This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.

Among infertile couples, 25% involve both male and female factors, while male factor alone accounts for another 25% due to oligo-, astheno-, teratozoospermia, a combination of the three, or even a complete absence of sperm cells in the ejaculate and can lead to a poor prognosis even with the help of assisted reproductive technology (ART). Intracytoplasmic sperm injection (ICSI) has been with us now for a quarter of a century and in spite of the controversy generated since its inception, it remains in the forefront of the techniques utilized in ART. The development of ICSI in 1992 has drastically decreased the impact of male factor, resulting in millions of pregnancies worldwide for couples who, without ICSI, would have had little chance of having their own biological child. This review focuses on the state of the art of ICSI regarding utility of bioassays that evaluate male factor infertility beyond the standard semen analysis and describes the current application and advances in regard to ICSI, particularly the genetic and epigenetic characteristics of spermatozoa and their impact on reproductive outcome.

In addition to aneuploidy assessment, the speed of embryo development to the blastocyst stage and an evaluation of blastocyst morphology are critical to selecting the best embryo.

Derepressionof chromatin-mediated transcriptional repression of paternal and maternal genomes is considered the first major step that initiates zygotic gene expression after fertilization. The histone variant H3.3 is present in both male and female gametes and is thought to be important for remodeling the paternal and maternal genomes for activation during both fertilization and embryogenesis. However, the underlying mechanisms remain poorly understood. Using our H3.3B-HA-tagged mouse model, engineered to report H3.3 expression in live animals and to distinguish different source of H3.3 protein in embryos, we show here that sperm-derived H3.3 protein (sH3.3) is removed from the sperm genome shortly after fertilization and extruded from the zygotes via the second polar bodies (PB II) during embryogenesis. We also found that the maternal H3.3 (mH3.3) protein is incorporated into the paternal genome as early as 2h postfertilization and is detectable in the paternal genome until the morula stage. Knockdown of maternal H3.3 resulted in compromised embryonic development both of fertilized embryos and of androgenetic haploid embryos. Furthermore, we report that mH3.3 depletion in oocytes impairs both activation of the Oct4 pluripotency marker gene and global de novo transcription from the paternal genome important for early embryonic development. Our results suggest that H3.3-mediated paternal chromatin remodeling is essential for the development of preimplantation embryos and the activation of the paternal genome during embryogenesis. [1,2]. At the time of fertilization, both the sperm and oocyte genomes are transcriptionally repressed, whereas the maternal stored factors in the oocyte support and control the process of early embryogenesis. Maternal-to-zygotic transition (MZT) is an embryonic development stage under the exclusive control of the newly formed zygotic genome. This developmental process requires the zygotic genome activation (ZGA) to allow for the transition from specified germ cells to a totipotent embryo, in which both paternal and maternal genomes undergo dramatic epigenetic reprogramming regulated by maternal factors [3]. Overcoming chromatin-mediated transcriptional repression of paternal and maternal genomes is thought to be the first major step to initiate zygotic gene expression after fertilization [4][5][6][7][8][9].The mammalian sperm genome is packaged into highly condensed chromatin consisting primarily of protamine but 5-15% residual histones. Following fertilization, ZGA occurs first in the paternal genome (male pronucleus) at the 1-cell stage embryo, while activation of the maternal genome is usually delayed and occurs at the 2-cell stage in mice [10][11][12][13]. Soon after fertilization, protamine is removed from the sperm genome. The paternal genomes subsequently undergoes chromatin remodeling through a massive and highly regulated exchange of canonical and variant histones including H1FOO, H3.3, microH2A and H2A.Z. The incorporation of histone variants into paternal genome is ...