Bleeding in early pregnancy

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10 Bleeding in early pregnancy

Vaginal bleeding in the first trimester is a common event, occurring in up to 30% of all pregnancies, and about one-half of these will eventually miscarry by 12 weeks’ gestation. More than 90% of spontaneous miscarriage occurs in the first trimester.

Causes of bleeding in the first trimester include spontaneous abortion, physiological bleeding of a normal pregnancy, ectopic pregnancy, trophoblastic disease and non-obstetrical causes such as cervical lesions, e.g. polyps, ectropion or carcinoma.

Miscarriage

Definition

Miscarriage (abortion) is the involuntary loss or termination of pregnancy prior to 24 weeks’ gestation. Other definitions include the loss of pregnancy before viability. The World Health Organization definition is ‘expulsion or extraction of an embryo or fetus weighing 500 g or less from its mother’. However, this weight criterion corresponds to a gestational age of 20–22 weeks, the irreducible age for fetal viability. An empty sac (formerly known as blighted ovum or anembryonic pregnancy) occurs when an embryo has failed to develop although there is an identifiable gestational sac and placental tissue. This is, in fact, an early form of missed miscarriage.

Types of miscarriage (Fig. 10.1)

• Threatened – uterine bleeding without dilatation of cervix or passage of products of conception (POC). The fetus is still viable and the uterus is the expected size for dates. Only one-quarter of these will go on to miscarry.

• Inevitable – heavy bleeding with cervical dilatation, but without passage of POC. The fetus may still be alive, but miscarriage will occur.

• Incomplete – bleeding with cervical dilatation and passage of some, but not all, POC.

• Complete – bleeding which diminishes with complete passage of POC. Pain and bleeding ease, uterus returns to normal size and cervix is closed.

• Missed – fetal death, bleeding or pain; the fetus or embryo has been dead for some weeks, but no tissue has been passed. This is often not recognized until bleeding occurs, the patient complains that she feels ‘less pregnant than before’ and an ultrasound has been performed confirming fetal demise.

• Septic – any of the above that becomes infected, resulting in endometritis and often parametritis and peritonitis.

Figure 10.1 Stages of miscarriage.

Pathophysiology

Up to 50% of spontaneous miscarriages are the result of a major genetic abnormality, e.g. trisomy. The remainder have been linked to other factors such as uterine abnormalities (such as fibroids or müllerian duct abnormalities), cervical incompetence (usually mid-trimester loss), maternal systemic disease, progesterone deficiency in the luteal phase of the cycle and immunological factors.

Once the woman has a positive pregnancy test and the pregnancy fails, there is usually a cessation of the symptoms of pregnancy and the serum human chorionic gonadotrophin beta-subunit (βhCG) levels plateau or fall. Eventually, she will begin to bleed and after hours or weeks of bleeding in varying amounts she will experience lower abdominal cramping or back pain. At this point the eventual outcome is recognized even if the pregnancy failed weeks previously. The final event in this sequence is the passage of POC as the body attempts to evacuate the contents of the uterus, and this is often associated with severe pain, bleeding and often symptoms and signs of shock if products remain in the cervix.

This sequence of events is often mimicked by ectopic pregnancy and, therefore, this must always be excluded. Both entities have positive pregnancy tests, variable symptoms of pregnancy, vaginal bleeding and pelvic pain. However, a ruptured ectopic pregnancy will produce signs of shock and signs of a haemoperitoneum, such as rebound tenderness, rigid abdomen or shoulder-tip pain (caused by diaphragmatic irritation).

Assessment

When a patient presents with first-trimester bleeding, begin with an accurate history including careful questioning on the sequence of events, symptoms, menstrual history, method of contraception, previous obstetrical, gynaecological, surgical and medical history. Attempting to establish estimated/expected gestation of the pregnancy is imperative.

General examination including vital signs and cardiovascular status must be performed. An abdominal examination is important, particularly if one suspects an ectopic pregnancy, assessing for signs of a haemoperitoneum. A speculum examination will eliminate any local cause of vaginal bleeding and will reveal any cervical dilatation, and at this stage POC can be removed with a sponge holder if seen in the cervix. A bimanual examination may be necessary if the speculum examination is normal and this will allow assessment of uterine size, cervical dilatation, cervical excitation – pain on movement of the cervix (an indicator of a possible ectopic or pelvic infection) – and the presence of an adnexal mass.

Investigations

• Full blood count, blood group and consider serum βhCG assay

• Ultrasound scan of pelvis.

Management

• Conservative

• Uterine curettage (evacuation of retained POC – ERPC) if incomplete or non-viable pregnancy

• Anti-D immunoglobulin if patient is Rhesus D-negative.

The management of bleeding in early pregnancy will depend on clinical, ultrasound and biochemical factors.

Complications

• Haemorrhage or infection if tissue is retained

• Uterine perforation at time of ERPC with possible bowel trauma

• Later problems can include Asherman’s syndrome (with recurrent or overzealous curettage) or cervical incompetence.

Follow-up

All patients should be adequately counselled and assured that this was an unfortunate outcome that could not have been prevented. The emotional reaction of patients may require bereavement counselling and the Miscarriage Association is a patient-organized group which many patients and their partners find useful.

Therapeutic abortion

Definition

Therapeutic termination of pregnancy is defined as medical or surgical termination of pregnancy before 24 weeks’ gestation. However, in the UK, 90% of terminations are performed before 12 weeks’ gestation.

Legal aspects of pregnancy termination

In 1967 the Abortion Act was passed in England and Wales; this allowed termination of pregnancy to be carried out by a medical practitioner in a licensed institution. Two medical practitioners must agree with the patient’s request and sign the consent form (certificate A). The grounds for termination are stated in certificate A and must be indicated by the consenting practitioners. These grounds are that continuation of the pregnancy will:

A. Endanger the life of the woman

B. Endanger the physical or mental well-being of the woman

C. Endanger the physical or mental well-being of the children of the pregnant woman

D. Involve substantial risk that the child would suffer physical or mental handicap.

The vast majority of terminations are performed for reason B.

Assessment

All patients requesting termination of pregnancy should be fully counselled to ensure that their decision is definite and that they are committed to proceeding with the surgery. Usually these patients will have seen their family doctor for this, but all clinics should provide a support service.

History and examination should include menstrual history for pregnancy dating and suitability for anaesthesia. Ultrasound scan should be performed to confirm gestation. A full blood count should be taken and group and antibody status ascertained.

Methods of termination

1. Suction curettage is most commonly performed prior to 12–14 weeks’ gestation. The cervix must be dilated and often in nulliparous patients the cervix is ‘ripened’ prior to the procedure with a prostaglandin pessary for ease of dilatation.

2. Antiprogesterone tablets (RU486) are effective up to 9 weeks’ gestation when taken in conjunction with a prostaglandin pessary so that anaesthesia can be avoided.

3. Dilatation of the cervix and evacuation of the uterine contents can be performed after 12 weeks’ gestation until 16–20 weeks. This involves dilatation of the cervix and destruction of the fetal parts followed by evacuation of the uterine contents.

4. Prostaglandin induction is used after 14–16 weeks’ gestation and an oxytocin infusion may also be necessary to expedite what can sometimes be a long, arduous and painful process. Antiprogesterone tablets can be administered 48 hours beforehand to improve the efficacy of this procedure.

Complications

The complications of surgical evacuation of the uterus include those of anaesthesia, bleeding, infection and uterine perforation with its association of possible bowel damage. Longer-term complications related to the surgery include Asherman’s syndrome and cervical incompetence.

Recurrent miscarriage

Definition

Recurrent miscarriage is defined as the loss of three or more consecutive pregnancies before 24 weeks’ gestation.

Prevalence

Between 12% and 15% of clinically recognized pregnancies miscarry. This implies that the risk of three consecutive pregnancy losses occurring by chance alone is around 0.3%. However, the incidence quoted for couples experiencing recurrent miscarriage is accepted to be 1%. The fact that the observed frequency of recurrent miscarriage is significantly higher than that expected by chance alone implies that in some women there is a persistent underlying cause to account for their pregnancy losses.

Aetiology

This will depend on the gestation at which the miscarriage occurs.

First trimester

Polycystic ovaries (PCO) are found more commonly in women with recurrent miscarriage (58%) than the general population (22%), and 56% of women with PCO hypersecrete luteinizing hormone (LH). An association with this raised or hypersecretion of LH and recurrent miscarriage has been implicated, although the mechanism of pregnancy failure is unclear.

Women with a history of recurrent miscarriage tend to lose fetuses that have a normal karyotype. However, a parental chromosome abnormality is found in 3–5% of couples with recurrent miscarriage. It is, therefore, essential that blood karyotyping is performed on both partners in order to identify those couples with a genetic cause for their pregnancy losses. These couples should be referred for genetic counselling in order that they may be given a prognosis for future pregnancies and prenatal diagnosis should be offered in ongoing pregnancies.

Recurrent miscarriage has been shown to be associated with antiphospholipid antibodies – lupus anticoagulant and anticardiolipin antibodies – in up to 15% of women. The primary antiphospholipid syndrome (APS) is the association between either recurrent miscarriage and/or thrombosis with antiphospholipid antibodies. Recurrent miscarriage is also thought to be associated with other thrombophilic defects, including deficiencies of antithrombin III and factor XII deficiency, and low levels of the naturally occurring anticoagulants protein C and protein S. Activated protein C resistance, a recently identified thrombophilic defect, is found in 20% of women with a history of second-trimester miscarriage where fetal loss is associated with placental thrombosis. As well as accounting for recurrent first-trimester loss, these abnormalities are associated with second-trimester loss and poor obstetric outcome.

The alloimmune theory, that the genetic dissimilarity between the mother and fetus may give rise to a rejection mechanism causing recurrent miscarriage, has not been proven.

Second trimester

Up to 10% of patients with recurrent miscarriage have some uterine abnormality. These include intracavity fibroids and congenital structural abnormalities such as bi/unicornuate uteri. Cervical incompetence is a recognized cause of recurrent mid-trimester miscarriage and patients classically give a history of a painless pregnancy loss after 16 weeks’ gestation. The role of cervical cerclage in these patients is still controversial, but each patient should be considered individually.

Any severe infection may cause a sporadic miscarriage but to be responsible for recurrent loss the infection must persist (often asymptomatically) in the genital tract for a long period of time. Bacterial vaginosis is one such organism that may play a part in the aetiology of recurrent miscarriage and also in preterm delivery.

Assessment

A full history and examination should include a detailed background of the pregnancy losses, at what gestation they occurred and whether an ultrasound scan was performed, pain/bleeding preceding the loss, same partner, cycle length and ease of conception. Is there a history of systemic disease or thrombosis, surgery to the cervix, family history of miscarriage or thrombosis?

Investigations

• Blood – LH, follicle-stimulating hormone, testosterone on day 5–8 of cycle (PCO syndrome (PCOS) screen)

• Antiphospholipid antibody, anticardiolipin antibody and lupus anticoagulant for APS or systemic lupus erythematosus screening

• Chromosomes of both partners

• Ultrasound scan to exclude PCOS or uterine abnormality.

Management

These patients and their partners are often distressed and require a great deal of psychological support. Often the investigations are negative and few treatments are of proven value. Once a pregnancy has been achieved then support with regular ultrasound reassurance is vital and has been shown to be of value.

Patients with systemic lupus erythematosus and APS should be referred to a specialist centre. Recent studies suggest that these patients have a better outcome when treated with low-dose aspirin 75 mg daily and heparin 5000 IU subcutaneously throughout pregnancy.

Ectopic pregnancy

Definition

An ectopic pregnancy is when the embryo implants outside the uterine cavity. The most common site is in the fallopian tube, although implantation can occur in the cornua of the uterus, the cervix, ovary or abdominal cavity (Fig. 10.2). These sites are unable to contain the growing trophoblast and embryo, so rupture may occur, leading to catastrophic bleeding.

Figure 10.2 Sites of ectopic pregnancies.

Incidence

This is now becoming more common in the UK, representing 4% of direct and indirect maternal deaths in 1997–99. Its incidence has doubled over the last 30 years (from 4.9 to 9.6 per 1000 pregnancies or 1 in 100 pregnancies). In the USA, deaths due to ectopic pregnancy comprised 9% of all maternal deaths in 1992 and its incidence has apparently increased fourfold (from 4.5 to 20 per 1000 pregnancies) between 1970 and 1992. The mortality, however, has decreased 10-fold in the USA and fivefold in the UK during these timeframes, indicating improved diagnosis and management.

Aetiology

In many cases the cause is unknown. Ectopic pregnancy is often very difficult to diagnose as the clinical presentation can vary from vaginal spotting to haemoperitoneum and shock. Risk factors are present in 25–50% of patients with an ectopic pregnancy and include:

• Previous pelvic inflammatory disease (PID) (increases the risk of ectopic pregnancy 10-fold). The recent increase in PID is thought to have contributed to the increased incidence of ectopic pregnancy.

• Previous tubal surgery, including reconstruction and sterilization (increases the risk of ectopic pregnancy 4½-fold).

• Previous ectopic pregnancy (10-fold). Even if a tube has been previously removed, the initial causative pathology is often bilateral.

• Assisted reproductive techniques (in vitro fertilization or gamete intrafallopian transfer).

• Intrauterine contraceptive device (IUCD). This is a risk if pregnancy occurs whilst in situ. Most current contraceptive methods protect against ectopic pregnancy except when the method fails. However, modern copper-bearing IUCDs (Copper T 380, Multiload Cu 375) and the levonorgestrel-releasing intrauterine system (Mirena) are extremely effective contraceptives with failure rates of around 1 in 100 after 5 years of use, making them acceptable contraceptive choices for women with a previous history of ectopic pregnancy.

• The progesterone-only contraceptive pill.

Assessment

The diagnosis is often difficult clinically (accuracy of 50%), but should always be considered in a woman of childbearing age with amenorrhoea, abnormal bleeding, abdominal pain or collapse. It is a diagnosis of exclusion in any such women and has been made simpler with advances in early diagnostic techniques, in particular the quantitative measurement of βhCG, transvaginal ultrasonography and dedicated early pregnancy assessment clinics. Assessment includes:

• A history of pain, irregular scanty bleeding and amenorrhoea

• General examination of vital signs, evidence of acute abdomen, cervical excitation with a bulky uterus and a tender adnexae on vaginal assessment

• Checking for the presence of βhCG, which is detected in the urine as early as 14 days postconception or in the serum 5–9 days postconception by sensitive assays. Between 2 and 4 weeks after ovulation serum βhCG levels double approximately every 2 days in a normal intrauterine pregnancy; a lesser increase (<66% over 48 hours) is associated with ectopic pregnancy and spontaneous abortion. In order to increase the sensitivity of quantitative βhCG, a discriminatory zone has been described whereby a titre of 1000–1500 IU/l (international reference preparation) will be associated with the presence of an intrauterine sac on transvaginal ultrasound

• Transvaginal ultrasound: positive signs of an intrauterine pregnancy on ultrasound scan include a gestation sac (at approximately 4 weeks’ amenorrhoea), the double decidual sign (at 5 weeks), the yolk sac (5–6 weeks) and, finally, the fetal heartbeat (7 weeks). Ectopic pregnancy should be suspected if there are ultrasonic appearances of an empty uterus, an intrauterine pseudosac, evidence of a tubal swelling or ring sign with a fetal heartbeat, or fluid in the pouch of Douglas. Demonstration of a viable intrauterine pregnancy does not exclude the possibility of heterotopic pregnancy (frequency 1/30 000–40 000 spontaneously to 1–3% after assisted reproduction), i.e. a coexisting ectopic and intrauterine pregnancy.

Management

If an ongoing ectopic is suspected, the patient should be admitted to hospital for further investigation, with blood taken for crossmatching and intravenous access (Fig. 10.3).

Figure 10.3 Management of suspected ectopic pregnancy. βhCG, beta human chorionic gonadotrophin; POD, pouch of Douglas; MTX, methotrexate; TVS, transvaginal scan.

Acute presentation

The patient is resuscitated and arrangements made for immediate laparoscopy/laparotomy with salpingectomy of the affected tube, if the other tube appears normal.

Subacute presentation

Women in whom an ectopic pregnancy is visualized should be managed surgically or medically as described below. Where the location of the pregnancy cannot be initially confirmed (‘pregnancy of uncertain location’), then serial hCG monitoring should be established, with clear advice to the woman to reattend urgently if she develops pain. Where a woman has significant pelvic pain or echogenic free peritoneal fluid suggestive of haemoperitoneum, then laparoscopy should be considered, even in the absence of positive ultrasound visualization of an ectopic pregnancy.

Surgical treatment

Laparoscopic treatment of ectopic pregnancy will depend on the patient’s physical condition, the location, size and state of the ectopic pregnancy, the experience of the surgeon, and the availability of equipment. The advantages of the laparoscopic approach have been well documented in terms of shorter hospital stay, quicker return to normal routine, fewer postoperative analgesic requirements, as well as reduced costs. The laparoscopic approach is also superior compared with laparotomy in terms of subsequent rate of intrauterine pregnancy and recurrent ectopic. The operation of choice for ectopic pregnancy is controversial, but clear guidelines are now available from bodies such as the Royal College of Obstetricians and Gynaecologists:

• Linear salpingotomy can be performed for an ampullary ectopic and fimbrial expression for an ectopic that is extruding from the fimbrial end. Salpingotomy is a reasonable approach when there is only one tube, but is associated with a 20% rate of further ectopic.

• Salpingectomy is preferred to salpingotomy when the contralateral tube is healthy as it is associated with a lower rate of persistent trophoblastic tissue, lower subsequent ectopic pregnancy and a similar subsequent intrauterine pregnancy rate. Salpingectomy is also indicated in the presence of uncontrolled bleeding, a second ectopic in the same tube, a severely damaged tube and occasionally when childbearing is complete.

• If patient is haemodynamically compromised or the surgeon has little experience in laparoscopic surgery, then a laparotomy is a reasonable approach.

Medical treatment

Early diagnosis has made medical management of ectopic pregnancy an option in centres with relevant expertise. It is appropriate in patients that are haemodynamically stable, reliable and compliant (as careful follow-up is important), with an ectopic pregnancy within the tube, measuring 3.5 cm or less in its greatest diameter, and with no evidence of rupture or significant bleeding. The advantages of this are that surgery and anaesthesia are avoided, there is less tubal damage, it is cost-effective and future fertility potential is maintained. Methotrexate has been used by single or multiple intramuscular doses or by injection directly into the ectopic pregnancy with good success.

Gestational trophoblastic disease

This is a general term used to describe hydatidiform mole, invasive mole, placental-site tumour and choriocarcinoma. It occurs when trophoblastic tissue, which is part of the blastocyst and normally invades the endometrium to form the placenta, proliferates abnormally and aggressively. The incidence in the UK is approximately 1 in 2000 pregnancies, compared with 1 in 200 in Asia.

Definitions

A hydatidiform mole is a benign tumour of the trophoblast and can be either partial or complete.

Partial mole

This is the commonest type: fetus or fetal tissue is present, cells are triploid derived from two sperm and one egg, and rarely become malignant.

Complete mole

This is much less common: no fetus is present, the cells are entirely paternal in origin, usually occurring when a sperm fertilizes an empty egg and then undergoes mitosis so that the cells are diploid, usually 46,XX; there is a 5–10% risk of malignant change.

Invasive mole

This is a tumour-like process invading the myometrium with metastatic potential. It usually follows a complete mole and may resolve spontaneously as it is less aggressive than a true cancer.

Choriocarcinoma

This is a carcinoma arising from the trophoblast after a mole, a miscarriage or even following a normal pregnancy.

Assessment

Moles usually present with bleeding in early pregnancy. They are associated with grossly elevated βhCG levels and so symptoms of pregnancy are exaggerated, such as excessive hyperemesis. Patients may present with early-onset pre-eclampsia or hyperthyroidism.

The uterus is large for dates and ultrasound may show a ‘snowstorm’ appearance due to the presence of the hydropic ‘grape-like’ vesicles within the uterine cavity.

Serum βhCG is grossly elevated. Chest X-ray should be performed to exclude metastases.

Management

Suction curettage with oxytocin infusion should be performed by an experienced surgeon as there is significant risk of incomplete evacuation or perforation. Hysterectomy may be considered if the patient’s family history is complete.

Urgent histological analysis of tissue must be carried out and anti-D immunoglobulin must be administered if appropriate. The patient should be registered with the regional specialist centre.

Follow-up

All patients with molar pregnancy should be registered with a centre for trophoblastic disease. These patients require detailed follow-up that will be arranged by these centres. Serum βhCG samples should be obtained at 2-weekly intervals postevacuation until normal levels are reached. Following these, urinary βhCG samples are requested at 4-weekly intervals until 1 year postevacuation, then every 3 months in the second year of follow-up. Further serum samples are only requested if subsequent βhCG becomes abnormal. If the patient’s βhCG values reach normal range within 8 weeks of evacuation, follow-up will be limited to 6 months. Adverse sequelae have not so far been observed in these patients. The majority of patients with partial hydatidiform mole, and patients with lesions suspicious of hydatidiform mole, fall into this short-term follow-up group. It also includes some patients with complete hydatidiform mole. Patients in the 6-month follow-up group may consider starting a new pregnancy at the end of that 6-month period.

Patients who do not have normal βhCG values within 8 weeks of evacuation should have 2-year follow-up. If these women are keen to pursue a further pregnancy it is only advisable after βhCG levels have been normal for 6 months. In this group the risk of choriocarcinoma occurring is 1 in 286.

Further estimations of βhCG 6 and 10 weeks after any future pregnancy are recommended because of the small risk of choriocarcinoma developing in such patients. In some cases the choriocarcinoma arises from the new pregnancy.

Hormonal preparations taken for contraceptive or other purposes between evacuation of a mole and the return to normal βhCG levels appear to increase the risk of choriocarcinoma developing. It is suggested that these be avoided until βhCG has become undetectable in serum.

Prognosis

The diagnosis of malignancy is usually made from persistently elevated or rising βhCG levels, persistent vaginal bleeding or evidence of metastatic spread to the lungs. The tumour is highly malignant, but also very chemosensitive, with 5-year survival rates of 95%. The mortality from trophoblastic disease is six to eight women per year in the UK.

Summary

• Detailed history and examination are vital in the assessment of early-pregnancy bleeding.

• Transvaginal ultrasound assessment is a key part of the assessment of early-pregnancy complications.

• Ectopic pregnancy should always be considered, as the presentation is highly variable and the consequences can be devastating if diagnosis is missed.

• Pregnancy loss is highly emotive and psychological support should always be offered.

• Patients with recurrent pregnancy loss must be fully investigated, as causes such as APS can be managed successfully.

• Cases of gestational trophoblastic disease must be registered at regional centres, as follow-up of these patients is vital.

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Types of miscarriage (Fig. 10.1)

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