Recurrent pregnancy loss (RPL) is defined as having a history of three miscarriages in the first trimester or a single loss in the second trimester. The basic work up of RPL is typically started after experiencing two consecutive losses in the first trimester, unless there are other identifiable causes for the miscarriages.

Genetic and Chromosomal Causes of RPL

The risk of miscarriage increases with the reproductive age and is estimated to be 10-15% between the ages of 20-30; 15-30% between 30 to 40 and 30-60% at 40-45. These percentages are based on clinically recognizable pregnancies and the rates may be higher if patients are monitored closely following fertilization, implantation and during early embryo development. Some of these pregnancy losses are not clinically recognized because the timing of the miscarriage may coincide with the expected period. In some cases, menses are late a few days to a week and may be due to a pregnancy loss that may go unrecognized because of lack of early monitoring with a pregnancy test. The outcome does not change even if monitoring is done early in such pregnancies, because they are mostly abnormal genetically and chromosomally; such are called biochemical pregnancies.

The main etiology (cause) of miscarriage in the first trimester is due to a numerical abnormality in the chromosomes of the conception (embryo). It’s estimated that between 70-90% of all miscarriages in the first trimester are due to genetic/chromosomal abnormalities such as trisomy (extra chromosome – 47), monosomy (lacking one chromosome – 45) or other numerical abnormalities (any number other than 46 chromosomes). In cases of repeated pregnancy loss compared to having a single miscarriage, the rate of chromosomal abnormalities may be just slightly lower because of other associated factors such as problems with the uterus, thyroid function, diabetes or immunological issues.

Specific genetic factors such as translocations of genes (4-8%) can be the cause of RPL aside from the numerical chromosomal abnormalities of the embryos (~80%). These genetic problems are called balanced or unbalanced translocations in the genes, where a piece of the chromosome may exchange places with another site on another chromosome. In such cases, genetic material is generally not lost, but there is exchange of the location for the specific genetic material (DNA), which is called balanced reciprocal translocation. In other cases, genetic material may be lost during the translocation resulting in abnormal chromosomal arrangement (unbalanced translocation).

In both of the above cases, carriers of such translocations (parents) are phenotypically normal and “genetically balanced”. When the egg and sperm of such individuals undergo meiosis (maturation and cell division) abnormal genetic makeup (egg and sperm) can form with normal, excessive or deficient genetic material. Normal, balanced or unbalanced genetic format can result in a normal pregnancy, a miscarriage occurs (or rarely a genetically abnormal fetus depending on the specific abnormality).

Anatomical Causes of RPL

Anatomical factors can impact on pregnancy outcome and include uterine malformations (abnormal development of the uterus from birth), fibroids and intrauterine adhesions (Asherman’s syndrome). Uterus forms by the elongation and unification of two embryonic tubes that eventually become the mature uterus and abnormalities during these developmental stages can result in uterine anomalies (Mullerian anomalies).

Uterine Anomalies

Uterine malformations include unicornuate uterus (only one tube forming into the mature uterus), septate uterus (excessive tissue [septum] at the center of the uterus), bicornuate uterus (heart shaped), didelphic uterus (two separate uteri with two cavities connected with two cervices), DES exposed uterus and various degrees of T-shaped uterus. Uterine anomalies can result in first and second trimester losses and preterm labor along with associated complications. The problem can be related to compromised blood vessel development with limited blood flow to the uterus. Additionally, endometrial cavity may be limited in its volume to accommodate a developing fetus. In such cases, the pregnancy can attach to a weaker area in the uterus, such as the “septum” and result in a miscarriage.

Among all of the above anomalies, septum of the uterus is the type of abnormality that can be corrected surgically with high success rates. Other abnormalities are best treated with a conservative approach, including close monitoring in early pregnancy, cerclage procedure for second trimester losses and very rarely by surgical correction of the uterus (metroplasty-rarely done).

Fibroids

Fibroids (myomas) are relatively common in women and generally asymptomatic (without pain, bleeding or pelvic pressure) throughout the reproductive years. In some women, the presence of such symptoms can necessitate an ultrasound examination of the uterus and fibroids can be diagnosed. Additionally, fibroids can be diagnosed with gynecological examination, if they reach a certain size and palpated through bi-manual examination. In most cases fibroids can be observed over time, but in others medical or surgical treatment is nec