IVF or ICSI: The Dilemma

If there is a sufficient number of highly progressive motile sperm of good morphology in the pre‐ and post‐preparation, then the chances of fertilization following conventional IVF insemination should theoretically be high. However, it should be noted that low fertilization, and even complete failure of fertilization, may result even when the sperm quality is good. Frapsauce et al. (2009) estimated that despite normal sperm parameters, 5% of IVF attempts result in an unpredicted failure of fertilization, with 56% of cases having no obvious oocyte anomaly other than a complete lack of ZP–sperm binding. In such instances, the cause of failed fertilization cannot be ascertained without cytogenetic analysis of the unfertilized oocyte (see Table 24.2).

In Europe, there is a marked variation in the relative proportions of IVF and ICSI procedures. According to a report in 2013 from the European IVF‐Monitoring (EIM) Consortium for the European Society of Human Reproduction and Embryology (ESHRE), the difference seems to be related to geographic distribution. IVF remains the dominant technology in several countries from northern and eastern Europe (Denmark, Finland, Iceland, Ireland, Kazakhstan, Lithuania, Romania, Russia, Sweden, and the Netherlands). Whilst, in contrast, most countries from western and central Europe (Germany, Italy, Spain, Austria, and Switzerland) use ICSI for over 75% of cases (Ferraretti et al. 2013).

A review by Palermo et al. (2015) showed that ICSI does not yield higher pregnancy rates than IVF but acts as a normalizer of fertilization, mollifying absent or low fertilization. These conclusions are supported by another study which showed that when compared with conventional IVF insemination, ICSI was not associated with improved post‐fertilization reproductive outcomes, irrespective of male factor infertility diagnosis (Boulet et al. 2015). However, some clinics prefer to reduce the risk of a failed fertilization and therefore promote frequent use of ICSI rather than IVF. This is despite the additional risks associated with the ICSI procedure.

Timing of Insemination

The timing of fertilization is based on the time when the oocytes are considered to be at their most competent level in terms of meiotic and cytoplasmic maturity. At this stage, the oocytes should be most receptive to sperm penetration and the fertilization process. Prior to collection, the oocytes mature in vivo during ovarian stimulation. When the follicles reach the desired size, an injection of human chorionic gonadotrophin (hCG) or GnRH agonist is administered to provide the final maturation ‘trigger’. The hCG injection is intended to mimic the surge of luteinizing hormone that takes place in the natural menstrual cycle. The oocyte collection takes place around 36 h after the hCG trigger. The oocytes are thought to be most competent around 4 h later.

Traditionally, the insemination time is usually based on the number of hours elapsed from the time of administration of the hCG trigger injection (hours post‐hCG), rather than the time from oocyte retrieval. If oocyte collection takes place at around 36 hours post‐hCG, then the insemination takes place at around 40 h post‐hCG.

Individual clinics may set their own variation in the standard timings, which may also need to take into account the workload of the theatre and lab (i.e. the number of cases to be dealt with, and the number of staff available to perform them). The embryology team may also need to adjust the timing of insemination due to anticipated difficulty with ICSI cases. For example, to perform ICSI on a difficult case (e.g. twenty metaphase II oocytes with very poor quality sperm derived from testicular surgery) will take longer than a simpler case (e.g. three metaphase II oocytes with good quality sperm). The start time for the former insemination may be brought forward as a result. The embryologist should keep a record of the time of insemination in the embryology notes. For ICSI, this should include the start and end time of the injection procedure.

The equipment required for conventional IVF insemination and ICSI is listed in Table 24.3.

Conventional IVF Insemination

Prior to conventional IVF insemination, the COCs should be transferred to the dishes in which the insemination will take place. The prepared sperm sample should be incubated and equilibrated to the same temperature (37 °C) and gas/pH levels of the media containing the COCs. Many laboratories use the same media for the prepared sperm sample and the COC culture to ensure there are no differences in media constituents, pH, and osmolality.

The number of sperm to be inseminated should already have been calculated, along with the required volume of the post‐preparation (see Box 24.1). These figures should be sufficient to maximize the chance of fertilization. A too high concentration risks an increased chance of polyspermy and also compromised embryo development due to the high levels of free radicals introduced with high sperm numbers. Typically, a sperm concentration of 100 × 10⁶/mL is recommended, although this can be as low as 20 × 10⁶/mL or as high as 300 × 10⁶/mL.

For the actual insemination process, a sterile tip should be fitted to a micropipette, set to the required insemination volume. The sperm sample should be removed from the incubator, and placed in a hotblock. The COC dish should be removed from the incubator and placed on a heated stage in a laminar flow hood.

In many countries, it is mandatory to perform a double identity check at the time of the insemination procedure. This involves both the embryologist and a witness checking that the oocytes and sperm belong to the same patients beyond a shadow of a doubt. The development of fail‐safe mechanisms to prevent assisted reproductive technology (ART) mix‐ups is critical (de los Santos and Ruiz 2013).

The required volume of sperm should then be taken up into the pipette tip and gently dispensed into the media containing the COCs. The insemination should be directed away from the COCs, to allow the dispensed sperm to then swim towards the oocytes. In theory, this allows the better swimming sperm to reach the oocyte first.

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