**9. Premature chromosomal condensation**

When a cell, with chromosomes in MII, fuses with an inter-phase cell, the nuclear membrane of the cell in the inter-phase dissolves and its chromatin condenses. This phenomenon is called premature chromosomal condensation (PCC) [76]. Following penetration of sperm into an oocyte; oocyte activation is triggered, resulting in completion of meiosis and formation of both male and female pronuclei. Under some circumstances although the sperm is within the oocyte, fertilization fails to occur, the oocyte remains in the MII stage and the sperm head transforms into PCC, separate from the oocyte chromosomes [77, 78]. Chromatin analysis of human oocytes has revealed that sperm PCC is one of the prevalent causes of fertilization failure in both IVF and ICSI [77].

It is not yet fully understood how the sperm activates the oocytes. The failure of fertilization after ICSI may result from either the lack or deficiency of activating factors in sperm or from the lack of ooplasmic factors triggering sperm chromatin decondensation [79, 80]. Several pieces of evidence point to PLCζ being the physiological agent of oocyte activation and is detectable in different localities within the sperm head: the equatorial segment and acrosomal/post-acrosomal region [81].

During normal spermiogenesis, 85% of histones are replaced with protamines [82], which results in sperm chromatin condensation. A sperm with a condensed nucleus is in the G1 stage when entering an MII oocyte and is protected from PCC because an active maturationpromoting factor (MPF) is not capable of reacting with protamine-associated DNA. Once sperm nuclear decondensation factors from the ooplasm enter the sperm, the sperm head swells and sperm associated oocyte activating factor is released. This results in MPF inactivation [83], the completion of meiosis 2 and the oocyte enters the G1 stage. During this time, protamines are slowly replaced by histones and cell cycle synchronization takes place. Under some circumstances, the oocyte fails to activate and remains arrested at MII. Because of the presence of an active MPF, sperm chromatin transforms into condensed chromatin. Sperm with excessive histones are prone to PCC.

Sperm PCC has been associated with the type of ovarian stimulation protocol. Some protocols, such as clomiphene citrate and human menopausal gonadotropin stimulation may tend to recruit immature oocytes with immature cytoplasm [84]. Immature cytoplasm is believed to make sperm susceptible to a high incidence of PCC after insemination because of the inability of these immature oocytes to undergo oocyte activation [85]. The incidence of sperm PCC reported in the literature ranges from 10.1 to 85 % [86, 87], with higher values noted in cases of round headed sperm injection as they fail to activate the oocyte. Furthermore, other studies suggest a correlation between fertilization outcome post-ICSI and percentage of sperm with protamine deficiency [88]. The effect of sperm protamine deficiency on fertilization rate emphasizes the need for accurate sperm selection during ICSI as protamine-deficient sperm, in the form of slightly amorphous head, may find the chance of being injected due to inappropriate sperm selection [88].
