Sperm Injection: The good, the bad and the ugly.

June 15, 2010Carole 8 Comments »

Everybody is doing it. Sixty-two percent of IVF cycles performed in the US in 2006 used intra-cytoplasmic sperm injection  (ICSI).  In contrast, only 37.5% of IVF cycle were done using the “traditional IVF” method of simply adding some swimming sperm to a droplet containing one or more eggs, and letting the sperm find the egg, bind the egg and fertilize the egg. Traditionally, ICSI was invented to help men with male factor; namely men whose sperm was rare, unable to swim or unable to bind and penetrate eggs. Sperm injection could bypass all these barriers to conception by having a technician select a single good looking sperm and shoving it into the egg with a needle. ICSI, first invented in Brussels, Belgium in 1993, was and is a medical miracle for men with severe male factor who previously had zero chance to conceive children.

In 2006, half of the ICSI cases performed were done for men without male factor.  Why were these cases done?

1.To avoid the dreaded “fertilization failure”. We would do ICSI for couples who had no obvious cause of  infertility just to remove one variable. If we use ICSI, we could be sure that a sperm got into the egg. As I discussed in an earlier post, even using ICSI does not guarantee fertilization. There are other biological steps that must occur after the sperm gets into the egg in order for the egg to be fertilized. Still, nothing happens if the sperm can’t get into the egg.

2. To avoid DNA contamination from other sperm. If the IVF case was being done to generate embryos for pre-implantation genetic diagnosis and if a very sensitive  type of DNA amplification technique called polymerase chain reaction (PCR) was to be used,  we always used ICSI. With ICSI, because we are only creating embryos from one egg and one sperm, only parental DNA ends up in the test tube when the resulting embryonic cell is dissolved for the test. If many sperm are added to the egg drop, many sperm will bind to the egg and may contaminate the single embryonic cell when it is removed at embryo biopsy so traditional IVF is likely to contaminate your PCR starter DNA.

3. For other medical reasons depending on the program.  Ask your doctor about his indications for doing ICSI. Some programs like Cornell University’s program list only male factor indications for performing ICSI and propose to limit the use of ICSI because quote”  Given the relatively brief history of ICSI, and its potential effects on progeny, it would seem to be prudent to avoid over-application of this new technology. Therefore, ICSI should not be recommended to couples for whom it has no documented benefit, since unknown risk may exist” Unquote. ASRM lists other indications for ICSI here.

For couples who don’t have male factor problems, are better pregnancy outcomes achieved if ICSI is used? If you look at Fig 31. in the 2007 CDC report on pregnancy outcomes, you will notice that for couples without male factor, ICSI actually didn’t result in better outcomes. The “with ICSI” percent pregnancy (blue) bars are actually lower in every age group. The “without ICSI” group got “traditional IVF” in which sperm must find the egg in the culture drop, bind the egg and penetrate the egg on their own.

Figure 31 text below

I don’t really know why couples without male factor did worse with ICSI but I could suggest some possible reasons for the relatively inferior outcome when ICSI is used in non-male factor couples.

1. Women do the heavy lifting in achieving pregnancy. Think about it, women are responsible for egg production,  combining the genetics of gametes within the egg, embryo implantation, placentation, and embryonic/fetal growth. The men just have to bring some sperm to the party. (Sorry, guys but it’s true. Remember to hug your woman today!). So if the cause of fertility lies with the women (by definition) in these couples without male factor, we might expect that fertilization may not be the only or even the main barrier to pregnancy, so ICSI alone may not solve this problem. Conversely, if male factor is the only problem, ICSI can solve this problem pretty effectively.

2. ICSI is not completely without technical error and risks. There is a steep learning curve for techs that are learning ICSI. In the beginning, they break a lot of eggs, literally. Don’t worry, good programs don’t let their techs practice on clinical cases- they use donated non-clinical eggs or animal eggs. But egg breakage is a real risk of the procedure. Even good fully-trained techs can break eggs but it is much more rare and usually has more to do with egg membrane problems than technically proficiency. But you can expect that one of your eggs (or more) may break when this relatively brutal mechanism is used to get the sperm in the egg. Remember, evolution perfected fertilization over millions of years. ICSI has been around for only 17 years.

3. Our standards for selecting sperm are superficial- ICSI bypasses natural selection. We are picking out sperm that have no obvious defects. We can avoid the really ugly big headed guys that don’t fit in the pipette and also the multi-tailed uglies or crooked tail guys. We are looking for signs of life when we pick a sperm- even a tremble or quiver will do in a really poor sample, though we prefer good forward swimming ability. Also, pragmatically, we need to be able to catch the little bugger so we might not chase after the very fastest one. What we can not tell is which sperm is going to be able to properly decondense when it’s inside the egg so that fertilization can happen.  We can’t tell which sperm has the “good” genes either. Some critics of ICSI are concerned that ICSI completely bypasses the natural selection of sperm in nature in which the hardiest, fastest, strongest sperm got the egg. Presumably, this super fertilizing sperm will also have other good genetic traits to pass on. I don’t know if this presumption has any scientific evidence to back it up but it  makes sense.

Okay, so what about the genetic risks associated with ICSI? How safe is this technique? The American Society for Reproductive Medicine has this 2008 summary statement on it’s website.  The main points are:

1. In a multi-center trial of five year olds, kids who were conceived using ICSI had a 4.2% increased risk of a congenital abnormality. However, the study could not determine if the increased risk was due to the procedure itself or due to an underlying genetic load that patients who needed ICSI may have. More studies are needed.

2. The prevalence of sex chromosome abnormalities in children conceived with ICSI was as high as 1%. The general IVF population had a risk of 0.2%. The studies could not determine if this observed effect was due to the technique itself or due to the fact that men with male factor who needed ICSI were more likely to have genetic defects on the X and Y chromosomes in their sperm. Ironically, with ICSI, these sex chromosome abnormalities can now be passed on to the children conceived using this technique.

3. ICSI permits the inheritance of  defects on the Y-chromosome. Three to fifteen percent of men who need ICSI because of severe male factor have Y-chromosome microdeletions which are the reason they produce few or poor quality sperm. With ICSI, these men can pass on this infertility trait to their sons.

4. ICSI permits the inheritance of disease genes that are more common in men who need ICSI. One reason to do ICSI is for men who are born without a vas deferens, the duct used to carry semen out of the testis, a condition known as Congenital Bilateral Absence of the Vas Deferens or CBAVD. Men with CBAVD are at much higher risk of having the gene for cystic fibrosis (CF). If ICSI is used, men with CF genes can pass this gene on to their kids. Most fertility clinic routinely order CF testing on men with CBAVD so that they can be counseled regarding their genetic risk of using ICSI.

In spite of these concerns ASRM advises that “ICSI appears to be a safe and effective therapy for the treatment of male factor infertility.” ASRM also recommends genetic counseling for couples who appear to be at greater risk for transmission of some genetic diseases and in some cases, pre-implantation genetic diagnosis on embryos to detect genetic problems before the embryo transfer.

So the bottom line is, there is no magic bullet. The Good: ICSI is a medical breakthrough that has brought fatherhood to men who previously had no hope of every having children. The Bad: We know that ICSI can allow men with abnormal genes to pass these genes on. The Ugly: Because ICSI was introduced clinically in humans before any long term studies could be done, it is possible that there are some risks that we don’t even know about yet that may reveal themselves years from now. Unlike some European countries, we don’t mandate follow-up studies on ICSI babies here, so the data is incomplete at best.

So my take home advice is find out why your doctor wants to do ICSI. Not every case warrants it. Make sure you understand and agree with the reasons. Consider genetic testing if you fall in a high risk group. Usage of ICSI is approaching 100% in some clinics. Obviously, some of that must be practicing defensive medicine so that clinics can say “We used every tool in the tool kit to get you pregnant”. Well, everything might be too much in some cases. Be informed.

© 2010 – 2011, Carole. All rights reserved.

8 Responses to this entry

  • E Says:

    this is so interesting. My DH has a morphology of 23% (WHO standards, I think) but his other numbers are normal, and our RE has recommended ICSI for our upcoming IVF….this has given me a lot to think about!

  • E Says:

    Based on this post, I decided to let the lab decide about ICSI on the egg retrieval day based on the sperm sample.

    We didn’t need ICSI based on the sample, and out of 5 eggs harvested, the 4 mature eggs retrieved fertilized normally WITHOUT ICSI! (and now they are 4 Excellent Grade embryos waiting for our Day 5 transfer on Tuesday!)

    Thank you so much for this post- it gave me to confidence to help decide my own course of treatment.

  • Carole Says:

    Fantastic!! I am sending you warmest wishes for a BFP!!! Wishing you all the best!!

  • Anonymous Says:

    Carole,

    Thought you might be interested to see this journal article.

    http://www.andrologyjournal.org/cgi/content/abstract/31/6/566?maxtoshow=&hits=10&RESULTFORMAT=&author1=huszar&titleabstract=sperm+hyaluronan&searchid=1&FIRSTINDEX=0&fdate=1/1/2010&resourcetype=HWCIT

  • Carole Says:

    Thanks for the link. There are new sperm tests being developed which hopefully will extend the information obtained through the traditional semen analysis which is usually limited to sperm count, sperm appearance and sperm swimming ability, with no sperm function testing. The ability of sperm to bind to a hyaluronan-coated substrate has been associated with better fertilizing ability and this article also suggests hyaluronan-binding is associated with good sperm DNA integrity. These new tests are slowly moving into clinical practice.

  • Jane Says:

    This is one of the best articles talking about this subject I have read. Interestingly, we did half ICSI and half traditional and my husband had great looking sperm and had 90% fertilication with ICS and 30% naturally! The embryologist was shocked. No idea why that happened.

  • Carole Says:

    I don’t know why that happened either but the 90% fertilization rate is not unexpected for ICSI done well with good eggs. ICSI bypasses problems with sperm locomotion, sperm attachment to the egg and sperm penetration so possibly these barriers to fertilization were bypassed when ICSI was used. Sometimes we focus so much on the woman’s problem, that less obvious male issues are overlooked.

  • ICSI Says:

    […] GT Hi GT, I wrote a blog post on this topic that might help ICSI, the Good, The Bad and the Ugly Sperm Injection: The good, the bad and the ugly. | Fertility Lab Insider. Some kinds of PGD require that ICSI be used to get a clean genomic sample. ICSI avoids the […]

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