Fertilization and Cleavage Axes Differ In Primates Conceived By Conventional (IVF) Versus Intracytoplasmic Sperm Injection (ICSI)

Abstract

With nearly ten million babies conceived globally, using assisted reproductive technologies, fundamental questions remain; e.g., How do the sperm and egg DNA unite? Does ICSI have consequences that IVF does not? Here, pronuclear and mitotic events in nonhuman primate zygotes leading to the establishment of polarity are investigated by multidimensional time-lapse video microscopy and immunocytochemistry. Multiplane videos after ICSI show atypical sperm head displacement beneath the oocyte cortex and eccentric para-tangential pronuclear alignment compared to IVF zygotes. Neither fertilization procedure generates incorporation cones. At first interphase, apposed pronuclei align obliquely to the animal-vegetal axis after ICSI, with asymmetric furrows assembling from the male pronucleus. Furrows form within 30° of the animal pole, but typically, not through the ICSI injection site. Membrane flow drives polar bodies and the ICSI site into the furrow. Mitotic spindle imaging suggests para-tangential pronuclear orientation, which initiates random spindle axes and minimal spindle:cortex interactions. Parthenogenetic pronuclei drift centripetally and assemble astral spindles lacking cortical interactions, leading to random furrows through the animal pole. Conversely, androgenotes display cortex-only pronuclear interactions mimicking ICSI. First cleavage axis determination in primates involves dynamic cortex-microtubule interactions among male pronuclei, centrosomal microtubules, and the animal pole, but not the ICSI site.

First cleavage is a manifestation of the geometry of the unfertilized oocyte: implications for monozygotic twinning in mice

“…More recently, also another study reported that a substantial proportion (73%) of mouse zygotes divided equatorially (Zheng et al ., 2013). Apart from mice, equatorial division was observed in ICSI zygotes of Rhesus monkeys (Simerly et al ., 2019). An important difference between our study and the prior studies in mice is that we did not assume lack of oocyte rolling and rotation – we imposed it (our oocytes were immobilized using a micromanipulator).…”

Fertilization by ICSI generates a higher number of live births than IVF in a pioneer facility applying >90% single blastocyst-stage embryo transfers

“…Although heavily criticized for a number of deficiencies, two Cochrane studies of 2000 and 2003 have actually supported ICSI for borderline sperm disorders as well as normozoospermic cases [52,53]. The most recent reported study also supports the IVF-ICSI Split model showing a higher blastocyst development rate for those oocytes inseminated by ICSI [54].…”

Intracytoplasmic sperm injection for all or for a few?

“…Completing the physiological story, studies on nonhuman primates (macaques and baboons) demonstrate differences between IVF-and ICSI-generated zygotes (146). These differences can be summarized in 3 points:…”