Strategies and outcomes of PGD of familial adenomatous polyposis

Moutou, Céline; Gardes, Nathalie; Nicod, Jean-Christophe; Viville, Stéphane

doi:10.1093/molehr/gal102

Cited by 28 publications

(17 citation statements)

References 19 publications

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“…Generally, hereditary cancer predisposition syndromes are inherited in an autosomal dominant manner such that offspring of an individual with a deleterious mutation have a 50% risk of inheriting the mutation [19]. Therefore, when a deleterious mutation associated with a hereditary cancer predisposition syndrome is identified in an individual, it can dramatically impact the health and well being of the individual [20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Knowledge, attitudes, and clinical experience of physicians regarding preimplantation genetic diagnosis for hereditary cancer predisposition syndromes

Brandt

Tschirgi²,

Ready

et al. 2010

Familial Cancer

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Approximately 5-10% of cancers are caused by an inherited predisposition. Individuals affected by hereditary cancer are often concerned about transmitting a predisposition to cancer to their children. Preimplantation genetic diagnosis (PGD) is a technology that allows embryos without a deleterious mutation associated with a hereditary cancer syndrome to be identified and implanted. The aim of this study is to assess the knowledge, attitudes, and clinical experience of physicians regarding PGD for hereditary cancer predisposition syndromes. Hereditary Breast and Ovarian Cancer (HBOC) and Familial Adenomatous Polyposis (FAP) are two hereditary cancer syndromes highlighted in this present study. A survey assessing physicians' attitudes, knowledge, and clinical practice was completed by a total of 373 gynecologic oncologists (GYN ONCs) and obstetrics and gynecologists (OB/GYNs). Physicians had a limited knowledge of PGD for hereditary cancer; however, physicians reported PGD was an appropriate option for patients with either HBOC or FAP. Although GYN ONCs were more likely to care for patients with hereditary cancer (P < 0.001), they were less likely than OB/GYNs to refer their patients to a PGD specialist (P = 0.004). While 80% of GYN ONCs and 91% of OB/GYNs would refer patients to a PGD specialist, clinical experience indicates that only 29% actually referred their patients. Since 68% of physicians had incorrect or limited knowledge of PGD for hereditary cancer, there is a need for additional education.

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Section: Introductionmentioning

confidence: 99%

Knowledge, attitudes, and clinical experience of physicians regarding preimplantation genetic diagnosis for hereditary cancer predisposition syndromes

Brandt

Tschirgi²,

Ready

et al. 2010

Familial Cancer

View full text Add to dashboard Cite

show abstract

“…PGD for hereditary cancer is particularly controversial and is still not widely used. [4][5][6][7] Lavery et al 8 found that PGD users (for diseases other than FAP) and who also had experience with PND reported that the experience of PND followed by termination had a negative impact and that PGD is a potentially valuable alternative. Although the first PGD procedures for FAP were already performed in 1998, 3 the availability of both PND and PGD for FAP still varies between countries.…”

Section: Introductionmentioning

confidence: 99%

Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis

et al. 2009

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Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study, questionnaires were sent to individuals from families at high risk for FAP assessing attitudes toward and experiences with childhood testing, PND and PGD, as well as several sociodemographic, clinical and psychosocial variables. Of the individuals from FAP families invited to participate in the study, 525 members participated (response rate¼64%). Most parents who had children who were minors (n¼93) (82%) were satisfied with the DNA testing procedure. One-third of all individuals wanted DNA testing for their children before age 12. Forty percent of FAP patients indicated that the disease influenced their desire to have children. Only 15% considered termination of pregnancy for FAP acceptable. Approximately 30% of individuals with a FAP diagnosis and their partners considered PND and PGD as acceptable for themselves. A positive attitude was associated with higher levels of guilt and a positive attitude toward termination of pregnancy. Importantly, of those with FAP at childbearing age, 84% had had no previous information at all about either PND or PGD. Future efforts should be aimed at educating FAP family members about reproductive options, allowing them to make an informed choice about family planning. Routine discussion of all reproductive options with a medical specialist should be encouraged.

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“…12 The use of prenatal invasive tests, such as chorionic villus sampling and amniocentesis, to confirm PGD results is controversial in adult-onset diseases with incomplete penetrance with the need for termination of pregnancy if the fetus is affected. 13 In our case series, only one couple out of three accepted the use of invasive prenatal tests and the possibility of termination. A recent study revealed that a proportion of couples with HBOC refused prenatal testing even following natural conception.…”

Section: Discussionmentioning

confidence: 80%

Preimplantation genetic diagnosis for hereditary cancer syndrome: local experience

et al. 2016

Hong Kong Med J

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A 33-year-old woman was referred for consideration of PGD because she was a BRCA2 gene mutation carrier. She had cancer of the right breast at the age of 24 years and underwent modified radical mastectomy with axillary dissection and immediate latissimus dorsi flap reconstruction. Adjuvant chemoradiotherapy was given and she was prescribed tamoxifen for 5 years after the operation. Her paternal grandmother had breast cancer diagnosed at the age of 60 years. Genetic screening was performed and confirmed the patient to be a BRCA2 mutation carrier. Her elder brother and her father underwent the spot test and were found to carry a BRCA2 mutation but her younger sister was not affected. Laparoscopic ovarian cystectomy was performed for a hyperechoic cyst noted over the right ovary, which was confirmed to be an endometriotic cyst. After a multidisciplinary meeting of clinical geneticists, breast surgeons, oncologists, gynaecologists, psychologists, nurses, and academics in the ethics department, followed by psychological assessment and also counselling, she was offered in-vitro fertilisation (IVF) and PGD. Her IVF and PGD cycle was performed in 2011, using an antagonist protocol with letrozole co-treatment. Fifteen oocytes were retrieved and 12 were fertilised following intracytoplasmic sperm injection (ICSI). Blastomere biopsy was performed on eight goodquality cleaving embryos and five were confirmed to be free of the BRCA2 mutation. Two unaffected blastocysts were transferred, resulting in a singleton pregnancy and one unaffected blastocyst was cryopreserved. She delivered a baby boy at term by caesarean section. Postnatal cord blood confirmed that the baby boy did not carry the BRCA2 mutation. Case 2A 33-year-old woman was referred for PGD because she was a carrier of FAP truncating germline mutation APC c.532-8G>A (NG_008481:g93262G>A) with a strong family history of colonic cancer. She underwent colonoscopy surveillance and more than 100 small colonic polyps were found. She was advised to have a prophylactic colectomy but was firm in her request to get pregnant with PGD treatment before the definitive treatment while fully understanding the risks of malignancy because of the delay in definitive treatment. She underwent an IVF cycle in 2012. Of 19 oocytes retrieved, 16 underwent ICSI. Fifteen were fertilised and 15 embryos were available for blastomere biopsy on day 3. Five embryos were found without the FAP mutation and four goodquality blastocysts were cryopreserved due to the risk of ovarian hyperstimulation syndrome. She failed to conceive in two frozen embryo transfer (FET) cycles with one blastocyst replaced in each cycle. She subsequently underwent the last FET cycle with two blastocysts transferred, and a consequent singleton pregnancy. The pregnancy is 26 weeks' gestation at the time of writing. The couple refused an invasive prenatal test and requested postnatal cord blood confirmation. Case 3A 37-year-old patient was referred from a clinical geneticist for PGD as her husband was diagnosed to have neuro...

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Strategies and outcomes of PGD of familial adenomatous polyposis

Cited by 28 publications

References 19 publications

Knowledge, attitudes, and clinical experience of physicians regarding preimplantation genetic diagnosis for hereditary cancer predisposition syndromes

Knowledge, attitudes, and clinical experience of physicians regarding preimplantation genetic diagnosis for hereditary cancer predisposition syndromes

Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis

Preimplantation genetic diagnosis for hereditary cancer syndrome: local experience

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