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.)

Question:

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.

Answer:

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

http://www.montereybayivf.com/

Monterey, California, U.S.

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