Rescue intracytoplasmic sperm injection A systematic review

A literature search using the term “rescue ICSI” was performed. Thirty-eight studies were included, describing 1,863 patients and 194 offspring. Pregnancy rates and procedure safety are discussed.

Ronit Beck-Fruchter, M.D., Michal Lavee, M.D., Amir Weiss, M.D., Yoel Geslevich, M.D., Eliezer Shalev, M.D.

Volume 101, Issue 3, Pages 690-698, March 2014


To assess the feasibility, efficacy, and safety of rescue intracytoplasmic sperm injection (ICSI) in cases of fertilization failure, using a scientific literature search.

Systematic review.

Centers for reproductive care.

Infertility patients with total or partial fertilization failure during an IVF cycle.

An electronic literature search was performed in PubMed from 1992 through May 2013. The search was then expanded by using listed references from selected articles.

Main Outcome Measure(s):
Pregnancy rate. The secondary outcome measures were fertilization rate, normal fertilization rate, cleavage rate, birth rate, and malformation rate.

Thirty-eight studies including 1,863 patients were included. The pooled pregnancy rate was 14.4%; 194 babies were delivered.

Rescue ICSI can result in the delivery of a healthy newborn, although the pregnancy rates are low. The clinical evidence did not indicate an elevated rate of malformations, although the data are limited and incomplete.

  • Amita Tuteja


    visualization of meiotic spindles : relevance to Rescue ICSI


    We read the meta-analysis on Rescue ICSI by Ronit Beck Fruchter et al with great
    interest. The variation in timing of micro manipulation, the limited trials reviewed , with many being case reports , and the lack of detailed fetal and neonatal
    outcome , make it very difficult to collect and summarize the published data .

    The authors discuss the use of the Poloscope for meiotic spindle visualization after
    ICSI and differentiate between oocytes showing a single spindle and those with
    two spindles. Following this they inject only single spindle oocytes to prevent
    three pronuclei formation after rescue ICSI. The authors have reviewed the promising
    data of Moon et al (2013) which reveals that limiting micromanipulation to
    single spindle oocytes improved fertilization rates from 43.7 % to 68.7%. This
    apparent increase in fertilization rates is primarily due to decrease in the
    total number of oocytes being selected for rescue ICSI . The total number of
    unfertilized mature oocytes in the group undergoing rescue ICSI with and
    without poloscopy was 81 and 87 respectively. Poloscopic screening revealed
    single spindle in only 67 oocytes and out of them 38 had two pronuclei post the
    procedure, thus no difference in overall fertilization rates to the non-rescue ICSI group (56.7%).

    It is worth noting that a single spindle does not confirm absence of sperm
    penetration (Coticchio,2013) .Many cases of failed fertilization show the
    presence of spermatozoa in the ooplasm , but lack microtubular activation after penetration.Furthermore silent sperm chromatin can also organize spindle like structure but fail to proceed to cleavage(Rawe et al., 2000, Edirisinghe et al., 1997, Van Blerkom et al., 2004). Even if we presume that single spindle suggests no
    sperm penetration, visualization is affected by many factors. Parallel studies
    have revealed that the spindle could not be imaged in 16.5-24% of mature
    oocytes(Wang et al., 2001, Moon et al., 2003, Cohen et al., 2004, Rienzi et al., 2005, Rama Raju et al., 2007). Maternal age , temperature , in-vitro manipulation and other unknown factors affect the highly sensitive micro tubular arrangement of spindles and therefore play an important role in visualization.(Cooke et al., 2002)

    There are some vital concerns about the timing of spindle imaging in oocytes.
    Video-cinematography has been used to study the dynamics of spindle formation
    during oocyte maturation. On light microscopy , many oocytes classified as
    metaphase II were actually reclassified on Poloscopy as telophase I , when spindle remnants lining the polar body and ooplasm were observed .
    Subsequently it was revealed that the spindle disintegrates in Telophase I and
    reforms 40-60 min later. Montag et al (2006) further substantiated this with
    their serial poloscopic visualization of oocytes .The data suggested that even
    if the spindle was not seen at first observation, it was imaged in more than
    50% of cases at subsequent examination. Hence the usefulness of poloscopy for
    early ICSI seems questionable (Montag et al., 2006, Montag and van der Ven, 2008) . This is confirmed in the study by Jin et al (2014), which clearly showed success of rescue ICSI, when performed on oocytes not extruding a polar body at 4h. Rescue ICSI was performed before oocyte aging (4-6h post IVF), and all parameters measured were not different to regular ICSI, culminating in live birth rates of 32.6% compared to 41.7% respectively (Jin et al., 2014). Interestingly only 7/433 (1.6%)
    rescue ICSI eggs were classed as polyspermic, whereas Moon et al reported
    polyspermy rates up to 21% without the use of the Poloscope, and 4.5%
    polyspermy, even with Poloscope. . Rescue ICSI is commonplace at 4-6h in Japan
    and China with results appearing not inferior to normal ICSI. Thus, the use of
    a poloscope, the day following failed IVF, is perhaps an obsolete technique as,
    even with one spindle present, the ‘aged egg’ is more likely to cause abnormal
    activation and fertilization events.
    Also, the technique is neither conclusive or reliable for all eggs.

    Yours truly

    Amita Tuteja , Sally Catt
    MCE 2014
    Monash Medical Centre


    Cohen, Y., Malcov, M., Schwartz, T.,
    Mey-Raz, N., Carmon, A., Cohen, T., Lessing, J. B., Amit, A. and Azem, F.
    (2004) ‘Spindle imaging: a new marker for optimal timing of ICSI?’, Hum Reprod, 19(3), pp. 649-54.

    Cooke, S., Tyler,
    J. P. and Driscoll, G. (2002) ‘Objective assessments of temperature maintenance
    using in vitro culture techniques’, J
    Assist Reprod Genet, 19(8), pp. 368-75.

    Coticchio, G.
    (2013) ‘Polarization microscopy and rescue ICSI’, Reprod Biomed Online, 26(3), pp. 222-3; discussion 224-5.

    Edirisinghe, W.
    R., Murch, A., Junk, S. and Yovich, J. L. (1997) ‘Cytogenetic abnormalities of
    unfertilized oocytes generated from in-vitro fertilization and intracytoplasmic
    sperm injection: a double-blind study’, Hum
    Reprod, 12(12), pp. 2784-91.

    Jin, H., Shu, Y.,
    Dai, S., Peng, Z., Shi, S. and Sun, Y. (2014) ‘The value of second polar body
    detection 4 hours after insemination and early rescue ICSI in preventing
    complete fertilisation failure in patients with borderline semen’, Reproduction, Fertility and Development,
    26(2), pp. 346-350.

    Montag, M.,
    Schimming, T. and van der Ven, H. (2006) ‘Spindle imaging in human oocytes: the
    impact of the meiotic cell cycle’, Reprod
    Biomed Online, 12(4), pp. 442-6.

    Montag, M. and
    van der Ven, H. (2008) ‘Symposium: innovative techniques in human embryo
    viability assessment. Oocyte assessment and embryo viability prediction:
    birefringence imaging’, Reprod Biomed
    Online, 17(4), pp. 454-60.

    Moon, J. H.,
    Hyun, C. S., Lee, S. W., Son, W. Y., Yoon, S. H. and Lim, J. H. (2003) ‘Visualization
    of the metaphase II meiotic spindle in living human oocytes using the Polscope
    enables the prediction of embryonic developmental competence after ICSI’, Hum Reprod, 18(4), pp. 817-20.

    Rama Raju, G. A.,
    Prakash, G. J., Krishna, K. M. and Madan, K. (2007) ‘Meiotic spindle and zona
    pellucida characteristics as predictors of embryonic development: a preliminary
    study using PolScope imaging’, Reprod
    Biomed Online, 14(2), pp. 166-74.

    Rawe, V. Y.,
    Olmedo, S. B., Nodar, F. N., Doncel, G. D., Acosta, A. A. and Vitullo, A. D.
    (2000) ‘Cytoskeletal organization defects and abortive activation in human
    oocytes after IVF and ICSI failure’, Mol
    Hum Reprod, 6(6), pp. 510-6.

    Rienzi, L.,
    Ubaldi, F., Iacobelli, M., Minasi, M. G., Romano, S. and Greco, E. (2005)
    ‘Meiotic spindle visualization in living human oocytes’, Reprod Biomed Online, 10(2), pp. 192-8.

    Van Blerkom, J.,
    Davis, P. and Alexander, S. (2004) ‘Occurrence of maternal and paternal
    spindles in unfertilized human oocytes: possible relationship to nucleation defects
    after silent fertilization’, Reprod
    Biomed Online, 8(4), pp. 454-9.

    W. H., Meng, L., Hackett, R. J. and Keefe, D. L. (2001) ‘Developmental ability
    of human oocytes with or without birefringent spindles imaged by Polscope
    before insemination’, Hum Reprod,
    16(7), pp. 1464-8.

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