This article goes through common reasons for miscarriage: chromosomal abnormalities, blood disorders, and endocrine abnormalities (including anatomical abnormalities, luteal phase defect, and LH hypersecretion).
Here are some high points:
“Chromosomal anomalies are known to be the single most common cause of spontaneous abortion. . . . In up to 7% of couples with at least 2 spontaneous abortions, one partner carries a balanced chromosome rearrangement.”
“Given that about 50% to 60% of patients with recurrent miscarriages harbor a coagulation defect and that identification of the defect, followed by appropriate therapy, will lead to normal-term delivery in 98%, the cost of evaluation (about $1200) can be justified. . . . All patients found to have a blood-protein or platelet defect associated with recurrent fetal loss caused by hypercoagulability and thrombosis (thrombosis/vasculitis) of placental vessels are treated preconception with low-dose aspirin at 81mg/day. . . . Several studies have assessed the role of the postconception addition of heparin; however, most have used higher doses than those used in our clinical practice.[16]Rosove and colleagues[31] reported a 93% success rate with dose-adjusted subcutaneous heparin, the mean heparin doses being about 25,000 units/day. Kuttah,[32] in a population of 25 patients, treated with aspirin plus dose-adjusted subcutaneous heparin, noting a success rate of 76% (mean heparin dose of 26,000 units/day). In the study by Many and colleagues,[25] patients treated with prednisone plus aspirin plus heparin at 5000 units twice a day had a better outcome (69%) than those treated with aspirin plus prednisone (43%) or prednisone alone (7%).”
“Thus, well-documented, persistently low levels of progesterone in the luteal phase of the cycle are likely to be the consequence of abnormal folliculogenesis. This condition is more likely to be improved by low doses of clomiphene citrate in the early follicular phase of the cycle than by postovulatory administration of progesterone. A search for subtle ovulatory dysfunction, such as that related to hyperprolactinemia, should be conducted, and treatment should be administered accordingly.”
“This study indicates that midfollicular (cycle day 8) LH hypersecretion (random serum LH of 10 mIU/mL or greater) is associated with a marked increase in the incidence of spontaneous abortion. Those findings, which have since been confirmed by others, suggest that hypersecretion of LH is associated with subfertility and early pregnancy failure. To date, however, prepregnancy treatments to suppress elevated serum concentrations of LH with GnRH agonists have not improved pregnancy outcome when compared with expectant management/supportive care during early pregnancy.”
“However, the percentage of miscarriages in which a chromosome abnormality is detected decreases from 70%-80% for a first miscarriage to 40%-50% after 3 or more miscarriages. Therefore, 50% of recurrent miscarriages may be preventable.”
Well, we know we have “chromosomally normal” embryos (they were tested) and we do not have translocations (we’ve been tested). We’ve also been tested for clotting disorders—no issues there. We (I) have also been evaluated for uterine abnormalities—all is good there. The stuff about luteal phase defect and LH hypersecretion is interesting.
Unfortunately, for about half of all women with recurrent miscarriages, also known as idiopathic recurrent miscarriage, there is no known cause:
“Idiopathic recurrent miscarriage is defined as 3 consecutive pregnancy losses with no contributing features found on investigations. At present there are no treatments of proven efficacy for idiopathic recurrent miscarriage.”
Here’s another article on recurrent spontaneous miscarriage (RSM):
It suggests that RSM (3 or more miscarriages before 20 weeks) affects 1-2% of women. It notes that there is no known cause for 40-60% of RSMs. Women who have RSM without a live birth have a 50% chance of giving birth. Women who have RSM after a live birth have a 70% chance.
Reasons can be (1) genetic (3-5% of RSMs), with balanced translocations being the most common chromosomal issue in RSM; (2) anatomical (between 1.8-37.6% of RSMs), more common for women who have already had a child or second trimester losses; (3) antiphospolipid syndrome—an autoimmune condition (15-20% of RSMs) also discussed with thrombophilias; (4) endocrine disorders; (5) immune-related factors and natural killer cells (controversial) – the article suggests that reducing NK cells may increase pregnancy chances, and increased NK cells may be associated with implantation failure; (6) infection.
The article discusses a bunch of tests that can be run to evaluate the diagnosable causes.
The article suggests that for unexplained RSMs, the reason may be immunological or chromosomal abnormalities.
The authors seem to like heparin, but not steroids, for treatment of antiphospolipid syndrome. It notes that corticosteroids are associated with “significant fetal and maternal morbidity.” Yuck.
Anyway, it’s a good read for anyone suffering from RSMs to think about what testing and treatment options they might have.
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