#2259 Preimplantation genetic testing in inherited kidney diseases
Authors: Furlano Monica , Tinoco Adria , Sampani Erasmia , Almeida Catarina , Gonçalves Pedro Lisboa , Polo Ana , Martínez Olga , Teran Melissa Pilco , Ramírez Elizabeth Romelia Viera , Ars Elisabet , Torra Roser 
Published: May 2024

Background and Aims

Identifying the underlying genetic cause in individuals with monogenic kidney disease allow counselling to provide prognosis and therapeutic options. In addition, discussions may extend to assessing the risk of having affected children and exploring family planning alternatives. Pre-conception counselling covers a wide range of considerations, including the expected pregnancy outcome for both mother and child, the risk of recurrence, invasive prenatal diagnosis, and the option of pre-implantation genetic testing (PGT). In this study we provide a clinical overview of PGT for monogenic kidney disease in our centre.

Methods

This is a retrospective cohort study of individuals with monogenic kidney disease counselled on our fertility clinic for PGT, in the Fundació Puigvert—Hospital de Sant Pau, Barcelona-Spain from January 2016 to 2023.

Results

During the study period, 751 visits were made to the fertility clinic, of which 8.3% (63/751) had a monogenic inherited kidney disease (IKD).

Regarding the baseline characteristics of individuals with monogenic conditions, most were females (70%; 44/63). The mean age of the women was 33 years, most had no history of pregnancy prior to the first visit (73%). The mean anti-Mullerian hormone (AMH) level was 2.67 ng/ml, with 22% having levels below 1.1 ng/ml.

Most cases (84%; 53/63) showed an autosomal dominant pattern of inheritance, with autosomal dominant polycystic kidney disease (ADPKD) being the primary cause in 66% of cases (42/63), followed by tuberous sclerosis complex in 8% (5/63). Autosomal recessive and X-linked disorders were each present in 8% (5/63). Table 1 shows the complete list of genetic kidney disease cases that consulted the fertility clinic.

In terms of renal function, affected women had a mean renal function measured by estimated glomerular filtration rate (eGFR) of 90 mil/min/1.73 m2, with 74% having chronic kidney disease (CKD) category G1. Affected male had mean eGFR of 65 mL/min/1.73 m2, with only 38% (6/19 patients) having CKD-G1. Two (13%; 2/19) of the affected men had received a kidney transplant.

Of the 63 couples who were counseled, 51% (32/63) agreed to proceed with PGT; 81% (26/32) underwent at least one cycle of ovarian stimulation, in vitro fertilization, and PGT. Fifty per cent (13/26) had a live birth child and 19% (5/26) are currently pregnant. Six couples (10%; 6/32) have pending tests.

Among patients who decided not to proceed with PGT (31/63), the main reason for not doing so was that they had a spontaneous pregnancy before the first PGT cycle (35%; 11/31). Low ovarian reserve and couple´s refusal to proceed with PGT were the second most common reasons, each accounting for 22.5% of cases.

In 10% (3/31) of cases, the indication for PGT was not yet approved in Spain (mainly because these patients already had a healthy living child). Maternal age over 40 years and the age of the prospective father were the reasons for not performing PGT in 6% and 3% respectively.

Of note, a patient with ADPKD presented with a ruptured hepatic cyst after ovarian hormone stimulation. Therefore, PGT was discontinued after two cycles.

Conclusion

Women with IKD are most likely to request PGT than affected males. The most frequent condition is, by far, ADPKD. Once the technique is explained less than 50% of couples keep wishing to undergo PGT. Low ovarian reserve (which correlates quite well with age) is an important reason that impedes to go through PGT.

Larger international studies are needed to understand the patient's uptake of PGT for IKD as well as the access to this technique depending on the country.