Reproductive health and genetics

Reproductive Health and Genetics


The inability of couples who want to have children to conceive for at least 1 year is considered infertility. About 15% of all married couples have this problem. In 1/3 of the infertility events with identifiable cause, infertility is caused by men, 1/3 is caused by women, and in 1/3 is caused by both men and women. In approximately 25-30% of all infertility events, the cause cannot be determined. These events are mostly caused by genetic reasons. The most common genetic cause of infertility in men and women is chromosomal. Chromosomal disorders are found in 20% of men with problems in sperm count, and small deletions in the Y chromosome are detected in 20%. Apart from chromosomal diseases, many single gene diseases can also cause infertility in both men and women. For this reason, couples who have problems in conceiving should definitely be evaluated by a Medical Geneticist.

Pregnancy Losses

According to the definition of the World Health Organization, pregnancy losses up to the 24th week and weighing less than 500 g are considered as spontaneous abortion (miscarriage), while pregnancy losses that occur after the 24th week are defined as dead birth. About 15% of clinically diagnosed pregnancies end in miscarriage. If the losses in the earlier period are also taken into account, this rate rises above 50%. Two or more pregnancy losses before the 20th week of pregnancy is considered recurrent pregnancy loss. 5% of couples who want to have children have a history of recurrent pregnancy loss. The higher the number of miscarriages, the higher the risk of recurrence. Miscarriage weeks are often similar. Despite all investigations, the factor causing recurrent pregnancy loss cannot be determined in 40-50% of couples. It is known that genetic reasons in parents play a role in 2-5% of the factors leading to recurrent pregnancy loss. The earlier the pregnancy loss occurs, the higher the chance of a genetic problem. 50-60% of first trimester losses, 10-15% of second trimester pregnancy losses and 5% of third trimester pregnancy losses occur due to genetic anomalies.

Chromosomal Anomalies in Pregnancy Loss

The most common cause of pregnancy loss is chromosomal abnormalities. When all pregnancy losses are considered, the rate of chromosomal anomaly is 50%. The risk of chromosomal anomaly increases in cases such as advanced maternal age, early gestational age, presence of malformation in the fetus, and a small fetus for gestational age. Numerical chromosomal abnormalities are seen in 94% of abortions with chromosomal anomalies, while 6% have structural problems such as translocation and inversion. Of all fetal chromosomal anomalies that cause pregnancy loss, 56% are trisomies, 20% are polyploidy, 18% are X chromosome monosomy, and 6% are unstable translocations. The most common trisomy in miscarriages is trisomy 16 with a rate of 32%. Other common trisomies belong to chromosomes 13, 18, 21 and 22. While the risk of trisomies increases with maternal age, the risk of monosomy X decreases with increasing maternal age. It has been reported that 6% of couples with recurrent pregnancy loss have translocation and inversion carriers. The higher the number of miscarriages, the higher the risk of having translocation carriers in the couple. In couples with recurrent miscarriage, the risk of structural chromosomal anomaly in women is higher than in men. Structural chromosomal abnormalities in women have a higher risk of causing miscarriage, while structural chromosomal abnormalities in men have a higher risk of causing infertility. Although chromosomal abnormalities are not detected in approximately half of early pregnancy losses, genetic issues such as other single gene diseases or multifactorial polygenic diseases may cause spontaneous abortion. Submicroscopic chromosomal abnormalities (microdeletions, microduplications, DNA copy number variants-CNVs) that cannot be detected by conventional cytogenetic formulas, but can be detected by Array-CGH procedure, may cause pregnancy loss, especially if they are de novo.

Thrombophilia and Pregnancy Loss

One of the valuable genetic factors that play a role in late pregnancy loss is hereditary thrombophilia. Pregnancy itself is a condition that increases coagulation. Antiphospholipid antibodies, an acquired thrombophilic defect, are a valuable treatable cause of pregnancy loss. Activated protein C resistance can also lead to pregnancy loss by increasing the risk of venous thromboembolism during pregnancy. Factor V Leiden mutation (FVL), which has an autosomal dominant inheritance pattern, is the most common cause of hereditary thrombophilia. Rey et al. of 31 different studies investigating the effect of hereditary thrombophilia on pregnancy loss. In a meta-analysis conducted by FVL mutation, it was found to be associated with recurrent pregnancy loss in both early and late periods, and also with non-recurrent pregnancy loss in the late period. F2 G20210A mutation was found to be an increased risk factor for pregnancy loss that recurs in the early period and does not recur in the late period. However, the correlation of these mutations with late period pregnancy losses was found to be stronger than in the early period.