Recurrent miscarriage is defined as two or more consecutive miscarriages before the 15 week of pregnancy. Sporadic miscarriages can occur in 10-15% of all pregnancies in the first or second trimester and typically before the 12 week of pregnancy.
The risks of having subsequent miscarriages increases as follows:
24% after two miscarriages
30% after three miscarriages
40% after four consecutive miscarriages
GENETIC CAUSES OF MISCARRIAGE
In approximately 2-4% of couples with recurrent miscarriages, one partner will have a genetically balanced chromosomal abnormality. Balanced translocations account for the majority of chromosomal abnormalities. A blood test of both the husband and wife can detect these abnormalities.
Approximately 60% of miscarriages are due to chromosomal abnormalities in the fetus. The most common cause is an aneuploidy which is an abnormal number of chromosomes. Chromosomes can also be broken or have other abnormalities. A chromosomal analysis from the conceptus is obtained during a dilitation and curettage to rule out abnormalities in the fetus. PGD can often be used to rule out chromosomal abnormalities.
HORMONAL AND METABOLIC DISORDER
Luteal phase defect (LPD) – Occurs when the corpus luteum (The site of egg release) fails to produce sufficient progesterone to establish a mature endometrial lining suitable for proper placental attachment. This can be treated by progesterone supplementation post ovulation.
Polycystic Ovarian Syndrome (PCOS) – Studies have shown that as much as 36-56% of women with recurrent miscarriages have PCOS. Women with PCOS who miscarry may have higher levels of androgens and a significant insulin resistance. The risk of miscarriages can be reduced with insulin lowering agents like metformin. Preconception management with lowering of insulin as well as androgens appears to be imperative for reducing miscarriages.
Other Metabolic Abnormalities
Type I insulin-dependent diabetes mellitus
Congenital uterine abnormalities include the bicornuate (uterus with two cavities), septate (uterus with a midline wall) uterus or uterus didelphic (duplication of uterus and cervix). These abnormalities account for 10-15% of miscarriages. This is because the embryo cannot implant and get the nourishment it needs to survive. Uterine submucosal fibroids (fibroids in the uterine cavity) as well as scars inside the uterus can also be associated with recurrent miscarriages. Many uterine abnormalities can be corrected surgically.
Infectious Causes of Miscarriage:
*Bacterial vaginosis has been associated with mid trimester pregnancy loss.
*Most often there are no symptoms, and when diagnosed, these infections can be treated very effectively with antibiotics.
Hereditary disorders can lead to thrombus (blood clot) and result in miscarriage.
Factor V leiden mutation
Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Sometimes immunologic factors may be present which cause the female’s body to mistake the fetus for an invading pathogen. When this happens, her body makes antibodies to the fetus and attempts to destroy it. This antibody reaction causes increased clotting and is responsible for approximately 5% of miscarriages. The physician can perform blood tests to detect some of the immunologic causes of miscarriage.
PRE-IMPLANTATION GENETIC DIAGNOSE (PGD)
Chromosomal abnormalities are the leading cause of both random and recurrent miscarriages.One of the most effective treatments of recurrent miscarriages is PGD. PGD is performed in conjunction with IVF where the mother undergoes stimulation with fertility drugs and under ultrasound guidance the eggs are extracted, placed with her husband’s sperm, and allowed to grow for three days. In the third day, the embryos (union of sperm and egg) now have 6-8 cells and a single cell is removed analyzed for the abnormality.
At the Center for Women’s Medicine we have developed a unique PGD method in which the abnormality can be identified on the third day and the embryo can be transferred to the women’s uterus that afternoon leading to a higher pregnancy rate. Certain abnormalities may require additional analysis for two days and than the healthy embryos are transferred on the fifth day.