The majority of sporadic spontaneous miscarriages in the general population are due to genetic abnormalities of the conceptus. These are due in part to chromosomal abnormalities of the egg or sperm. Since it is now well established that a woman’s eggs deteriorate with age, it is not surprising then to see increased rates of miscarriages in older women. The etiology of this phenomenon is directly linked to the chromosomal deterioration of eggs with time.
Normal fertilization and early embryo development in the humans can occur despite the presence of genetic abnormalities. Studies of 3 day old human embryos have shown chromosomal abnormalities in 20-60% of perfectly normal embryos. More than likely, most of these chromosomally abnormal embryos would arrest in early development and subsequently miscarry. Actually, in clinically recognized first-trimester miscarriages where fetal material is available, about 50-60% have chromosomal abnormalities.
The evaluation of couples with recurrent miscarriages by Karyotype or chromosomal analysis, has demonstrated a small proportion (2-6%) have indeed abnormal chromosomal rearrangements. The most common is called “balanced translocation”.
Several uterine abnormalities have been associated with recurrent miscarriages. Approximately 15% of patients have a uterine abnormality accounting for their fetal losses. Losses from anatomical causes are most commonly occurring in the second trimester.
These abnormalities could be secondary to congenital defects, i.e. the patient was born with the abnormality or acquired, i.e. develop it later in life such as fibroids.
Women can be born with an abnormal uterus with an abnormal shape. Examples of these abnormalities include unicornuate, didelphic or bicornuate uteri.
The normal uterus is a pear shaped organ with a triangular cavity. Some patients have a uterus with a smaller abnormal cavity or two adjacent attached cavities. Some can have a membrane sticking into the cavity from the top, called a septum which can interfere with conception or the normal maintenance of a pregnancy.
The mechanism in these cases is probably related to an insufficient blood supply to the septum resulting in inadequate nutritional support of the fetus that implants on the septum, or possibly to a mechanical pressure effect.
Uterine fibroids are benign tumors of the uterine musculature.
Up to 20% of patients with recurrent miscarriages due to uterine anomalies have fibroids. Fibroids usually do not cause infertility or miscarriages unless they are located inside the uterine cavity or in very close proximity to the endometrial lining. Alterations in the blood supply of the lining are though to be the cause of the abnormal implantation. The presence of what we call “submucosal” fibroids may also cause distortion of the uterine cavity with damage to the overlying lining or endometrium and mechanical interference of fetal and placental growth resulting in recurrent miscarriages.
Intrauterine adhesions or scarring are bands of fibrotic connective tissue which can partially or completely obliterate the uterine cavity. These scars can occur following surgical procedures such as a dilatation & curettage done for incomplete miscarriages, for abortions or abnormal bleeding.
These adhesions can be detected by an x-ray test called HSG or Hysterosalpingogram, whereby a dye is injected through the cervix and it flows through the uterine cavity and tubes followed with x-rays. Intrauterine scarring may cause miscarriages due to lack of sufficient endometrium or lining for implantation, poor blood supply or mechanical restriction of the uterine cavity expansion during pregnancy. Symptoms associated with these adhesions depend on the extent and location of the scarring. In extreme cases, called Asherman’s Syndrome, the whole cavity is taken over and the patient will usually have very scant periods or total absence of menses.
Another common abnormality is the presence of uterine polyps which are benign growths (like skin tags) of the lining of the uterus.
Polyps usually present as abnormal bleeding or spotting and are usually easily treated by removal.
Endocrine or hormonal causes have also been implicated as causes of recurrent miscarriages, such as Hypothyroidism and Diabetes Mellitus.
Antiphospholipid antibody syndrome is a condition that can lead to miscarriages and increased risk of blood clots. The diagnosis is made when patients have elevated levels of anticardiolipin antibodies and/or test positive for Lupus Anticoagulant. For a proper diagnosis the test should be positive twice, 12 weeks apart. Patients who have this disease should receive a blood thinner and baby aspirin during pregnancy.
If after extensive evaluation the cause of the recurrent miscarriages is not elucidated, then the term “Unexplained” is used. unfortunately, 50% of patients will end up in this category of patients. These patients can continue trying on their own, consider IVF with preimplantation genetic screening or surrogacy as the ultimate treatment.
Up to 20% of patients with recurrent miscarriages due to uterine anomalies have fibroids.
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