Thursday, October 7, 2010

Genetic Defect In Husband's Sperm Leading To IVF Failure: Screening With CGH Recommended

(If the blog radio program turns on, go to the Oct. 1st blog post and pause it...I will be keeping the show up for the month of October.)


Dear Dr. Ramirez,

My husband and I have been infertile for two years. The second year, we began IVF. We have completed 3 IVF rounds. The first was not successful. The second resulted in a chemical pregnancy / early miscarriage at 6 weeks. The third resulted in an ectopic pregnancy. My husband and I are both in good health, with no known infertility factors (endometriosis, etc.). We do not have antisperm antibodies. All our bloodwork was good. On our second IVF round, 1/2 of the eggs were fertilized by standard IVF and none of them merged. 1/2 of the eggs were fertilized by ICSI and did very well. On our third IVF round, all the eggs were fertilized with ICSI and did very well. We have 9 frozen embryos waiting.

After this ectopic pregnancy, we had genetic testing done. Mine were normal. My husband's were abnormal. The interpretation was:

"A male karyotype with a small supernumeray bisatellited marker chromosome was noted in all metaphases analyzed. The majority of bisattellited markers are derived from an inversion duplication of the pericentromeric area of chromosome 15. Apparently this market carries minimal with no phenotypic significance to the patient; however it may lead to decreased fertility, repeated pregnancy loss, or chromosomally abnormal offsrping. Parental follow up chormosome studies are recommended to determine if the marker is familiar or de novo in origin, and to further evaluete its clinical significance. De novo markers are associated with an increased risk for phenotypic abnormalities. Genetic counseling is recommended."

We are going to receive genetic counseling in the future, but what is your opinion about this chromosome 15 abnormality and its effect on conception and offspring? Thanks! A. from the U.S.


Hello A. from the U.S.,

Unfortunately I am not a geneticist and will usually go by what the geneticists advise me in terms of the consequences of chromosomal abnormalities.

However, in general, this is what it means to me. Your husband is carrying a genetic abnormality that is "recessive" in nature, meaning that it does not necessarily present itself as an abnormality. Because his sperm can contain this trait, it is possible that this can result in abnormal embryos, which will lead to early embryo death (and lack of implantation) or an early miscarriage. The ectopic pregnancy you had was for a different reason and does not need to be considered in this discussion.

What I would recommend is that the embryos be tested by the relatively new CGH (Array Comparative Genomic Hybridisation) process or PGS (Preimplantation Genetic Screening) prior to transfer. Last year, in England, a 41 yr. old woman who had failed IVF 13 times had her embryos tested with CGH and in September delivered a healthy baby (see article here). If your embryos are D#3 embryos, they should be thawed, and biopsied for genetic testing done by CGH. They would then be cultured to blastocyst and transferred at that time. If they are already blastocysts, then they would need to be thawed, biopsied then frozen again for a later transfer. In any future IVF cycles, the embryos should be similarly tested to look for the normals so that the abnormal embryos are not transferred leading to a negative pregnancy, miscarriage and further disappointment.

Not knowing how the genetic transference of this abnormality is done i.e. does it occur every time with every embryo, or is there a chance that some embryos will not have the disorder? it is hard for me to give any more specific recommendations. Once you have your genetic counseling, they will be able to answer these questions for you, which will help to determine a more specific strategy.

Good Luck,

Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
Monterey, California, U.S.

Comment: Thank you. You are an angel for helping with this guidance.


  1. Hello,
    I am a genetic counselor and your question caught my eye. I'm glad to hear you are going to see a GC, as this is a complicated topic. I personally do not believe that CGH will help you with a satellite marker and pericentric inversion, but I would need to see the complete genetic test report to confirm that. Your GC will ask for that, so be sure to bring it. To answer your question, yes, this could certainly be the reason for your fertility problems. It could also be a risk factor for chromosomal defects in offspring, but again, more information is needed to be able to give you any risk estimates. I would ask your fertility center or your GC to discuss this result with a PGD lab (prenatal genetic diagnosis) to see whether there is any testing which can be done on the 9 embryos to look for defects related to those findings. One such lab who does custom work like this is Gene Security Network in Redwood City, CA.(I do not work for them, I just know of their good reputation. I once interned there and I respect their work.)

    I would not call this condition recessive, as it's not a condition which requires both parents to carry a genetic trait. Instead, it affects the process of meiosis when sperm are created, causing the resulting sperm to potentially have an incorrect chromosome complement, or extra or missing pieces of chromsomes. When one parent passes something like this along to a fetus, the fetus can be affected, even though the other parent's chromosomes are normal.

    Not all sperm would necessarily be affected; since he has two copies of c15, that should mean that approx 50% of the sperm would be affected. Once the genetic details are known, it can be better predicted how often conception may be affected, and how often an affected pregnancy will proceed or abort.

    So, go see the GC and get the ball rolling on a discussion with a PGD lab. Best wishes to you and your husband!

  2. Dear DCD,

    See this is the great thing about the internet and blogs. You can get the specialty opinions that are wanted and/or needed. Thank you for your input. Not being an expert in genetics (as I mentioned in the first line of my reply to this question), I urged counseling by a geneticist and here you are.

    Just to clarify, CGH is a testing method and PGD or PGS is the overall name for testing prior to embryo transfer. CGH, being the new technique, allows for a wider array of testing than standard PGD by FISH technique, where specific chromosomes have to be looked for. There is also a new microarray CGH technique as well. Again, I am not an expert in the specific testing method, that would be an embryologist or cellular biologist, but that is my understanding. I currently have a patient that has an unusual form of muscular dystrophy gene. She will undergo PGD by CGH looking for this specific gene type in her embryos. The above patient will probably benefit from such a testing method as well. The lab that I use is called Reprogenetics (and I do not belong to that lab either)that was one of the very first PGD labs started by Santiago Munne and Jacques Cohen. There are others in the country as well.

    Also, just to clarify, the term "recessive" that I used in the answer was as a lay term and not the medical/genetic term. I used it to mean that there was incomplete penetrance i.e that it was not 100% transmitable, as you have described, so I appologize for the confusion for those that have a medical background and understand medical terminology.

    Again, thanks for the great input.



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