Recurrent Miscarriage Causes And Management Biology Essay
Relatively common, occurs in approximately 25% of all pregnancies. As it is so upsetting for parents, the utmost sensitivity is required, even at very early gestations. Clinical management should be founded on 2 important principles:
The most extreme care must be taken not to advise uterine evacuation if there is any possibility of foetal viability. It should not be assumed that the pregnancy is non-viable simply because the gestation does not agree with the expected dates
There should be a low threshold of suspicion for ectopic pregnancy. The absence of an ectopic pregnancy on USS does not mean that there is no ectopic pregnancy.
Miscarriage includes a wide range of clinical and pathological conditions and accurate definition is important.
Miscarriage can be defined according the gestation or the weight of the foetus. The WHO definition is the expulsion from its mother of an embryo or foetus weighing less than or equal to 500g (50th centile for 20wks gest).
Note the word abortion has connotation of induced abortion and should not be used for miscarriage.
In the UK, any pregnancy loss before 24weeks is regarded as a miscarriage, and any foetus born dead at or after 24weeks of gestation is registered as a stillbirth.
If a foetus shows signs of life after delivery at any gestiation, however the loss can be considered to be a live birth and subsequently a neonatal death.
Miscarriage has traditionally been classified in a clinical way:
Threatened: vaginal bleeding and ongoing pregnancy
Inevitable: the cervix begins to dilate
Incomplete: passage of some, but not all, of the products of conception
Complete: all products of conception have been expelled from the uterus.
Missed(silent):where the foetus has died in utero before 20wks but has not been expelled
Anembryonic pregnancy: a variety of ‘missed’ miscarriage in which embryonic development fails at a very early stage in the pregnancy; the sac continues to develop, but there are no foetal parts evident on USS
Septic: a complication of incomplete miscarriage, when intrauterine infection occurs
Recurrent: arbitrary definition of 3 or more consecutive miscarriages
The miscarriage ratio is probably around 10-25%. This risk is highest early in pregnancy and falls as the pregnancy advances. The quoted ratio however refers to the clinically recognized pregnancies and it is possible for the embryo to die before any signs of pregnancy have appeared. Evidence from very early hCG assays and from assisted conception units suggest that the rates of such very early miscarriage may be as high as 50-60%.
The incidence of miscarriage has been shown to increase with maternal age, rising by a factor of 10 after the age of 40yrs compared to before 35yrs. Overall, when the foetus is found to be viable on ultrasound scan, the chance of a successful outcome is high.
The knowledge is important for parent counselling. While a few women have a specific recurring cause, which excludes them from general risk estimation, it is reasonable to reassure the couple that outlook for future pregnancies is good. A woman who has had 3 consecutive miscarriages, still has a 60-75% chance of a successful pregnancy.
Firm evidence about the causes is scant and there is a real danger of confusing association with cause. There, are however a number of known conditions causing both sporadic and recurrent miscarriage.
Foetal chromosomal abnormalities
About half of all clinically recognized first trimester losses are chromosomally abnormal, with 50% of these being autosomal trisomy, 20 % 45XO monosomy, 20% polyploidy and 10% with various other abnormalities.
In second trimester miscarriage, the incidence of chromosomal abnormality is lower at about 20% overall. Attempts to confirm the presence of chromosomal abnormality in a particular instance are often unsuccessful owing to failure of culture
Patients with PCOS have an increased incidence of both sporadic and recurrent miscarriage and although this has been attributed to high circulating levels of LH in the follicular phase of the cycle , there is no evidence of any effective therapy. Inadequate luteal function has been reported in association with recurrent miscarriage in 20-60% of cases.Again, there is no evidence to support the use of artificial progestogens and there is the additional problem that they may carry significant androgenic side effects.
In those with diabetes mellitus who have poor control around the time of conception, the incidence of miscarriage is high at around 45%, possibly for teratogenic reasons. Those whose control is good are no more likely to have a miscarriage than those who do not have diabetes. There is no clear association between thymus dysfunction and miscarriage.
Recent advances in reproductive immunology have revealed both autoimmune and alloimmune associations with miscarriage.
Approx 15% of women who are investigated for recurrent miscarriage (3 or more) are found to be positive for either lupus anticoagulant, antiphospholipid antibodies or both. Untreated they have a subsequent rate of foetal loss approaching 90%. There is some evidence that to give lose dose aspirin (75mg) daily from time of first positive pregnancy test until delivery results in 70% incidence of live births. These antibodies are also associated with arterial and venous thrombosis, foetal growth restriction, pre-eclampsia, and thrombocytopaenia, this should be kept in mind for later pregnancy management.
Lupus anticoagulant is not synonymous with SLE. It is present in 5-15% of patients with SLE and occurs more commonly in isolation.
Immunological tolerance of pregnancy is partly related to special properties of the fetomaternal interface:
The lack of classic major histocompatibility antigen from the trophoblastic cells of the chorionic villi
The presence of antigens, encoded by paternal genes, which are thought to stimulate production of ‘blocking’ antibodies.
This process is complex and it has been suggested that some miscarriages may result from maternal immunological rejection of foetal trophoblast cells. Attempts to immunize women against paternally derived antigens have been unsuccessful.
Structural anomalies, such as bicornuate or septate uteri, may cause miscarriage in a few instances, particularly if the loss has occurred in the second trimester.
Uterine fibroids may also interfere with early pregnancy growth, but the extent to which they cause miscarriage is difficult to determine because of other associated factors such as age, hormonal dysfunction and subfertility.
Any serious maternal infection causing high fever at any time in pregnancy may adversely affect the foetus and lead to pregnancy loss. There are also a number of specific maternal infections, however which may precipitate miscarriage. Viruses such as rubella and CMV have the ability to cross the placenta and affect the placenta and foetus.
Such congenital infection in early pregnancy may lead to miscarriage as well as to later foetal abnormality and neonatal illness. Malaria, trypanosomiasis, Chlamydia trachomatis, mycoplasma, listeria monocytogenes and syphilis have also been implicated in early pregnancy loss.
Cigarette smoking, both active and passive and high alcohol consumption have been shown to be associated with sporadic and recurrent miscarriage.
At least 50% of miscarriages either sporadic or recurrent, have no identifiable cause.
Clinical presentation and management
Usually a history of bleeding PV and lower abdominal pain, and the passage of tissue is sometimes reported. The bleeding can be life-threateningly severe, requiring urgent and aggressive resuscitation, or there may only be the smallest of brown spotting.
Occasionally there may be no symptoms at all and an empty gestational sac, foetal pole with absent foetal heartbeat may be found at routine booking scan. It is not possible to make consistently reliable diagnoses based on clinical exam alone, USS scan are usually the basis of management.
Normal ultrasound findings weeks 0-9
Pregnancy test +ve, menses due
Gestational sac (hCG>2000)
Nausea, breast tenderness
Yolk sac, foetal heartbeat on transvaginal scan
Foetal pole 4mm
Foetal pole 10mm
Foetal heartbeat on transabdominal scan
Foetal pole 14mm
Foetal pole 22mm
Recurrent spontaneous miscarriage
This is the consecutive loss of 3 or more foetuses weighing <500g. Investigations include:
Karyotype from both parents. The incidence of chromosomal abnormality in this group, usually a balanced reciprocal or Robertsonian translocation is around 3-5% and should prompt genetic referral.
Maternal blood for lupus anticoagulant and anticardiolipin antibodies
Thrombophilia screen- retrospective studies have indicated an increased incidence of thrombophilic defects in those with recurrent spontaneous miscarriage( activated protein C resistance, antithrombin 3 def, protein C def,protein S def,possibly hyperhomocystinaemia). Evidence for effective treatment in this group is poor.
Possible hysterosalpingogram +/or USS to look for uterine abnormalities.
In those with recurrent mid-trimester loss, the possibility of cervical incompetence should be considered. Inserting a cervical suture may be of benefit, but at the risk of infection developing after insertion. Transabdominal cerclage has also been used, but is not without considerable risk.
Where no specific abnormalities are found, counselling and reassurance are the mainstay of treatment. 60-75% of women who have suffered 3 consecutive miscarriages will have a successful pregnancy at next attempt. The use of unproven treatments should be resisted.
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