IVF Training in India: IVF v/s ICSI

IVF Training in India: IVF v/s ICSI

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Today, we shall be comparing and contrasting IVF, which is in vitro fertilization, with ICSI, ICSI or intracytoplasmic sperm injection. The first ICSI baby was presented to the world by professor Paul Devroy and professor Andre van Streatijim in 1992 in Belgium. Now in this class, we the learning objectives will be about physiology of fertilization, why there is failure, how is IVF different from natural cycle, and how is ICSI different from IVF? And finally, is there any evidence for using ICSI over IVF in non-male factor infertility?

This is a very similar slide about physiology of fertilization. On the left side, you can see the normal process of fertilization, which involves sperm transport, capacitation or sperm activation, acrosome reaction or dissolution of the zona pellucida, and on the maternal side, on the woman's side, oocyte activation, which involves the calcium channels, and finally, phosphorylation. So all these things need to happen during the fertilization of the sperm with the oocyte. The capacitation and acrosome reaction occurs in the natural fertilization. The penetration of cumulus oophorus and zona pellucida. The zed p three glycoprotein requires activation of signaling pathways, and this is known as capacitation. In turn, capacitation is necessary for acrosome reaction. So these steps imply further selective pressure on the sperms. So it follows that those sperms that lack the signaling mechanisms cannot or do not reach the oocyte in natural fertilization. Again, it is the selection of the fittest in the sense those sperms that are capable of having these signaling mechanisms are the ones that reach the oocyte.

Now for oocyte activation, there should be this calcium channel activation, which is a very complex process, and that gets initiated by the sperm entry. And that time, it is necessary to seal the zona pellucida from other sperms. So with the entry of the selected sperm, all other sperms are prevented from entering into the oocyte. And this also is a signal for removing the arrest of meiosis that has occurred in the, oocyte. So the the meiosis is resumed when at the time of fertilization. Now natural and manual sperm selection. In natural selection, the sperm with the signaling power is selected, and we presume that it is a sperm with normal genetics. In ICSI, a normal looking sperm is without signaling power is selected, but we are still not sure about the normal genetics. So here, we are playing god. In the sense, we are selecting the sperm. Whereas in natural selection, it is those sperms are selected naturally because they have the signaling power and probably good, genetic makeup. But in ICSI, we are not sure about the genetic makeup. Then if we compare the normal conception to IVF, in normal conception, obviously, the sperms should pass through the cervical mucus, and only actively moving sperms can reach the oocyte. Of course, both these factors are not there in IVF because the fertilization is done in vitro. So the slower sperms are near the oocyte in the IVF, which we can expect.

There have been several studies, randomized consoles-controlled studies and meta-analysis, and ICSI has been proved to be a more efficient technique in terms of fertilization, but not in terms of outcome when we compare it with IVF, especially in patients with non-male factor infertility. This is very important because we have con, we have taken cases with non-male factor infertility. The outcomes may be the same, but it's an efficient technique for fertilization. Apart from that, there's not much of a change when there is a non-male factor infertility. The Canadian data also says similar, that IVF and ICSI have similar outcomes.

Conventional IVF versus ICSI in patients with borderline semen. So this is where the importance of ICSI comes in whenever there is a male factor infertility. When you see the results, there is no difference in pregnancy rates, but twenty five percent of the cycles got rescued by ICSI. Now the zona pellucida acrosome reaction failure, the fertilization failure due to this zona pellucida acrosome reaction has been cited as one of the causes in failed fertilization in unexplained infertility. So twenty nine percent of the patients with unexplained infertility with a normal semen analysis may have this disorder. So it is argued that ICSI should be offered in such cases of unexplained infertility, and patients are likely to benefit. However, doing ICSI in non male factor infertility is there is no clear evidence of improved outcome with ICSI, and this has been well demonstrated if there is a non male factor in fertility. What about isolated teratosispermia? Do we do ICSI in these cases? No.

There is no advantage of ICSI over conventional IVF in women over 40 years of age. Therefore, ICSI may not be for all patients. It does not increase the cumulative live birth rates in non male factor infertility. That's what all these slides are telling us. Even The Lancet in 2021 comparing intracytoplasmic sperm injection versus conventional IVF in couples with infertility in whom the male partner had normal total sperm count and motility showed that there was no increase in the live birth rate and no difference in the fertilization failure. Half ICSI. ICSI may not improve clinical outcomes despite its positive effect on the embryo results. There are certain ongoing, randomized controlled trials about, IVF versus ICSI in patients without severe male factor infertility. Now, with, in severe male factor infertility, these studies are going on, about whether ICSI is better than IVF. Another one, the about, the comparison of IVF and ICSI when it comes to live birth rates and neonatal outcome is also an ongoing study since twenty nineteen September.

Epidemiologic studies have also reported association between ART and imprinting disorders, especially Beckwith Wiedemann syndrome. But these disorders may be basically related to an underlying infertility diagnosis. Then the reproductive health of these ICSI children, onset of puberty and pubertal development is similar between ICSI and naturally conceived boys and girls. However, breast developments may be lesser in ICSI conceived girls. ICSI conceived men may have lower sperm concentration, total sperm count, and total motile sperm count when compared to age matched naturally conceived PS. Ovarian reserve parameters including atrial follicle count, anti mularian hormone levels, and follicular stimulating hormone levels are similar between women conceived naturally or via ICSI. However, the worrisome trend globally is using ICSI for non-male factor infertility. There's a constant increase in the number of ICSI over night over a period of many years starting from 1993 up to 2019. Finally, to conclude, what are the strength of ICSI? Increases the fertilization rate and decreases fertilization failure in patients with unexplained infertility.

No evidence of cost benefit definitely, and there is a lack of specific randomized studies. The opportunity is for selection of oocytes and the technical improvement that is InC and PyXI, artificial oocyte activation, and genome editing. These are the opportunities that ICSI can offer us. The perceived threat of ICSI could be indiscriminate application of the technique despite evidence showing that there is no benefit in non-male factor infertility. And ICSI may be overused during pre-implantation genetic diagnosis. And there is a possible long-term effect of ICSI on children, whether it is infants and adults.

Finally, the take home messages are that there should be a careful choice of patients for ITC in spite of expertise and affordability. So just because we have the facility, we have the expert, it does not mean that ICSI should be performed for all patients. Management of fertilization failure can be done with risky. However, using ICSI correctly awaits, results of ongoing RCTs. The patients must be counselled regarding the safety. All the available evidences, about the risks and benefits should be offered to the patient, and the patient should be counselled regarding transmission of father's genetic profile. Finally, more long-term follow-up of ICSI children, especially regarding development and fertility is very much essential.

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