Recurrent Miscarriages

What is Miscarriage?

Early pregnancy loss is a nonviable, intrauterine pregnancy with either an empty gestational sac or a gestational sac containing an embryo or foetus without foetal heart activity within the first 13 weeks of gestation. Also called miscarriage, or spontaneous abortion.

Incidence of Miscarriage

It is estimated that 1 in 4 pregnancies ends in miscarriage, with 85% of those happening in the first trimester (early pregnancy loss). About 1 in 100 women in the UK experience recurrent miscarriage. Recurrent miscarriage is defined as two or more spontaneous pregnancy losses. It is one of the most upsetting experiences in women’s lives.

Conception

In normal circumstances, after an egg is ovulated, if there is sperm in the area, fertilisation can occur. When the DNA from these two gametes is combined, it becomes a zygote. After going through cleavage (division), it becomes a morula and on day 5, a blastocyst. The blastocyst will ultimately hatch from the protective 'shell' which has surrounded the embryo through its early development. This is called the Zona Pellucida. It is this mass of hatched cells which, once free from its shell, will implant into the lining of the uterus.

Implantation is defined as the process by which the embryo attaches to the endometrial surface of the uterus and invades the epithelium and then the maternal circulation to form the placenta. Before the initiation of implantation, however, both embryo and endometrium should embark on an elaborated process of cross-talk. From the clinical point of view, implantation is considered to be successful when gestational sac is diagnosed by ultrasound.

Causes of Recurrent Miscarriage

Foetal factors:

• Chromosomal abnormality (50-60%)
• Low production of hCG

Placental factors:

• Abnormal placental implantation
• Premature separation of the normal implanted placenta

Maternal Factors:

• Age (aneuploidy risk)
• Low production of progesterone
• Uterine structural abnormalities, endometrial lining, infections

Stages of Miscarriage

Stage 1 Threatened miscarriage:
Implanted blastocyst slightly separates from the uterus. Blood collects between the chorionic membrane and the wall of the uterus. There is spotting, the cervix is closed and the pregnancy is still viable. Bed rest and progesterone may be able to rescue the pregnancy

Stage 2 Inevitable miscarriage:
Blood leaks in the cervix. There is minimal vaginal spotting/bleeding, mild abdominal cramps and the cervix is open. At this point the miscarriage is inevitable.

Stage 3 Incomplete miscarriage:
Severe subchorionic bleeding can lead to rupture of subchorionic membrane. Disruption of blood flow, containing oxygen and nutrients to the developing foetus. Foetus is compromised and there is passage of tissue.

Stage 4 Complete miscarriage:
the cervix closed and there is no more tissue present.

Depending on how advanced the embryonic development was, this process can take a few days to a couple of weeks.

Which tests can be done?

1. Maternal Blood Tests

• Clotting screen: this test looks for likelihood of blood clots which are a known cause for failed implantation. If needed Aspirin or Heparin injections can be given to thin the blood and prevent it from happening again.
• Immune screen: this test looks for increased levels of uterine natural killer cells and auto antibodies which can be responsible for repeat failures. Steroids, intralipids and medication can be given to suppress the immune system but its use is controversial.

2. Uterine lining tests

• Hysteroscopy: to check for scar tissue, fibroids, polyps which might impact implantation.
• Endometrial receptivity array: a small amount of endometrium is removed and analysed for 200 genes known to be associated with implantation. It also helps identify the ‘window of implantation’ and plan for the next transfer.

3. Paternal tests

• Sperm DNA Fragmentation: to check the sperm DNA for damage. ICSI might be suggested if DNA damage is identified.

4. Embryo factors

• Genetic screening: includes a biopsy of the embryo before transfer to identify chromosome abnormalities.
• Assisted hatching: consists in weakening an area of the embryo’s shell to improve the chances of implantation.