A NEW ALGORITHM FOR THE EVALUATION OF RPL

Recurrent early pregnancy loss (RPL) is a tragedy to couples seeking parenthood and has been a clinical challenge to their physician. Recent data on the genetics from the products of conception may help to clarify a new strategy for evaluation and management. In 2013 the American Society for Reproductive Medicine released committee opinions on the evaluation and treatment of RPL.  RPL occurs in about 1-2% of reproductive aged women and a definite cause of pregnancy loss can be established in over half of couples after a thorough evaluation. An evaluation of an RPL patient should always include a complete history, including prior pregnancies, any tests performed on prior miscarriages, evidence of chronic or acute infections or diseases, any recent physical or emotional trauma, history of cramping or bleeding with a previous miscarriage, any family history of pregnancy loss, and any previous gynecologic surgery or complicating factors. A complete evaluation will include investigations into genetic, endocrine, anatomic, infectious, immunologic and iatrogenic causes. Successful outcomes will occur in over two-thirds of all couples.

We describe a new algorithm for the evaluation and treatment of RPL. Miscarriage chromosome testing is recommended with the second and all subsequent miscarriages. Miscarriage tissue obtained from early nonviable pregnancies should be sent for conventional cytogenetic analysis or 23-chromosome pair microarray evaluation. No diagnostic/therapeutic action is recommended following one miscarriage unless there was some abnormal finding as a part of the routine evaluation. These would include an abnormal shape to the uterus on ultrasound that might suggest a uterine anomaly, a high blood sugar on routine blood or urine suggesting a diabetic condition, or a false positive test for syphilis which could suggest the antiphospholipid syndrome.

If the miscarriage chromosome results are aneuploid, no further evaluation or treatment is recommended at that juncture because the cause for the loss is known, though chromosomes should be evaluated on all future miscarriages. If an unbalanced chromosomal translocation or inversion were identified in the miscarriage tissue, then the workup would focus on performing parental karyotypes.  If a parental translocation is found, evaluation for other factors is warranted followed, with close monitoring in subsequent pregnancies.  If there is a history of an ongoing pregnancy >10 weeks of gestation subsequently found to be an unbalanced translocation, genetic counseling and potentially preimplantation genetic diagnosis (PGD) may be warranted.  If the miscarriage tissue is found to be chromosomally normal, then a full RPL workup is advised. If the fetal POC karyotypes have not been performed, then we recommend a full RPL workup after two or more miscarriages.