Review 2007;9:102 108 10.1576/toag.9.2.102.27311 www.rcog.org.

uk/togonline The Obs tetrician & Gynaecologist Review Modern management of miscarriage Authors Haritha Sagili / Mike Divers Key content: Miscarriage has traditionally been treated by surgical evacuation, on the assumption that any retained tissue increases the risk of infection and haemorrhage. Over the last decade, effective non-surgical alternatives have been advocated to minimise unnecessary surgical intervention while maintaining low rates of morbidity and mortality. Improved access to early pregnancy assessment units and greater awareness among women has led to increasing demand for more conservative management of miscarriage. Learning objectives: To learn about the use of appropriate miscarriage terminology. To learn about the advantages and disadvantages of expectant, medical and surgical management. To understand that women s choice is paramount in planning treatment. Ethical issues: Guidance on the sensitive disposal of fetal remains is essential. Keywords early pregnancy assessment units / expectant management / medical management / miscarriage / surgical evacuation Please cite this article as: Sagili H, Divers M. Modern management of miscarriag e. The Obstetrician & Gynaecologist 2007;9:102 108. Author details Haritha Sagili MD MRCOG DFFP Mike Divers FRCOG Senior House Officer Obstetrics and Consultant Obstetrician and Gynaecologist Gynaecology Department of Obstetrics and Gynaecology Department of Obstetrics and Gynaecology Nobles Hospital Nobles Hospital Isle of Man, IM4 4RJ, UK Isle of Man, IM4 4RJ, UK Email: harithas@hotmail.com (corresponding author) 102 2007 Royal College of Obstetricians and Gynaecologists

The Obstetrician & Gynaecologist 2007;9:102 108 Review Introduction Miscarriage accounts for approximately 50 000 inpatient admissions in the United Kingdom annually (Department of Health statistics, 2005).1 It is common, occurring in 15 20% of all pregnancies, and can have both medical and psychological consequences. While maternal death is rare after miscarriage, particularly in the first trimester, on which this review focuses, it has featured in previous Confidential Enquiries into Maternal Deaths in the UK, particularly after surgical procedures in association with sepsis. Ectopic pregnancy, recurrent miscarriage, gestational trophoblastic disease and pregnancy of unknown location are not discussed. Early pregnancy assessment units The benefits of an early pregnancy assessment unit service were first described by Bigrigg and Read in 1991.2 Thorough assessment can occur in the presence of a supportive multidisciplinary team, with a confirmed diagnosis made at the first visit in most cases. The admission time was reduced for women requiring evacuation of the uterus from 3 days (range 1.5 5.0) to 1 day and from 1.5 days (range 0.5 3.0) to 2 hours in those requiring no treatment. Women were no longer separated from their families for long periods and the reduced use of inpatient beds produced significant economic benefits for the National Health Service. According to the Association of Early Pregnancy Units (AEPU) 2004 guidelines,3 an effective unit should be located in a dedicated area with goodquality ultrasound equipment, easy access to laboratory facilities (for rhesus grouping, sensitive urine pregnancy testing and -hCG assay with results within 24 hours) and gynaecological procedures. The National Chlamydia Screening Programme recommends opportunistic screening for all women under 25 years of age attending early pregnancy assessment units.4 Although the gold standard would be to have a unit open 7 days a week, from 8 am to 5 pm, the minimum requirement would be a unit open 5 mornings only. Staffing varies between units but the multidisciplinary team should ideally include doctors, nurses, midwives, ultrasonographers and support staff. Clear and consistent verbal and written information should be available. Direct access to an appointment system should be available to all women and practitioners in the primary care setting (including general

practitioners, nurses, midwives and health visitors), as well as other hospital departments (for example, accident and emergency departments, wards). The AEPU recommends using clinical guidelines to standardise management of early pregnancy problems, record keeping and data collection. Speculum examination A prospective study published in 2004 of 236 women with early pregnancy bleeding found that, after speculum examination, 3 (1.3%) women had a change of management plan but only 10 (4.2%) women had a change of diagnosis, suggesting that it contributes to a minority of management decisions.5 The need for speculum examination should be assessed on a case-by-case basis, depending on whether the findings on bimanual examination are conclusive. The role of ultrasound The use of transvaginal ultrasound has revolutionised the management of early pregnancy problems. Along with the development of highly sensitive urinary -hCG assays, early pregnancy ultrasound has resulted in women presenting earlier but with the knock-on effect of an increase in the number of inconclusive scans and the requirement for repeat assessments. Knowledge of the typical ultrasound appearances of normal early pregnancy development and a good understanding of its pitfalls are essential for the diagnosis and management of early pregnancy problems. It is vital to describe clinical and ultrasound findings in early pregnancy using appropriate terminology (Table 1):3,6 8 the word miscarriage Recommended term Previous term Ultrasound appearance Clinical presentation Table 1 Threatened miscarriage Threatened abortion Intrauterine gestation sac Fetal pole with cardiac activity seen Vaginal bleeding abdominal pain; closed cervix Clinical correlates of ultrasound appearances.3,6 8 Complete miscarriage Complete abortion Endometrial thickness 15 mm No evidence of retained products Cessation of vaginal bleeding and of conception abdominal pain; closed cervix Incomplete miscarriage Incomplete abortion Heterogenous tissues sac Passage of s ome pregnancy-related distorting midline endometrial echo tissue bleeding and/or abdominal Any endometrial thickness pain; open cervix Missed miscarriage Missed abortion Fetal pole > 6 mm with no fetal heart Minimal vaginal bleeding or pain; loss of Delayed miscarriage Anembryonic pregnancy activity. Gestation sac diameter pregn ancy symptoms; closed cervix Silent miscarriage Blighted ovum 20 mm with no fetal pole or yolk sac

Early fetal demise (These reflect different stages (These reflect different stages in in the same process) the same process) Inevitable miscarriage Inevitable abortion Bleeding without passage of tissue bu t with an open cervix Miscarriage with infection Septic abortion Vaginal discharge, bleeding, fever, (sepsis) abdominal pain 2007 Royal College of Obstetricians and Gynaecologists 103

Review 2007;9:102 108 The Obstetrician & Gynaecologist should replace abortion in clinical practice. The use of the term indeterminate in relation to location or viability is confusing and should be replaced by the terms pregnancy of unknown location (positive pregnancy test but no signs of intra- or extrauterine pregnancy or retained products of conception) and pregnancy of uncertain viability (intrauterine sac 20 mm mean diameter with no obvious yolk sac or fetus, or fetal echo 6 mm crown-rump length with no obvious fetal heart activity). In these circumstances a repeat scan at a minimum interval of 1 week is necessary.9 No single ultrasound measurement of the different anatomical features in the first trimester has been shown to have a high predictive value for determining early pregnancy outcome. Similarly, Doppler studies and 3D ultrasound have failed to predict those pregnancies that will subsequently end in miscarriage and are, therefore, unlikely to have a clinical role.10,11 Treatment 3,4,6 See Figure 1. Viable intrauterine pregnancy (threatened miscarriage) Ninety percent of women in whom fetal heart activity is detected at 8 weeks will not miscarry. The therapeutic value of progesterone in preventing or treating threatened miscarriage has not yet been established.12 There is also insufficient evidence to support the use of uterine muscle relaxant drugs13 or a policy of bed rest.14 A small study published in 200515 showed no evidence of a difference in the outcome of threatened miscarriage when treated with hCG in the first trimester. Non-viable pregnancy The term non-viable pregnancy includes incomplete, silent, delayed and missed miscarriage and early fetal demise. Expectant management Up to 70% of women will choose expectant management if given the choice.16 A review by Butler17 showed that expectant management is successful within 2 6 weeks without increasing complications in 80 90% of women with incomplete spontaneous miscarriage and 65 75% of women with delayed miscarriage or an empty

sac. Women s experiences with expectant management revealed a mean worst pain of 5.9 on an 11-point scale.18 The satisfaction rates were 92.9% with family physician care and 84.6% with hospital care. Bleeding varied, but was often very heavy. The median daily levels of bleeding and pain were highest during the first 8 days from the start of bleeding and decreased thereafter in the 188 women managed expectantly.19 Expectant management can be continued as long as the woman is willing and provided there are no signs of infection. The duration can sometimes be as long as 6 8 weeks; this is reflected in the higher success rates with prolonged follow-up. An increasing bleeding pattern at inclusion19 and ultrasound findings such as blood flow within intervillous spaces7 can be used to predict the likelihood of successful expectant management. Biochemical markers (including serum hCG, progesterone, inhibin A and inhibin pro-alpha C RI) also show significant differences in those pregnancies that resolve spontaneously (P 0.05).20 Other ultrasound parameters such as endometrial thickness and the presence or absence of a gestational sac did not add any further information to the likely outcome.7 Medical management Incomplete miscarriage A variety of equally effective prostaglandin regimens have been described, including gemeprost 0.5 1 mg, vaginal misoprostol 800 g3 and oral misoprostol 400 g.21 Single and repeated doses of oral misoprostol 600 g (with the dose repeated after 4 hours to a total of 1 200 g) have been shown to be equally effective, although with a lower incidence of diarrhoea in the single dose group.22 However, vaginal misoprostol is as effective as oral misoprostol, with a significant reduction in the incidence of diarrhoea.23 Success rates varied from 61 95%, mild moderate bleeding lasted 4 6 days, side effects were tolerable in 96% and satisfaction rates were 95%.21 23 Misoprostol has the advantage of being cheap and not requiring refrigeration, although it is not licensed for use in the management of miscarriage. Silent, delayed, missed miscarriage or early fetal demise A confusing number of alternative regimens have been described using prostaglandin alone (oral, sublingual or vaginal misoprostol, 400, 600 or 800 g in single or repeated doses), or the antiprogestogen mifepristone (200, 400 or 600 mg orally) followed 36 48 hours later by either misoprostol or gemeprost (0.5 1mg vaginally).

Mifepristone 200 mg, in combination with oral misoprostol, was equally effective and better tolerated than mifepristone 600 mg.24 Sublingual misoprostol 400 g appears to be a safe, effective alternative to the oral or vaginal routes.25 Success rates with mifepristone and misoprostol varied from 70 84%, the median induction to miscarriage interval was 8 hours, overall the satisfaction rate was 91% and bleeding stopped, on average, by 8 days.24,25 Since progesterone levels are low in non-viable pregnancy, in contrast to medical termination of pregnancy, mifepristone can be avoided and 2007Royal College of Obstetricians and Gynaecologists

Figure 1 Algorithm for management of miscarriage3,4,6

Review 2007;9:102 108 The Obstetrician & Gynaecologist Table 2 Expectant Medical Surgical Comparison of management regimes6,16,17,21,23,24,26,28,36,38 40,42 1. Success rates (%) Incomplete miscarriage 80 91 61 95 (prostaglandin) 95 100 Early fetal demise/ 25 76 40 93 (prostaglandin) 95 100 delayed/silent/missed miscarriage 70 84 (mifepristone 95 100 prostaglandin) 2. Net societal cost per woman () 1086.20 1410.40 1585.30 3. Risk of infection (%) 2 3 2 3 2 3 4. Unplanned surgical curettage (%) 10 44 10 36 2 5 5. Intrauterine adhesions (%) 0 0 7.7 6. Long-term conception rates and pregnancy outcomes No differences between diff erent treatment modalities prostaglandins only administered. Misoprostol by the vaginal route may be preferable, as the mean time to expulsion is longer by the oral route and the incidence of diarrhoea and fatigue higher with sublingual regimens.26,27 Single-dose vaginal misoprostol 800 g was more effective than 400 g (55.4% versus 40.2%, P 0.05) and more effective in delayed miscarriage compared with cases where there was an empty sac (50.3% versus 40.2%, P 0.05), which may require larger or repeat doses as they seem to respond less readily to medical treatment.28 One trial29 showed that an additional 1-week course of sublingual misoprostol did not improve either the success rate or the duration of bleeding, but increased the incidence of diarrhoea. Women receiving misoprostol experienced more pain and required more analgesia compared with a placebo.30 Higher success rates (85%) using 800 g vaginal misoprostol were reported in one study, which demonstrated that bleeding for at least 2 weeks after vaginal misoprostol is common, although heavy bleeding is usually limited to a few days after treatment.31 Factors that seem to predict success include active bleeding, nulliparity32 and higher dosages of misoprostol.28 Surgical evacuation Surgical evacuation remains the treatment of choice if endometrial thickness is 50 mm, bleeding is excessive, vital signs are unstable or infected tissue is present in the uterine cavity (in which case surgery must be done under antibiotic cover). Fewer than 10% of women who miscarry fall into these categories.33 Certain women will still prefer to undergo surgical evacuation and their choice should be acknowledged. Rare surgical risks are: uterine perforation (1%), cervical tears, intra-abdominal trauma (0.1%), intrauterine adhesions,haemorrhage, infection and anaesthetic complications. The Cochrane review34 on surgical procedures to evacuate incomplete miscarriage included two trials showing that vacuum aspiration is safe, quick

to perform, has significantly decreased blood loss and is less painful than sharp curettage. Serious complications, such as uterine perforation, and other morbidity were rare. Analgesia and sedation should be provided as necessary for the procedure. In all women in whom surgery is being considered, the need for cervical priming should be assessed. While women with Chlamydia trachomatis, Neisseria gonorrhoea or bacterial vaginosis in the lower genital tract at the time of induced abortion are at increased risk of subsequent pelvic inflammatory disease,35 there is insufficient data to recommend routine antibiotic prophylaxis before surgical uterine evacuation for miscarriage. Screening for infection, including C. trachomatis, should be considered in all women. Antibiotic prophylaxis should be given based on individual clinical indications.6 An appropriate regimen would be 1 g rectal metronidazole at the time of surgery followed by 100 mg oral doxycycline twice daily for 7 days.35 Comparison of different methods of management There are few robust randomised controlled studies with sufficient numbers of women to enable true comparison between expectant, medical and surgical management for incomplete miscarriage and early fetal demise (Table 2). The MIST trial36 revealed significantly more unplanned admissions and unplanned surgical curettage procedures after expectant management and medical management than after surgical management, although the risk of infection was low (2 3%), regardless of treatment modality. A recent meta-analysis37 to quantify the relative benefits and risks of different management options for first-trimester miscarriage reported that surgical treatment had the best success rate, followed by medical and expectant treatment, although many studies were of poor methodological quality. The 2006 Cochrane review38 identified five trials comparing expectant with surgical management. Expectant care led to a higher risk of incomplete miscarriage, bleeding and need for surgical evacuation of the uterus, while surgery resulted in a significantly greater risk of infection (relative risk 0.29, CI 0.09 0.87, P 0.03). However, there was no strong medical argument for either approach and the individual woman s preference was considered the major concern. Filmy intrauterine adhesions are present in 7.7% of women examined hysteroscopically following surgical evacuation but not in those managed conservatively or medically. Long-term conception rates and pregnancy outcomes are no different

following medical or surgical evacuation for miscarriage, the median time to pregnancy being 8 months in both groups.39,40 2007Royal College of Obstetricians and Gynaecologists

The Obstetrician & Gynaecologist 2007;9:102 108 Review Cost analysis Conflicting results have been reported on the cost effectiveness of different treatment strategies.41 43 Analysis of pooled data from 29 reports found misoprostol the least costly alternative ($1 000 [US dollars] per woman), followed by expectant care ($1 172) and surgical evacuation ($2 007).41 Misoprostol and expectant care groups were shown to be less costly than the surgical evacuation group 100% and 88% of the time, while the misoprostol group was less costly than the expectant group 100% of the time. In an economic evaluation of the MIST trial,42 expectant management was shown to be cheaper (net societal cost per woman estimated at 1 086.20) than both medical (1 410.40) and surgical management (1 585.30). Overall, it was the most cost effective. In a study by Rocconi et al, 43 expectant management ($915 [US dollars] cost per cure) was, similarly, more cost effective than both medical ($1 149) and conventional surgical management ($2 333), although manual vacuum aspiration, a technique little used in the UK, was the most cost effective ($793). have adopted these recommendations found that only 71% of records contained evidence of histological examination of tissue. Around 50% of women reported involvement with decisions about tissue disposal, although documentation was found in only 29% of records. It was concluded that the national guidance on these issues was contentious, implementation variable and that wide consultation with stakeholders was needed prior to publication of any revised guidance. Conclusion Modern treatment of miscarriage should provide a rapid, sympathetic diagnosis and adequate counselling. All women with early pregnancy problems should preferably have prompt access to a dedicated early pregnancy assessment unit that provides efficient management, counselling and access to appropriate information. At all times women should be supported in making informed choices about their care and management: Given the lack of clear superiority of either approach, the woman s preference should play a dominant role in decision making. Expectant and medical management of first-trimester miscarriage possess significant economic advantages over traditional

surgical management. 48 Women s perspective about different choices A survey44 of women attending a family planning clinic found a strong preference for expectant treatment in the event of a miscarriage, although physician recommendation would influence their decision. From a clinical viewpoint, the role of free choice is supported by the fact that health-related quality of life over time is best when women with miscarriage choose their own treatment.45 With no single best way to treat miscarriage to suit all individuals, the largest qualitative study of women s views on expectant, medical and surgical treatment concluded that informed choice was paramount. When surgical evacuation became necessary, women in the medical group resented having a second procedure, although a subsequent operation for failed expectant treatment was not perceived by women in the wait and see group in such a negative way.46 Disposal of products of conception Guidance from the Royal College of Obstetricians and Gynaecologists6 on early pregnancy loss recommends that tissue obtained at the time of a miscarriage should be submitted for histological examination to exclude trophoblastic disease and ectopic pregnancy. Each hospital trust should have a clear system and protocol for the sensitive disposal of fetal remains.3 A Scottish study47 to determine the extent to which health professionals References 1 Hospital Episode Statistics [www.hesonline.nhs.uk/Ease/servlet/ ContentServer?siteID=1937&categoryID=214]. 2 Bigrigg MA, Read MD. Management of women referred to early pregnancy assessment unit: care and cost effectiveness. BMJ 1991;302:577 9. 3 Association of Early Pregnancy Assessment Units. Guidelines 2004 [www.earlypregnancy.org.uk/guidelines.asp]. 4 National Chlamydia Screening Programme England. Core Requirements. 3rd ed. London: Health Protection Agency; 2006 [www.hpa.org.uk/infections/topics_az/hiv_and_sti/sti-chlamydia/ publications/NCSP_corereq3rdedition.pdf]. 5 Hoey R, Allan K. Does speculum examination have a role in assessing

bleeding in early pregnancy? Emerg Med J 2004;21:461 3. doi:10.1136/emj.2003.012443 6 Royal College of Obstetricians and Gynaecologists. The Management of Early Pregnancy Loss. Green-top Guideline No. 25. London: RCOG; 2006 [www.rcog.org.uk/resources/Public/pdf/green_top_25_ management_epl.pdf]. 7 Jauniaux E, Johns J, Burton GJ. The role of ultrasound imaging in diagnosing and investigating early pregnancy failure. Ultrasound Obstet Gynecol 2005;25:613 24. doi:10.1002/uog.1892 8 Recommendations from 33rd RCOG Study Group. In: Grudzinkas JG, O Brien PMS, editors. Problems in Early Pregnancy: Advances in Diagnosis and Management. London: RCOG Press; 1997. p. 327 31. 9 Hately W, Case J, Campbell S. Establishing the death of an embryo by ultrasound: report of public enquiry with recommendations. Ultrasound Obstet Gynecol 1995;5:353 7. doi:10.1046/j.1469 0705. 1995.05050353.x 10 Pellizzari P, Pozzan C, Marchiori S, Zen T, Gangemi M. Assessment of uterine artery blood flow in normal first-trimester pregnancies and in those complicated by uterine bleeding. Ultrasound Obstet Gynecol 2002;19:366 70. doi:10.1046/j.1469-0705.2002.00667.x 11 Acharya G, Morgan H. Does gestational sac volume predict the outcome of missed miscarriage managed expectantly? J Clin Ultrasound 2002;30:526 31. doi:10.1002/jcu.10107 12 Oates-Whitehead RM, Haas DM, Carrier JAK. Progestogen for preventing miscarriage. Cochrane Database of Systematic Reviews 2003;4: Art. No. CD003511. doi:10.1002/14651858.CD003511 13 Lede R, Duley L. Uterine muscle relaxant drugs for threatened miscarriage. Cochrane Database of Systematic Reviews 2005;3: Art. No. CD002857. doi:10.1002/14651858.CD002857.pub2 14 Aleman A, Althabe F, Belizn J, Bergel E. Bed rest during pregnancy for preventing miscarriage. Cochrane Database of Systematic Reviews 2005;2: Art. No. CD003576. 15 Qureshi NS, Edi-Osagie EC, Ogbo V, Ray S, Hopkins RE. First trimester threatened miscarriage treatment with human chorionic gonadotrophins: a randomised controlled trial. BJOG 2005;112:1536 41. doi:10.1111/j.1471-0528.2005.00750.x 2007 Royal College of Obstetricians and Gynaecologists

Review 2007;9:102 108 The Obstetrician & Gynaecologist 16 Luise C, Jermy K, May C, Costello G, Collins WP, Bourne TH. Outcome of expectant management of spontaneous first trimester miscarriage: observational study. BMJ 2002;324:873 5. doi:10.1136/bmj. 324.7342.873 17 Butler C, Kelsberg G, St Anna L, Crawford P. Clinical inquiries. How long is expectant management safe in first-trimester miscarriage? J Fam Pract 2005;54:889 90. 18 Wiebe E, Janssen P. Conservative management of spontaneous abortions. Women s experiences. Can Fam Physician 1999;45:2355 60. 19 Wieringa-de Waard M, Ankum WM, Bonsel GJ, Vos J, Biewenga P, Bindels PJ. The natural course of spontaneous miscarriage: analysis of signs and symptoms in 188 expectantly managed women. BrJ Gen Pract 2003;53:704 8. 20 Elson J, Tailor A, Salim R, Hillaby K, Dew T, Jurkovic D. Expectant management of miscarriage - prediction of outcome using ultrasound and novel biochemical markers. Hum Reprod 2005;20:2330 3. doi:10.1093/humrep/dei038 21 Coughlin LB, Roberts D, Haddad NG, Long A. Medical management of first trimester incomplete miscarriage using misoprostol. J Obstet Gynaecol 2004;24:67 8. doi:10.1080/01443610310001620341 22 Nguyen TN, Blum J, Durocher J, Quan TT, Winikoff B. A randomized controlled study comparing 600 versus 1200 microg oral misoprostol for medical management of incomplete abortion. Contraception 2005;72:438 42. doi:10.1016/j.contraception.2005.05.010 23 Pang MW, Lee TS, Chung TK. Incomplete miscarriage: a randomized controlled trial comparing oral with vaginal misoprostol for medical evacuation. Hum Reprod 2001;16:2283 7. doi:10.1093/humrep/ 16.11.2283 24 Coughlin LB, Roberts D, Haddad NG, Long A. Medical management of first trimester miscarriage (blighted ovum and missed abortion): is it effective? J Obstet Gynaecol. 2004;24:69 71. doi:10.1080/ 01443610310001620332 25 Wagaarachchi PT, Ashok PW, Smith NC, Templeton A. Medical management of early fetal demise using sublingual misoprostol. BJOG 2002;109:462 5. doi:10.1111/j.1471-0528.2002.01075.x 26 Ngoc NT, Blum J, Westheimer E, Quan TT, Winikoff B. Medical treatment of missed abortion using misoprostol. Int J Gynaecol Obstet 2004;87:138 42. doi:10.1016/j.ijgo.2004.07.015 27 Tang OS, Lau WN, Ng EH, Lee SW, Ho PC. A prospective randomized study to compare the use of repeated doses of vaginal with sublingual misoprostol in the management of first trimester silent miscarriages. Hum Reprod 2003;18:176 81. doi:10.1093/humrep/deg013 28 Vejborg TS, Rorbye C, Nilas L. Management of first trimester spontaneous abortion with 800 or 400 microg vaginal misoprostol. Int J Gynaecol Obstet 2006;92:268 9. doi:10.1016/j.ijgo.2005.11.007

29 Tang OS, Ong CY, Tse KY, Ng EH, Lee SW, Ho PC. A randomized trial to compare the use of sublingual misoprostol with or without an additional 1 week course for the management of first trimester silent miscarriage. Hum Reprod 2006;21:189 92. doi:10.1093/humrep/dei303 30 Blohm F, Fridn BE, Milsom I, Platz-Christensen JJ, Nielsen S. A randomised double blind trial comparing misoprostol or placebo in the management of early miscarriage. BJOG 2005;112:1090 5. 31 Davis AR, Robilotto CM, Westhoff CL, Forman S, Zhang J; for the NICHD Management of Early Pregnancy Failure Trial group. Bleeding patterns after vaginal misoprostol for treatment of early pregnancy failure. Hum Reprod 2004;19:1655 8. doi:10.1093/humrep/deh291 32 Creinin MD, Huang X, Westhoff C, Barnhart K, Gilles JM, Zhang J; National Institute of Child Health and Human Development Management of Early Pregnancy Failure Trial. Factors related to successful misoprostol treatment for early pregnancy failure. Obstet Gynecol 2006;107:901 7. 33 Ballagh SA, Harris HA, Demasio K. Is curettage needed for uncomplicated incomplete spontaneous abortion? Am J Obstet Gynecol 1998;179:1279 82. doi:10.1016/S0002-9378(98)70147-4 34 Forna F, Gulmezoglu AM Surgical procedures to evacuate incomplete abortion. Cochrane Database Syst Rev 2001;1:CD001993. 35 Royal College of Obstetricians and Gynaecologists. The Care of Women Requesting Induced Abortion. Evidence-based Clinical Guideline No. 7. London: RCOG Press; 2004 [www.rcog.org.uk/resources/Public/pdf/ induced_abortionfull.pdf]. 36 Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). BMJ 2006;332:1235 40. doi:10.1136/bmj.38828.593125.55 37 Sotiriadis A, Makrydimas G, Papatheodorou S, Ioannidis JP. Expectant, medical, or surgical management of first-trimester miscarriage: a metaanalysis; Obstet Gynecol 2005;105:1104 13. 38 Nanda K, Peloggia A, Grimes D, Lopez L, Nanda G. Expectant care versus surgical treatment for miscarriage. Cochrane Database Syst Rev 2006;2:CD003518. 39 Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. Intrauterine adhesions after conservative and surgical management of spontaneous abortion. J Am Assoc Gynecol Laparosc 2002;9:182 5. doi:10.1016/S1074-3804(05)60129-6 40 Tam WH, Tsui MH, Lok IH, Yip SK, Yuen PM, Chung TK. Long-term reproductive outcome subsequent to medical versus surgical treatment for miscarriage. Hum Reprod 2005;20:3355 9. doi:10.1093/humrep/dei257 41 You JH, Chung TK. Expectant, medical or surgical treatment for spontaneous abortion in first trimester of pregnancy: a cost analysis. Hum Reprod 2005;20:2873 8. doi:10.1093/humrep/dei163

42 Petrou S, Trinder J, Brocklehurst P, Smith L. Economic evaluation of alternative management methods of first-trimester miscarriage based on results from the MISTtrial. BJOG 2006;113:879 89. doi:10.1111/j.14710528.2006.0099 8. x 43 Rocconi RP, Chiang S, Richter HE, Straughn JM Jr. Management strategies for abnormal early pregnancy: a cost-effectiveness analysis. J Reprod Med 2005;50:486 90. 44 Molnar AM, Oliver LM, Geyman JP. Patient preferences for management of first-trimester incomplete spontaneous abortion. J Am Board Fam Pract 2000;13:333 7. 45 Wieringa-De Waard M, Hartman EE, Ankum WM, Reitsma JB, Bindels PJ, Bonsel GJ. Expectant management versus surgical evacuation in first trimester miscarriage: health-related quality of life in randomized and non-randomized patients. Hum Reprod 2002;17:1638 42. doi:10.1093/humrep/17.6.1638 46 Smith LF, Frost J, Levitas R, Bradley H, Garcia J. Women s experiences of three early miscarriage management options: a qualitative study. BrJ Gen Pract 2006;56:198 205. 47 Cameron MJ, Penney GC. Are national recommendations regarding examination and disposal of products of miscarriage being followed? A need for revised guidelines? Hum Reprod 2005;20:531 5. doi:10.1093/humrep/deh617 48 Sagili H, Divers M. Economic evaluation of alternative management methods of first-trimester miscarriage based on results from the miscarriage treatment (MIST) trial by Petrou et al. BJOG 2007;114:116 117. doi:10.1111/j.1471-0528.2006.01164.x The Obstetrician & Gynaecologist CPD QUESTIONS A reminder to UK CPD participants and overseas CPD participants. Are you taking part in the CPD exercise provided in each issue of the journal? I f not, please note that a maximum of 20 personal category CPD credits per year may be available to you for undertaking this activity. Full instructions are provided in each issue. Please submit your answers online using the CPD submission system, which can be found on the RCOG website (www.rcog.org.uk). Please sign in as a registered user, then from the me nu on the left choose Fellows and Members , proceed to TOG Online and then select CPD submission . If you have any queries, do not hesitate to contact the CPD Office on 020 7772 6 307 or email cpd@rcog.org.uk 2007Royal College of Obstetricians and Gynaecologists