Endometrial Cell Co-culture in Patients Receiving Assited Reproduction Treatments

PICHON RIVIERE, A.; AUGUSTOVSKI, F. A.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPONI, A

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2012 p. 1 - 30

1668-2793

The rate of infertility ranges from 10-15%. In Argentina, more than 10,000 in vitro fertilization (IVF) cycles are carried out per year, with an estimate of less than 100 treatments every million people in Latin America.At present, the rate of live newborns with this type of treatments ranges from 40% under 35 years old and 20% near the 40s. The effectiveness of assisted reproductive treatments have increased in the last decade, mostly due to changes in the culture media and embryo management and storage conditions until embryo transfer. However, in spite of these better results, it is still difficult to determine what the best culture media is since many labs make changes to the commercially available media thus making it difficult to generalize any result.In addition, at present, there is a subgroup of patients with repeated negative outcomes. It is believed that one of the factors which may be of benefit for these couples is culture media improvement. That is why the use of embryo co-culture with endometrial cells in order to yield a medium containing certain factors that might not be present in the commonly used artificial culture media is proposed.TechnologyIn endometrial cell co-culture embryos are cultured in the regularly used culture media to which endometrial cells have been added. These cells are obtained from the same patient (autologous) or from other patient (heterologous). When obtained from the same patient, an endometrial biopsy is performed during the luteal phase of a previous cycle. These cells undergo an incubation, centrifugation, resuspension and sedimentation process until a sample rich in glands which, after approximately one week incubation, is cryopreserved. Some days before the embryo culture takes place, these cells are thawed and seeded. Then, the embryos will be placed in the culture media used.PurposeTo assess the available evidence on the efficacy, safety and coverage policy related aspects on the use of endometrial cell co-culture in patients undergoing assisted reproductive treatment.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation 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.ResultsThis report includes one systematic review, one RCT presented as summary at a scientific meeting and four case report series.One systematic review published in 2008 on the use of co-culture in assisted reproductive treatments did not find any randomized clinical trials on endometrial cell co-culture. This search was updated and no RCTs published in peer-reviewed journals were found; therefore the following identified publications are reported.In 2006, the summary of one RCT presented at the annual meeting of the ASRM (American Society for Reproductive Medicine) was published. Data from an interim analysis where 87 females less than 39 years old were randomized with at least one high complexity assisted reproductive treatment failure were presented. No statistically significant differences were found between the co-culture group and the control group (pregnancy rates of 61.9% vs. 73.3%, p=ns). No publication of this completed study was found in peer-reviewed journals.In four case series reports published between 2004 and 2010, co-culture of endometrial cells was carried out in couples with repeated failures, showing rates of pregnancy and of live newborns similar to the historical ones, ranging between approximately 40% and 50%, according to the patient?s age.ConclusionsThis document only presents data from case series reports in addition to the data coming from one RCT presented as an interim analysis summary, consequently the available evidence is of poor quality.Also, these results might be difficult to interpret due to the heterogeneity of the culture media used in the different assisted reproductive programs.In summary, there is no published evidence that allows drawing conclusions on the effectiveness of endometrial cell co-culture.