Mifepristone-misoprostol for menstrual regulation in public sector facilities in Bangladesh.

OBJECTIVE: To examine the use of mifepristone and misoprostol for menstrual regulation among Bangladeshi women attending public sector facilities. METHODS: In a prospective study, women (aged ≥18 years) with up to 9 weeks of amenorrhea were enrolled at 24 government health facilities in Bangladesh from November 2012 to June 2015. Paramedics or female welfare visitors provided most menstrual regulation care. Participants took 200 mg mifepristone followed by 800 µg buccal misoprostol after 24 hours, and were asked to return to the clinic 10-14 days later for clinical assessment and an exit interview. The primary outcome was successful evacuation of the uterus without need for surgical intervention. Women who completed follow-up were included in analyses for the primary outcome. RESULTS: Among 1744 enrolled participants, 1738 completed follow-up. Most (1674, 96.3%) had a successful uterine evacuation without the need for surgical intervention. A successful outcome was significantly more common in primary (724/744, 97.3%) and secondary facilities (861/895, 96.2%) than in the specialty hospital (89/99, 89.9%; P<0.001 and P=0.004, respectively). CONCLUSION: Menstrual regulation with mifepristone and misoprostol can be provided effectively in public sector facilities in Bangladesh. CLINICALTRIALS.GOV: NCT01798017.

The regulatory cliff edge between contraception and abortion: the legal and moral significance of implantation.

In regulating the voluntary interruption of pregnancy, English law has accorded particular significance to two biological events. First, 'viability', the moment when a fetus is said to acquire the capacity for independent life, plays an important role in grounding restrictions on access to legal abortion later in pregnancy. Second, equally significantly but far less frequently discussed, 'implantation' marks the point in pregnancy from which abortion laws apply. This paper focuses on this earlier biological event. It suggests that an unquestioning reliance on implantation as marking an appropriate moment of transition between two radically different legal frameworks is deeply problematic and is rendered still less sustainable in the light of the development of new technologies that potentially operate shortly after the moment of implantation.

Acceptability and feasibility of mifepristone-misoprostol for menstrual regulation in Bangladesh.

CONTEXT: Annually, more than 700,000 women turn to menstrual regulation, or uterine evacuation with vacuum aspiration; many more resort to unsafe abortion. Using pills for the evacuation of the uterus could increase women's access to safe menstrual regulation services and reduce the high levels of abortion- and menstrual regulation- related morbidity in Bangladesh. METHODS: At 10 facilities in Bangladesh, 651 consenting women who were seeking menstrual regulation services and who were 63 days or less past their last menstrual period received 200 mg of mifepristone followed 24 hours later by 800 mcg of buccal misoprostol, administered either at home or in the clinic. Prospective data were collected to determine women's experience and satisfaction with the procedure, menstrual regulation outcome, and the human and physical resources required for providing the method. Focus group discussions were conducted with a purposively sampled group of service providers at each site to understand their attitudes about the introduction of menstrual regulation with medication. RESULTS: The majority of women (93%) with known menstrual regulation outcomes evacuated the uterus without surgical intervention. Overall, most women (92%) were satisfied with use of pills for their menstrual regulation. Providers faced initial challenges and concerns, particularly related to the additional counseling requirements and lack of control over the final outcome, but became more confident after successful use of the medication regimen. CONCLUSIONS: Mifepristone-misoprostol can be safely offered within existing menstrual regulation services in urban and periurban areas in Bangladesh and is highly acceptable to women. Providers' initial concerns diminish with increased experience with the method.

Endometrial shedding effect on conception and live birth in women with polycystic ovary syndrome.

OBJECTIVE: To estimate whether progestin-induced endometrial shedding, before ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS). METHODS: A secondary analysis of the data from 626 women with PCOS from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed). RESULTS: Although ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live births per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; P<.001). The difference was more marked when rate was calculated per ovulation (live births per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; P<.001). CONCLUSION: Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared with anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin before ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS. LEVEL OF EVIDENCE: II.

Intratumoral hemorrhage of mammary phyllodes tumor after menstrual induction: a puzzling presentation.

BACKGROUND: Mammary phyllodes tumor is an uncommon stromal-epithelial neoplasm with a reported incidence of 0.3% to 0.5% of female breast tumors. Sudden, rapid growth of a mammary phyllodes tumor with intratumoral hemorrhage was noted in a 45-year-old woman after menstrual induction with progesterone and norethindrone acetate. This case is presented here to highlight the possibility of such an onset of phyllodes tumor in order to facilitate its prompt diagnosis. CASE PRESENTATION: A 45-year-old woman suffered from missed periods for 2 months and received progesterone for menstrual induction. After treatment, rapid enlargement of her left breast was noted. Tracing the history of the patient, we found that she had already felt an about 3 cm painless lump in her left breast 5 months before this episode. Sonography of the left breast showed a large cystic lesion with some echogenic content and about 150 mL of old blood was obtained by aspiration. Surprisingly, follow-up breast sonography 3 weeks later revealed a large irregular solid mass and a small amount of peripheral cystic content with markedly increased vascularity. Surgery was suggested. A large encapsulated mass consisting of heterogeneous yellow soft tissue and a cystic component measuring 10 x 8 cm was totally excised. Microscopically, the sections revealed branching and cystically dilated glands lined by cuboidal to columnar epithelial cells in a myxoid hypercellular fibroblastic stroma with hyperchromatic nuclei and frequent mitotic figures. The final histological diagnosis was malignant phyllodes tumor. CONCLUSION: Progesterone for menstrual induction may cause rapid growth of a phyllodes tumor with resultant internal hemorrhage. Only with the awareness of this entity can a prompt diagnosis be made and optimal treatment be given.

A pilot study of mifepristone and misoprostol administered at the same time for abortion in women with gestation from 50 to 63 days.

INTRODUCTION: In the interest of decreasing the amount of time it takes to achieve a medical abortion, we performed a pilot study to evaluate the simultaneous administration of mifepristone and vaginal misoprostol for women with gestation from 50 to 63 days. MATERIALS AND METHODS: Forty women were enrolled with undesired pregnancies from 50 to 56 days' gestation (group 1) and 40 from 57 to 63 days' gestation (group 2). All women used misoprostol 800 mug vaginally immediately after having swallowed the 200 mg mifepristone tablet. Follow-up evaluations with transvaginal ultrasonography occurred at 24 h and 2 weeks after treatment. RESULTS: The 24-h expulsion rates were 88% (95% CI, 77-98) and 83% (95% CI, 7-94) in groups 1 and 2, respectively. The complete abortion rates at 2 weeks were 93% (95% CI, 84-100) and 90% (95% CI, 81-99), respectively. DISCUSSION: Simultaneous administration of oral mifepristone and vaginal misoprostol provides 24-h expulsion rates in women with gestation from 50 to 63 days, comparable to those reported in the medical literature for standard treatment regimens. Further study of this regimen in a large randomized trial is warranted.

Willing and able? Provision of medication for abortion by future internists.

INTRODUCTION AND BACKGROUND: The development of medications such as mifepristone (RU486) has created the opportunity to introduce medication abortion as a component of office practice. METHODS: Two hundred twelve residents training in internal medicine, family practice, and gynecology at 11 residency programs completed anonymous surveys assessing willingness to provide medication for abortion and perceived barriers to future provision of mifepristone. RESULTS: Residents training in internal medicine knew less about mifepristone and preabortion screening than other primary care trainees. Forty-two percent of internists, 84% of family practitioners, and 83% of gynecologists were willing to prescribe mifepristone (p < .001). Many internists were concerned about lacking adequate "backup" access to vacuum aspiration services (84% of internists, 74% of family practitioners, 35% of gynecologists; p < .001). In multivariable analysis, the training-related factors most predictive of whether an internist was willing to provide medication for abortion were feeling that mifepristone is very safe, abortion services are needed by the patients served, knowing to check an ultrasound before inducing abortion, and having no concern of how to manage bleeding or of lacking adequate backup should vacuum aspiration be needed. CONCLUSIONS AND DISCUSSION: Many (42%) future internists are willing to provide mifepristone, but most lack adequate knowledge of mifepristone and preabortion screening. As access to abortion services is limited in many U.S. counties, internists who are willing to provide mifepristone should be offered the necessary training to do so safely.

Emergency postcoital contraception.

Emergency postcoital contraception, a method used to prevent pregnancy after unprotected sexual intercourse, is a highly effective but underutilized birth control option. Two hormone regimens, ethinyl estradiol (100 microg) with levonorgestrel (0.5 mg) or high-dose levonorgestrel (0.75 mg), given within 72 hours of intercourse and repeated 12 hours later, are available for this purpose. These regimens are packaged as Food and Drug Administration labeled, dedicated products or can be adapted for use from standard oral contraceptive pills. Emergency postcoital contraception should be considered as a primary prevention health service to women of childbearing age.

Nonsteroidal progestins and antiprogestins related to flutamide.

From the dual progestin/antiandrogenic properties of certain synthetic steroids (e.g. cyproterone acetate), it was apparent that the progesterone (P) and androgen (A) receptors must have some common ligand binding features. The nonsteroidal antiandrogen (aA) hydroxyflutamide was therefore considered a possible starting point for medicinal chemistry aimed at antiprogestin (aP) activity. Various modifications to the side chain and aryl ring substituents of flutamide yielded both P and aP activity, but always coupled with varying degrees of A or aA activity. Mineralocorticoid activity was present in some structures, but glucocorticoid and antiglucorticoid activities were not detected. Species (rat, rabbit and monkey) and chiral differences presented formidable difficulties in developing simple structure activity patterns, and low ( < 1%) in vitro uterine receptor binding belied in vivo potency of some aPs. One of the most active aPs, ZM172406, the R enantiomer of ZM150271, N-(3-chloro-4-cyanophenyl)-3,3, 3-trifluoro-2-hydroxy-2-methylpropanamide, had comparable oral potency to mifepristone in rats and monkeys. The racemate ZM150271 was an effective abortifacient during early pregnancy in pigtailed monkeys (3 x 10 mg/kg) but less effective in cynomolgus monkeys. One of the most active progestins (Pn), ZM182345, N-(4-nitro-3-trifluoromethylphenyl)-4-phenyl-2-hydroxy-2-trifluoromet hyl-pentanamide, was at least as potent as P in rats and rabbits but also possessed A activity.

Once-a-month treatment with a combination of mifepristone and the prostaglandin analogue misoprostol.

In this two centre study, the efficacy of 200 mg mifepristone orally followed 48 h later by 0.4 mg misoprostol orally for menstrual regulation was investigated. The dose of mifepristone was taken the day before the expected day of menstruation. Each volunteer was planned to participate for up to 6 months. A plasma beta human chorionic gonadotrophin (HCG) was measured on the day of mifepristone intake. The study was disrupted prematurely due to low efficacy. In 125 treatment cycles the overall pregnancy rate was 17.6% (22 pregnancies) and the rate of continuing pregnancies (failure) was 4.0%. Eight women discontinued the study due to bleeding irregularities which were seen in 15 cycles (12%). These effects on bleeding pattern made the timing of treatment day difficult. Late luteal phase treatment with a combination of mifepristone and misoprostol is not adequately effective for menstrual regulation.

PIP: A 2-center study was undertaken to examine the efficacy, safety and acceptability of a once-a-month administration of a combination of 200 mg mifepristone and 0.4 mg misoprostol for menstrual regulation in the late luteal phase. About 24 women from Shanghai and 8 from Stockholm were administered 200 mg mifepristone taken orally before or on the day of menstruation, followed by 0.4 mg misoprostol taken orally after 48 hours. Urine samples were collected during 3 days before to 4 days after ovulation for an analysis of luteinizing hormone. In addition, a plasma beta human chorionic gonadotrophin was measured immediately before intake of mifepristone. Volunteers were to participate for 6 months, but the study was disrupted prematurely due to low efficacy. In 125 treatment cycles, the total pregnancy rate was 17.6% (22 pregnancies) and the failure pregnancy rate was 4.0%. Discontinuation of the study among 8 women was due to bleeding disturbances seen in 15 cycles (12%). In conclusion, late luteal phase treatment with a combination of mifepristone and misoprostol was not effective enough to be used for menstrual regulation.

[Should antiprogesterone be used in pregnancy termination?]. / Bør antiprogesteron tas i bruk ved svangerskapsavbrudd?

PIP: The antiprogesterone mifepristone (RU-486) and a prostaglandin preparation (misoprostol), in combination, have been documented to be effective for inducing abortion in France, Sweden, and Great Britain. They are effective up to 63 days of gestation with a slightly longer period of bleeding, pain requiring analgesia, diarrhea, and nausea. In Sweden, 70% of abortions are carried out by the use of drugs. In Norway, medically induced abortion has been introduced as an alternative to surgical intervention. The patient takes mifepristone in a hospital under the supervision of health personnel, then 48 hours later the prostaglandin is administered transvaginally in the hospital where the abortion also takes place. About 4 weeks later, a check-up follows with clinical examination and a pregnancy test. The political debate about medical abortion has also flared up in Norway as in many other countries, mainly in connection with the issue of abortion decided by the individual. In 1989 there was a motion introduced in the Parliament to ban medically induced abortion, but it failed to be adopted. The argument that abortion could be used for contraception is not supported, because there was almost the same rate of decline of abortions in Sweden, where this had been used for several years during the period of 1991-94, as in Denmark, Finland, and Norway, where it had not been. From an ethical point of view, abortion should be the simplest and least invasive, and it could also be less stigmatizing in a hospital because of the outpatient status. The better use of resources for other women waiting for operations also advocates this method as does its acceptability to women.^ieng

Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women.

The effectiveness of a sequential regimen consisting of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles was assessed in 10 surgically sterilized volunteers who were followed for one pretreatment and three treated cycles. Hormonal determinations in blood and urine, ovarian ultrasonography, bleeding records in all cycles and an endometrial biopsy taken on day 22-25 of the third treatment cycle were used to monitor the effects of treatment. During treatment, 24 monophasic (no sustained progesterone rise above 12 nmol/l) and six biphasic cycles were recorded. Nine follicular ruptures were detected echographically in these 30 treated cycles, five of which occurred in monophasic cycles. All follicular ruptures occurred on days 1-7 of NOMA treatment. Echographic and endocrine features of ovulatory cycles were both present in only four treated cycles (13.3%). Development of a secretory endometrium was achieved in all cases, but it was always irregular. Regular withdrawal bleeding occurred in all subjects and no adverse reactions were recorded. The ovarian and endometrial effects of this regimen justify testing its contraceptive effectiveness in phase 2 clinical trials.

PIP: This study investigated the efficacy of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles in 10 surgically sterilized volunteers. To monitor the effects of treatment, hormonal determinations in blood and urine, ovarian ultrasonography, bleeding records in all cycles and endometrial biopsy were taken on day 22-25 of the third treatment cycle. About 24 monophasic and 6 biphasic cycles were recorded during treatment. About 9 follicular ruptures were echographically detected in these 30 cycles, 5 of which occurred in monophasic cycle. All follicular ruptures occurred in days 1-7 of NOMA treatment. Echographic and endocrine features of ovulatory cycles were both present in only four treated cycles (13.3%). Development of a secretory endometrium was achieved in all cases, but it was always irregular. Regular withdrawal bleeding occurred in all subjects and no adverse reactions were observed. The ovarian and endometrial effects of this regimen justify testing its contraceptive effectiveness in phase 2 clinical trials.

Anti-implantation activity of luteal phase mifepristone administration is not mimicked by prostaglandin synthesis inhibitor or prostaglandin analogue in the rhesus monkey.

The use of mifepristone as an anti-implantation agent in the primate has been explored in the rhesus monkey with two specific aims: (i) to determine the contraceptive efficacy of very low-dose mifepristone administered on mated cycle days 16, 17, and 18; and (ii) to test the hypothesis that alteration in endometrial prostaglandin milieu by using either prostaglandin analogue or prostaglandin synthesis inhibitor can intervene the antifertility effect induced by mifepristone. Thirty female monkeys were randomly assigned to one of the six treatment groups. Five monkeys in the control group (group 1) were subjected to mating during cycle days 8-22. Four out of five monkeys became pregnant in the first mated cycle (80%) with detection of serum mCG by 12.7 +/- 1.5 days after ovulation. In group 2, 12 mated cycles were studied in five monkeys, mifepristone [RU486, 2 mg/day/animal, s.c. in 1 ml vehicle (1:4, benzyl benzoate:olive oil, v/v)] was given on cycle days 16, 17, and 18. In this group, no pregnancy was observed, thus providing complete pregnancy protection. Though there was an apparent extension of treatment cycle lengths in five cases with no incidence of inter-menstrual bleeding or spotting, there were no significant changes in serum estradiol (E) and progesterone (P). In group 3, four monkeys received prostaglandin (PG) synthesis inhibitor, diclofenac sodium (D, 25 mg/day/animal, i.m.) on cycle days 16, 17, and 18 in seven ovulatory menstrual cycles. Four of these cycles (57%) resulted in normal pregnancies; however, mCG detection (16.8 +/- 1.2 days after ovulation) was significantly (p < 0.05) delayed as compared to group 1. In group 4, four monkeys received 100 micrograms misoprostol (M), a PGE1 analogue, by gavage on mated cycle days 16, 17, and 18. Four pregnancies occurred in five treatment cycles (80%) with normal profiles of serum E and Pi mCG was first detected 13.2 +/- 1.7 days after ovulation. In group 5, seven monkeys received same dosages of RU486 and D on mated cycle days 16, 17, and 18. One hundred percent pregnancy protection was observed with luteal phase lengthening in eight treatment cycles but with unaltered E and P profiles. In group 6, five monkeys in nine treatment cycles received same dosages of RU486 and M on mated cycle days 16, 17, and 18. One pregnancy occurred; evaluation of E and P levels showed that the drug was given in the preovulatory period, which delayed ovulation and implantation, as mCG was detected 19 days post-ovulation. A delay in vaginal bleeding was observed in four treatment cycles with unaltered E and P profiles. Low-dose mifepristone appears to be a potential candidate for luteal phase and post-coital emergency contraception. However, the hypothesis that altered endometrial prostaglandin milieu may be responsible for mediating the anti-implantation effect of RU486 does not appear to be tenable based on our results in the rhesus monkey.

Mifepristone: a potential contraceptive.

Use of standard estrogen-progestin contraception remains problematic in several subgroups of patients (e.g., those in whom exogenous estrogens are contraindicated, such as survivors of hormone-dependent cancer, or patients with endometriosis or uterine fibroids). In addition, the postcoital contraception, even if already available, remains at least underused. Additionally, continuous intake of contraceptive steroids is under increasing scrutiny. Would antiprogestins, and specifically the applications of mifepristone such as the ones reviewed in this article offer significant improvements at such problematic occasions? The most attractive novel contraceptive application of mifepristone is that of emergency postcoital contraception after unprotected intercourse. In addition, various options in the endometrial category, specifically those requiring drug administration only during a limited time, might be used in the future. Mifepristone might offer contraceptive and therapeutic relief to patients suffering from endometriosis or uterine fibroids, both conditions that have been shown to benefit from mifepristone therapy. However, the use of mifepristone in contraceptive preparations that are widely available would pose an additional problem of possible misuse of the compound, the reason for currently limiting access to mifepristone. However, such risk should be easily avoidable in the case of postcoital contraception in which only one dose of mifepristone is needed. Regarding the future of mifepristone, and more broadly that of antiprogestins in contraception, the authors believe that they will have a place in the future contraceptive armament. As already emphasized, the strongest clinical areas are those of immediate postcoital and endometrial contraception. Additional studies evaluating parenteral modes of administration, the long-term endometrial effects, and safety and metabolic effects of prolonged antiprogestin administration are needed before mifepristone can be considered a part of the contraceptive arena.

PIP: The evaluation of mifepristone (RU-486) as a potential contraceptive has entailed three strategies: endocrine, endometrial, and postcoital. Both animal and human studies have indicated that continuous preovulatory administration of RU-486 (at least 2 mg/day) inhibits ovulation, presumably through its perturbation of the hypothalamo-pituitary-ovarian axis and disruption of normal folliculogenesis. However, the return of menses after RU-486 termination is unpredictable. Early luteal phase or continuous RU-486 administration eliminates this side effect and delays endometrial maturation. On the other hand, late luteal phase administration of a high single dose is associated with failure rates of 3-16%. The use of RU-486 for immediate postcoital contraception lengthens the subsequent menstrual cycle, but is highly effective and well tolerated. At present, the immediate postcoital and endometrial strategies appear most promising. Urged is further research evaluating parenteral modes of administration, the long-term endometrial effects, and the safety and metabolic effects of prolonged antiprogestin use.

Factors associated with withdrawal bleeding after administration of oral dydrogesterone or medroxyprogesterone acetate in women with secondary amenorrhea.

The effectiveness of two treatment regiments in inducing withdrawal bleeding in secondary amenorrhea was compared and correlated with the endometrial thickness and endogenous E2 and progesterone concentrations. A prospective, randomized and double-blind study was designed at the Outpatient Clinic of Reproductive Endocrinology, Central Emek Hospital, Afula, Israel. Seventy-seven premenopausal women with oligomenorrhea or amenorrhea, 48 of whom qualified for the study, underwent a 5-day course of either medroxyprogesterone acetate (MPA) 5 mg b.i.d. or dydrogesterone (DG) 10 mg b.i.d. Endogenous pretreatment values of E2 and progesterone and endometrial thickness (by transvaginal ultrasonography) were correlated with the bleeding response. Withdrawal bleeding occurred in 93% of women taking either MPA or DG. Side effects occurred similarly among the groups. Lipid concentrations were unchanged. Endogenous E2 and progesterone were limited predictive value for withdrawal bleeding. Endometrial thickness as measured by transvaginal sonography correlated significantly with the bleeding response.

Review of the embryologic development of the pituitary gland and report of a case of hypophyseal duplication detected by MRI.

We describe the clinical manifestations, associated abnormalities, MRI appearances and pathologic significance of a case of hypophyseal duplication. A 16-year-old girl presented with delayed sexual development and history of midline craniofacial anomalies. MRI revealed paired infundibula extending inferiorly to two small pituitary glands, a midline hypothalamic mass, and a midline cleft in the basisphenoid. Twelve cases of pituitary duplication have previously been described. The suggested pathogenesis is duplication of the prechordal plate and anterior end of the notochord during early embryologic development.

[Yuanhuacin film for menstruation induction and termination of early pregnancy: analysis of 382].

Yuanhuacin Film was used in 382 cases, 26 cases for menstrual induction (successful rate 100%) and 356 for termination of early pregnancy. Among the latter group 336 cases resulted in complete abortion (94.4%), 12 cases in incomplete abortion (3.4%) and 8 cases in failure (2.2%). The embryonic sacs were discharged within 34.66 +/- 33.73 (means +/- s) hours. The amount of vaginal bleeding was less than or equal to that of menstruation, which lasted for 8.18 + 9.14 (means +/- s) days with mild abdominal pains. In the complete abortion group 237 cases (70.5%) were followed up and 236 cases were found to restore their menses within 40 days (99.6%), and 157 cases have decreased amount or the same amount of menstrual flow (66.2%), while in 80 cases the amount was increased (33.8%).

Menstrual regulation by intramuscular injections of 16-phenoxy-tetranor PGE2 methyl sulfonylamide (sulprostone). A multicentre study. World Health Organization.

In a previous study we have shown that three intramuscular injections of 0.5 mg of the prostaglandin analogue, sulprostone (16-phenoxy-W-17,18,19,20-tetranor PGE2 methyl sulfonylamide), were equally effective as vacuum aspiration for menstrual regulation in women with a delay of up to 21 days in the onset of expected menses. To assess whether lower doses of the prostaglandin could be effective if treatment were restricted to women with a delay of menses of up to 14 days, a multicentre trial investigated the effect of two injections of 0.25 mg sulprostone given with a 4-h interval. After an interim analysis showed a clinically unacceptable low rate of complete abortion (41%) amongst the 64 pregnant women thus treated, the dose was doubled to two injections of 0.5 mg. In the group of 51 pregnant women treated with the increased dose, the frequency of complete abortion (67%) was significantly higher although still well below the 91% success rate achieved in our previous study. Both the duration and the subjective vaginal blood loss were greater in women with complete abortion than in those with incomplete abortion or continuing pregnancy. It is concluded that the sulprostone dose used in our previous study (3 x 0.5 mg) represents the minimal, required dose for menstrual regulation.