P0050PRE-IMPLANTATION GENETIC TESTING FOR MONOGENIC KIDNEY DISEASE: TWENTY-FIVE YEAR EXPERIENCE IN THE NETHERLANDS
Authors: Snoek R , Stokman Marijn F , Lichtenbelt Klaske D , Simcox Cindy E , Van Tilborg Theodora C , Paulussen Aimee D C , Dreessen Jos C M F , Van Reekum Franka , Knoers Nine , De Die-Smulders Christine , Van Eerde Albertien M 
Published: June 2020

Background and Aims

Due to the fast-paced developments in human genetics, a genetic cause can now be identified for an increasing number of pediatric and adult-onset kidney diseases. A monogenic kidney disease (MKD) can impact prognostication and therapy decisions. It also provides patients with options regarding family planning such as preimplantation genetic testing (PGT), a reproductive technology that helps prospective parents prevent passing on a disease-causing mutation to their offspring.

There are limited reports on PGT for MKD and most are focused on severe pediatric-onset diseases. The Dutch system of insurance reimbursement and nationwide regulation is unique, and it has allowed the Netherlands to be one of a handful of countries where couples have the option to choose PGT for MKD, including adult-onset forms of kidney disease. Here we provide the 25-year Dutch experience with PGT for MKD.

Method

We performed a retrospective cohort study of all couples counselled on PGT for MKD in the Maastricht University Medical Center+, the expert centre where all Dutch single cell genetic testing on embryos is performed, from January 1995 until June 2019.

Results

99 couples were counseled for PGT, of which currently 15% is waiting for the genetic test to be validated. In the early years of PGT for MKD, referrals were incidental and only for couples at risk for offspring with paediatric-onset disease. From 2009 onwards, the number of referrals has steadily increased as has the number of couples referred for adult-onset MKD. Overall, the most frequent indications for referral for PGT were ADPKD (37%), X-linked Alport syndrome (25%) and ARPKD (9%).

After counselling, 36% of n=99 couples started PGT treatment. In total n=80 cycles with oocyte retrieval were performed (median 2 cycles [range 1-4]). These cycles led to a median of n=10 embryos (range 2-31) suitable for biopsy and a median of n=3 embryos (range 1-14) being genetically unaffected. Seventy-five percent (n=) of couples achieved at least one live birth.

Of n=99, 48% did not proceed with PGT, for various personal and technical reasons. Major reasons for opting out of PGT were that prospective parents did not want to wait for the lengthy PGT procedure (9%) or had a wish for natural conception with prenatal genetic testing (11%). Live birth rate was 40% (n=19) in the non-PGT group, with notably a similar duration to a live birth as the PGT group (2 years, range 0-5 years).

Conclusion

We provide the largest overview to date of the indications, uptake and results of PGT for MKD. Referrals for PGT, including adult-onset disease, have increased steadily over the past decade. PGT has favorable outcomes, with 75% of couples having at least one live birth, though this is likely due to our small sample size. Genetic and reproductive counseling, including information on PGT, should be provided to all patients and prospective parents from families with MKD to enable informed decision making.