Recurrent Miscarriage

If you have suffered repeated miscarriages, you may be feeling considerably distressed and frustrated. Discovering you are pregnant can be one of the most wonderful feelings in the world and experiencing miscarriage just once is incredibly difficult. After several disappointments, it can be tempting to give up.

Here at The Gynae Centre, we specialise in the treatment of recurrent miscarriage. Our experts have years of experience in successfully investigating the causes of, and effectively treating this problem. We are proud to have helped many women carry a baby to term after they were previously told it was unlikely to happen.

While 1 in 6 pregnancies result in a miscarriage due to chromosome abnormality, only 1-2% of couples suffer more than 3 miscarriages – a problem known as Recurrent Pregnancy Loss (RPL). The possible reasons for RPL are varied and include Chromosome Abnormality, Uterine Abnormality, Genital Tract Infection, Endocrine problems or Thrombophilia. In 50% of RPL cases, the causes remain unexplained and may include possible immunological problems. Here at the Gynae Centre, our esteemed Head of Treatment Dr Eskander has a special interest in reproductive immunology.

Immunological reasons for RPL

Immunological reasonsfor RPL are believed to lead to inflammation in the bed of the placenta (in a similar way to immunological disorders present in rheumatoid arthritis and systemic lupus disease). The most frequently documented and recorded risk factors for these immunological problems are anti-phospho lipid antibodies, a high level of natural killer cells (NK), and high levels of pro-inflammatory cytokines. Here we will discuss the possible causes in turn:

Anti-phospho lipids anti-bodies (APA)

The incidence of APA among women with unexplained infertility, recurrent embryo implantation failure and recurrent miscarriage is 20-30%. There are several types of APA. When compared with fertile women, research has shown a significantly higher level of IgG and IgM antibody levels among women with recurrent reproductive failure. The major effect of APA is directed towards blood vessels, early placenta and pre-implantation embryo. This leads to clotting inside blood vessels, decreased formation of new blood vessels and inhibition of early placental cells, leading to implantation failure – which appears as unexplained fertility, recurrent RPL and IVF failure.

The administration of Heparin alongside aspirin has proved to be successful in the prevention of placental blood clotting. Its use has been associated with a live birth rate of 80%, compared with 40% of women receiving aspirin alone.

Increased natural killer cells (NK) activity:

In a normal pregnancy, there is an increase in the number of natural killer cells and macrophages. Both of these are members of the white blood cell population responsible for the body’s natural defence system at the implantation site. It is now known that these cells secrete chemicals named cytokines that assist in implantation and the formation of new blood vessels (angiogenesis). However in women with Recurrent Miscarriage and IVF failure, a greater than normal increase in the number of NK cells and pro inflammatory cytokines TNF alpha has been found, which can in fact be hazardous to a pregnancy.

In such cases, Predisolone Steroids have been found to be anti-inflammatory and effective in calming the immune system.

In some cases the administration of Immunoglobulins (pooled human plasma administered intravenously and often referred to as IVIgs) can be effective. IVIg action has been shown to be successful due to suppression of the killing activity of Natural Killer cells, increased anti-inflammatory activity of Treg cells, and suppression of B cell production of auto antibodies. In 4 studies the technique has shown significant increase in live birth, and in 6 studies it showed no benefit – however variations in success seemed to be associated with the point at which the Immunoglobulins were given. For example Immunoglobulins showed increase in live birth if given before conception but made no difference if provided after conception in a further 5 trials. A recent meta-analysis of the various research studies (Clarke et al 2006) concluded that IVIg significantly increases the probability of one or more live births in patients with infertility, Recurrent Pregnancy Loss and IVF failures who display elevated APA and NK cells.

Intralipids is a nutritional supplement made up of fat emulsion which is known to accumulate in macrophages and NK cells. A number of studies have shown that intravenous intralipids suppress NK and pro-inflammatory cytokines cytotoxicity as efficiently as Immunoglobulins. All in all, Intralipids has been shown to improve pregnancy rate and live birth rate in women with Recurrent Pregnancy Loss compared with women not given the supplement.

Other reasons for recurrent miscarriage and implantation failure:

Chromosome abnormalities: Here at the Gynae Centre, we always advocate mother and father chromosome analysis in cases of RPL, since 2-5% of couples carry balanced translocation, which can lead to fetal abnormalities.

Uterine anomalies: The incidence of uterine anomalies in women with recurrent miscarriages is 1.8-36.7%. Severe abnormalities have been associated with 1st trimester miscarriage, whereas mild abnormalities were found to be associated with 2nd trimester miscarriages. At the Gynae Centre we suggest HYCOSY (also known as AQUA) scanning in combination with a 3D scan, to check for anomalies.

Genital tract infection: Vaginal, cervical or uterine infection can lead to inflammation and a rise in NK cells. Here at the Gynae Centre, we check for mycoplasma, ureaplasma, candida and Chlamydia infection by swabs and PCR testing.

Inherent thrombophilia: Inherent tendency to clotting within the blood vessels in the body such as Prothrombin gene mutation, Protein S and activated Protein C resistance and factor V lieden has been found to be associated with increased risk of early and late miscarriages. Thrombosis at the placental bed can compromise blood supply in early pregnancy and lead to miscarriages. The use of low molecular Heparin helps to keep these blood vessels opened.

Whatever, the cause of RPL may be, here at The Gynae Centre we are meticulous in our investigations. While a successful pregnancy can never be completely assured, our many years of experience have demonstrated that with thorough testing and sophisticated interventions, your chances of a live birth can be significantly increased.

To find out more about how we can help you, contact The Gynae Centre.

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