Egg maturity assessment prior to ICSI prevents premature fertilization of late-maturing oocytes

Abstract

Propose The presence of metaphase II (MII) spindle together with the polar body (PB) indicates completion of oocyte maturation. This study was designed to explore if spindle imaging can be used to optimize timing of intracytoplasmic sperm injection (ICSI). Methods The study involved 916 oocytes from 234 conventionally stimulated ICSI cycles with an unexpectedly poor ovarian response. All PB-displaying oocytes were subjected to polarized light microscopy (PLM) prior to ICSI. When MII spindle was absent in the majority of oocytes, ICSI was postponed and performed after additional spindle imaging. Fertilization, embryo development, and clinical outcome were evaluated with respect to the observed spindle pattern. Results The visible spindle was absent in 32.64% of PB-displaying oocytes. The late-maturing oocytes extruding PB in vitro were less likely to exhibit a spindle signal than in vivo matured MII oocytes (38.86% vs. 89.84%). When fertilization was postponed, 59.39% of initially spindle-negative oocytes developed detectable MII spindle. Spindled eggs had significantly higher developmental potential, and the presence of the spindle has been identified as an independent measure for predicting the formation of the blastocyst. Embryos derived from spindle-positive oocytes also showed a higher chance to implant and develop to term. Notably, 11 children were conceived by finely timed fertilization of late-maturing oocytes which are normally discarded. Conclusions The study confirms the prognostic value of spindle imaging and demonstrates that immature oocytes can be clinically utilized and give rise to live births when the timing of ICSI is adjusted to their developmental stage. Electronic supplementary material The online version of this article (10.1007/s10815-018-1393-0) contains supplementary material, which is available to authorized users.

Human Egg Maturity Assessment and Its Clinical Application

“…Due to its non-invasive character, it can be used to safely assess the human egg's readiness for fertilization in clinical settings 11,12,13,14 . Spindled oocytes are more likely to give rise to viable embryos than oocytes without a spindle 9,15,16,17,18,19,20,21,22,23 . Also, oocytes featuring a distinct bipolar spindle appear to have a higher developmental competence than oocytes with dysmorphic spindles 9,21,22 .…”

“…Spindled oocytes are more likely to give rise to viable embryos than oocytes without a spindle 9,15,16,17,18,19,20,21,22,23 . Also, oocytes featuring a distinct bipolar spindle appear to have a higher developmental competence than oocytes with dysmorphic spindles 9,21,22 . Taken together, spindle imaging can serve as a tool to identify the oocytes with the greatest potential to be successfully fertilized, undergo preimplantation development and support full-term pregnancy 9,15,16,17,18,19,20,21,22,23 .…”

“…The reported incidence of the spindle varies (44−97%) reflecting the diversity of the studied population 9,15,16,17,18,19,20,21,22,23,26,27,28 . In vivo matured oocytes from normal responders typically show bipolar MII spindle at 40 h after hCG trigger 9,18,27,29 . However, in slow responders, the pool of oocytes retrieved from preovulatory follicles is affected by maturation delay 9,27 .…”

“…Since the polarized light is of normal intensity, the technique could be safely used in clinical settings to view the dynamics of the division apparatus 11,12,13,14 . The presence of the MII spindle birefringence within the oocyte has been identified as a marker of an egg's developmental competence 9,15,16,17,18,19,20,21,22,23 . Thus, it has been suggested that non-invasive meiotic spindle imaging could be used for egg quality control in clinical practice 11,14,20 .…”

How disparities in gamete maturity influence the nascent conceptus, and beyond

“…Even though we rest comfortably in attributing maturity to the status of oocytes bearing signs of having arrested at metaphase of meiosis 2 (M2s), reality is far different given when maturation is measured in its full form. Routine practices of controlled ovarian stimulation do not always yield a basket full of M2s and even if they look mature, timing is essential without an accurate estimate of just when an hCG trigger did its thing to the oocyte (2). Exactly what is regulating the differential processing of chromatin from maternal and paternal chromatin has been a mystery until recently where protamine specific patterns of phosphorylation have now been reported to make a difference in assuring the correct timing for matching chromatin states (3).…”