The best method for monitoring in early pregnancy is ultrasonography. If used, serum βhCG levels should be serially monitored from the time of a missed menstrual period until the level is approximately 1,200 to 1,500 mIU/mL, at which time an ultrasonographic scan is performed and blood sampling is discontinued. Ultrasonographic assessment may then be performed every 2 weeks until the gestational age at which previous pregnancies were aborted. The prognostic value of serial ultrasonography and a variety of hormonal and biochemical measurements during early pregnancy in women with histories of recurrent losses has been reported (341).
If a pregnancy has been confirmed, but fetal cardiac activity cannot be documented by approximately 6 to 7 weeks of gestation (by sure menstrual or ultrasonographic dating), intervention is recommended to expedite pregnancy termination and to obtain tissue for karyotype analysis. First trimester screening with maternal chemistries and fetal nuchal lucency measurement or chorionic villus sampling are recommended for obstetrical indications. Maternal serum can also be obtained for assessment at 16 to 18 weeks of gestation. Amniocentesis may be recommended to assess the fetal karyotype after the pregnancy has progressed past the time of prior losses.
The importance of obtaining karyotypic analysis from tissues obtained after pregnancy demise in a woman experiencing recurrent losses cannot be overemphasized. Results may suggest karyotypic anomalies in the parents. The documentation of aneuploidy may have important prognostic implications and may direct future interventions. Cost analysis has demonstrated that karyotypic analysis is financially prudent among patients with histories of recurrent pregnancy loss (342). Obtaining karyotypic data from aborted specimens incurs many difficulties in culturing cells from tissues that may have significant inﬂammation or necrosis and contamination of specimens with maternal cells. Efforts to develop methods that avoid such difficulties include the application of comparative genomic hybridization technology to recurrent pregnancy loss (343). This technology was used successfully on archived and paraffin-embedded pregnancy tissues (344). In the future, fetal karyotype assessment may also be performed using DNA isolated from nucleated fetal erythrocytes in maternal blood (345)
Advances in the treatment of patients with recurrent pregnancy loss have been regrettably slow. Despite a rapid expansion in understanding the molecular and subcellular mechanisms involved in implantation and early pregnancy maintenance, extension of these concepts to prevention of recurrent early pregnancy loss has lagged. In addition to these limitations, progress toward treatment of most causes of recurrent pregnancy loss has been hampered by a variety of factors. The condition itself has been inconsistently defined. The results of clinical trials involving recurrent pregnancy loss patients therefore are nearly impossible to compare and evaluate. Trial design is frequently substandard, with lack of rationale, lack of appropriate controls, and poor statistical analysis, limiting the ability to draw rational conclusions from reported results. Finally, epidemiologic data indicate that most patients with a history of recurrent pregnancy loss will, in fact, have a successful pregnancy the next time they conceive (7). For these reasons, with few exceptions, most therapies for recurrent pregnancy loss must be considered experimental. Until further study is completed, treatment protocols involving these therapies should be undertaken only with informed consent and in the setting of a well-designed, double-blind, placebo-controlled clinical trial.
Common therapeutic options available for patients with recurrent pregnancy loss include the use of donor oocytes or sperm, the use of preimplantation genetic diagnosis, the use of antithrombotic interventions, the repair of anatomic anomalies, the correction of any endocrine abnormalities, the treatment of infections, and a variety of immunologic interventions and drug treatments. Psychologic counseling and support should be recommended for all patients.