Clinical evaluation of IVF with PGD for BRCA1/2 mutations

Female carriers of a mutation in the BRCA1 of BRCA2 gene are at increased risk of breast and ovarian cancer. Hereditary breast and ovarian cancer is one of the most prevalent indications for PGD in the Netherlands. The decision whether or not to opt for PGD is difficult to make for many couples with the genetic predisposition for breast- and ovarian cancer. For female carriers, the safety of the IVF treatment involved in PGD is an important issue. The purpose of ovarian stimulation and subsequent IVF is to obtain a surplus of embryos, since half of them will not be transferrable due to the presence of the BRCA mutation. A sufficient ovarian reserve is a prerequisite to do so. A diminished ovarian reserve in BRCA mutation carriers might therefore affect success chances in IVF/PGD.

thesis Inge Derks-SmeetsThese questions are addressed in the PhD research of Inge Derks-Smeets. She succesfully defended her thesis ‘Clinical evaluation of preimplantation genetic diagnosis for BRCA1/2 mutations’ on the 17th of January 2018 in Maastricht University. The Dutch Cancer Society and Stichting Pink Ribbon supported her studies financially.

The chance of pregnancy is equal for women with a mutation in the BRCA1/2 gene when compared to women who opt for PGD because of another genetic predisposition. No evidence is found for a reduced ovarian reserve affecting the success chances in IVF/PGD in women with a BRCA1/2 mutation. Additionally, no increased risk for breast cancer is found after exposure to IVF in BRCA1/2 mutation carriers.

When studying reproductive decision-making, it is obvious that couples with a BRCA1/2 mutation take many advantages and disadvantages into account when deciding on PGD. The final decision whether or not to opt for PGD is often difficult to make and has a long-lasting impact in many couples. A digital decision aid is currently into development in order to facilitate decision-making.

During her PhD trajectory Inge Derks-Smeets was supervised by prof. Christine de Die-Smulders MD, PhD (clinical geneticist), prof. Vivianne Tjan-Heijnen MD, PhD (medical oncologist), Ron van Golde MD, PhD (gynecologist), all affiliated to Maastricht UMC+ and prof. Willem Verpoest MD, PhD (gynecologist, Vrije Universiteit Brussel, Brussels, Belgium).