An historical overview of second trimester abortion methods.

The methods used for abortion in the second trimester have changed considerably in recent years. The surgical procedure dilatation and evacuation (D&E) has replaced hysterotomy. Instead of injecting different compounds, such as hypertonic saline, prostaglandin analogues are administered by non-invasive routes. The most effective medical method is combining a prostaglandin analogue with mifepristone. The consequence of these developments is that abortion in the second trimester can be be performed significantly more effectively and that the currently recommended methods being used are associated with fewer side effects and complications.

Studies on uterine contractility following mifepristone and various routes of misoprostol.

During pregnancy, uterine contractility is suppressed by progesterone. The progesterone receptor inhibitor, mifepristone, increases uterine contractility and sensitizes the myometrium to prostaglandin. The maximum effect is achieved when prostaglandins are administered 36 to 48 h after mifepristone. The recommended prostaglandin analogue used with mifepristone for medical abortion is misoprostol. It is licensed for oral use but other routes are used to improve efficacy. The difference in the effect of various routes of administration can be explained by pharmacokinetics and the effect on uterine contractility. Oral misoprostol leads to an increased uterine tonus without regular contractions. In contrast, vaginal and sublingual administration leads to a longer-lasting effect on the myometrium and subsequent development of regular contractions. Recently, a new oral slow-release preparation of misoprostol has been studied. Future studies will show whether prostaglandin analogues with a prolonged effect on the myometrium may further improve the regimens for medical abortion.

Effect of emergency contraception with levonorgestrel or mifepristone on ovarian function.

The mechanism of action of levonorgestrel (LNG) and mifepristone (MIF) in emergency contraception (EC), is still not fully known. The purpose of this study was to evaluate the effect of preovulatory treatment with LNG and MIF on luteal function in more detail. Two days prior to ovulation (day -2; assessed by ultrasound), we administered LNG (0.75 mg twice, 12 h apart) or MIF (10 mg, single dose) to seven women in different cycles. Follicle development was followed by ultrasound. Urinary estrone glucuronide (E1), pregnanediol glucuronide (P4) and luteinizing hormone (LH) were analyzed by enzyme immunoassays daily starting with day -2 for the rest of the menstrual cycle, along with urinary creatinine (C). The treatment caused either a delay or an inhibition of the LH peak in all subjects. A significant delay in P4 levels and an initial suppression of E1 levels were also noted. The development of the leading follicle was either arrested or continued without signs of rupture. This study indicates that, when used for EC, LNG or MIF administered prior to ovulation acts through an impaired ovulatory process and luteal function.

From research to reality: the challenges of introducing medical abortion into service delivery in Vietnam.

Following the inclusion of mifepristone + misoprostol for early pregnancy termination into the Vietnam National Reproductive Health Guidelines in 2002, a team from the Ministry of Health, World Health Organization and Ipas assessed how best to move from clinical research to widespread public sector availability. After field visits to hospitals and discussions with stakeholders, the team endorsed the phased introduction of medical abortion alongside vacuum aspiration services to expand choice. They stressed the importance of patient-oriented information on what to expect as the abortion process takes place and the need for follow-up, also crucial in training of providers. Routine use of ultrasound to detect ectopic pregnancies or determine that abortion was complete was considered unnecessary The mandated four-hour observation period following misoprostol administration could be reduced. The National Guidelines, appropriately conservative at the start of the programme, should be amenable to modification as experience grows. Introduction is not possible without a steady supply of drugs at affordable prices. Ways to reduce the high price of mifepristone and deal with provider expectations of extra allowances, as with surgical abortion, are needed. Making medical abortion a viable option for most Vietnamese women will require provision at commune-level clinics through mid-level providers, and with home use an option. Other challenges include use of misoprostol alone and regulating provision in the private sector.

The possibility of using mifepristone for menstrual induction.

Menstrual induction is a variant of suction aspiration that was originally defined to be performed in women with a menstrual delay of up to 2-3 weeks without knowing if the women is pregnant or not. Prerequisites for a pharmacological method for menstrual induction are a high efficacy to induce a bleeding in nonpregnant women and an expulsion of the pregnancy in pregnant women. Treatment with prostaglandins, specifically intramuscular sulprostone, can be as effective as suction aspiration for menstrual induction. However, the administration of prostaglandin in therapeutically effective doses was associated with a high frequency of gastrointestinal side effects and, to a lesser extent, of strong abdominal pain, which limited their routine use. More recent studies indicate that mifepristone in combination with either misoprostol or gemeprost is a more promising alternative. Further studies to identify the best treatment schedule are, however, needed, as is a randomized comparison with suction aspiration before a pharmaceutical method can be recommended.

Effects of mifepristone on endometrial receptivity.

At the development of receptivity the endometrium undergoes specific changes. Several factors have been suggested as markers of endometrial receptivity. A common feature for most of these factors is that they are directly, or indirectly, regulated by progesterone. The effect of various doses and regimens of mifepristone on endometrial development and markers of receptivity has been studied. Timed endometrial biopsies were assessed by immunhistochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and electron microscopy. In addition the contraceptive efficacy of these regimens was investigated. Administration of 200 mg of mifepristone immediately post ovulation has a pronounced effect on endometrial development and on suggested markers of receptivity. This regimen has been shown to be an effective contraceptive method. When 10 mg is given pre or post ovulation, only minor effects on the endometrium are observed. Our studies show that mifepristone, when administered in low doses that do not affect ovulation, significantly affects some of the studied markers of endometrial receptivity and reduces pregnancy rates; however, these activities are more pronounced with the higher dose, which is more effective. Our findings provide insight into the regulation of progesterone receptors of various suggested markers of endometrial receptivity and the possibility of using mifepristone for endometrial contraception.

Pharmacokinetics of prostaglandins.

Naturally occurring prostaglandins (PGs) are rapidly metabolized in the human circulation. For clinical use a number of PG analogues have therefore been developed which are resistant to rapid inactivation. Among these are carboprost, gemeprost and misoprostol. Following intramuscular injection of carboprost, plasma levels peaked after 20 minutes and declined slowly thereafter. In amniotic fluid the half-life was between 31 and 37 hours. Gemeprost is administered vaginally, and maximum plasma levels were reached after 2-3 hours, with detectable levels for at least 6-8 hours. Pharmacokinetic data on misoprostol are available following oral, vaginal and sublingual administration. Following oral treatment, plasma levels peaked at about 30 minutes, while after vaginal administration of the tablets the levels increased gradually and reached maximum levels after 70-80 minutes, but remained detectable for a significantly longer time. After sublingual administration the peak concentration was the same as for oral treatment but declined significantly more slowly. Endocervical administration of PGE(2) might be regarded as a local therapy, while following vaginal administration increased plasma levels of metabolites can generally be found. The plasma profile varies with the vehicle used.

Verifying the effectiveness of medical abortion; ultrasound versus hCG testing.

OBJECTIVES: The combination of mifepristone and misoprostol is an established method for termination of pregnancy. However, there is no general agreement about how best to evaluate the treatment outcome. STUDY DESIGN: In 217 women with an unwanted pregnancy below 49 days of amenorrhoea, ultrasound examination and serum hCG test were performed before treatment and at follow-up. RESULTS: Treatment was successful in 98.2%. At follow-up their hCG dropped to a mean of 3% (S.D. 3) of initial levels and the endometrium measured a mean of 10 mm (S.D. 4). Interpretation of endometrium was difficult in some cases because of inhomogeneous structure. Using hCG was reliable in 98.5% of successful abortions. For ultrasound the corresponding figure was 89.8% for the cases with a confirmed intrauterine pregnancy before treatment but only 66% if all pregnancies were included. CONCLUSION: Measuring serum hCG before treatment and at follow-up is more effective than ultrasound to confirm a successful medically induced abortion in early pregnancy.

Options for early therapeutic abortion: a comparative review.

Vacuum aspiration, either manual or electric, has for many years been the most commonly used method for termination of an early pregnancy. More recently, new medical methods have been developed which for many women are attractive alternatives to the surgical procedure. The compounds mainly used are prostaglandin analogues, methotrexate, and mifepristone in combination with a suitable prostaglandin analogue. However, only the last method has been registered for routine clinical use. The treatment schedule mainly used is mifepristone 200 to 600 mg followed 36 to 48 hours later by oral misoprostol 0.4 to 0.6 mg in pregnancies up to 49 days and vaginal gemeprost 1.0mg or misoprostol 0.8 mg if the treatment period is extended to 63 days of amenorrhoea. The ability to compare medical and surgical methods is limited by the fact that there are few randomised studies and the definitions of successful outcome (complete abortion), adverse effects and complications vary from one study to the other. Experience with the method used is also important for the outcome. However, it seems adequate to state that the medical method is equally, or almost equally, as effective as vacuum aspiration. Duration of bleeding and amount of blood loss is greater following medical abortion. Also the frequency of uterine pain, vomiting and diarrhoea is higher following medical abortion than following vacuum aspiration. On the other hand, the frequency of major complications such as excessive bleeding, blood transfusion and pelvic infection does not seem to differ between the two procedures. Surgical complications, for example, uterine perforation and cervical tears, are obviously not a risk associated with medical abortion. Both methods are equally well accepted provided the woman is allowed to choose. It is not possible to state which method is best. Medical termination of early pregnancy will not replace, but is an alternative to, vacuum aspiration and ideally both methods should be available to give the woman a choice.