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Influence of clinical and ultrasound factors on the efficacy of misoprostol in first trimester pregnancy failure

2005; Elsevier BV; Volume: 84; Issue: 4 Linguagem: Inglês

10.1016/j.fertnstert.2005.04.032

1556-5653

A. Agostini, Isabelle Ronda, Mariane Capelle, Fanny Romain, Florence Bretelle, Bernard Blanc,

Maternal and fetal healthcare

An observational study including 276 patients with early pregnancy failure was performed to evaluate the clinical and ultrasound factors influencing the efficacy of misoprostol in the treatment of first trimester pregnancy failure. Gestational age did not influence the efficacy of this treatment and the success rate was inversely proportional to parity. An observational study including 276 patients with early pregnancy failure was performed to evaluate the clinical and ultrasound factors influencing the efficacy of misoprostol in the treatment of first trimester pregnancy failure. Gestational age did not influence the efficacy of this treatment and the success rate was inversely proportional to parity. For some years numerous investigators have been proposing medical treatment of early pregnancy failure as an alternative to aspiration or expectative management (1Autry A. Jacobson G. Sandhu R. Isbill K. Medical management of non-viable early first trimester pregnancy.Int J Gynaecol Obstet. 1999; 67: 9-13Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 2Ayres-de-Campos D. Teixeira-da-Silva J. Campos I. Patricio B. Vaginal misoprostol in the management of first-trimester missed abortions.Int J Gynaecol Obstet. 2000; 71: 53-57Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 3Demetroulis C. Saridogan E. Kunde D. Naftalin A.A. A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure.Hum Reprod. 2001; 16: 365-369Crossref PubMed Scopus (106) Google Scholar, 4Herabutya Y. O-Prasertsawat P. Misoprostol in the management of missed abortion.Int J Gynaecol Obstet. 1997; 56: 263-266Abstract Full Text PDF PubMed Scopus (60) Google Scholar, 5Murchison A. Duff P. Misoprostol for uterine evacuation in patients with early pregnancy failures.Am J Obstet Gynecol. 2004; 190: 1445-1446Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 6Wakabayashi M. Tretiak M. Kosasa T. Sharma S. Aeby T. Kamemoto L. Diniega L. Intravaginal misoprostol for medical evacuation of first trimester missed abortion.Prim Care Update Ob Gynecol. 1998; 5: 176Crossref PubMed Google Scholar, 7Bagratee J.S. Khullar V. Regan L. Moodley J. Kagoro H. A randomized controlled trial comparing medical and expectant management of first trimester miscarriage.Hum Reprod. 2004; 19: 266-271Crossref PubMed Scopus (129) Google Scholar). Medical treatment of early pregnancy failure usually administered is misoprostol. The success rate is high but varies with the protocol used and the success criteria applied. A large number of protocols have been proposed. These protocols differ regarding dose, route, and frequency of administration, as well as their duration of administration. None of these studies have looked at or demonstrated clinical or ultrasound risk factors for medical treatment failure. It seems important to identify such factors for several reasons. First, misoprostol dosage and treatment duration could be defined according to patient characteristics. Second, information given to the patient about the risk of failure would be better adapted. The aim of this study is to evaluate the influence of clinical and ultrasound characteristics on the efficacy of misoprostol treatment of early pregnancy failure. This was an open prospective study carried out within the gynecological emergency service at La Conception Hospital, Marseille, France from 01/06/2000 to 01/06/2004. Inclusion criteria were informed consent, 18 years of age or older, closed cervical os, absence of pelvic pain requiring analgesic, absence of bleeding or bleeding not requiring more than one sanitary pad per day, single pregnancy, ultrasound dating of less than 12 weeks from measurement of the crown–rump length (CRL) (<50 mm) or the diameter of the gestational sac ( 4 mm with no embryonic cardiac activity, gestational sac diameter >20 mm with no visible fetal pole. In doubtful cases, the patient was asked to undergo a confirmatory ultrasound examination 1 week later. All pelvic ultrasound dating was performed the day of misoprostol administration. Treatment was ambulatory. The patient received 4 misoprostol tablets in one dose (800 μg) intravaginally with clinical and ultrasound examination 24 hours later (3Demetroulis C. Saridogan E. Kunde D. Naftalin A.A. A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure.Hum Reprod. 2001; 16: 365-369Crossref PubMed Scopus (106) Google Scholar). After misoprostol administration, the patient received a prescription for analgesics comprising an antispasmodic (phloroglucinol, 2 tablets per day) and an anti-inflammatory (ibuprofen 400, 1 tablet per day). In all cases, the patient was invited to a consultation in the event of persistent bleeding, fever, or pelvic pains. The treatment was considered effective if the expulsion was complete, without uterine retention with an endometrial thickness of 15 mm measured by ultrasound. In this case curettage was carried out. All the patients were seen again or had been recontacted 3 months later. Variables studied were clinical (patient age, gravidity, parity, number of vaginal delivery, gestational age according to the date of the last menstrual period) and ultrasound-based (CRL and gestational sac diameter). Informed consent was obtained from all the patients participating in the study. The ethical board on medical research as defined by the French law was consulted. The committee in accordance with French public health law considered that its approval was not necessary because the management was standard and did not lead to any additional, unusual, or innovative diagnostic or follow-up procedures. For univariate statistical analysis, we used the χ2 test or the Fisher test for qualitative variables and the Student test for quantitative variables. Difference was considered significant at P<.05. For the multivariate analysis, a logistical regression was used (Wald ascending method), taking account of the variables that gave a P<.2 after univariate analysis. During this period, 318 patients presented with the inclusion criteria. There were 42 patients (13.2%) who refused to participate in the study. Therefore 276 patients were included in the study. The success rate was 180/276 (65.2%). No patient who presented a uterine retention of 2 (32/59) (P=.03). The success rate of our series was 65%. This rate is comparable to that found in the literature. The success rate of vaginal misoprostol alone in early pregnancy failure varies between studies from 56% to 89% (1Autry A. Jacobson G. Sandhu R. Isbill K. Medical management of non-viable early first trimester pregnancy.Int J Gynaecol Obstet. 1999; 67: 9-13Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 2Ayres-de-Campos D. Teixeira-da-Silva J. Campos I. Patricio B. Vaginal misoprostol in the management of first-trimester missed abortions.Int J Gynaecol Obstet. 2000; 71: 53-57Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 4Herabutya Y. O-Prasertsawat P. Misoprostol in the management of missed abortion.Int J Gynaecol Obstet. 1997; 56: 263-266Abstract Full Text PDF PubMed Scopus (60) Google Scholar, 5Murchison A. Duff P. Misoprostol for uterine evacuation in patients with early pregnancy failures.Am J Obstet Gynecol. 2004; 190: 1445-1446Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 6Wakabayashi M. Tretiak M. Kosasa T. Sharma S. Aeby T. Kamemoto L. Diniega L. Intravaginal misoprostol for medical evacuation of first trimester missed abortion.Prim Care Update Ob Gynecol. 1998; 5: 176Crossref PubMed Google Scholar). We chose vaginal administration of misoprostol because it seems the most effective and best tolerated (9Dickinson J.E. Evans S.F. The optimization of intravaginal misoprostol dosing schedules in second-trimester pregnancy termination.Am J Obstet Gynecol. 2002; 186: 470-474Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 10el-Refaey H. Rajasekar D. Abdalla M. Calder L. Templeton A. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol.N Engl J Med. 1995; 332: 983-987Crossref PubMed Scopus (348) Google Scholar, 11Kulier R. Gulmezoglu A.M. Hofmeyr G.J. Cheng L.N. Campana A. Medical methods for first trimester abortion.Cochrane Database Syst Rev. 2004; 2 (CD002855)PubMed Google Scholar, 12Pang M.W. Lee T.S. Chung T.K. Incomplete miscarriage a randomized controlled trial comparing oral with vaginal misoprostol for medical evacuation.Hum Reprod. 2001; 16: 2283-2287Crossref PubMed Scopus (54) Google Scholar). We used a short protocol of 24 hours because it involved implementing a medical treatment with which we were unfamiliar. In so doing, we hoped, without proven medical argument, to reduce the risk of complications (e.g., hemorrhage, higher levels of infection) that might have been favored by a longer protocol or a larger number of patients with whom contact was lost. Some researchers carry out a second vaginal administration of 800 μg 24 hours later, in cases of initial treatment failure (5Murchison A. Duff P. Misoprostol for uterine evacuation in patients with early pregnancy failures.Am J Obstet Gynecol. 2004; 190: 1445-1446Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 13Creinin M.D. Moyer R. Guido R. Misoprostol for medical evacuation of early pregnancy failure.Obstet Gynecol. 1997; 89: 768-772Crossref PubMed Scopus (106) Google Scholar, 14Wood S.L. Brain P.H. Medical management of missed abortion a randomized clinical trial.Obstet Gynecol. 2002; 99: 563-566Crossref PubMed Scopus (99) Google Scholar). This protocol increases the success rate but patient morbidity and acceptability need assessment. We chose a single dose to have a simple protocol, acceptable to patients. In our study, gestational age, be it theoretical or ultrasound-based, has no influence on the success of the treatment. These data are important both in terms of information to be given to the patient and choice of treatment. On the other hand, the only factor that seems to influence the effectiveness of the treatment is parity. It seems that the effectiveness of the treatment is inversely correlated with parity. Prostaglandins affect both cervical maturation and uterine contractility (15Christin-Maitre S. Bouchard P. Spitz I.M. Medical termination of pregnancy.N Engl J Med. 2000; 342: 946-956Crossref PubMed Scopus (117) Google Scholar). It is possible that the sensitivity and contractility of the myometrium vary as a function of parity. It can be imagined that uterine sensitivity decreases with parity. In our study, the rate of success diminished with parity, although it remained above 50%. Ultrasonographic biometries of the gestational sac and the embryo were not able to predict the outcome. Based on the initial clinical and sonographic findings, medical treatment was feasible as a first-intention management procedure. These results need to be confirmed by other studies and with other protocols. Within the framework of a protocol such as ours, with a single dose, it would be interesting to assess the benefits of a repeat dose in failure cases. It would then be possible to assess whether the success rate obtained after repeat doses in failure cases is still dependent on parity. The other important variable is the timing of the examination. A later (48 hours) examination could be carried out. It is possible that the expulsion of the products of conception is a function of parity and that the duration is correlated to parity. The success rate at 24 hours of the treatment of early pregnancy failure by a single intravaginal 800-μg dose of misoprostol is a function of parity and independent of gestational age. This knowledge is important both in terms of information to be given to the patient and choice of treatment.