Physical Examination A general physical examination should be performed to detect signs of metabolic illness, including PCOS, diabetes, hyperandrogenism, and thyroid or prolactin disorders. During the pelvic examination, signs of infection, DES exposure, and previous trauma should be ascertained. Estrogenization of mucosal tissues, cervical and vaginal anatomy, and the size and shape of the uterus should also be determined.
Laboratory assessment of couples with recurrent pregnancy losses should include the following: 1.
Chromosome analysis of the products of conception 2.
Parental peripheral blood karyotyping with banding techniques, 3.
Assessment of the intrauterine cavity with either office hysteroscopy, sonohysterography, three-dimensional transvaginal sonography, or hysterosalpingography, followed by operative hysteroscopy if a potentially correctable anomaly is found (324), 4.
Thyroid function testing, including serum thyroid-stimulating hormone levels, 5.
Anticardiolipin, anti-β2 glycoprotein-1, and lupus anticoagulant testing (aPTT or Russell Viper Venom testing) 6.
Tests with Unproven Utility
A number of laboratory assessment tools are under investigation for use in patients with a history of recurrent pregnancy loss. At present, results are either too preliminary to warrant unfettered recommendation or studies of their use have been too contradictory to allow final determination of their value. Tests with unproven or unknown utility include: 1.
Evaluation of ovarian reserve using day 3 serum follicle–stimulating hormone or antim¨ullerian hormone levels. It appears that decreased ovarian reserve may portend a poor outcome in all patients, including those with recurrent pregnancy loss (110,111).
2.
Thrombophilia testing: a.
Factor V Leiden, G20210A prothrombin gene mutation, protein S activity b.
c.
If there is a family or personal history of venous thromboembolic events, obtain protein C activity and antithrombin activity.
d.
Consider altering these screening paradigms based on ethnic background. Factor V Leiden and prothrombin promoter mutations are rare in African and Asian populations. Among Asian populations, protein C and protein S are the most common inherited thrombophilias.
3.
Testing for serologic evidence of PCOS using luteinizing hormone or androgen values may be useful (89–92).
4.
Testing for peripheral evidence of TH1/TH2 cytokine dysregulation. Although large studies failed to demonstrate association between peripheral cytokine alterations and pregnancy outcome among patients with recurrent pregnancy loss, smaller studies reported peripheral shifts toward TH1 profiles only in those recurrent pregnancy loss patients who subsequently lose their pregnancy (212,213). One study documented a shift toward TH1 profiles at the time of fetal demise in these patients; however, it is particularly difficult to determine cause and effect in this situation (325).
5.
Preconceptional testing for the prevalence and activity of peripheral NK cells has been reported in small studies to reﬂect prognosis and to facilitate patient counseling (326,327). Still, peripheral NK cells may not adequately reﬂect those at the site of implantation, and this testing remains unproven.
6.
Testing for antithyroid antibodies among women with recurrent pregnancy loss remains controversial, but is rapidly gaining support (98–100,103,271–273). Investigators have recently demonstrated an increased prevalence of these antibodies among women with a history of recurrent pregnancy loss, even in the absence of thyroid endocrinologic abnormalities (99,100,102,272).
7.