and Misoprostol. However, only 1% of women experience it, and surgery should be used to treat it. In research, women desiring to end a pregnancy up to 49 days gestation used 600 mg of Mifepristone followed by 400? of Misoprostol orally, and 92% of patients experienced a complete abortion; 8% of patients required a Surgical Abortion. In the latter, incomplete abortion accounted for 5% of Surgical Abortions, and continued pregnancy accounted for 1%. While 0.6 percent of the patients asked for intervention, 2 percent had a medical need for one. (2) Using 200 mg of Mifepristone orally followed by 800 mg of Misoprostol orally, 2,000 women with pregnancies up to 63 days of gestation were treated in a series of cases, and 97.5 percent of the patients experienced a complete abortion. 2.5 percent of the patients required surgical evacuation, with the causes being an incomplete abortion in 1.4 percent of cases, a missed abortion in 0.4 percent of cases, and a continuing pregnancy in 0.6 percent of cases. (3)

Birth Control

In addition to the technique itself, counseling for post-abortion contraception is a crucial component of the process. This is because the lady can become pregnant immediately or even before her next period. Therefore, the patient must start using contraception right away following the abortion. As soon as it is recognized that the pregnancy is over, birth control techniques should be used. Almost all forms of contraception are usable.

Contraindications

One of the safest medical treatments is abortion overall, and medication abortion in particular. But unfortunately, there aren't many situations where a Medical Abortion is unavoidable. These\s include:
  1. An allergy to one of the medications implicated in the past 1.
  2. Porphyria inherited.
  3. Continual adrenal dysfunction.
  4. Ectopic pregnancy, either known or suspected.

Exercise Caution When

  1. A woman (including those with severe, uncontrolled type 1 asthma) is receiving long-term corticosteroid medication.
  2. She suffers from the hemorrhagic disease.
  3. She is seriously anemic.
  4. She already has cardiovascular risk factors or a history of heart disease (i.e., hypertension and smoking).

Special Circumstances

Age

Neither adolescent nor advanced age (such as 35 years or more) should be viewed as a barrier to getting a Medical Abortion.

Anemia

This may not necessarily constitute a contraindication. But any anemia discovered at the time of the abortion must be treated. In addition, average blood loss and the likelihood of severe bleeding may be higher in medicinal abortions than in surgical ones.

Breastfeeding

Mifepristone is probably excreted in breast milk. Soon after administration, trim levels of Misoprostol also make their way into breast milk. However, it is unknown if this could impact the baby. It has been suggested that Misoprostol be taken immediately after a feed and the next feed given after 4 hours in case of oral administration because Misoprostol levels rapidly fall. However, Misoprostol levels remain high for a more extended period after vaginal administration. Hence the meal should ideally be given more than 6 hours later. Unfortunately, specific advice on the ideal time cannot be made given the data at hand.

Continuation of Pregnancy Following Administration (Medication Abortion Failure)

Mifepristone

There is no other approved use for Mifepristone during pregnancy outside the termination of pregnancies (up to 49 days gestation). There is a chance that the medication will cause a fetal abnormality in patients who were still pregnant at their most recent visit. Medical Abortion therapy failures are managed by surgical termination.

Misoprostol

According to several publications in the literature, prostaglandins, including Misoprostol, may have teratogenic effects on humans. After exposure during the first trimester, there have been reports of limb deformities, face malformations, cranial nerve palsies, delayed growth and psychomotor development, and skull defects. Insulin-dependent diabetes or a thyroid condition There is no proof that Medical Abortion affects women with these diseases in a particular way. Mifepristone has been demonstrated to alter insulin sensitivity in vitro. However, whether these changes are reflected in blood sugar and insulin levels is unknown. Several Pregnancies (Current Gestation) There is no proof that multiple pregnancies necessitate a different dosing schedule or that the failure rate of Medical Abortion increases. Obesity There is no proof that Medical Abortions are more likely to fail or that obese women need a modified dosing schedule. respiratory asthma You can use Misoprostol with Mifepristone. Previous Caesarian Section According to one study, prior cesarean sections have no impact on the safety and effectiveness of early Medical Abortion. Smoking There is no proof that the dangers of smoking and Medical Abortion interact. Smoking, however, raises cardiovascular risk. Thus this aspect should be considered when determining a woman's general fitness for a Medical Abortion. Congenital and acquired uterine malformations; prior cervical surgery. No proof exists that these are contraindications.

FAQ's

The following list includes some of the problems that need to be solved. Of course, there are more questions than one can possibly address, but we hope the following may be helpful:

1. Is it important how long passes between administering Mifepristone and administering prostaglandin?

The uterus is most susceptible to prostaglandin after being primed with Mifepristone during the licensed and most frequently used interval of 36–48 hours; as a result, the therapeutic dose can be decreased to the absolute minimum. Recently, it has been demonstrated that the interval can be extended to 72 hours or reduced to 24 hours without losing effectiveness when Mifepristone is combined with 800? of vaginally delivered Misoprostol. If 400mcg of Misoprostol is administered orally, the 36–48 hour window should be followed. There is currently research being done on other periods.

2. What type of painkillers ought to be offered to women having Medical Abortions?

Both the act of having an abortion and the prostaglandin's adverse effects result in pain. When the gestational sac or embryo is being ejected from the uterus a few hours after the prostaglandin was administered, this is when it is most likely to be felt. Therefore, all women who seek analgesia for a Medical Abortion should have easy access to appropriate analgesia. Paracetamol 500–1,000 mg and non-steroidal anti-inflammatory medications (NSAIDs), including ibuprofen 200 mg, are two examples of frequently used formulations. Codeine 30–40 mg may be administered to either of the treatments above in cases of extreme discomfort.

3. Are the medications used for Medical Abortion having any unfavorable side effects?

The medical procedure is intended to cause the uterine cramping and vaginal bleeding required to cause an abortion. However, almost all the women who get Mifepristone and Misoprostol will experience side effects, and many of them are likely to experience several side effects. These are listed below:
  1. Gastrointestinal side symptoms include nausea, vomiting, headache, dyspepsia, stomach pain, diarrhea, and constipation.
  2. Shivering.
  3. Hyperthermia.
  4. Dizziness.
  5. Uterine contraction-related discomfort.
  6. Profound genital bleeding.
  7. Shock.
  8. Back pain.
  9. Uterine rupture (requiring a hysterectomy, salpingo-oophorectomy, or other surgical procedure).

4. Is there a chance of Misoprostol and Mifepristone being overdosed?

Mifepristone

Mifepristone was given to healthy, non-pregnant women for intolerance tests in single doses larger than three times of 600 mg (1,800 mg) for the termination of pregnancy without any significant adverse responses being noted. However, a patient who consumes a considerable overdose should be thoroughly monitored for indications of adrenal failure. For the mouse, rat, and dog, the oral acute fatal dose of Mifepristone is more significant than 1,000 mg/kg.

Misoprostol

The clinical symptoms of sedation, tremor, convulsions, dyspnea, stomach pain, diarrhea, fever, palpitations, hypotension, or bradycardia could point to an overdose. Supportive therapy should be used to treat the symptoms. If Misoprostol acid can be dialyzed is unknown. However, it is unclear whether dialysis would be a suitable treatment for an overdose because Misoprostol is metabolized similarly to a fatty acid. 5. Are there any dangers or warnings to be heeded before, during, or after a Medical Abortion?
  1. All non-sensitized RhD-negative women should receive Anti-D IgG (250 IU before 20 weeks of gestation and 500 IU after). Injection into the deltoid muscle within 72 hours of an abortion, whether it was performed surgically or medically.
  2. Facilities for intravenous fluids and emergency curettage should be offered or dependably established. 2. for using other suppliers.
  3. Please verify that the patient is not anemic and rule out any other conditions that would make the drugs being given to them contraindicated. In addition, confirm that there is no suspicion of an ectopic pregnancy.
  4. Inform the patient of what to anticipate (pain, bleeding, product passing, etc.) and what to report and when.
  5. Clearly explain to the patient what to do and who to call in an emergency.
Women value having various abortion options available, and in an ideal world, these options would be provided as part of comprehensive abortion services. Mifepristone and Misoprostol are used in Medical Abortions, which are safe, viable, and acceptable options for women.

6. Is Surgical Uterus Evacuation Necessary If a Woman Has an Incomplete Abortion?

After a Medical Abortion, vaginal bleeding typically lessens gradually over around two weeks, but spots can occasionally linger up to 45 days. Bleeding following a Medical Abortion typically lasts longer than bleeding after a vacuum aspiration. Both prolonged bleeding and the presence of tissue in the uterus (as seen by ultrasound) do not call for surgical intervention if the mother is healthy. Instead, the remainder of the fetus will be thrown out with the ensuing vaginal hemorrhage. Surgery to remove the uterus may be performed:
  1. Upon the woman's wish.
  2. If there is excessive, continuous bleeding or anemia resulting from it.
  3. Prior to surgery, antibiotics should be started if there are signs of infection.

7. Which Contraception Techniques Can a Woman Use After a Medical Abortion?

  • When misoprostol is delivered, combined oral contraceptives can be started when expulsion usually occurs. It does NOT affect complete abortion rates, side effects, and duration of bleeding. In addition, it does not impact the frequency, severity, or length of complete abortions.
  • Breakthrough bleeding is frequently linked to progestogen-only treatments, which may be similar to an incomplete abortion.
  • Amenorrhea and depot-medroxyprogesterone injections and implants are frequently linked. Erratic bleeding, which could make it challenging to tell whether a pregnancy has ended. Therefore, it might be best to wait to use these techniques until it has been determined that the pregnancy has been terminated.
  • Delaying sterilization and inserting an intrauterine device until verification that the Abortion is finished.
  • Barrier techniques can be applied as soon as sex is resumed, ideally after the bleeding has ceased.
  • Natural family planning techniques can only be restarted if regular cycles have returned.
References 1. Contraception 2006; 74: 66-86. Christian Fiala, Kristina Gemzell-Danielsson 2. NEJM 1998; 338: 1241-7. Spitz IM, Bardin CW, Benton L, Robbins A. 3. Human Reprod. 1998; 13 (10): 2962-2965. Ashok PW, Penney GC, Flett GMM, Templeton A. 4. Adapted from WHO 2018: Frequently asked clinical questions about Medical Abortion.