Pregnancy loss is a frustrating and challenging problem for couples and clinicians alike. Miscarriage is often associated with guilt, embarassment and depressive states. This is particularly true when the patient presents with subsequent pregnancy with added concerns of primary or secondary infertility, irregular menses, absent or irregular ovulation, a known history of uterine fibroids, a family history of miscarriage, advancing age, medical history and a prior history of pregnancy complications. It certainly warrants a detailed consultation and reassurance with a practitioner committed to pregnancy loss evaluation.
A significant immunologically mediated contributor to pregnancy loss is the anti-phospholipid antibody (APLA) syndrome. This syndrome reflects a subtle autoimmune condition that can lead to enhanced clot formation in certain micro vessels with low flow or low pressure. It is believed that APLA can bind to phospholipids in the lining of blood vessels, platelets and trophoblasts in the placenta, leading to thrombosis. When thrombosis occurs in the early microvasculature of the implanting placenta and endometrium, the pregnancy does not receive adequate nourishment, gas exchange or blood flow. An otherwise normal pregnancy can miscarry at any stage of pregnancy. Women with APLA are at higher risk in later pregnancy of pre-eclampsia, fetal growth retardation and fetal demise.
The emotional issues surrounding pregnancy loss become magnified exponentially when miscarriage occurs on a repetitive basis. When evaluation of women for recurrent pregnancy loss is done, an underlying contributing factor can be identified in 40–50%. If a contributing factor is found and treated, the prognosis for successful pregnancy outcome is typically around 80%. Even in couples where no underlying problem is found, the chances for a successful pregnancy can typically be in the 50–70% range. If a couple had a normal pregnancy and delivery previously, the prognosis tends to be better.
It is estimated that 50–60% of all first trimester pregnancy losses harbor a chromosomal abnormality, which leads to abnormal growth and development of the pregnancy. The large majority of these abnormal pregnancies fail in the first trimester. Maternal age is generally believed to be a significant factor leading to potentially abnormal egg development and genetic make-up of the pregnancy. In some instances, either the maternal or paternal chromosomal make-up can predispose couples to chromosomally abnormal pregnancies.
A common aspect of the evaluation to uncover causes for miscarriage will typically involve inspection of the macro and the micro environment within the uterus. If a pregnancy does occur, the endometrium must develop optimally to provide ongoing attachment and nourishment for the developing pregnancy. Any process, which interferes with normal embryo-endometrium interaction can lead to pregnancy failure.
Acquired problems could include polyps, fibroids and adhesions, which even if small, could interfere with an otherwise normal pregnancy. Congenital uterine problems include the septate uterus, bicornuate uterus or a T-shaped uterus (related to in-utero diethylstilbestrol (DES) exposure).
Gestational diabetes mellitus (GDM) is defined as abnormal glucose tolerance during pregnancy. GDM can be associated with significant morbidity and mortality in the fetus and newborn.
Recurrent miscarriage (RM ≥ 3 consecutive early pregnancy losses) affects around 1% of pregnancies. Parental chromosomal anomalies, maternal thrombophilic disorders and structural uterine anomalies have been directly associated with recurrent miscarriage. However, in the vast majority of cases the pathophysiology remains unknown.
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