Gab Kovacs1 and 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 |