Recurrent pregnancy loss is defined as two or more consecutive pregnancy losses of clinically recognized pregnancies prior to 20 weeks of gestation.
Clinically recognized pregnancies are those in which an ultrasound examination has confirmed the pregnancy or those in which pregnancy tissue has been identified after miscarriage. The condition usually affects >1% of the female population and thorough examination and tests are usually advised after two consecutive miscarriages.
Most pregnancy losses are random events and result from chromosomal, or genetic, abnormalities. The abnormality may come from the egg, the sperm, or the early embryo. Approximately 12-15% of all clinically recognized pregnancies end in miscarriage; however, it is estimated that at least 30-60% of all conceptions will end within the first 6 weeks of gestation.
Advancing maternal age is associated with an increased risk of miscarriage, which is thought to be due to poor egg quality leading to chromosomal (genetic) abnormalities.
Sometimes, the mother or father themselves may have a slight irregularity in their genes, but the offspring could be more severely affected and thus results in a miscarriage. In a small number of couples who have repeated miscarriages, one partner has a chromosome in which a piece is transferred to another chromosome. This is called a translocation.
People who have a translocation usually do not have any physical signs or symptoms, but some of their eggs or sperm will have abnormal chromosomes. If an embryo gets too much or too little genetic material, it often leads to a miscarriage. Sometimes, there could be an abnormality in the uterus (the womb) that leads to miscarriage. The miscarriage may be due to poor blood supply to the pregnancy or inflammation. Some women may be born with an irregularly shaped uterus, and some women may develop abnormalities with their uterus over time such as Asherman’s syndrome in which dense adhesions are formed in the womb itself or fibroids.
A woman’s immune system may also play a role in recurrent pregnancy loss. Women who have certain medical conditions may have an increased risk of repeated miscarriages. Autoimmune disorders are in which a person’s immune system mistakenly makes antibodies to certain substances involved in normal blood clotting. APS is associated with repeated miscarriages and fetal deaths. Another disease that can lead to miscarriage is diabetes mellitus. In this disease, high levels of sugar called glucose are present in the blood.
Women with diabetes, especially those in whom the disease is poorly controlled, have an increased risk of pregnancy loss. Women with a condition called polycystic ovary syndrome also have an increased risk of miscarriage. Hormone abnormalities may also impact pregnancy loss, including thyroid diseases. Abnormalities in a mother’s blood clotting may also affect pregnancy loss.
Generally speaking, environmental factors, stress, and occupational factors do not seem to be related to pregnancy loss.
At first, the detailed medical and surgical obstetric and genetic history of both partners is taken and a complete physical evaluation is done. The main objective is to point out the possible diagnoses in history examination itself so that a limited number of tests will be needed.
In blood tests, apart from routine tests, thyroid profile, prolactin levels, tests for ovarian functions, and diabetic profile are done. Some tests are needed to rule out autoimmune diseases like Antiphospholipid Antibody Syndrome (APLA) or Systemic Lupus Erythematosus (SLE) in the mother. Karyotyping of both partners and products of conception is done to rule out genetic diseases.
To evaluate the genital structures USG or saline sonography is done. They diagnose more than 95% of abnormalities. Other tests for evaluation are hysterosalpingogram, MRI, and hysteroscopy. Hysteroscopy can be done for both diagnostic and therapeutic purposes. Testing for inherited thrombophilia, or abnormally increased blood clotting, is not routinely recommended in women who have experienced a recurrent fetal loss because studies have not shown the benefit of giving medicine to prevent clots in these patients.
However, testing for abnormal blood clotting should be done if there is a personal history of blood clots associated with risk factors such as surgery, bone fractures, or prolonged immobilization, or if a patient has a parent or sibling with a disorder of excessive blood clotting.
If a uterine abnormality is found, surgery may be performed depending on the defect. If the antiphospholipid syndrome is diagnosed, certain medications that reduce blood clot formation may be given. If thyroid dysfunction or diabetes are diagnosed, specific medications can be prescribed. Individuals in whom a karyotypic (a chromosomal or genetic) abnormality is found are often referred for genetic counseling.
There, a specialist can discuss what the genetic abnormality is and the likelihood of having a chromosomally normal or abnormal pregnancy in the future. Some affected couples may choose to undergo prenatal genetic studies during pregnancy to check the genetic make-up of the offspring with either:
(1) chorionic villus sampling (CVS), in which a piece of placenta is biopsied late in the first trimester or early in the second trimester, or
(2) amniocentesis, which removes some of the amniotic fluid (the fluid that surrounds the baby during pregnancy) for analysis. In Invitro Fertilization, preimplantation genetic diagnosis (PGD) can also be done.
Over one-half of patients with recurrent pregnancy loss will have an unexplained recurrent pregnancy loss, which means that no specific cause could be identified in the work-up. No matter what the results of the work-up are, the chance for a successful future pregnancy is high: 77% if the work-up showed no abnormalities, and 71% if an abnormality was found.
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