Carolyn R. Jaslow

Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses

OBJECTIVE To determine whether the frequency of abnormal results for evidence-based diagnostic tests differed among women with recurrent pregnancy loss (RPL) based on the number of prior losses (n = 2, 3, or > or =4) and to determine whether abnormal results for additional investigative diagnostic tests differed in prevalence among women with different numbers of pregnancy losses. DESIGN Single-center, retrospective study. SETTING Patients with RPL at a private practice. PATIENT(S) One thousand twenty women who had two or more consecutive spontaneous pregnancy losses with the same partner. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities; pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; thrombophilic tests for the factor V Leiden mutation; and blood tests for thyroid-stimulating hormone [TSH] and fasting blood glucose). We also measured the frequency of abnormal results for nine additional investigative tests in the same patients (antiphosphatidyl serine antibodies, microbial infection, midluteal P, PRL, functional protein C activity, functional protein S activity, antithrombin activity, fasting homocysteine and methylenetetrahydrofolate reductase polymorphisms, and factor II mutation). RESULT(S) The prevalence of abnormal results for evidence-based and investigative diagnostic tests did not differ among women with different numbers of pregnancy losses. CONCLUSION(S) Evaluation of all couples with two, three, or more consecutive miscarriages is recommended.

Effect of prior birth and miscarriage frequency on the prevalence of acquired and congenital uterine anomalies in women with recurrent miscarriage: a cross-sectional study.

OBJECTIVE To determine whether a prior live birth or an increase in number of miscarriages impacted the prevalence of congenital or acquired uterine anomalies in women with predominantly early recurrent miscarriage (RM). DESIGN Single-center, cross-sectional study. SETTING Patients with RM at a private practice. PATIENT(S) Eight hundred seventy-five women who had two or more consecutive miscarriages. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Frequencies of congenital uterine anomalies (bicornuate, didelphic, septate, t-shaped, and unicornuate uteri) and acquired uterine anomalies (fibroids, polyps, and adhesions). RESULT(S) A uterine anomaly was identified in 169 (19.3%) of the patients. Patients with primary RM were more likely to have congenital anomalies than patients with secondary RM, particularly septa. The occurrence of a prior live birth, however, did not influence the frequency of acquired uterine anomalies, which were detected in equal frequencies in patients with three or more miscarriages when compared with patients with only two miscarriages. CONCLUSION(S) Although RM patients with a prior viable birth are less likely to have a uterine anomaly than those who have never given birth, our results support a recommendation for diagnostic imaging of the uterus after two losses in women with secondary RM as well as for those with primary RM.

CD9 Expression by Human Granulosa Cells and Platelets as a Predictor of Fertilization Success during IVF

Objective. To determine whether CD9 expression on human granulosa cells (GCs) and platelets could predict the success of conventional fertilization of human oocytes during in vitro fertilization (IVF). Methods. Thirty women undergoing IVF for nonmale factor infertility participated. Platelets from venous blood and GCs separated from retrieved oocytes were prepared for immunofluorescence. Flow cytometry quantified the percent of GCs expressing CD9, and CD9 surface density on GCs and platelets. Fertilization rate was determined for the total number of oocytes, and the number of mature oocytes per patient. Correlations tested for significant relationships (P < .05) between fertilization rates and CD9 expression. Results. CD9 surface density on human GCs is inversely correlated with fertilization rate of oocytes (P = .04), but the relationship was weak. Conclusion. More studies are needed to determine if CD9 expression on GCs would be useful for predicting conventional fertilization success during IVF.

Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients

STUDY QUESTION Will the addition of 24-chromosome microarray analysis on miscarriage tissue combined with the standard American Society for Reproductive Medicine (ASRM) evaluation for recurrent miscarriage explain most losses? SUMMARY ANSWER Over 90% of patients with recurrent pregnancy loss (RPL) will have a probable or definitive cause identified when combining genetic testing on miscarriage tissue with the standard ASRM evaluation for recurrent miscarriage. WHAT IS KNOWN ALREADY RPL is estimated to occur in 2-4% of reproductive age couples. A probable cause can be identified in approximately 50% of patients after an ASRM recommended workup including an evaluation for parental chromosomal abnormalities, congenital and acquired uterine anomalies, endocrine imbalances and autoimmune factors including antiphospholipid syndrome. STUDY DESIGN, SIZE, DURATION Single-center, prospective cohort study that included 100 patients seen in a private RPL clinic from 2014 to 2017. All 100 women had two or more pregnancy losses, a complete evaluation for RPL as defined by the ASRM, and miscarriage tissue evaluated by 24-chromosome microarray analysis after their second or subsequent miscarriage. PARTICIPANTS/MATERIALS, SETTING, METHODS Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities, and 24-chromosome microarray evaluation for products of conception (POC); pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; and blood tests for thyroid stimulating hormone (TSH), prolactin and hemoglobin A1c) were evaluated. We excluded cases where there was maternal cell contamination of the miscarriage tissue or if the ASRM evaluation was incomplete. A cost analysis for the evaluation of RPL was conducted to determine whether a proposed procedure of 24-chromome microarray evaluation followed by an ASRM RPL workup (for those RPL patients who had a normal 24-chromosome microarray evaluation) was more cost-efficient than conducting ASRM RPL workups on RPL patients followed by 24-chromosome microarray analysis (for those RPL patients who had a normal RPL workup). MAIN RESULTS AND THE ROLE OF CHANCE A definite or probable cause of pregnancy loss was identified in the vast majority (95/100; 95%) of RPL patients when a 24-chromosome pair microarray evaluation of POC testing is combined with the standard ASRM RPL workup evaluation at the time of the second or subsequent loss. The ASRM RPL workup identified an abnormality and a probable explanation for pregnancy loss in only 45/100 or 45% of all patients. A definite abnormality was identified in 67/100 patients or 67% when initial testing was performed using 24-chromosome microarray analyses on the miscarriage tissue. Only 5/100 (5%) patients, who had a euploid loss and a normal ASRM RPL workup, had a pregnancy loss without a probable or definitive cause identified. All other losses were explained by an abnormal 24-chromosome microarray analysis of the miscarriage tissue, an abnormal finding of the RPL workup, or a combination of both. Results from the cost analysis indicated that an initial approach of using a 24-chromosome microarray analysis on miscarriage tissue resulted in a 50% savings in cost to the health care system and to the patient. LIMITATIONS, REASONS FOR CAUTION This is a single-center study on a small group of well-characterized women with RPL. There was an incomplete follow-up on subsequent pregnancy outcomes after evaluation, however this should not affect our principal results. The maternal age of patients varied from 26 to 45 years old. More aneuploid pregnancy losses would be expected in older women, particularly over the age of 35 years old. WIDER IMPLICATIONS OF THE FINDINGS Evaluation of POC using 24-chromosome microarray analysis adds significantly to the ASRM recommended evaluation of RPL. Genetic evaluation on miscarriage tissue obtained at the time of the second and subsequent pregnancy losses should be offered to all couples with two or more consecutive pregnancy losses. The combination of a genetic evaluation on miscarriage tissue with an evidence-based evaluation for RPL will identify a probable or definitive cause in over 90% of miscarriages. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this study and there are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER Not applicable.