Unexplained Recurrent Pregnancy Loss

Approximately 50% of women with recurrent pregnancy lost (RPL) remain unexplained despite thorough investigations. A number of possible etiologies and treatments have been proposed to explain the occurrence of RPL. An obvious treatment is Tender Loving Care (TLC). Women with RPL who conceive again do worry that it will end up with yet another miscarriage. They welcome reassurance, close monitoring, including serial ultrasonography to reassure them that the pregnancy is ongoing.

TLC and psychological support in women with RPL is associated with better outcomes. TLC in the form of continued psychological support and serial first trimester ultrasonography should be offered in a dedicated clinic. However, TLC is not a well-defined entity. Further studies are required to define what exactly constitutes TLC and the mechanism through which it operates.

Now, a procedure called preimplantation genetic diagnosis (PGD) offers hope of normal pregnancy to women who have experienced the anguish of unexplained recurrent miscarriages. PGD is performed after a couple has created embryos through in vitro fertilization. Before implanting the embryos, CRH tests a single cell from each embryo for a variety of conditions. We then implant in the woman’s womb only those embryos which are chromosomally normal.

Luteal phase defect and endometrial receptivity

Concentration of MUC1, a cell-surface and secretory product of endometrial epithelium, is reduced in women with RPL. These observations suggest that there is defective secretion of endometrial protein in a significant proportion of women with RPL. E₂ and P₄ from the corpus luteum stimulate epidermal growth and transforming growth factor expression in the spiral arteries and stroma of the endometrium. It is also involved in the rapid expansion of placental cells (the syncytiotrophoblast and cytotrophoblast) and the formation of the lacunae during placentation. The development of the placenta starts 11–12 days after ovulation with the formation of the primary villi, which then develop further and maintain the pregnancy. Retarded endometrial development and maturation resulting from inadequate corpus luteum E₂ and P₄ production is known to be a cause of early pregnancy loss. The evaluation of luteal phase requires special expertise and E₂ and P₄ hormone measurements; consequently it is not routinely carried out except in centers like ours.

Immunological factors

Human leukocyte antigen (HLA) sharing in couples, especially HLA B and DR has been proposed as a possible explanation for unexplained RPL. Further studies are required to confirm or refute the claim.

Immunotherapy with intravenous infusion of immunoglobulins, or paternal leukocytes, has been tried in attempts to improve the pregnancy outcome in women with RPL. Current evidence, however, suggests that there is no benefit from this treatment.

Environmental factors

Environmental factors including smoking and alcohol have also been associated with RPL. These appear to increase the risk by 1.5-2 times.

Placental microthrombosis and necrosis

Placental microthrombosis, vasospastic changes, and necrosis, resulting from a deficiency of vasodilatory prostacyclin and a dominance of its antagonist and platelet aggregant thromboxane in early pregnancy, could be a factor in RPL. However, further studies are required to confirm or refute the claim.

Fetal chromosomal anomalies

Repeated sporadic fetal chromosomal anomalies occurring by chance, such as repetitive fetal aneuploidies due to increasing maternal age, may be responsible for RPL. A number of studies suggest that fetal chromosomal anomalies accounts for approximately 50% of sporadic first trimester miscarriage, and possibly a similar proportion of RPL.

Abnormal karyotype leading to a miscarriage often occurs before 8-10 weeks gestation; including cases with fetal heart beats which suddenly disappear around 8-10 weeks. Miscarriages occurring after 8-10 weeks gestation are less likely to be associated with aneuploidy. Women over the age of 37 years are more likely to have miscarriages associated with fetal aneuploidy.

 

>> Causes & Treatments | Chromosomal Abnormalities | Unexplained RPL

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