After studying this chapter you should be able to:
List the causes of bleeding and/or pain in early pregnancy
Describe the epidemiology, aetiology and clinical features of: miscarriage, ectopic pregnancy, and molar pregnancy
Discuss the use of ultrasound and endocrine assessments in early pregnancy problems
Describe the management of the common complications of early pregnancy including the conservative, medical and surgical management of miscarriage (including cervical shock), recurrent miscarriage, ectopic pregnancy, molar pregnancy and hyperemesis gravidarum
Take a relevant gynaecological history in a woman complaining of vaginal bleeding and/or abdominal pain in early pregnancy
Perform a urinary pregnancy test and interpret the result
Perform a circulatory assessment and abdominal examination of a woman with an early pregnancy problem and identify those requiring immediate intervention
Initiate appropriate resuscitation of a woman presenting in early pregnancy with cardiovascular collapse
Be able to communicate effectively and sensitively with patients and relatives
Professional skills and attitudes
Consider the need for a supportive environment that addresses religious and cultural issues around early pregnancy loss
Bleeding in early pregnancy
Vaginal bleeding occurs in up to 25% of pregnancies prior to 20 weeks. It is a major cause of anxiety for all women, especially those who have experienced previous pregnancy loss, and may be the presenting symptom of life-threatening conditions such as ectopic pregnancy. Bleeding should always be considered as abnormal in pregnancy and investigated appropriately.
A small amount of bleeding may occur as the blastocyst implants in the endometrium 5–7 days after fertilization (implantation bleed). If this occurs at the time of expected menstruation it may be confused with a period and so effect calculations of gestational age based on the last menstrual period.
The common causes for bleeding in early pregnancy are miscarriage, ectopic pregnancy and benign lesions in the lower genital tract. Less commonly it may be the presenting symptom of hydatiform mole or cervical malignancy.
The recommended medical term for pregnancy loss less than 24 weeks gestation is ‘miscarriage’. In some countries, such as the US, this term is used to describe pregnancy loss before fetal viability or a fetal weight of less than 500 g. In some states in Australia the term is used for any pregnancy loss under 20 weeks gestation. Most miscarriages occur in the second or third month and occur in 10–20% of clinical pregnancies. It has been suggested that a much higher proportion of pregnancies miscarry at an early stage if the diagnosis is based on the presence of a significant plasma level of beta-subunit human chorionic gonadotrophin (hCG).
The aetiology of miscarriage
In many cases no definite cause can be found for miscarriage. It is important to identify this group as the prognosis for future pregnancy is generally better than average.
Chromosomal abnormalities are a common cause of early miscarriage and may result in failure of development of the embryo with formation of a gestation sac without the development of an embryo or with later expulsion of an abnormal fetus. In any form of miscarriage, up to 55% of products of conception will have an abnormal karyotype. The most common chromosomal defects are autosomal trisomies, which account for half the abnormalities, while polyploidy and monosomy X account for a further 20% each. Although chromosome abnormalities are common in sporadic miscarriage, parental chromosomal abnormalities are present in only 3–5% of partners presenting with recurrent pregnancy loss. These are most commonly balanced reciprocal or Robertsonian translocations or mosaicisms.
Progesterone production is predominately dependent on the corpus luteum for the first 8 weeks of pregnancy, and the function is then assumed by the placenta. Progesterone is essential for the maintenance of a pregnancy, and early failure of the corpus luteum may lead to miscarriage. However, it is difficult to be certain when falling plasma progesterone levels represent a primary cause of miscarriage and when they are the index of a failing pregnancy. The prevalence of polycystic ovarian syndrome (PCOS) is significantly higher in women with recurrent miscarriage than in the general population. Women with poorly controlled diabetes and untreated thyroid disease are at higher risk of miscarriage and fetal malformation.
Maternal illness and infection
Severe maternal febrile illnesses associated with infections, such as influenza, pyelitis and malaria, predispose to miscarriage. Specific infections such as syphilis, Listeria monocytogenes, Mycoplasma spp. and Toxoplasma gondii also cause miscarriage, but there is no evidence that these organisms cause recurrent miscarriage particularly in the second trimester. The presence of bacterial vaginosis has been reported as a risk factor for preterm delivery and second, but not first trimester, miscarriage. Other severe illnesses involving the cardiovascular, hepatic and renal systems may also result in miscarriage.
Maternal lifestyle and drug history
Antidepressant use and periconceptual non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with miscarriage. Smoking, alcohol (more than 5 units a week), caffeine (more than 3 cups per day), cocaine and cannabis use increase the risk of miscarriage. There is some evidence that stress may also be associated with pregnancy loss.
Abnormalities of the uterus
Congenital abnormalities of the uterine cavity, such as a bicornuate uterus or subseptate uterus, may result in miscarriage ( Fig. 18.1 ). Uterine anomalies can be demonstrated in 15–30% of women experiencing recurrent miscarriages. The impact of the abnormality depends on the nature of the anomaly. The fetal survival rate is 86% where the uterus is septate and worst where the uterus is unicornuate. It must also be remembered that over 20% of all women with congenital uterine anomalies also have renal tract anomalies. Following damage to the endometrium and inner uterine walls, the surfaces may become adherent, thus partly obliterating the uterine cavity (Asherman’s syndrome). The presence of these synechiae may lead to recurrent miscarriage.
Cervical incompetence clinically results in second trimester miscarriage or early preterm delivery. The miscarriage tends to be rapid, painless and bloodless. The diagnosis is established by the passage of a Hegar 8 dilator without difficulty in the non-pregnant woman or by ultrasound examination or by a premenstrual hysterogram. Cervical incompetence may be congenital, but most commonly results from physical damage caused by mechanical dilatation of the cervix or by damage inflicted during childbirth.
Antiphospholipid antibodies – lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) – are present in 15% of women with recurrent miscarriage, but only 2% of women with normal reproductive histories. Without treatment the live birth rate in women with primary antiphospholipid syndrome may be as low as 10%. Pregnancy loss is thought to be due to thrombosis of the uteroplacental vasculature and impaired trophoblast function. In addition to miscarriage there is an increased risk of intrauterine growth restriction, pre-eclampsia and venous thrombosis.
Defects in the natural inhibitors of coagulation – antithrombin III, protein C and protein S – are more common in women with recurrent miscarriage. The majority of cases of activated protein C deficiency are secondary to a mutation in the factor V (Leiden) gene.
Research into the possibility of an immunological basis for recurrent miscarriage has generally explored the possibility of a failure to mount the normal protective immune response or if the expression of relatively non-immunogenic antigens by the cytotrophoblast may result in rejection of the fetal allograft. There is evidence that unexplained spontaneous miscarriage is associated with couples who share an abnormal number of HLA antigens of the A, B, C and DR loci. Treatment with paternal lymphocytes and immunoglobulins has been shown not to be effective and is potentially dangerous.
Clinical types of miscarriage
The first sign of an impending miscarriage is the development of vaginal bleeding in early pregnancy ( Fig. 18.2 ). The uterus is found to be enlarged and the cervical os is closed. Lower abdominal pain is either minimal or absent. Most women presenting with a threatened miscarriage will continue with the pregnancy irrespective of the method of management.
The patient develops abdominal pain usually associated with increasing vaginal bleeding. The cervix opens, and eventually products of conception are passed into the vagina. However, if some of the products of conception are retained, then the miscarriage remains incomplete ( Fig. 18.3 ).
Distension of the cervical canal by products of conception can cause hypotension and bradycardia (cervical shock).
A 32-year-old Asian woman presented with a history of 12 weeks amenorrhoea and vaginal bleeding followed by severe lower abdominal pain. On admission to hospital, she was sweating, pale and hypotensive. Her pulse rate was 68 beats/min. She complained of generalized lower abdominal pain. Initially, a ruptured tubal pregnancy was suspected because of the pain and shock, until vaginal examination revealed copious products of conception protruding from an open cervical os. Removal of these products largely relieved the pain and allowed the uterus to contract, thus reducing the blood loss. Subsequent evacuation of retained products of conception was performed after appropriate resuscitation and preparation.
An incomplete miscarriage may proceed to completion spontaneously, when the pain will cease and vaginal bleeding will subside with involution of the uterus. Spontaneous completion of a miscarriage is more likely in miscarriages over 16 weeks gestation than in those between 8 and 16 weeks gestation, when retention of placental fragments is common.
Miscarriage with infection (sepsis)
During the process of miscarriage – or after therapeutic termination of a pregnancy – infection may be introduced into the uterine cavity. The clinical findings of septic miscarriage are similar to those of incomplete miscarriage with the addition of uterine and adnexal tenderness. The vaginal loss may become purulent and the patient pyrexial. In cases of severe overwhelming sepsis, endotoxic shock may develop with profound and sometimes fatal hypotension. Other manifestations include renal failure, disseminated intravascular coagulopathy and multiple petechial haemorrhages. Organisms which commonly invade the uterine cavity are Escherichia coli , Streptococcus faecalis , Staphylococcus albus and S. aureus , Klebsiella , Clostridium welchii and C. perfringens .
Missed miscarriage (empty gestation sac, embryonic loss, early and late fetal loss)
In empty gestation sac (anembryonic pregnancy or blighted ovum) a gestational sac of ≥25 mm is seen on ultrasound ( Fig. 18.4 ), but there is no evidence of an embryonic pole or yolk sac or change in size of the sac on rescan 7 days later. Embryonic loss is diagnosed where there is an embryo ≥7 mm in size without cardiac activity or where there is no change in the size of the embryo after 7 days on scan. Early fetal demise occurs when a pregnancy is identified within the uterus on ultrasound consistent with 8–12 weeks size, but no fetal heartbeat is seen. These may be associated with some bleeding and abdominal pain or be asymptomatic and diagnosed on ultrasound scan. The pattern of clinical loss may indicate the underlying aetiology, for example, antiphospholipid syndrome tends to present with recurrent fetal loss.
Spontaneous second trimester loss
Pregnancy loss occurs between 12 and 24 weeks associated with spontaneous rupture of membranes or cervical dilatation despite the presence of fetal heart activity.
Recurrent miscarriage is defined as three or more successive pregnancy losses prior to viability. The problem affects 1% of all women, approximately three times the number that would be expected by chance alone. Most women who have had two or more consecutive miscarriages are anxious to be investigated and reassured that there is no underlying cause for the miscarriage. However, it is important to remember that after two consecutive miscarriages the likelihood of a successful third pregnancy is still around 80%. Even after three consecutive miscarriages, there is still a 55–75% chance of success. This implies that recurrent miscarriage is unlikely to be a random event and that it is necessary to seek a cause.
Examination of the patient should include gentle vaginal and speculum examination to ascertain cervical dilatation. If there is pyrexia, a high vaginal swab should be taken for bacteriological culture.
Some women may prefer not to be examined because of apprehension that the examination may promote miscarriage, and their wishes should be respected. Management in dedicated early pregnancy assessment units (EPAU) reduces the need for hospital admission and length of stay. An ultrasound scan is valuable in deciding if the fetus is alive and normal. One effect of the routine use of scans in early pregnancy is that the diagnosis of miscarriage may be established before there is any indication that the pregnancy is abnormal. It is sometimes preferable to repeat the scan a week later than proceed to immediate medical or surgical uterine evacuation, to enable the mother to come to terms with the diagnosis.
Miscarriage may be complicated by haemorrhage and severe pain, and may necessitate blood transfusion and relief of pain with opiates. If there is evidence of infection, antibiotic therapy should be started immediately and adjusted subsequently if the organism identified in culture is not sensitive to the prescribed antibiotic.
Septic miscarriage complicated by endotoxic shock is treated by massive antibiotic therapy and adequate, carefully controlled fluid replacement.
If there is evidence of ‘cervical shock’, any products of conception protruding through the cervical os should be removed by grasping them with tissue holding forceps.
Anti-D immunoglobulin should only be given for threatened miscarriages under 12 weeks gestation when bleeding is heavy or associated with pain. It is not required for cases of complete miscarriage under 12 weeks of gestation when there has been no formal intervention to evacuate the uterus.
There is no evidence that bed rest improves the prognosis in cases of threatened miscarriage, although it may be beneficial in prolonging pregnancy in women at high risk of second trimester loss or where there is prolapse of membranes into the cervical canal as a result of cervical weakness.
Surgical evacuation of retained products of conception involves dilatation of the cervix and suction curettage to remove the products ( Fig. 18.5 ). This is the modality of choice when there is heavy bleeding or persistent bleeding, if the vital signs are unstable or in the presence of infected retained tissue. Serious complications of surgical treatment occur in 2% of cases and include perforation of the uterus, cervical tears, intra-abdominal trauma, intrauterine adhesions and haemorrhage. Intrauterine infection may result in tubal infection and tubal obstruction with subsequent infertility. Screening for infection including Chlamydia trachomatis should be considered and antibiotic prophylaxis given if clinically indicated. If uterine perforation is suspected and there is evidence of intraperitoneal haemorrhage or damage to the bowel, then a laparoscopy or laparotomy should be performed.