Lectures in Obstetrics, Gynaecology and Women’s Health

24. Early Pregnancy Loss and Ectopic Pregnancy

Gab Kovacsand Paula Briggs2

(1)

Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia

(2)

Sexual and Reproductive Health, Southport and Ormskirk Hospital, Southport, UK

Early Pregnancy Loss

Definition

Incidence

Aetilogy and Pathogenesis

Clinical Assessment

Treatment

Complications

Prognosis

Recurrent Pregnancy Loss

Definition

Incidence

Aetilogy and Pathogenesis

Clinical Assessment

Treatment

Complications

Prognosis

Ectopic Pregnancy

Definition

Incidence

Aetilogy and Pathogenesis

Clinical Assessment

Treatment

Complications

Prognosis

Gestational Trophoblast Diseases (GTD); Hydatiform Mole and Choriocarcinoma

Definition

Incidence

Aetilogy and Pathogenesis

Clinical Asessment

Treatment

Complications

Prognosis

Early Pregnancy Loss

Definition

First trimester pregnancy loss is usually called a “miscarriage”. However “early pregnancy loss”(EPL) is all encompassing as it also includes ectopic pregnancy.

Incidence

The reported incidence for EPL varies with age.

·               12–19 years : 13 %

·               20–24 years: 11 %

·               25–29 years: 12 %

·               30–34 years: 15 %

·               35–39 years: 25 %

·               43–44 years: 51 %

·               >45 years: 93 %

In addition to the reported incidence described above, subclinical pregnancy loss is common and often occurs without the woman being aware of having been pregnant.

Increased paternal age is also a risk factor for early pregnancy loss.

Aetilogy and Pathogenesis

Congenital

Most early pregnancy loss is unexplained. Chromosomal analysis is not usually carried out on the products of conception, unless the woman has had several pregnancy losses. A woman who has suffered three EPLs is called a “habitual aborter”. However from examining the products of conception of spontaneous aborters it appears that one of the commonest causes for EPL is aneuploidy (chromosomal abnormality).

Traumatic

Surgical trauma can be a cause of early pregnancy loss. With ready access to legal abortion this is a rare cause of EPL.

Inflammatory

Many infections can result in EPL. These include rubella, toxoplasma, herpes infection, CMV, Listeria, Syphilis, or any febrile illness.

Vascular

Many women experience bleeding in early pregnancy, but this is not always associated with EPL. Implantation bleeding is a common cause of blood loss in early pregnancy. This occurs in the process of the placenta burrowing into the endometrium. If this results in disruption of placental function to a degree where survival of the embryo/foetus is not possible, EPL occurs.

Haematogenous

It is believed that thrombophilia (increased tendency for thrombosis) may be a cause for EPL. The hypothesis is that the small arterioles in the placenta are blocked by blood clot, and hypoxia results.

Endocrine

Thyroid disease, diabetes, and PCOS are associated with a higher risk of EPL.

Psychogenic

Stress and emotional problems may be associated with EPL, but there is no evidence for this.

Iatrogenic

Removal of the corpus luteum before 12 weeks of gestation will cause EPL. The placenta does not produce sufficient oestrogen and progesterone until that time, to maintain the early pregnancy.

Clinical Assessment

History

The important questions are:

·               Gestation (time since last normal menstrual period)

·               Amount of bleeding and whether tissue has been lost

·               Presence of pain

Examination

·               Is the cervix is open or closed

·               Uterine size

·                      does this correspond to gestation

Investigations

·               Biochemistry – quantitative measurement of bHCG (each laboratory has its own normal range). Serial measurements of bHCG are useful as in a viable pregnancy, the level should double every 36 h.

·               Ultrasound – this is the best diagnostic test to assess early pregnancy with bleeding. However a single ultrasound examination is not diagnostic especially if the time of conception is uncertain. A second scan 7 days later should show appropriate growth and development. The important diagnostic features include the gestational sac diameter, the presence of a yolk sac, crown-rump length and foetal heart beat and rate (Table 24.1).

Table 24.1

Summary of the clinical features of threatened, inevitable, incomplete and missed EPL

 

Bleeding

Pain

Cervix

Ultrasound

Threatened

Slight

Nil

Closed

Foetal heart

Inevitable

Significant

Yes

Open

No fetal heart

Incomplete

Clots/tissue

Yes

Open

Products/clot

Missed

Nil

Nil

Closed

No foetal heart

Treatment

Threatened Abortion

There is no proven treatment for threatened abortion. The use of hormone supplements (eg. progesterone) is of no benefit. Bed rest is of no benefit.

Inevitable Abortion/Incomplete Abortion/Missed Abortion

These can be managed conservatively, waiting for the products to be expelled, or actively with medical or surgical techniques.

·               Medical

·                      Hormonal:

·                                          Misoprostol (vaginally or orally)

·                                          Pain relief

·                                          Anti-emetics.

A pregnancy test should be performed after 3 weeks.

·               Surgical – evacuation of retained products of conception (ERPC)

·                      Minor – Manual vacuum aspiration under local anaesthetic in an outpatient setting, or suction termination under general anaesthetic

Anti D prophylaxis should be provided to all Rh negative women

Complications

These include infection, bleeding, hypotension, or Rh immunisation- in Rh negative women with a Rh positive foetus.

Infection

If this is associated with an incomplete miscarriage, it is known as a septic abortion. This can be a serious complication. Symptoms include pain, fever, rigors and offensive discharge. On examination the uterus may be tender. Antibiotics should be administered as soon as possible once swabs for microscopy and culture have been taken. Blood cultures may be required if septicaemia is suspected.

Bleeding

Bleeding is most common with an incomplete abortion, especially if placental tissue is extruded into the cervix. A speculum examination and removal of the tissue will decrease the pain, bleeding, and treat cervical shock (hypotension).

Rh Immunisation

Rh immunisation can be prevented by administering anti D (250 IU) IM.

Prognosis

EPL is common. Most women will go on to have a successful pregnancy.

Recurrent Pregnancy Loss

Definition

Three or more pregnancy losses up to 24 weeks gestation

Incidence

About 1 % of couples (see age related data above regarding incidence with age) After three EPLs the risk of a fourth is 40 %.

Aetilogy and Pathogenesis

The risk factors for recurrent pregnancy loss include maternal age and the number of previous EPLs. Cigarette smoking caffeine and alcohol (>5 units per week) may be associated with EPL.

Congenital

·               Genetic factors – a balanced translocation on karyotyping is found in 2–5 % of couples with recurrent EPL. Embryonic aneuploidy occurs in 30–50 % of subsequent embryos.

·               Uterine abnormalities – the incidence of uterine abnormalities in women with recurrent EPL varies from 2 to 40 %. It is not known whether these are causative.

Inflammatory

·               Antiphospholipid syndrome (lupus anticoagulant, anticardiolipin antibodies and anti-b2 glycoprotein- 1 antibodies) is a treatable cause of EPL. The effect of this condition is to inhibit trophoblast function as a result of a local inflammatory response.

·               Systemic infection with a bacteraemia or viraemia can cause EPL. Toxoplasma, rubella, CMV, herpes and listeria have all been implicate but there is no good evidence for these agents to be responsible for recurrent EPL.

Vascular

Thrombophilia correlates better with late rather than early pregnancy loss. Both Factor V Leiden, and Prothrombin gene mutation have been associated with recurrent EPL.

Endocrine

Thyroid disease, diabetes and PCOS are associated with recurrent EPL.

Clinical Assessment

History

Outcome of previous pregnancies

Examination

Of little benefit

Investigations

Thrombophilia screen

·               Cytogenetics – on products of conception, and paternal and maternal karyotype

·               Uterine ultrasound (looking for uterine structural abnormality)

Treatment

Medical

·               Hormonal –There is no proven benefit in progesterone supplementation

·               Other medical – women with thrombophilias should be treated with low dose heparin and/or aspirin

Surgical

·               Minor

·                      Resection of uterine septa is logical, but there is no evidence to prove its efficacy

·                      Suspected cervical weakness can be treated by cervical cerclage

Complications

The same as EPL

Prognosis

Many women with unexplained recurrent EPL have a good prognosis for future pregnancy outcome without intervention

Ectopic Pregnancy

Definition

A pregnancy outside the uterine cavity

Incidence

Between 1 and 2 % of pregnancies

Aetilogy and Pathogenesis

The most common site is the fallopian tube, but ectopic pregnancies can also occur on the surface of the ovary or anywhere in the peritoneal cavity. Ectopic pregnancy is caused by the failure of the fallopian tube to transport the embryo into the uterine cavity. It is sometimes associated with tubal damage following salpingitis, but often the tube looks macroscopically normal. A previous tubal ectopic increases the risk of recurrence.

Clinical Assessment

History

·               Amenorrhoea associated with a positive pregnancy test and symptoms of pregnancy

·               Pain- this can be abdominal or pelvic. If there is intraperitoneal bleeding it can be referred to the shoulder tips. Sometimes the woman may feel faint due to blood loss

·               Bleeding- this can be minimal or heavy

Examination

·               Abdominal – there can be tenderness and if there is blood in the peritoneal cavity, guarding and rebound may be present

·               Vaginal examination – there can be cervical motion tenderness (cervical excitation), adnexal and/or pelvic tenderness

Investigations

·               bHCG – this confirms that there is a pregnancy “somewhere” but does not localise it. If the bHCG level exceeds 1,500 IU/l, an intrauterine pregnancy should be visualised on trans-vaginal ultrasound scanning

·               Ultrasound examination. In the presence of a bHCG >1,500 IU/l, products of conception should be visible in the uterine cavity. It is not always possible to see an ectopic pregnancy. However, an empty uterus in association with a positive pregnancy test (>1,500 IU/l) is a pregnancy of unknown location and, should be treated as “ectopic pregnancy till proven otherwise”. A CT scan may help identify the location of the pregnancy.

Treatment

Medical

·               Hormonal – Theoretically an antiprogesterone such as mifepristone could be used to abort the pregnancy. However a therapeutic protocol is not yet available.

·               Other medical  Systemic methotrexate is now a first line treatment for tubal ectopic, as long it has not ruptured, it measures less than 35 mm in diameter, there is no foetal heart beat, the bHCG is less than 5,000 IU/L, and there is not an intrauterine twin.

The administration of methotrexate needs to be followed up with serial bHCG measurements.

Surgical

·               Minor – The usual treatment for ectopic pregnancy is operative laparoscopy. Whether the products of conception are aspirated through salpingostomy, or whether partial or total salpingectomy is undertaken, is a clinical decision depending on condition of the tube and that of the contralateral tube.

·               Major – Laparotomy is undertaken if the woman’s medical condition contraindicates a laparoscopy ie. severe hypotension.

Complications

If the tube ruptures, massive haemorrhage can occur, resulting in an acute abdomen, shock, and this is a medical emergency.

Rh negative women require anti D to be administered.

Prognosis

Whether methotrexate treatment results in a better outcome for future fertility than salpingostomy, is unknown.

Gestational Trophoblast Diseases (GTD); Hydatiform Mole and Choriocarcinoma

Definition

Abnormalities of the development of the placenta including hydatiform mole, partial mole and chorioncarcinoma, characterised by elevated levels of bHCG.

Incidence

In the UK, 1/714 live births are associated with GTD. It is more common in Asian women. Neoplastic versions (choriocarcinoma) are very rare, 1:50,000 births.

Aetilogy and Pathogenesis

Complete Moles

These consist of diploid chromosomes and are androgenic in origin. There is no evidence of any foetal tissue. They result from the duplication of a single sperm following fertilisation of an empty ovum, or the dispermic fertilisation of an empty ovum

Partial Moles

These are triploid and arise from two sets of haploid paternal genes (dispermic fertilisation) and a haploid set of maternal genes. There is usually a co-existing foetus.

Clinical Asessment

History

Vaginal bleeding and hyperemesis in the first trimester

Examination

Uterus larger than dates

Investigations

·               Significantly raised bHCG

·               Ultrasound

·                      complete mole: anembryonic pregnancy

·                      partial mole: cystic spaces within the placenta

Treatment

Medical

·               Follow up evacuation with serial bHCG measurement

·               The use of medical termination and oxytocics is contraindicated because of the potential to embolise abnormal trophoblast cells

·               If there is evidence of neoplasia, methotrexate is the main chemotherapeutic agent used

Surgical

·               Minor – Suction curettage is the method of choice unless in a partial mole, foetal parts are too large.

Complications

Choriocarcinoma can metastasise to lung, spleen, liver, kidney, brain and the gastrointestinal tract

Prognosis

All women with GTD should be followed up with serial assays of bHCG

·               Once HCG reverts to normal, 6 months of follow up is recommended

·               Women should be advised not to conceive until their follow up is completed

·               Women who need chemotherapy should not conceive for 12 months

·               Women with GTD should be advised to use barrier contraception until follow up is completed

·               Women treated with methotrexate are likely to have an earlier menopause

·               HRT can safely be used in women with a history of GTD (Table 24.2)

Table 24.2

Differential diagnosis of bleeding in early pregnancy

1

Threatened/ inevitable/incomplete/complete EPL

2

Ectopic pregnancy

3

Hydatiform mole



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