PCRS Highlights - 2014
One of the meetings some of the doctors and staff at PFC regularly attend is the Pacific Coast Reproductive Society (PCRS) annual meeting which is typically held in Palm Springs in the spring. This year, our attending team included myself, Dr. Philip Chenette, Dr. Jean Popwell and Carmela Thompson, genetic counselor.
One of the most interesting talks was given by Julian Martinez-Agosto, MD, a medical geneticist at UCLA School of Medicine in the Department of Human Genetics. His talk was entitled "Genetic and Parental Risk Factors in Autism." First, he defined autism as a spectrum of disorders "characterized by difficulties in social interaction, verbal and non-verbal communication and repetitive behaviors" that can be associated with intellectual disability and motor coordination. A Centers for Disease Control (CDC) survey has reported that 1 in 50 children (2%) aged 6-17 appear to fit the characteristics of Autism Spectrum Disorder (ASD). Boys have a 4-fold increased risk as compared to girls. There is also considerable overlap between ASD and schizophrenia and epilepsy (seizure disorders).
Autism may be a one symptom of a genetic condition. One fairly common genetic disorder that is associated with autism is Fragile X syndrome, which involves repetitive duplication of a small sequence of DNA found on the X chromosome. Since males only have one X chromosome, the full-blown syndrome is only seen in boys. Advances in understanding the genetic basis of many syndromes that include autism as a symptom indicate that very small deletions and duplications of DNA may cause a small percentage of cases of autism.
Twenty-five to 40 per cent of autism cases are due to known medical conditions involving chromosome imbalances or genetic disorders. Some cases are associated with fetal exposures including maternal exposure to the anti-seizure medication valproic acid during pregnancy or maternal Rubella (German measles) infection during pregnancy. The percentage of cases of autism explained by specific gene mutations appears to be increasing as we increase the number of people that can have their entire genome sequenced.
New data also demonstrates that both increased maternal and paternal age are associated with an increased risk of ASD, but special interest has focused on paternal age. Children of men 40 years of age or older are 6 times more likely to have ASD as compared with children of men younger than 30 years of age. Because fertility patients tend to be older than parents that do not have fertility problems, we must be aware that risks of autism will be higher in the infertile population.
Another talk I found interesting was about one of the scientific papers presented at the meeting, which was the presentation of a survey of sperm donors in Canada. This study was entitled "Barriers to Sperm Donor Recruitment in Canada: Donor Disclosure" and was presented by Lucky Sekhon, MD, a 3rd year ob/gyn resident at Mount Sinai School of Medicine. As background, Dr. Sekhon presented the fact that ever since Canada passed the Assisted Human Reproduction Act in 2004, it has been illegal in Canada to financially compensate sperm donors. The only anonymous donors are donating for altruistic reasons. Consequently, there is only one sperm bank in the entire country and that sperm bank currently has only 51 donors! Ninety per cent of sperm used for insemination in Canada is imported, primarily from the U.S. Currently, there is legislation being considered to make it mandatory that sperm donors will no longer be anonymous. That is, in order to donate sperm, the donor must be willing to be identified to the future children. The current study attempted to survey the active Canadian sperm donors about their willingness to donate if it no longer becomes anonymous. The authors were able to survey only 12 of the donors but 7 of the 12 indicated they would no longer donate sperm if required to provide their identity to the offspring at age 18.
This small study brought up several interesting issues regarding both anonymous sperm donation and government regulation of reproductive choices. Mandatory donor ID disclosure is the law in several European countries as well as Australia and New Zealand and where applicable, sperm donation really doesn't exist. There are those that believe that all offspring have the right to know who their biologic parents are. Others believe that regulations and restrictions are burdens that will seriously restrict the practice of reproductive medicine and will only serve to harm the interests and needs of infertile patients and, in this case, also single and lesbian women seeking sperm donors. What do you think of this?
The last topic I found most interesting to discuss was a paper presented concerning attempts to biopsy blastocyst stage embryos for genetic testing. Current practice, including the usual practice at PFC, is to remove 3-4 cells from the day 5 embryo (blastocyst) in IVF cases in which we wish to know the chromosomal make-up of the embryo – what we call Comprehensive Chromosomal Screening, or CCS. The cells are typically removed from the outer ring of cells called the "trophectoderm," which are the future placental cells of the embryo. The cells of the "inner cell mass" are avoided, as these cells make up the future embryo itself. Inside the blastocyst, which is essentially a sphere, surrounding the inner cell mass is a fluid-filled cavity called the "blastocoel cavity." This paper was entitled "Comparative Genomic Hybridization Microarray (aCGH) Analysis of DNA isolated from the Blastocoel Fluid from 26 Blastocysts" and was presented by Dr. Kyle Tobler from Johns Hopkins University School of Medicine. The authors wanted to know if they could isolate DNA from this fluid and avoid removing any trophectoderm cells at all. What they found when they performed this technique on 26 donated blastocysts was that the fluid did not appear to contain free floating DNA but did contain small floating cells that were derived from the early embryo.
Analysis of the DNA from these floating cells revealed that the chromosome complement from these cells was abnormal in 77% of the samples, even if the embryo itself was normal. One possible explanation for this is that the early embryo excludes these abnormal cells from the growing embryo if most of the embryo is normal and only a few early cells are abnormal. Unfortunately, this study shows that blastocoel fluid is not going to be an alternative reliable DNA source for biopsy when we want to know the genetic make-up of the embryo, but it does provide an explanation as to why some embryos are able to correct their genetic status between the 8-cell stage and blastocyst stage.
Overall, this was a very good meeting. Most of the talks confirmed for me that PFC is on the leading edge of the implementation of appropriate and medically advantageous technologies. Our excellent laboratory scientists are truly leaders when it comes to bringing the best technology to our patients to achieve healthy pregnancies and babies.
- Carolyn Givens, M.D.