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1.
Hum Reprod ; 33(4): 579-587, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29538673

ABSTRACT

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.


Subject(s)
Abortion, Habitual/etiology , Chromosome Aberrations , Adult , Female , Genetic Testing , Humans , Karyotyping , Maternal Age , Middle Aged , Pregnancy , Pregnancy Outcome , Prospective Studies , Tissue Array Analysis
2.
J Morphol ; 214(3): 321-32, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1474599

ABSTRACT

The pattern of complexity of cranial sutures is highly variable both among and within species. Intentional cranial vault deformation in human populations provides a controlled natural experiment by which we were able to quantify aspects of sutural complexity and examine the relationship between sutural patterns and mechanical loading. Measures of sutural complexity (interdigitation, number, and size of sutural bones) were quantified from digitized tracings of 13 sutures and compared among three groups of crania (n = 70) from pre-European contact Peru. These groups represent sample populations deformed in 1) anteroposterior (AP) and 2) circumferential (C) directions and 3) an undeformed population. Intergroup comparisons show few differences in degree or asymmetry of sutural interdigitation. In the few comparisons which show differences, the C group is always more interdigitated than the other two while the AP group has more sutural bones. The sutures surrounding the temporal bone (sphenotemporal, occipitotemporal, and temporoparietal) most frequently show significant differences among groups. These differences are related to the more extreme binding of C type deformation and are consistent with hypothesized increases in tension at coronally oriented sutures in this group. The larger number of sutural bones in the AP group is consistent with the general broadening of the cranium in this group and with experimental evidence indicating the development of ossicles in areas of tension. We suggest that so few changes in sutural complexity occurred either because the magnitude of the growth vectors, unlike their direction, is not substantially altered or because mechanisms other than sutural growth modification are responsible for producing the altered vault shapes. In addition, the presence of fontanelles in the infant skulls during binding and the static nature of the binding may have contributed to the similarity in complexity among groups.


Subject(s)
Cranial Sutures/anatomy & histology , Paleontology , Skull/anatomy & histology , Adult , Humans , Peru
3.
J Biomech ; 23(4): 313-21, 1990.
Article in English | MEDLINE | ID: mdl-2335529

ABSTRACT

Many bones in mammalian skulls are linked together by cranial sutures, connective tissue joints that are morphologically variable and show different levels of interdigitation among and within species. The goal of this investigation was to determine whether sections of skull with cranial sutures have different mechanical properties than adjacent sections without sutures, and if these properties are enhanced with increased interdigitation. To test these hypotheses, bending strength and impact energy absorption were measured for samples of goat (Capra hircus) cranial bone without sutures and with sutures of different degrees of interdigitation. Bending strength was measured under both dynamic (9.7 mm displacement s-1) and relatively static (0.8 mm s-1) conditions, and at either speed, increased sutural interdigitation provided increased strength during three-point bending. However, except for very highly interdigitated sutures loaded slowly, sutures were not as strong in bending as bone. In contrast, sutures absorbed from 16% to 100% more energy per unit volume during impact loading than did bone. This five-fold increase in energy absorption by the sutures was significantly correlated with increased sutural interdigitation.


Subject(s)
Cranial Sutures/physiology , Skull/physiology , Animals , Biomechanical Phenomena , Cranial Sutures/ultrastructure , Female , Goats , In Vitro Techniques
10.
J Mich State Dent Assoc ; 50(5): 181-2, 1968 May.
Article in English | MEDLINE | ID: mdl-5244959
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