Pregnancy loss: French clinical practice guidelines.

In intrauterine pregnancies of uncertain viability with a gestational sac without a yolk sac (with a mean of three orthogonal transvaginal ultrasound measurements <25mm), the suspected pregnancy loss should only be confirmed after a follow-up scan at least 14 days later shows no embryo with cardiac activity (Grade C). In intrauterine pregnancies of uncertain viability with an embryo <7mm on transvaginal ultrasound, the suspected pregnancy loss should only be confirmed after a follow-up scan at least 7 days later (Grade C). In pregnancies of unknown location after transvaginal ultrasound (i.e. not visible in the uterus), a threshold of at least 3510IU/l for the serum human chorionic gonadotrophin assay is recommended; above that level, a viable intrauterine pregnancy can be ruled out (Grade C). Postponing conception after an early miscarriage in women who want a new pregnancy is not recommended (Grade A). A work-up for women with recurrent pregnancy loss should include the following: diabetes (Grade A), antiphospholipid syndrome (Grade A), hypothyroidism with anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies (Grade A), vitamin deficiencies (B9, B12) (Grade C), hyperhomocysteinaemia (Grade C), hyperprolactinaemia (Grade B), diminished ovarian reserve (Grade C), and a uterine malformation or an acquired uterine abnormality amenable to surgical treatment (Grade C). The treatment options recommended for women with a missed early miscarriage are vacuum aspiration (Grade A) or misoprostol (Grade B); and the treatment options recommended for women with an incomplete early miscarriage are vacuum aspiration (Grade A) or expectant management (Grade A). In the absence of both chorioamnionitis and rupture of the membranes, women with a threatened late miscarriage and an open cervix, with or without protrusion of the amniotic sac into the vagina, should receive McDonald cerclage, tocolysis with indomethacin, and antibiotics (Grade C). Among women with a threatened late miscarriage and an isolated undilated shortened cervix (<25mm on ultrasound), cerclage is only indicated for those with a history of either late miscarriage or preterm delivery (Grade A). Among women with a threatened late miscarriage, an isolated undilated shortened cervix (<25mm on ultrasound) and no uterine contractions, daily treatment with vaginal progesterone up to 34 weeks of gestation is recommended (Grade A). Hysteroscopic section of the septum is recommended for women with a uterine septum and a history of late miscarriage (Grade C). Correction of acquired abnormalities of the uterine cavity (e.g. polyps, myomas, synechiae) is recommended after three early or late miscarriages (Grade C). Prophylactic cerclage is recommended for women with a history of three late miscarriages or preterm deliveries (Grade B). Low-dose aspirin and low-molecular-weight heparin at a preventive dose are recommended for women with obstetric antiphospholipid syndrome (Grade A). Glycaemic levels should be controlled before conception in women with diabetes (Grade A).

Overview and expert assessment of off-label use of misoprostol in obstetrics and gynaecology: review and report by the Collège national des gynécologues obstétriciens français.

The literature suggests that misoprostol can be offered to patients for off-label use as it has reasonable efficacy, risk/benefit ratio, tolerance and patient satisfaction, according to the criteria for evidence-based medicine. Both the vaginal and sublingual routes are more effective than the oral route for first-trimester cervical dilatation. Vaginal misoprostol 800µg, repeated if necessary after 24 or 48h, is a possible alternative for management after early pregnancy failure. However, misoprostol has not been demonstrated to be useful for the evacuation of an incomplete miscarriage, except for cervical dilatation before vacuum aspiration. Oral mifepristone 200mg, followed 24-48h later by vaginal, sublingual or buccal misoprostol 800µg (followed 3-4h later, if necessary, by misoprostol 400µg) is a less efficacious but less aggressive alternative to vacuum aspiration for elective or medically-indicated first-trimester terminations; this alternative becomes increasingly less effective as gestational age increases. In the second trimester, vaginal misoprostol 800-2400µg in 24h, 24-48h after at least 200mg of mifepristone, is an alternative to surgery, sulprostone and gemeprost. Data for the third trimester are sparse. For women with an unripe cervix and an unscarred uterus, vaginal misoprostol 25µg every 3-6h is an alternative to prostaglandin E2 for cervical ripening at term for a live fetus. When oxytocin is unavailable, misoprostol can be used after delivery for prevention (sublingual misoprostol 600µg) and treatment (sublingual misoprostol 800µg) of postpartum haemorrhage. The use of misoprostol to promote cervical dilatation before diagnostic hysteroscopy or surgical procedures is beneficial for premenopausal women but not for postmenopausal women. Nonetheless, in view of the side effects of misoprostol, its use as a first-line treatment is not indicated, and it should be reserved for difficult cases. Misoprostol is not useful for placing or removing the types of intra-uterine devices used in Europe, regardless of parity.

[Epidemiology of loss pregnancy]. / Épidémiologie des pertes de grossesse.

OBJECTIVES: Study of epidemiology of pregnancy loss. MATERIALS AND METHOD: A systematic review of the literature was performed using Pubmed and the Cochrane library databases and the guidelines from main international societies. RESULTS: The occurrence of first trimester miscarriage is 12% of pregnancies and 25% of women. Miscarriage risk factors are ages of woman and man, body mass index greater than or equal to 25kg/m(2), excessive coffee drinking, smoking and alcohol consumption, exposure to magnetic fields and ionizing radiation, history of abortion, some fertility disorders and impaired ovarian reserve. Late miscarriage (LM) complicates less than 1% of pregnancies. Identified risk factors are maternal age, low level of education, living alone, history of previous miscarriage, of premature delivery and of previous termination of pregnancy, any uterine malformation, trachelectomy, existing bacterial vaginosis, amniocentesis, a shortened cervix and a dilated cervical os with prolapsed membranes. Fetal death in utero has a prevalence of 2% in the world and 5/1000 in France. Its main risk factors are detailed in the chapter.

[First trimester miscarriages: benefits and harms of different management options]. / Fausses couches du premier trimestre : bénéfices et risques des alternatives thérapeutiques.

The objective of this review was to assess early and late benefits and harms of different management options for first-trimester miscarriage. Surgical uterine evacuation remains the most effective and the quickest method of treatment. Depending on the clinical situation, medical treatment using misoprostol (missed miscarriage) or expectative attitude (incomplete miscarriage) does not increase the risk of complications, neither haemorrhagic nor infectious. However, these alternatives generally require longer outpatient follow-up, which leads to more prolonged bleeding and not planned surgical procedures.

[Misoprostol: off-label use in the first trimester of pregnancy (spontaneous abortion, and voluntary medical termination of pregnancy)]. / Misoprostol: utilisation hors AMM au premier trimestre de la grossesse (fausses couches spontanées, interruptions médicales et volontaires de grossesse).

OBJECTIVE: State of knowledge about misoprostol's use out of its marketing authorization during the first trimester of pregnancy, in early miscarriage or to induce abortion or medical termination of pregnancy. METHODS: French and English publications were searched using PubMed, Cochrane Library and international learned societies recommendations. RESULTS: Cervical ripening prior to surgical uterine evacuation during the first trimester of pregnancy facilitates cervical dilatation and reduces operative time and uterine retention risk. Misoprostol, mifepristone and osmotic cervical dilators are equally efficient. Concerning first trimester miscarriage, surgical uterine evacuation remains the most effective and the quickest method of treatment (EL 1). Depending on the clinical situation, medical treatment using misoprostol (missed miscarriage) or expectative attitude (incomplete miscarriage) does not increase the risk of complications, neither haemorrhagic nor infectious (EL 1). However, these alternatives generally require longer outpatient follow-up, which leads to more consultations, prolonged bleeding and not planned surgical procedures (EL 1). Concerning missed miscarriage, a vaginal dose of 800 µg of misoprostol, possibly repeated 24 to 48 hours later, seems to offer the best efficiency/tolerance ratio (EL 2). Concerning early abortion, medical method is a safe and efficient alternative to surgery (EL 2). Success rates are inversely proportional to gestational age (EL 2). According to the modalities of its marketing authorization, 400 µg of misoprostol can only be given by oral route, for less than 7 weeks of amenorrhea (WA) pregnancies and after 36 to 48 hours following 600 mg of mifepristone (EL 1). However, 200mg of mifepristone is as efficient as 600 mg (EL 1). Beyond 7WA, misoprostol buccal dissolution (sublingual or prejugal) or vaginal administration are more efficient and better tolerated than oral ingestion (EL 1). Between 7 and 9WA, the best protocol in terms of efficiency and tolerance is the association of 200mg of mifepristone followed 24 to 48 hours later by 800 µg of vaginal, sublingual or buccal misoprostol (EL 1). An additional dose of 400 µg can be given 3 hours later if necessary (EL 3). In case of buccal administration, the dose of 400 µg seems to offer the same efficiency with a better tolerance but further evaluation is needed (EL 2). Between 9 and 12WA, medical treatment is less efficient than surgery and its tolerance is lower (EL 2). However, a protocol of 200mg of mifepristone followed 36 to 48 hours later by 800 µg of vaginal or sublingual misoprostol, plus an additional 400 µg dose every 3-4 hours (until 4-5 doses maximum) seems safe and efficient (EL 5). CONCLUSION: Misoprostol use during the first trimester of pregnancy is a safe and efficient alternative to surgery as long as detailed protocols adjusted to each clinical situation are respected.

[Continuous medical evaluation of the prevention of fetomaternal rhesus-D allo-immunization]. / Évaluation des pratiques professionnelles sur la prévention de l'allo-immunisation Rhésus D.

OBJECTIVES: To evaluate the prevention of fetomaternal rhesus-D allo-immunization between 2008 and 2010. This evaluation was a part of the continuous medical evaluation (CME) that is compulsory in French hospitals. It was carried out using the tools recommended by the Haute Autorité de santé. We followed the national guidelines for the prevention of fetomaternal rhesus-D allo-immunization as outlined in 2005 by the national French college of Obstetrics and Gynecology. MATERIALS AND METHODS: We audited 3926 consultations in the first four months of 2008. Based on the results of the audit, actions were implemented to improve care. In 2009, we audited 4021 consultations to look for improvement, and another 3932 consultations in 2010. RESULTS: In 2008, 14% of the patients had an overall optimal prevention. After actions were taken, 44% of patients in 2009 and 58% of patients in 2010 demonstrated optimal prevention (P<0,05). Especially, the prevention of fetomaternal allo-immunization has been explained for 43% of the patients in 2008 and to 90% of them in 2010. And immunoprophylaxia has been prescribed to 70% of the patients in 2008 and to 93% of them in 2010. CONCLUSION: This CME has resulted in a statistically significant improvement of the prevention of allo-immunization.

[Iron deficiency anemia and pregnancy. Prevention and treatment]. / Anémie par carence martiale et grossesse. Prévention et traitement.

OBJECTIVE: To assess the effectiveness and the safety of prevention and treatment of iron deficiency anemia during pregnancy. METHODS: French and English publications were searched using PubMed and Cochrane library. RESULTS: Early screening of iron deficiency by systematic examination and blood analysis seemed essential. Maternal and perinatal complications were correlated to the severity and to the mode of appearance of anemia. Systematic intakes of iron supplements seemed not to be recommended. In case of anemia during pregnancy, iron supplementation was not associated with a significant reduction in substantive maternal and neonatal outcomes. Oral iron supplementation increased blood parameters but exposed to digestive side effects. Women who received parenteral supplementation were more likely to have better hematological response but also severe potential side effects during pregnancy and in post-partum. The maternal tolerance of anemia motivated the choice between parenteral supplementation and blood transfusion. CONCLUSION: Large and methodologically strong trials are necessary to evaluate the effects of iron supplementation on maternal health and pregnancy outcomes.

[Management of the first trimester miscarriages]. / Prise en charge des fausses couches spontanées du premier trimestre.

A first trimester miscarriage is most often painfully experienced by the patients. The practitioner should be able to offer appropriate, timely, efficient and safe medical management, allowing a shorter convalescence without effect on subsequent fertility. Each step of the process of the miscarriage results in clinical and ultrasonographic characteristics, and requires a specific therapeutic strategy. Vaginal ultrasound allows confirmation of early pregnancy failure (missed miscarriage) diagnosis and to estimate the complete or incomplete removal of trophoblastic material. However, the endometrial thickness does not appear to be predictive for the risk of persistent bleeding or secondary surgery. Surgical evacuation of the product of conception remains the most effective and the quickest method of treatment. Depending on the clinical situation, medical treatment with misoprostol (missed miscarriage) or expectative attitude (incomplete miscarriage) do not increase the risk of complications, particularly the infectious one. However, these alternatives generally require more prolonged outpatient follow-up leading to more frequent consultations and surgical emergencies.

[Medical treatment of early spontaneous miscarriages: a prospective study of outpatient management using misoprostol]. / Traitement médical des fausses couches spontanées précoces. Etude prospective d'une prise en charge ambulatoire à l'aide du misoprostol.

OBJECTIVES: Medical treatment using misoprostol has been recommended as an alternative to surgical evacuation for spontaneous miscarriages in the first trimester, in order to avoid anesthesia, a surgical operation and hospitalization. Our aim was to assess the efficacy and the safety of vaginal misoprostol in out-patient management of early miscarriages. MATERIAL AND METHODS: We conducted a prospective cohort study including patients with a spontaneous miscarriage of less than 14 weeks gestation. Exclusion criteria were hemorrhagic miscarriages, gestational sac larger than 40 mm and/or cranio-caudal length of the embryo of more than 30 mm. Our protocol used 4 intravaginal tablets (800 microg) of misoprostol on Day 1, out-patient follow-up, clinical and ultrasound reassessment on Day 2. If the intra-uterine antero-posterior diameter on ultrasound examination was greater than 15 mm (or the gestational sac persisted), a second dose of misoprostol was administered or surgical evacuation was performed (failure of medical treatment). RESULTS: One hundred two patients were included, of whom 30 had an inevitable or threatened miscarriage and 72 had a missed abortion. The success rate defined by complete expulsion of the products of conception without resorting to surgical evacuation and without short-term complications, was 78.4% (80 patients). Two patients were lost to follow-up at 48 hours. Complete expulsion occurred within 2 days in 94% of cases. There were 13 emergency consultations, including 8 for expulsion pain and five surgical evacuations (3 for hemorrhagic expulsion, 2 for hemorrhagic retention). All together, there were 15 surgical evacuations for retention of the products of conception after 1 or 2 doses of misoprostol. There was one case of endometritis (1%). Thirty-four patients were hospitalized, 22 for surgical evacuation and 12 for expulsion pain. CONCLUSION: It is possible to use misoprostol as a single vaginal dose (800 microg) as out-patient treatment, since it gives satisfactory efficacy (80%) and is sufficiently safe (5% needing emergency surgery). However, out-patient management should only be performed after explaining the treatment and its risks clearly to the patient.

[Management of first trimester miscarriages]. / Prise en charge des fausses couches spontanées du premier trimestre.

INTRODUCTION: First trimester miscarriages complicating 15 to 20% of pregnancies, are the leading cause of gynecology emergencies. OBJECTIVES AND METHODS: This review exhaustively summarized the French and English reports found on Medline data base about the management of first trimester miscarriage. RESULTS: The treatment of reference remains surgical evacuation. It is generally used to avoid haemorrhage and intrauterine infection but is also required for women who wish an immediate termination of pregnancy. Recently, alternatives have been proposed, such as expectant management or medical treatment by misoprostol, to improve patient satisfaction and to reduce complications and costs generated by surgery. Expectant management allows to avoid curettage in most of incomplete miscarriages without any increase of the rate of complications or bleeding duration. Vaginal misoprostol allows complete expulsion in 70 to 90% of missed pregnancies without any increase of the rate of complications. CONCLUSION: Today, we can propose to motivated and informed patients an alternative to surgical treatment but large randomized studies still are needed to assess benefits and risks for each method.

[Feasibility of bilateral sacrospinous ligament vaginal suspension with a stapler. Prospective studies with the 34 first cases]. / Faisabilité de la sacrocolpopexie vaginale bilatérale à l'agrafeuse. Etude prospective des 34 premiers cas.

OBJECTIVE: Evaluation of the feasibility of bilateral sacropinous ligament suspension with a stapler. Morbidity study and short term results. STUDY DESIGN: Prospective study from July 1994 to August 1996. RESULTS: Bilateral sacrospinous ligament suspension with a stapler was possible in 100% of cases and surgical technique is described. Our indications are stage III Bp and stage IV genital prolapses (according to the American Urogynecologic Society classification, 1996), with or without uterus, and when a Bologna's procedure is performed, in order to prevent enterocele. In 24 patients, the uterus was present. 20 vaginal hysterectomies and 4 conservative bilateral uterine suspensions were performed. The sacrospinous ligament suspension was associated to anterior colporrhaphy (in 74% of patients), repair of rectocele (82%), repair of enterocele (26%), posterior colpoperineorrhaphy (79%), bladder neck suspension (71%). No vascular injury nor post operative constipation was noted. In 2 patients, a small rectal laceration occurred, and in one patient one branch of the staple transfixed the rectal mucosa. Removal of the staple was easily performed without any post-operative complication. First results after an average 19 months follow-up (range 9 to 32) shows a perfect anatomic result in 77% of cases. We noted one recurrence of a vaginal vault prolapse; the patient underwent a second sacrospinous ligament fixation with good result. One patient had a stage II Aa cystocele post-operatively and three patients had a short vagina (< 6 cm). Patients who were continent before the sacrocolpopexy did not develop further urinary stress-incontinence. CONCLUSION: Bilateral transvaginal sacrospinous ligament suspension with a stapler facilitates the procedure. No post-operative constipation was noted with this method. Our first results are good. The cost of the stappler may limit its extensive use.