TITLE: Culture Media for Various Assisted Reproduction Procedures: Clinical Effectiveness DATE: 02 February 2010 RESEARCH QUESTION: What is the evidence of the effectiveness of different culture media for the various assisted reproduction procedures for gamete and embryo viability? METHODS: A limited literature search was conducted on key health technology assessment resources, including PubMed, the Cochrane Library (Issue 1, 2010), University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, EuroScan, international health technology agencies, and a focused Internet search. The search was limited to English language articles published between 2005 and January 2010. No filters were applied to limit the retrieval by study type. Internet links were provided, where available. The summary of findings was prepared from the abstracts of the relevant information. Please note that data contained in abstracts may not always be an accurate reflection of the data contained within the full article. RESULTS: HTIS reports are organized so that the higher quality evidence is presented first. Therefore, health technology assessment reports, systematic reviews, and meta-analyses are presented first. These are followed by randomized controlled trials, controlled clinical trials, and observational studies. One systematic review and six randomized controlled trials were identified regarding the effectiveness of different culture media for the various assisted reproduction procedures for gamete and embryo viability. No health technology assessments were identified. Due to the availability of studies associated with higher internal validity, controlled clinical trials and Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in which a third party owns copyright. This report may be used for the purposes of research or private study only. It may not be copied, posted on a web site, redistributed by email or stored on an electronic system without the prior written permission of CADTH or applicable copyright owner. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.
observational studies were moved to the appendix. Additional articles of potential interest may also be found in the appendix. OVERALL SUMMARY OF FINDINGS: A systematic review of the effectiveness of assisted reproductive technology concluded that there was not enough available evidence to provide a firm conclusion regarding the impact of differing culture media on assisted reproduction outcomes. 1 The six identified randomized controlled trials 2-7 presented outcomes from various culture and transfer media and are summarized in Table 1. The results from four of the six randomized controlled trials favored the study group. 2,3,5,6 Author de Araujo et al. 2 Meintjes et al. 3 Ge et al. 4 Hashimoto et al. 5 Friedler et al. 6 Mahani et al. 7 Table 1: Summary results of included RCTs Patient Study group Comparator population group Women with Human tubal fluid PCOS Couples routine IVF or ICSI Women with PCOS Women IVF/ET Women IVF/ET after failed transfer Women IVF/ET Supplemented tissue culture medium 199 supplemented with HSA + SSS with hcg with a novel stable glutamine derivative + vitamins medium with hyaluronan medium with hyaluronic acid supplemented with HSA without hcg with L-glutamine medium without hyaluronan medium with albumin Outcomes Significant increase in maturation rate, fertilization rate, and embryo quality in the study group Overall increase in implantation and birth rates in the study group Maturation rate and developmental potential of oocytes were not improved in the study group Significant increase in blastulation rate on day 5 and 6, supporting development of the embryo, in the study group Significantly higher implantation rate; and, significantly higher clinical, continuing, and delivered pregnancy rate in the study group Pregnancy rates were not significantly different between groups and the two media can be used interchangeably PCOS = polycystic ovary syndrome; IVF = in vitro fertilization; ICSI = intracyoplasmic sperm injection; HAS = human serum albumin; SSS = serum substitute supplement; hcg = human gonadotropin; ET = embryo transfer Culture Media for Assisted Reproduction 2
REFERENCES SUMMARIZED: Health technology assessments No literature identified Systematic reviews and meta-analyses 1. Myers ER, McCrory DC, Mills AA, Price TM, Swamy GK, Tantibhedhyangkul J, et al. Effectiveness of assisted reproductive technology. evidence report/technology assessment no. 167. [Internet]. Rockville (MD): Agency for Healthcare Research and Quality; 2008. [cited 2010 Jan 20]. Available from: http://www.ahrq.gov/downloads/pub/evidence/pdf/infertility/infertility.pdf Note: see last paragraph p. 71, and B. Embryo culture p. 89 Randomized controlled trials 2. de Araujo CH, Nogueira D, de Araujo MC, Martins Wde P, Ferriani RA, dos Reis RM. Supplemented tissue culture medium 199 is a better medium for in vitro maturation of oocytes from women with polycystic ovary syndrome women than human tubal fluid. Fertil Steril. 2009 Feb;91(2):509-13. PubMed: PM18304540 3. Meintjes M, Chantilis SJ, Ward DC, Douglas JD, Rodriguez AJ, Guerami AR, et al. A randomized controlled study of human serum albumin and serum substitute supplement as protein supplements for IVF culture and the effect on live birth rates. Hum Reprod. 2009 Apr;24(4):782-9. PubMed: PM19147504 4. Ge HS, Huang XF, Zhang W, Zhao JZ, Lin JJ, Zhou W. Exposure to human chorionic gonadotropin during in vitro maturation does not improve the maturation rate and developmental potential of immature oocytes from patients with polycystic ovary syndrome. Fertil Steril. 2008 Jan;89(1):98-103. PubMed: PM17524398 5. Hashimoto S, Nishihara T, Murata Y, Oku H, Nakaoka Y, Fukuda A, et al. Medium without ammonium accumulation supports the developmental competence of human embryos. J Reprod Dev. 2008 Oct;54(5):370-4. PubMed: PM18580042 6. Friedler S, Schachter M, Strassburger D, Esther K, Ron-El R, Raziel A. A randomized clinical trial comparing recombinant hyaluronan/recombinant albumin versus human tubal fluid for cleavage stage embryo transfer in patients with multiple IVF-embryo transfer failure. Hum Reprod. 2007 Sep;22(9):2444-8. PubMed: PM17644629 7. Mahani IM, Davar R. Hyaluronic acid versus albumin in human embryo transfer medium. East Mediterr Health J. 2007 Jul;13(4):876-80. PubMed: PM17955771 Available from: http://www.emro.who.int/emhj/1304/13_4_2007_876_880.pdf Culture Media for Assisted Reproduction 3
PREPARED BY: Michelle Clark, BSc, Research Assistant Jessie Cunningham, MISt, Information Specialist Health Technology Inquiry Service Email: htis@cadth.ca Tel: 1-866-898-8439 Culture Media for Assisted Reproduction 4
APPENDIX FURTHER INFORMATION: Controlled clinical trials 8. Aoki VW, Wilcox AL, Peterson CM, Parker-Jones K, Hatasaka HH, Gibson M, et al. Comparison of four media types during 3-day human IVF embryo culture. Reprod Biomed Online. 2005 May;10(5):600-6. PubMed: PM15949217 Observational studies 9. Reed ML, Hamic A, Thompson DJ, Caperton CL. Continuous uninterrupted single medium culture without medium renewal versus sequential media culture: a sibling embryo study. Fertil Steril. 2009 Nov;92(5):1783-6. PubMed: PM19523617 10. Filali M, Hesters L, Fanchin R, Tachdjian G, Frydman R, Frydman N. Retrospective comparison of two media for invitro maturation of oocytes. Reprod Biomed Online. 2008 Feb;16(2):250-6. PubMed: PM18284882 11. Jee BC, Han SH, Moon JH, Suh CS, Kim SH, Seoul National University College of Medicine Assisted Reproductive Technology (SMART) Study Group. Influence of well defined protein source on in vitro maturation of human oocyte: human follicular fluid versus human serum albumin. Fertil Steril. 2008 Feb;89(2):348-52. PubMed: PM17482173 12. Kanaya H, Fukuda A, Hashimoto S, Hosoi Y, Morimoto Y. In vitro maturation of human immature oocytes in culture medium supplemented with patient's own serum or donor follicular fluid. J Mamm Ova Res. [Internet] 2008 [cited 2010 Jan 20];25(3):163-166. Available from: http://www.jstage.jst.go.jp/article/jmor/25/3/163/_pdf 13. Loutradi KE, Prassas I, Bili E, Sanopoulou T, Bontis I, Tarlatzis BC. Evaluation of a transfer medium containing high concentration of hyaluronan in human in vitro fertilization. Fertil Steril. 2007 Jan;87(1):48-52. PubMed: PM17074336 14. Boldt J, Tidswell N, Sayers A, Kilani R, Cline D. Human oocyte cryopreservation: 5-year experience with a sodium-depleted slow freezing method. Reprod Biomed Online. 2006 Jul;13(1):96-100. PubMed: PM16820118 15. Borini A, Sciajno R, Bianchi V, Sereni E, Flamigni C, Coticchio G. Clinical outcome of oocyte cryopreservation after slow cooling with a protocol utilizing a high sucrose concentration. Hum Reprod. 2006 Feb;21(2):512-7. PubMed: PM16239316 Review articles 16. Biggers JD, Summers MC. Choosing a culture medium: making informed choices. Fertil Steril. 2008 Sep;90(3):473-83. PubMed: PM18847602 Culture Media for Assisted Reproduction 5
17. Lane M, Gardner DK. Embryo culture medium: which is the best? Best Pract Res Clin Obstet Gynaecol. 2007 Feb;21(1):83-100. PubMed: PM17090393 18. Maximizing the retention of antigen specific lymphocyte function after cryopreservation. J Immunol Methods. 2006 Jan 20;308(1-2):13-8. PubMed: PM16337957 19. Agarwal A, Gupta S, Sharma R. Oxidative stress and its implications in female infertility - a clinician's perspective. Reprod Biomed Online. 2005 Nov;11(5):641-50. PubMed: PM16409717 Culture Media for Assisted Reproduction 6