Since the first recorded use of frozen sperm for
insemination in 1953, the breakthroughs in fertility had been mostly confined to treatments for female
infertility. However, in the last decade, a technique known as Intra-cytoplasmic sperm injection
– ICSI for short – has transformed treatment for male infertility so much so that there are
almost no men who are completely unable to father children.
The first use of ICSI in humans was announced in 1992 – since then, ICSI has completely
revolutionized male infertility treatment , yet it is not without its risks and
shortcomings. It raises serious moral concerns surrounding our genetics, biology, and even
fatherhood. Furthermore, it does not fully address the needs of pre-pubertal patients who are in
need of fertility preservation options. To better understand these concerns, it is important to
understand the difference between conventional In-vitro fertilization (IVF) and IVF with ICSI.
In-vitro fertilization , which translates to “in-glass” fertilization, occurs in
much the same way natural conception does. Eggs are mixed with millions of sperm in a
carefully controlled vessel, and the sperm flood around the egg until one of them penetrates its
protective barrier , locking all the other sperm out. Just as in natural conception,
this requires a very high sperm-to-egg ratio, and therefore this option will not
help males with moderate to severe infertility to conceive.
Efforts to reduce the sperm-to-egg ratio needed for IVF led to the development of ICSI – in contrast
to conventional IVF, ICSI only needs a sperm-to-egg ratio of 1-to-1 . The process
begins in the same way as conventional IVF; eggs are collected from the woman by hyper-stimulating
her ovaries, and a sperm sample is collected through ejaculate or testicular sperm extraction (TESE
– a method of sperm extraction directly from the testicles) for more severe cases. However, once
these samples have been collected, instead of mixing them together, a single sperm is
selected for implantation into the egg. This sperm is drawn up into an extremely thin
pipette which is then pushed through the egg’s outer wall, allowing the sperm to be released into
the center of the egg, where it should hopefully achieve fertilization.
By reducing the number of sperm needed to fertilize an egg to just one (although in practicality more
than one sperm cell is required, just not millions), a vast number of men who were previously unable
to father children – including those due to genetic causes – now have the option to. This represents
a huge leap forward for the field of fertility, but it comes at a cost.
The use of ICSI has been well established in a variety
of conditions, such as vasectomy, cancers, or injury – all conditions that have no documented effects on
the future health of the offspring. Its efficacy has led to it gaining ground over conventional IVF – an
increasing number of IVF cycles now utilize ICSI even in cases where male infertility is not thought to
be significant factor, as it raises the overall success rate of IVF cycles. However, the use of
ICSI for persistent, natural causes of infertility can be a cause of concern. Although many
of the specific causes of severe male infertility remain unknown, it is estimated that almost
50% of cases may be due to contributing genetic factors , and there are over 30 known
genetic diseases that will cause infertility in men.
Throughout history, men afflicted by such diseases were faced with the tragic realization that they
would never father children of their own, yet their infertility also created a barrier to the
hereditary transmission of such illnesses. With the advent of ICSI, most of these men are now
capable of fathering children – and many are choosing to do so. The main concern of these men is the
chance of passing their condition to their offspring. Technologies such as pre-implantation
genetic screening (PGD) allow the selection of embryos that do not carry the problematic
gene. However, the technology is limited, as its application depends on the nature of
the particular genetic condition. For conditions caused by a single dominant gene, it is relatively
easy to screen and eliminate the embryos with the malfunctioning gene. For conditions caused by a
pair of recessive genes – such as in the case of cystic fibrosis – affected fathers will inevitably
pass one of the genes to their child. Said child must be vigilant as to whether their partners may
be carriers as well when they seek to have children of their own.
Furthermore, there are many heritable genetic defects that do not carry the same severe consequences
to overall health yet will cause severe refractory infertility. One of the most common, a microdeletion
in the azoospermia factor (AZF) region – specifically region AZFc– causes severe
infertility , yet TESE may yield enough sperm to pursue ICSI. Many men diagnosed with
AZFc choose to have children through ICSI, and unavoidably pass on the mutation to their offspring,
thus too becoming infertile. AZF deletions are relatively common in cases of severe male
infertility, and thus clinics will often screen severely infertile patients for the genetic defect.
Those found to have the defect are presented the choice of continuing with ICSI with full knowledge
of the consequences, yet one study found that almost four-fifths of prospective parents
decided to pursue ICSI regardless.
The moral consequences of such decisions cannot be taken lightly. Men with diseases such as cystic
fibrosis (or other deadly genetic illnesses) who choose to have children must also consider the
impact of their likely early death on their prospective children, as most of these men do not live
to see past 40. Children with inherited AZFc microdeletions will experience their infertility as an
established fact, and parents of such children will face hard decisions on how and when to tell
them. Furthermore, the cumulative societal effect of conceiving infertile children through
ICSI may become problematic. A study in the reputable journal Nature Genetics estimated
that, if 90% of men that are infertile due to genetic causes fathered children through ICSI, the
rate of male infertility due to a genetic basis could increase to 6.7% of all men in 10 generations.
Due to barriers in accessibility and cost, this dire situation is unlikely, yet still
illuminates a probable trend as assisted-reproduction technologies such as ICSI become
more ubiquitous in society.
Without a doubt, ICSI has been an incredibly helpful tool that has allowed many hopeful parents to
fulfill their dreams and conceive a child of their own. Almost always, children born through
ICSI are healthy and live normal lives. Nonetheless, many couples may be faced with
tough decisions about the degree of control they will have over their children’s genetic
characteristics and their willingness to expose their offspring to potentially risky conditions.