Management of early pregnancy loss

Management of early pregnancy loss -miscarriage 1st and 2nd trimester
• Definition ,purpose and scope
– The term ,,Early pregnancy loss ” describes the loss of pregnancy within the first 12 completed gestational weeks. It mainly reviews management of spontaneous miscarriage but is also relevant to women affected by ectopic pregnancy and gestational trophoblastic disease.
– Spontaneous miscarriage is the commonest complication of pregnancy. It occurs in up to 20% of clinical pregnancies. The number of this complication is approximately 14,000 miscarriages per year in Ireland [Poulose et al, 2006]. Historically, the majority of women who miscarried underwent „routine‟ surgical uterine evacuation; that is, evacuation of retained products of conception (ERPC). In the last 10 years, standard management has changed with the development of more refined diagnostic techniques and therapeutic interventions allowing more treatment to be carried out on an outpatient basis.
• Service Provision
All maternity units should provide a dedicated EPAU for the assessment of women with an early pregnancy loss.
All women attending the EPAU should be given a diagnosis and grouped under respective diagnostic groups, such as: viable pregnancy, pregnancy of uncertain viability, early pregnancy loss, incomplete miscarriage, complete miscarriage, pregnancy of unknown location (PUL), ectopic pregnancy and hydatidiform mole.
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• Criterias of RoyalInstitute of Obstetricians and College of Physicians of Ireland and Directorate of Strategy and Clinical Programmes, Health Service Executive for Early pregnancy loss
• Is when the:
• – MGSD( mean gestational sac diameter) > 20 mm with no fetal pole on TVS or a MGSD > 25 mm with no fetal pole on transabdominal scan (TAS) – Fetal pole > 7 mm with no fetal heart pulsation on TVS or a Fetal pole > 8 mm with no fetal heart pulsation on TAS – When the MGSD is ≤ 20 mm with no fetal pole or if the fetal pole is ≤ 7 mm and no fetal heart pulsation is seen and a repeat TVS organised at least 7 days from the original scan demonstrates little or no change in the dimensions – When the MGSD is ≤ 25 mm with no fetal pole or if the fetal pole is ≤ 8 mm and no fetal heart pulsation is seen and a repeat TAS organised at least 7 days from the original scan demonstrates little or no change in the dimensions.
• However it is important to keep in mind when making a diagnosis that the inter and intraobserver variability of the MGSD and fetal pole measurements reveals, for MGSD, the limits of agreement to be ±18 % [Pexsters et al, 2011]. So, a MGSD measurement of 20 mm by one examiner may translate to a measurement of anywhere between 17 and 25 mm for a second examiner. Taking inter- and intraobserver variation of measurements into account, an empty MGSD cut-off of 25 mm and a CRL cut-off of 7 mm could be introduced and, based on the available evidence, would be associated with a minimal risk of a false-positive diagnosis of miscarriage [Abdallah et al, 2011]. Emphasis should be placed on the need to repeat scans when measurements are around the decision boundaries.
• Other diagnosis :
: Viable intrauterine pregnancy:
Is when there is a normally sited gestational sac with a fetal pole and clearly identified cardiac activity. Demonstration of fetal heart activity is generally associated with a successful pregnancy rate of 85-97%, depending on the period of gestation [Johns et al, 2003]. A follow up appointment may be required in the following situations: there is significant vaginal bleeding, a subchorionic haematoma is noted, fetal bradycardia is noted, for reassurance at patients request because of previous miscarriages or after intrauterine contraceptive device removal.
Pregnancy of uncertain viability:
Is when there is a normally sited gestational sac and the mean gestational sac diameter (MGSD) ≤ 20 mm and no fetal pole is seen or when there is a normally sited gestational sac with a fetal pole ≤ 7 mm present and no fetal heart pulsation is seen on a TVS [Clinical Practice Guideline, 2011)]. In woman with a pregnancy of uncertain viability a follow up repeat scan needs to be organised at least 7 days from the original scan to assess growth of the gestation sac or embryo and to establish whether fetal heart activity develops.
Incomplete miscarriage:
• Is when on ultrasound scan the intrauterine tissue diameter is ≥ 15 mm
· Complete miscarriage
• Is when on ultrasound scan the endometrial thickness is < 15mm and there was previous evidence of an intrauterine gestational sac or retained products of conception.
• · Pregnancy of unknown location (PUL):
• Is when there are no signs of either intra- or extrauterine pregnancy or retained products of conception in a woman with a positive pregnancy test. There could be three reasons for a scan result to be classified as a PUL: a very early intrauterine pregnancy or a complete miscarriage or an early ectopic pregnancy. At subsequent follow up visits the diagnosis may become clear.
• Even with expert use of TVS using agreed criteria, it may not be possible to confirm if a pregnancy is intrauterine or extrauterine in 8–31% of cases at the first visit [Condus et al, 2003]. In specialised scanning units, the overall incidence of PUL is as low as 8–10%.
• Silent miscarriage
• Wilcox and colleagues (1988) studied 221 healthy women through 707 menstrual cycles. They found that 31 percent of pregnancies were lost after implantation. Importantly, using highly specific assays for minute concentrations of maternal serum -human chorionic gonadotropin (-hCG), two thirds of these early losses were designated as clinically silent.

• Aetiology
– Fetal factors :Chromosomal errors (this factor increases with maternal age after 35) Approximately 95 percent of chromosomal abnormalities are caused by maternal gametogenesis errors, whereas 5 percent are paternal, Autosomal trisomyis the most frequently identified chromosomal anomaly with first-trimester miscarriages.
– Paternal : balanced translocation, aging sperm
– Maternal : Endocrine abnormalities(Hypothyridism, Diabetes Melitus),Chronic debilitating disease(Tubercolosis ,Carciomatosis) ,Nutrition ,Imonological factors ,Inheritated Trombophilas ,Drug use and Enviromental Factors (tobaco ,alchocol, radiation) ,Anatomical defects of the uterus,Submocosal fibroid ,Infections( Chlamidia, Mycoplasma According to the American College of Obstetricians and Gynecologists (2001), infections are an uncommon cause of early abortion. Oakeshott and associates (2002) reported an association between second, but not first-trimester miscarriage and bacterial vaginosis ..

• Clinical examination in the EPAU
• A brief history should be taken to include:
• – Previous obstetric history, LMP and a urine pregnancy test in this pregnancy – If there is pain and, if so, its description – If there is bleeding and, if so, the amount and whether products of conception were passed
• Clinical examination should be considered if appropriate
In the absence of a clinical indication, pregnant women should be discouraged from presenting for an ultrasound scan before 8 weeks gestation. Examples of a clinical indication include pelvic pains, vaginal bleeding or a previous ectopic pregnancy. Pregnant women with a long menstrual cycle should be discouraged from presenting for a scan until two weeks after their first positive pregnancy test. If a scan is performed too early in pregnancy in an asymptomatic woman simply for reassurance, it may generate more anxiety than it alleviates if the findings are unequivocal.

• Diagnosis and investigation
• TVS will be required in the majority of women referred to an EPAU.
• When we have to arrange a second scan
• (i) The first scan was performed before 8 weeks gestation. (ii) The first scan was performed by a healthcare professional who is not formally trained in early pregnancy ultrasound. (iii) There is a concern about the reliability of the first scan, for example, a transabdominal scan in an obese woman. (iv) If a woman has a long or irregular menstrual cycle, a second scan in an asymptomatic woman should be offered at least seven days after the first scan. (v) The woman requests a second scan because she believes that the first scan may be unreliable.
• Particular caution should be taken in recommending a surgical or medical intervention for the diagnosis of miscarriage before 8 weeks gestation especially if a woman is asymptomatic.
• Serial serum hCG is particularly useful in the diagnosis of asymptomatic ectopic pregnancy.
• The majority of women attending an EPAU can be managed using urine based hCG tests. Modern monoclonal antibody based kits can detect hCG at 25iu/l, a level reached 9 days post conception (day 23 0f a day 28 cycle) [Unit specific discriminatory zones for serum hCG should be defined to exclude possible ectopic pregnancy. At levels above 1500 iu/l, an ectopic pregnancy will usually be visualised with TVS . In cases of twin pregnancy or heterotopic pregnancy, a suboptimal rise may be misleading. Serial hCG is also useful in the management of PULs and also in circumstances were a complete miscarriage is diagnosed in the absence of previous ultrasonographic evidence of an intrauterine pregnancy. In a study of 152 women with a history and TVS findings suggestive of a complete miscarriage, serial hCG assessment revealed a 5.9% incidence of ectopic pregnancy [Condus et al, 2005].
• Serum progesterone can be a useful adjuvant when ultrasound suggests a PUL.
• Serum progesterone levels below 25 nmol/l are associated with pregnancies subsequently confirmed to be non-viable . Progesterone levels above 25 nmol/l are likely to indicate and above 60 nmol/l are strongly associated with ongoing pregnancies. Care must be taken in terms of active intervention based on initial low progesterone level as viable pregnancies have been reported with low levels
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• Conservative management of a miscarriage
• Conservative management is an effective and acceptable method to offer women who miscarry provided there are no signs of infection (vaginal discharge), excessive bleeding, pyrexia or abdominal pain. Women should be counselled on what to expect, the likely amount of blood loss and what analgesics to take.
• Follow up scans may be arranged at 2 weekly intervals, until a diagnosis of complete miscarriage is made. However, if the woman requests a surgical or medical approach to their management at any stage it should be arranged.
• Patient counselling is particularly important for those women with an intact sac who wish to adopt an expectant approach. They should be aware that complete resolution may take several weeks and that overall efficacy rates are lower. Success rates are higher with prolonged follow-up. For incomplete miscarriage expectant management results in complete uterine evacuation over three days in 79% of cases [Nielsen et al, 1999]. The efficacy is reduced to 37% after seven days when expectant management is used to treat women with an intact sac (early pregnancy loss) [Wieringa-de Waard et al, 2002].
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• Medical management of a miscarriage
Misoprostol is an effective and acceptable method to offer women who miscarry provided there are no signs of infection (vaginal discharge), excessive bleeding, pyrexia or abdominal pain. Women should be counselled on what to expect, the likely amount of blood loss and what analgesics to take. Women undertaking medical management need to be informed that in case of heavy bleeding an ERPC may be required and an information leaflet on medical management should be provided.
• Medical management is an alternative technique that complements, but does not replace, surgical evacuation. Side effects of medical treatment include nausea, vomiting, cramping and diarrhoea.
• · Misoprostol is a cheap, highly effective prostaglandin analogue that is active orally or vaginally. Since progesterone levels are low in a non-viable pregnancy mifepristone is not required. Suggested protocol of administration: two sublingual/vaginal doses of Misoprostol 600µg at least three hourly . A follow up scan needs to be arranged after 2 weeks from the treatment.
• A meta-analysis of four studies found that vaginal and oral administration of misoprostol did not differ significantly in the rates of successful treatment, need for blood transfusion, nausea, and vomiting
• Outpatient medical management should be reserved to women with a MGSD < 50mm as increased bleeding may be encountered. In the case of a pregnancy occurring with an IUCD in-situ the device should be removed before administration of misoprostol. Women with uterine infections, severe anaemia, cardiovascular and cerebrovascular diseases, coagulopathy or current therapy with anticoagulants, severe hypertension or asthma were excluded from some clinical studies. In these cases, use of misoprostol should be evaluated on a case by case basis
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• Surgical management of a miscarriage
Surgical uterine evacuation (ERPC) should be offered to women that prefer that option. Clinical indications for offering ERPC include persistent excessive bleeding, haemodynamic instability, evidence of infected retained tissue and suspected gestational trophoblastic disease.
ERPC has been the standard treatment offered to women who miscarry. This was based on an assumption that retained tissue increases the risk of infection and haemorrhage, however, studies have shown that the incidence of gynaecological infection after surgical, expectant and medical management of first trimester miscarriage is low (2-3%) and no evidence exists of a difference by the method of management [Trinder et al, 2006]. ERPC remains the treatment of choice if there is persistent bleeding, if vital signs are unstable or in the presence of retained infected tissue.
• · Surgical evacuation should be performed using suction curettage and be preferably managed as a day case procedure unless there is heavy bleeding when the woman should be admitted.
• A Cochrane review concluded that vacuum aspiration is preferable to sharp curettage in cases of incomplete miscarriage. Two trials were included. Vacuum aspiration was associated with less blood loss, less pain and shorter duration of the procedure [Forna et al, 2001]. Routine use of a metal curette after suction is not required. Use of oxytocin at the time of the ERPC is also associated with less blood loss (17.6 vs 24.5 ml) [Ali et al, 1996]. Consider screening for infection (such as for Chlamydia trachomatis, Neisseria gonorrhoea or bacterial vaginosis) if clinically indicated in women undergoing ERPC. There is insufficient evidence to recommend routine antibiotic prophylaxis prior to ERPC. Antibiotic prophylaxis should be given on individual clinical indications. Where infection is suspected, delaying ERPC for 12 hours is recommended to allow intravenous antibiotic administration.
• ERPC is associated with anaesthetic and uncommon surgical risks and informed written consent need to need to be mentioned when obtaining consent include uterine perforation (1%), cervical tears, intra-abdominal e obtained. Risks trauma (0.1%), haemorrhage and infection. An information leaflet on surgical management of a miscarriage should also be provided to women undergoing an ERPC.
• Practitioners may consider oral or vaginal cervical preparation prior to the procedure based on individual patient circumstance. The advantages of prostaglandin administration are well established, with significant reductions in dilatation force, haemorrhage and uterine/cervical trauma. Suggested dose of misoprostol for cervical priming is 400 µg (vaginally/orally) three hours before the procedure [Weeks et al, 2007].

• Rhesus anti-D prophylaxis
• Non- sensitised Rhesus (Rh) negative women should receive prophylactic anti-D Immunoglobulin (Ig) in the following situations: ectopic pregnancy, all miscarriages over 12 week’s gestation (including threatened) and all miscarriages were the uterus is evacuated surgically.
• · Anti-D immunoglobulin should only be given for threatened miscarriage under 12 weeks gestation when bleeding is heavy or associated with pain. It is not required for cases of complete miscarriage under 12 week’s gestation where there has been no surgical intervention.
• There is minimal evidence that administering anti-D Ig for first trimester vaginal bleeding prevents maternal sensitization or development of haemolytic disease of the newborn. The risk of immunisation before 12 weeks’ gestation is negligible when there has been no instrumentation to evacuate the products of conception and anti-D Ig is not required in these circumstances [Hannafin et al, 2006].