Maximizing diagnostic yield
Many patients prefer surgical management of a missed abortion not for the procedural advantages, but to assist with tissue collection for cytogenetic testing of the pregnancy tissue. Given that embryonic chromosomal aneuploidy is implicated in 70% of miscarriages prior to 20 weeks’ gestation, genetic evaluation of the products of conception is commonly performed to identify a potential cause for the miscarriage.16 G-band karyotype is the most commonly performed genetic evaluation. Karyotype requires culturing of pregnancy tissue for 7-14 days to produce metaphase cells that are then chemically treated to arrest them at their maximally contracted stage. Cytogenetic evaluation is often curtailed when nonviable cells from products of conception fail to culture due to either time elapsed from diagnosis to demise or damage from tissue handling. Careful, directly observed tissue handling via a hysteroscopic approach may alleviate culture failure secondary to tissue damage.
Another concern with cultures of products of conception is the potential for maternal cell contamination. Early studies from the 1970s noted a significant skew toward 46, XX karyotype results in miscarried tissue as compared with 46, XY results. It was not until microsatellite analysis technology was available that it was determined that the result was due to analysis of maternal cells instead of products of conception.17 A 2014 study by Levy and colleagues and another by Lathi and colleagues that utilized single-nucleotide polymorphism (SNP) microarray found that maternal cell contamination affected 22% of all miscarriage samples analyzed and over half of karyotypes with a 46, XX result.18,19
Traditional “blind” suction and curettage may inadvertently collect maternal endometrial tissue and contaminate the culture of fetal cells, limiting the validity of karyotype for products of conception.20 The hysteroscopic approach may provide a higher diagnostic yield for karyotype analysis of fetal tissue by the nature of targeted tissue sampling under direct visualization, minimizing maternal cell contamination. One retrospective study by Cholkeri-Singh and colleagues evaluated rates of fetal chromosome detection without maternal contamination in a total of 264 patients undergoing either suction curettage or hysteroscopic resection. They found that fetal chromosomal detection without contamination was significantly higher in the hysteroscopy group compared with the suction curettage group (88.5 vs 64.8%, P< .001).21 Additionally, biopsies of tissue under direct visualization may enable the diagnosis of a true placental mosaicism and the study of the individual karyotype of each embryo in dizygotic twin missed abortions.
Finally, a hysteroscopic approach may afford the opportunity to also perform morphologic evaluation of the intact early fetus furthering the diagnostic utility of the procedure. With hysteroscopy, the gestational sac is identified and carefully entered, allowing for complete visualization of the early fetus and assessment of anatomic malformations that may provide insight into the pregnancy loss (ie, embryoscopy). In one series of 272 patients with missed abortions, while nearly 75% of conceptuses had abnormal karyotypes, 18% were found to have gross morphologic defects with a normal karyotype.22
Bottom line
When faced with a patient with an early pregnancy loss, physicians should consider the decreased iatrogenic risks and improved diagnostic yield when deciding between D&C versus hysteroscopy for surgical management. There are certain patients with pre-existing risk factors that may stand to benefit the most (TABLE 2). Much like the opening case, those at risk for intrauterine adhesions, retained products of conception, or in whom a successful and accurate cytogenetic analysis is essential are the most likely to benefit from a hysteroscopic approach. The hysteroscopic approach also affords concurrent diagnosis and treatment of intrauterine pathology, such as leiomyomas and uterine septum, which are encountered approximately 12.5% of the time after one miscarriage and 29.4% of the time in patients with a history of more than one miscarriage.10 In the appropriately counseled patient and clinical setting, clinicians could also perform definitive surgical management during the same hysteroscopy. Finally, evaluation of the morphology of the demised fetus may provide additional information for patient counseling in those with euploid pregnancy losses.
CASE Resolved
Ultimately, our patient underwent complete hysteroscopic resection of the pregnancy tissue, which confirmed both a morphologically abnormal fetus and a 45, X karyotype of the products of conception. ●