January Newsletter
Monthly Round up of interesting articles, webinars, and the release of the latest edition of The Reproductive Genetics Guidebook
It’s a new year, so a time to try a new platform for newsletters. Previous subscribers were automatically exported to the platform. Hope it feels easier to read but let me know your thoughts! :)
Lil Lit Review:
There is ongoing discussion regarding the impact of trophectoderm biopsies on embryos' reproductive potential. A recent retrospective review found a reduced risk of prematurity and low birth weight among infants born after biopsies for PGT. However, women in the biopsy group were older and had higher rates of prior pregnancies, spontaneous abortions, and risk factors like tobacco use and diminished ovarian reserve, which could suggest an opposite association.
While the physical impact of biopsies is crucial to study, the psychological effects also warrant attention. Do patients with tested embryos and known chromosome status approach transfers with greater confidence and less stress than those who don’t?
Love a good outcome study - from 2016-2023, this group tracked the cell-free DNA results of a cohort of patients that had “euploid” PGT-A results and those that had untested embryos. There were 13/1,204 of the PGT-A group that received positive cell-free DNA results for T21 (2), X0 (2), XXX (4), XYY (1), indeterminate sex (1), 22q11 del/dup (2), and 15q11.2del (1). Only one 22q11 dup was confirmed with amniocentesis. 27/1769 of the non-tested group had positive cfDNA results, of which 8 were confirmed with diagnostic tests. The study helps remind us both PGT-A and cfDNA screening are not diagnostic, so they can have conflicting results. It’s important to realize the limitations of the PGT-A test (and cfDNA) to adequately inform patients. For one, PGT-A has thresholds for its ability to detect deletions and duplication, usually 5-10Mb in size. Secondly, low levels of mosaicism would not be detected with PGT-A, such as <20-30%. I remember a case where mosaic T21 was confirmed for a pregnancy. The level of mosaicism was below the PGT-A threshold thus never expected to have been detected in the first place.
Updated 2023 guideline from ACMG to add to your Phenylalanine hydroxylate deficiency folder.
2024 Committee opinion from ASRM on the use of PGT-A.
Emerging Technology:
Testing of products of conception after a pregnancy loss is not yet a routine test order, but there are many reasons to consider providing this option to patients. Of greatest value is closure. 50-60% of pregnancy loss is due to chromosomal abnormalities. Instead of providing the statistic, POC testing allows for the ability to confirm whether the diagnosis applies or not. If not, it opens the door for additional assessment.
While testing of the POC is preferred, one company is instead offering cell-free DNA screening with the purpose of detecting the cause of a loss. The test appears to be international, but it opens the discussion of what kinds of assessments should we be offering our patients in these moments and what works best for the logistics of our clinics?
A good initial use case may be missed miscarriages diagnosed via ultrasound when the embryo is not developing/lacks a heartbeat. More specifically, this applies to those who choose expectant management (allowing the body to miscarry spontaneously) or medication to induce miscarriage. Patients who undergo a D&C have the advantage of provider-assisted sample collection, whereas those selecting the other two options may need to manage collection themselves.
Genetic Snapshot:
22q duplication syndrome
Don’t confuse it for 22q deletion syndrome! When googling, the deletion syndrome often prevails, so pay close attention.
I like starting with a quick review of the condition with resources like MedLine Plus and a Support Organization Website. In this case, Rare Chromo is an excellent place to go.
Next, I look more thoroughly at resources like OMIM and Gene Reviews. I like throwing in a few articles on the condition as well and searching specific prenatal considerations.
In short, 22q11.2 duplication syndrome occurs when a small segment (typically 1-6Mb) of the q arm of chromosome 22 is duplicated. It is considered a microduplication and is unlikely to be detected by screening tools like PGT-A or cfDNA screening due to their size detection thresholds. Diagnosis typically requires chromosomal microarray analysis, either through prenatal diagnosis (CVS/amniocentesis) or after birth. The features of this condition vary widely - some individuals experience developmental delays, intellectual disability, short stature, and hypotonia, while others have no noticeable differences. The duplication is often inherited, so if a pregnancy or child is diagnosed, parental testing may be beneficial. If a parent is confirmed to also have the microduplication, then subsequent pregnancies/children have a 50% to inherit it.
Webinars:
Sperm Donation Without Borders: Ethical, Legal, and Social Issues in a Global Industry (recorded)
Prenatal Sponsored Webinar: PGT: Instagram vs. Reality – What Every Genetic Counselor Should Know. Reach out for the link :)
The Reproductive Genetics Guidebook
A “genetic counselor in your pocket” - as a practicing prenatal and PGT genetic counselor, I use this guidebook frequently to quickly look up the ideal resources for my patients as well as educational aids. It’s intended for healthcare providers in the reproductive space, to quickly understand common genetic indications and results. For example - the limitations of PGT-A and cfDNA screening.
Check it out and empower yourself to provide the best care for your patients or share it with someone you think would appreciate additional guidance in the space.
