Intracytoplasmic morphologically selected sperm injection is beneficial in cases of advanced maternal age: a prospective randomized study A.S. Setti a,b , R.C.S. Figueira b , D.P.A.F. Braga a,b , T. Aoki c , A. Iaconelli Jr. a,b , E. Borges Jr. a,b, * a Instituto Sapientiae – Centro de Estudos e Pesquisa em Reproduc ¸a˜o Humana Assistida, Rua Vieira Maciel, 62, 04503-040 Sa˜o Paulo, SP, Brazil b Fertility – Centro de Fertilizac ¸a˜o Assistida, Av. Brigadeiro Luis Antonio, 4545, 01401-002 Sa˜o Paulo, SP, Brazil c Faculdade de Cieˆncias Me ´dicas da Santa Casa de Sa˜o Paulo, Rua Dr. Cesa ´rio Motta Junior, 61, 01401-002 Sa˜o Paulo, SP, Brazil 1. Introduction A new concept of observation of sperm at high magnification in real time, known as motile sperm organelle morphology exami- nation (MSOME), was recently introduced [1]. Its incorporation, together with a micromanipulation system, has allowed the introduction of a modified ICSI procedure, called ‘intracytoplasmic morphologically selected sperm injection’ (IMSI). Several publica- tions reported that the IMSI procedure is positively associated with implantation and pregnancy rates [2–9]. Moreover, a recently published meta-analysis showed that the IMSI procedure is associated with improved embryo quality and improved implan- tation and pregnancy rates as well as lower miscarriage rates [10]. The high magnification allows the detection of sperm contain- ing nuclear vacuoles. Previous studies demonstrated an association between sperm nuclear vacuoles and DNA decondensation [11], and DNA fragmentation [12,13]. It is known that human sperm have highly dynamic and essential participation in embryogenesis that clearly goes beyond the fertilization process. The first divisions of the newly formed embryo depend on the machinery of the oocyte. Activation of the embryonic genome occurs at the stage of 4–8 cells [14]. Studies suggest that this result reflects a late paternal effect, which is related to blockage of embryonic development observed during/ after the implantation of embryos with normal karyotype [15,16]. The ability of the human oocyte to repair sperm DNA damage has not been fully elucidated, but some gene expression studies showed that the oocyte is equipped with mechanisms that can repair some of the paternal DNA abnormalities [17,18]. The ability to repair, however, depends on the type and extension of DNA damage, and mainly on the woman’s age and oocyte quality [19,20]. European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 286–290 ARTICLE INFO Article history: Received 16 April 2013 Received in revised form 22 July 2013 Accepted 3 September 2013 Keywords: IMSI ICSI Oocyte quality Sperm morphology ABSTRACT Objective: To evaluate advanced maternal age as a rationale for performing intracytoplasmic morphologically selected sperm injection (IMSI). Study design: This study included couples undergoing intracytoplasmic sperm injection (ICSI) as a result of advanced maternal age (37 years old). Sample size calculations were based on the assumption that a 15% difference in implantation rate would mean a clinically significant difference. To achieve this difference, 33 cycles would be needed in each treatment arm (with a significance level of 5% and power of 85%). Couples were randomly allocated to one of two sperm selection procedures (ICSI, n = 33; or IMSI, n = 33). Sperm selection in the ICSI group was analyzed under a magnification of 400. Sperm selection in the IMSI group was analyzed under high magnification of 6600. The groups were compared with regard to the outcome of the cycles. Results: IMSI cycles showed significantly higher implantation (4/33, 12.1% vs. 18/47, 38.3%, p = 0.026) and pregnancy (4/29, 13.8 vs. 18/30, 60.0%, p < 0.001) rates. The IMSI procedure positively influenced the blastocyst formation rate (RC: 15.00, R 2 : 49.9%, p = 0.001) and implantation rate (RC: 24.04, R 2 : 9.6, p = 0.027), and was determinant to the increased odds of pregnancy (OR: 9.0, CI: 2.17–37.38, p = 0.001). Conclusion: It seems that the injection of a morphologically normal spermatozoon overcomes the low oocyte quality in older women, resulting in improved embryo quality and in a 9-fold increase in the clinical pregnancy rate in couples with advanced maternal age. ß 2013 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Av. Brigadeiro Luis Antonio, 4545, 01401-002 Sao Paulo, SP, Brazil. Tel.: +55 11 3018 8181; fax: +55 11 30188182. E-mail address: edson@fertility.com.br (E. Borges Jr.). Contents lists available at ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb 0301-2115/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejogrb.2013.09.006