Testing for the presence of a variety of autoantibodies (other than lupus anticoagulant and anticardiolipin antibody) has been hotly debated, but without consensus (245,246,249,262,328,329). Testing for some antiphospholipid antibodies, such as antiphosphatidylserine and anti-β2 glycoprotein-1, are particularly attractive because mechanistic connections between their presence and placental pathology were reported (246,260,261,263,264). Measurement of anti-β2 glycoprotein-1 antibodies was formally added to the criteria defining the antiphospholipid syndrome, and data are accumulating for specific relevance to pregnancy loss (245,246,251,330). Among patients with known autoimmune diseases and recurrent pregnancy loss additional antiphospholipid testing may also be warranted (331).
8.
Cervical cultures for mycoplasma, ureaplasma, and chlamydia may be considered.
9.
Interobserver reproducibility and accuracy are too low to reliably use the Noyes criteria to diagnose a luteal phase defect on timed endometrial biopsy (332). This tool lacks precision and does not alter clinical management (333). More specific and predictive methodology for diagnosing this disorder is not yet available.
The following investigations have no place in modern clinical care of patients with recurrent spontaneous pregnancy loss: 1.
Evaluations that involve extensive testing for serum or site-specific auto-or alloantibodies (including antinuclear antibodies and antipaternal cytotoxic antibodies) are both expensive and unproven. Their use often verifies the statistical tenet that if the number of tests performed reaches a critical limit, the results of at least one will be positive in every patient.
2.
Testing for parental HLA profiles is never indicated in outbred populations. Findings that HLA sharing is associated with poor pregnancy outcomes are strictly limited to those specific populations studied, which have very high and sustained levels of marriage within a limited community (279).
3.
Use of mixed lymphocyte cultures has not proved useful. Use of other immunologic tests is unnecessary also unless these studies are performed, with informed consent, under a specific study protocol in which the costs of these experimental tests are not borne by the couple or their third-party payers.
4.
Further work is necessary before suppressor cell or factor determinations, cytokine, oncogene, and growth factor measurements, or embryotoxic factor assessment can be clinically justified.
Following conception, close monitoring of patients with histories of recurrent pregnancy loss is advised to provide emotional support and to confirm intrauterine pregnancy and its viability. The incidence of ectopic pregnancy and complete molar gestation is increased in women with a history of recurrent spontaneous pregnancy loss. Although somewhat controversial, some data suggest that the risk of pregnancy complications other than spontaneous abortion are not significantly different between women with and without a history of recurrent losses (102,334–338). Two uncontested exceptions to this observation are those women who have antiphospholipid antibodies and those who have an intrauterine infection.
Determining serum levels of β-hCG may be helpful in monitoring early pregnancy until an ultrasonographic examination can be performed; however, not all investigators have found inadequate β-hCG levels in pregnancies that ultimately abort (339). Other hormonal determinations are rarely of benefit because levels are often normal until fetal death or abortion occurs (340).