The IMSI Procedure Improves Laboratory and Clinical Outcomes Without Compromising the Aneuploidy Rate When Compared to the Classical ICSI Procedure

Purpose The intracytoplasmic morphologically selected sperm injection (IMSI) procedure has been associated with better laboratory and clinical outcomes in assisted reproduction technologies. Less information is available regarding the relationship between embryo aneuploidy rate and the IMSI procedure. The aim of this study is to compare the clinical outcomes and chromosomal status of IMSI-derived embryos with those obtained from intracytoplasmic sperm injection (ICSI) in order to establish a clearer view of the benefits of IMSI in infertile patients. Methods We retrospectively analyzed a total of 11 cycles of IMSI and 20 cycles of ICSI with preimplantation genetic diagnosis. The fertilization rate, cleavage rate, embryo quality, blastocyst development, aneuploidy rate, pregnancy rate, implantation rate, and miscarriage rate were compared between the groups. Results Similar rates of fertilization (70% and 73%), cleavage (98% and 100%), and aneuploidy (76.9% and 70.9%) were observed in the IMSI and ICSI groups, respectively. The IMSI group had significantly more good quality embryos at day 3 (95% vs 73%), higher blastocyst development rates (33% vs 19%), and greater number of hatching blastocysts (43% vs 28%), cycles with at least one blastocyst at day 5 (55% vs 35%), and blastocysts with good trophoectoderm morphology (21% vs 6%) compared with the ICSI group (P < 0.001). Significantly higher implantation rates were observed in the IMSI group compared with the ICSI group (57% vs 27%; P < 0.05). Pregnancy and miscarriage rates were similar in both groups (80% vs 50% and 0% vs 33%, respectively). Conclusion The IMSI procedure significantly improves the embryo quality/development by increasing the implantation rates without affecting the chromosomal status of embryos. There is a tendency for the IMSI procedure to enhance the pregnancy rates and lower the miscarriage rates when compared with ICSI.

[1]  P. Kovacs,et al.  Embryo selection: the role of time-lapse monitoring , 2014, Reproductive Biology and Endocrinology.

[2]  J. Qiao,et al.  Impact of gonadotropins on oocyte maturation, fertilisation and developmental competence in vitro. , 2014, Reproduction, fertility, and development.

[3]  D. Gardner,et al.  Culture and transfer of human blastocysts. , 1999, Current opinion in obstetrics & gynecology.

[4]  A. Veiga,et al.  A physiological replacement for polyvinylpyrrolidone (PVP) in assisted reproductive technology. , 2001, Human fertility.

[5]  C. Laskin,et al.  Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos. , 2012, Fertility and sterility.

[6]  S. Kanjilal,et al.  Does human sperm nuclear DNA integrity affect embryo quality? , 2005, Indian journal of experimental biology.

[7]  H. Gaub,et al.  Interactions between trophoblast and uterine epithelium: monitoring of adhesive forces. , 1998, Human reproduction.

[8]  S. Al-Hasani,et al.  ICSI outcome is not associated with the incidence of spermatozoa with abnormal chromatin condensation. , 2005, In vivo.

[9]  K Lundin,et al.  An alternative to PVP for slowing sperm prior to ICSI. , 2003, Human reproduction.

[10]  D. Sakkas,et al.  Sperm nuclear DNA damage in the human. , 2003, Advances in experimental medicine and biology.

[11]  A. Giwercman,et al.  Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case-control study. , 2010, International journal of andrology.

[12]  Xuefeng Huang,et al.  Effect of sperm DNA fragmentation on the clinical outcomes for in vitro fertilization and intracytoplasmic sperm injection in women with different ovarian reserves. , 2015, Fertility and sterility.

[13]  Katja Knez,et al.  The IMSI procedure improves poor embryo development in the same infertile couples with poor semen quality: A comparative prospective randomized study , 2011, Reproductive biology and endocrinology : RB&E.

[14]  M. Thie,et al.  In vitro Studies on Endometrial Adhesiveness for Trophoblast: Cellular Dynamics in Uterine Epithelial Cells , 2002, Cells Tissues Organs.

[15]  B. Dale,et al.  Intracytoplasmic injection of morphologically selected spermatozoa (IMSI) improves outcome after assisted reproduction by deselecting physiologically poor quality spermatozoa , 2011, Journal of Assisted Reproduction and Genetics.

[16]  G. Belaaloui,et al.  Sperm DNA Fragmentation and Standard Semen Parameters in Algerian Infertile Male Partners , 2015, The world journal of men's health.

[17]  Javier I. García,et al.  Sperm chromatin stability and its relationship with fertilization rate after Intracytoplasmic Sperm Injection (ICSI) in an assisted reproduction program , 2007, Journal of Assisted Reproduction and Genetics.

[18]  Jens Peter Bonde,et al.  Sperm chromatin damage impairs human fertility , 2000 .

[19]  Roly Hilario,et al.  Sperm DNA Fragmentation is Significantly Increased in Those Men with Morphologically Abnormal Spermatozoa , 2014 .

[20]  D. Braga,et al.  Morphological nuclear integrity of sperm cells is associated with preimplantation genetic aneuploidy screening cycle outcomes. , 2011, Fertility and sterility.

[21]  S. Munné,et al.  Blastomere fixation techniques and risk of misdiagnosis for preimplantation genetic diagnosis of aneuploidy. , 2002, Reproductive biomedicine online.

[22]  Y. Nagao,et al.  Effect of PVP on sperm capacitation status and embryonic development in cattle. , 2009, Theriogenology.

[23]  J Cohen,et al.  Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage. , 2001, Human reproduction.

[24]  Vicente Goyanes,et al.  The sperm chromatin dispersion test: a simple method for the determination of sperm DNA fragmentation. , 2003, Journal of andrology.

[25]  J. Tesarik.  Paternal effects on cell division in the human preimplantation embryo. , 2005, Reproductive biomedicine online.

[26]  L Fraser,et al.  Structural damage to nuclear DNA in mammalian spermatozoa: its evaluation techniques and relationship with male infertility. , 2004, Polish journal of veterinary sciences.

[27]  Jacques Cohen,et al.  Improved implantation after preimplantation genetic diagnosis of aneuploidy. , 2003, Reproductive biomedicine online.

[28]  J. Tesarik,et al.  Assembly of the nucleolar precursor bodies in human male pronuclei is correlated with an early RNA synthetic activity. , 1990, Experimental cell research.

[29]  R. Aitken,et al.  Apoptosis and DNA damage in human spermatozoa. , 2011, Asian journal of andrology.

[30]  A. Ellenbogen,et al.  Does the presence of nuclear vacuoles in human sperm selected for ICSI affect pregnancy outcome? , 2006, Human reproduction.

[31]  M. Virro,et al.  Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. , 2004, Fertility and sterility.

[32]  J. Guérin,et al.  Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. , 2003, Human reproduction.

[33]  Y. Nagao,et al.  Effect of polyvinylpyrrolidone on sperm function and early embryonic development following intracytoplasmic sperm injection in human assisted reproduction , 2012, Reproductive medicine and biology.

[34]  D. Fortini,et al.  High-power microscopy for selecting spermatozoa for ICSI by physiological status. , 2008, Reproductive biomedicine online.

[35]  J. Alvarez,et al.  Sperm DNA Tests as Useful Adjuncts to Semen Analysis , 2008, Systems biology in reproductive medicine.

[36]  J. Tesarik,et al.  Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. , 2004, Human reproduction.

[37]  Bernard Lejeune,et al.  Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles. , 2008, Reproductive biomedicine online.

[38]  M. Antinori,et al.  Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial. , 2008, Reproductive biomedicine online.

[39]  R. Erickson,et al.  Transcription of paternal Y-linked genes in the human zygote as early as the pronucleate stage , 1994, Zygote.

[40]  J. Bonde,et al.  Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team. , 2000, Fertility and sterility.

[41]  H. Tournaye.  Male factor infertility and ART. , 2012, Asian journal of andrology.

[42]  J. Tesarik,et al.  High-magnification ICSI overcomes paternal effect resistant to conventional ICSI. , 2006, Reproductive biomedicine online.

[43]  P. Vanderzwalmen,et al.  A new real-time morphology classification for human spermatozoa: a link for fertilization and improved embryo quality. , 2009, Fertility and sterility.

[44]  A. Guay,et al.  Optimizing response to phosphodiesterase therapy: impact of risk-factor management. , 2003, Journal of andrology.

[45]  S. Dar,et al.  [Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?]. , 2015, Harefuah.

[46]  T P Fleming,et al.  A quantitative analysis of cell allocation to trophectoderm and inner cell mass in the mouse blastocyst. , 1987, Developmental biology.

[47]  A. Campana,et al.  Blastocyst development from supernumerary embryos after intracytoplasmic sperm injection: a paternal influence? , 1998, Human reproduction.

[48]  A. Iaconelli,et al.  Intracytoplasmic sperm injection outcome versus intracytoplasmic morphologically selected sperm injection outcome: a meta-analysis. , 2010, Reproductive biomedicine online.

[49]  L. Gianaroli,et al.  Paternal contribution to aneuploidy in preimplantation embryos. , 2009, Reproductive biomedicine online.

[50]  B. Balaban,et al.  Clinical outcome of intracytoplasmic injection of spermatozoa morphologically selected under high magnification: a prospective randomized study. , 2011, Reproductive biomedicine online.

[51]  R. Baruffi,et al.  Comparison of day 2 embryo quality after conventional ICSI versus intracytoplasmic morphologically selected sperm injection (IMSI) using sibling oocytes. , 2010, European journal of obstetrics, gynecology, and reproductive biology.

[52]  E. Blennow,et al.  A high degree of aneuploidy in frozen-thawed human preimplantation embryos , 1999, Human Genetics.

[53]  J. Dyce,et al.  Do trophectoderm and inner cell mass cells in the mouse blastocyst maintain discrete lineages? , 1987, Development.

[54]  Greta Verheyen,et al.  Influence of individual sperm morphology on fertilization, embryo morphology, and pregnancy outcome of intracytoplasmic sperm injection. , 2003, Fertility and sterility.

[55]  R. Mansour.  Minimizing embryo expulsion after embryo transfer: a randomized controlled study. , 2005, Human reproduction.

[56]  K. Charalabopoulos,et al.  Human Sperm DNA Fragmentation and its Correlation with Conventional Semen Parameters , 2014, Journal of reproduction & infertility.

[57]  J. Tesarik,et al.  Nucleic acid synthesis and development of human male pronucleus. , 1989, Journal of reproduction and fertility.

[58]  R. Baruffi,et al.  The effects of male age on sperm analysis by motile sperm organelle morphology examination (MSOME) , 2012, Reproductive Biology and Endocrinology.

[59]  A Berkovitz,et al.  How to improve IVF-ICSI outcome by sperm selection. , 2006, Reproductive biomedicine online.

[60]  M. Nichi,et al.  Sperm organelle morphologic abnormalities: contributing factors and effects on intracytoplasmic sperm injection cycles outcomes. , 2011, Urology.

[61]  M. Stieber,et al.  The effect of chromatin condensation (aniline blue staining) and morphology (strict criteria) of human spermatozoa on fertilization, cleavage and pregnancy rates in an intracytoplasmic sperm injection programme. , 1996, Human reproduction.

[62]  E. Moshier,et al.  Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages , 2013, Journal of Assisted Reproduction and Genetics.

[63]  A Berkovitz,et al.  Selection of spermatozoa with normal nuclei to improve the pregnancy rate with intracytoplasmic sperm injection. , 2001, The New England journal of medicine.

[64]  S. Yaari,et al.  The morphological normalcy of the sperm nucleus and pregnancy rate of intracytoplasmic injection with morphologically selected sperm. , 2005, Human reproduction.

[65]  D. Wells,et al.  Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos. , 2014, Molecular human reproduction.

[66]  A. Agarwal,et al.  Role of sperm chromatin abnormalities and DNA damage in male infertility. , 2003, Human reproduction update.

[67]  D. Brison,et al.  The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development. , 2002, Human reproduction.

[68]  J. Tesarik,et al.  Paternal effects acting during the first cell cycle of human preimplantation development after ICSI. , 2002, Human reproduction.

[69]  Yona Barak,et al.  Pregnancy rates are higher with intracytoplasmic morphologically selected sperm injection than with conventional intracytoplasmic injection. , 2003, Fertility and sterility.

[70]  Yona Barak,et al.  Real-time fine morphology of motile human sperm cells is associated with IVF-ICSI outcome. , 2002, Journal of andrology.

[71]  C. Benedetto,et al.  “Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial , 2014, Journal of Assisted Reproduction and Genetics.

[72]  F. Vialard,et al.  The nature of human sperm head vacuoles: a systematic literature review , 2013, Basic and Clinical Andrology.

[73]  D. Griffin,et al.  Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation, (FISH). , 1993, Human molecular genetics.

[74]  A. Barnes,et al.  Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques. , 2000, Human reproduction.

[75]  S. Kimber,et al.  Trophoblast-uterine interactions at implantation , 2004, Reproductive biology and endocrinology : RB&E.

[76]  N. Treff,et al.  The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. , 2014, Fertility and sterility.

[77]  G. Lo Monte,et al.  Clinical outcome after IMSI procedure in an unselected infertile population: a pilot study , 2013, Reproductive Health.

[78]  N. Desai,et al.  Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles , 2014, Reproductive Biology and Endocrinology.

[79]  J. Tesarik.  Paternal effects on cell division in the preimplantation embryo , 2005 .

[80]  Sjoerd Repping,et al.  Molecular origin of mitotic aneuploidies in preimplantation embryos. , 2012, Biochimica et biophysica acta.

[81]  F. Sendag,et al.  Comparison of short and long ovulation induction protocols used in ART applications according to the ovarian response and outcome of pregnancy , 2002, Archives of Gynecology and Obstetrics.

[82]  C. Flamigni,et al.  Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. , 2006, Human reproduction.

[83]  E. Seli,et al.  Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. , 2004, Fertility and sterility.

[84]  S. Lindenberg,et al.  The role of DNA strand breaks in human spermatozoa used for IVF and ICSI , 2000, Acta obstetricia et gynecologica Scandinavica.

[85]  P. Devroey,et al.  Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte , 1992, The Lancet.

[86]  V Sharma,et al.  Embryo quality and IVF treatment outcomes may correlate with different sperm comet assay parameters. , 2002, Human reproduction.

[87]  J. B. Oliveira,et al.  Significance of large nuclear vacuoles in human spermatozoa: implications for ICSI. , 2008, Reproductive biomedicine online.

[88]  Y. Ménézo,et al.  Evidence for a strong paternal effect on human preimplantation embryo development and blastocyst formation , 1994, Molecular reproduction and development.

[89]  R. Gilchrist,et al.  Increased gonadotrophin stimulation does not improve IVF outcomes in patients with predicted poor ovarian reserve , 2008, Journal of Assisted Reproduction and Genetics.