Androlog of the Fertility and Sterility Dialog

Isodicentric Y Chromosome

Started almost 3 years ago

I have a male with an isodicentric Y chromosome.  He is rare from what I can read, in that he is phenotypically male and has sperm in his ejaculate in the severe oligospermia range.  His blood karyotype shows his Y chromosome has 2 centromeres, 2 SRY regions, and duplication of the AZF regions.  I assume his gonadal karyotype must be similar and stable, given his male phenotype, descended testicles, and impaired but functional sperm production.

He presented to us after multiple failed cycles overseas and we ordered the karyotype.  The question is, with PGT, would you transfer a male embryo?  In theory, the best case scenario would be his same Y chromosome.  But you would think due to the instability of duplicated centromeres, there would be a significant risk of mosacisim in the inner cell mass and gonadal cells, that could result in loss of some or all of the Y function, leading to either sex reversal or Turner syndrome in most of his male embryos.  Given the high risk of instability, a trophectoderm biopsy wouldn't be guaranteed to reflect the ICM and even knowning the ICM wouldn't guarantee the future gonadal cell line would not become mosaic.  So if he wanted a male offspring and you had PGT result that confirmed his same Y chromosome in the trophectoderm, would you allow transfer of that embryo?  Or would you only allow transfer of XX embryos? Anything else Im missing in thinking through this?  Im having a hard time finding a case report of anyone with isodicentric Y with adequate sperm production for use with ICSI.

The best study on isodicentric Y chromosome is by Lange in 2009 - Outcomes with transfer of embryo with the Y chromosome elements is unpredictable - therefore would prefer transfer of only XX embryos to be safe. 

Interesting patient and question, Micah.  The article Ranjith pointed to looks good for this couple, and I agree that transferring and XX embryo would have the lowest risk of aneuploidy or other chromosomal abnormalities for their offspring.  That being said, if they are set on having a male offspring, then I think doing PGT would offer them some some reassurance, but as you said, they couldn't be certain that the ICM has the same chromosomal make up.  I tend to approach situations like this with a lot of counseling, having them see a genetic counselor, and then helping them make a choice and understand the implications of that choice.  But, it does seem that an XX embryo would be safest.