Detection of Sperm DNA Fragmentation (TUNEL, SCSA, SCD, COMET) and Use of Annexin Columns (MACS) in Assisted Reproduction Treatments

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; ALCARAZ, A.; GLUJOVSKY, D.; LOPEZ, A.; REY-ARES, L.; BARDACH, A.; CIAPPONI, A; MEGARELLI, C

Documento de Evaluación de tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

It is estimated that one every six couples can not have children after one year of frequent sexual intercourse without using contraceptive methods. Forty to fifty percent of the cases show some kind of disorder in males. Sperm DNA fragmentation is associated to varicocele, undescended testicles, advanced age in males, severe teratozoospermia and history of chemotherapy or radiotherapy. It has also been associated to repeated assisted reproductive treatment failures, poor quality embryos and early miscarriages after assisted reproduction treatments.The rate of births after in vitro fertilization treatments (IVF) is 13% when DNA fragmentation is above 50 %, increasing to 33 % when it is below 25%.The methods to measure it include TUNEL (Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling), SCSA (Sperm Chromatin Structure Assay), SCD (Sperm Chromatin Dispersion) and Comet (rate of fragmented sperm).The annexin columns have been proposed as a treatment method, screening the sperm sample, which would allow improving rates of success in patients with increased sperm DNA fragmentation.This report will assess the usefulness of the different detection techniques of sperm DNA fragmentation and annexin column within the framework of assisted reproduction treatments.TechnologySperm DNA fragmentation measurement techniques quantify DNA ruptures.The annexin V column (MACS, Magnetic-Activated Cell Sorting) uses metal microspheres that bind to the sperm with fragmented DNA thus allowing to choose the best quality sperm cells.PurposeTo assess the available evidence on the efficacy, safety and coverage policy related aspect on the use of sperm DNA fragmentation and the use of annexin columns in assisted reproduction treatments.MethodsA bibliographic search was carried out on the main data bases (such as MEDLINE, Cochrane and CRD), in general Internet engines, in health technology assessment agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsThree SRs and three cohorts assessing the use of DNA fragmentation techniques have been found; additionally one quasi-experimental study and 6 case series assessing MACS have also been identified. Four GCPs on the diagnosis and treatment of infertility have been found.Sperm DNA Fragmentation Detection TechniquesThe three systematic reviews found included cohort studies on couples undergoing reproductive treatment (in vitro fertilization or intracytoplasmatic sperm injection). They assessed the rates of miscarriages or pregnancies using the TUNEL, SCSA and COMET techniques for the diagnosis of sperm DNA fragmentation. One SR included 16 studies (2,969 couples with 1,252 pregnancies and 225 miscarriages), another one, 18 studies with 2,162 treatment cycles and the last one, 11 cohort studies with 1,459 cycles. The rates of sperm DNA damage detection ranged from 10 to 36%. The meta-analyses showed a significant increase in miscarriages when the patients presented sperm DNA damage versus those who did not present it (RR: 2.16 to 2.48, 95%CI:1.54 to 3.03). Sperm DNA abnormalities detected with TUNEL and SCSA are associated with a higher risk of miscarriage, while this was not observed with COMET.Annexin Column TreatmentNo randomized studies on the use of the annexin column technique as a treatment for sperm DNA fragmentation have been found. The only quasi-experimental study found did not show differences in the rates of clinical pregnancy. The case series (13-42 sperm samples) published show that this technique might improve the sperm motility in asthenoteratospermic and teratozoospermic patients.The European, British and Argentine GCPs describe the different disorders that should be assessed in sterile males; they do not make recommendations on sperm DNA fragmentation assay.In the 2013 report, the American Society of Reproductive Medicine recommends not to perform the sperm DNA fragmentation assay routinely when assessing and treating an infertile couple due to lack of clinical evidenceThe US health sponsors do not cover any of the tests used to diagnose sperm DNA fragmentation.The cost of the sperm DNA fragmentation detection techniques is AR$ 200 (Argentine pesos, November 2013) approximately U$S 32 (US dollars, November 2013) and AR$ 3,500 approximately U$S 575 for the treatment with annexin columns.ConclusionsThe quality of the evidence found for sperm DNA fragmentation assessment is poor. Observational studies show that the alterations diagnosed with Tunel and SCSA are associated with higher rates of miscarriages, however, so far, there have not been interventions which, based on this information, may allow improving the assisted reproductive treatment outcomes.That is why, the GPCs and health sponsors do not recommend sperm DNA fragmentation assays routinely.As regards, the annexin columns, there is no evidence on the benefit of its use in assisted reproduction.