The primary indication for preimplantation genetic diagnosis (PGD) is to improve the chances of having healthy infants in families at high risk for a specific genetic disease (409). Following embryo biopsy, genetic testing can be performed on a blastomere (cell from day 3 embryo), polar body, or on blastocyst trophectoderm prior to transferring the embryo. Aneuploidy in embryos most commonly affects chromosomes X, Y, 13, 14, 15, 16, 18, 21, and 22. Fluorescence in situ hybridization (FISH) is a technique that assesses aneuploidy, translocation, other structural chromosomal defects and sex chromosome content (410). FISH is technically limited by the number of distinct chromosomes that can be evaluated, which results in an inherently high false-negative rate. Newer methods are being developed that assess the entire genome using comparative genomic hybridization or DNA microarrays (411). One-quarter of the cases of PGD are performed for single gene disorders, most commonly myotonic dystrophy, Huntington disease, cystic fibrosis, fragile X syndrome, spinal muscular atrophy, tuberous sclerosis, Marfan syndrome, thalassemia, and sickle cell anemia. Because polymerase chain reaction (PCR) is required for single gene disorder diagnosis, ICSI is performed during ART to avoid contamination from sperm bound to the zona pellucida. PGD can be used for HLA antigen tissue matching in an effort to produce a child whose cord blood or stem cells could potentially help an existing affected child. Disadvantages to PGD include decreased postbiopsy embryo survival, requirements for extended culture with an associated possibility that no embryos will be available for transfer or cryopreservation, false-positive and false-negative testing results, and controversies regarding disposition of nontransferred embryos (409,410). PGD is not synonymous with preimplantation genetic screening (PGS), which is performed in couples without known chromosomal anomaly, mutation, or other genetic abnormality. Although it seems intuitive that replacing only euploid embryos should improve pregnancy and live birth rates in patients with advanced age, recurrent pregnancy loss, or implantation failure, study outcomes have not been consistent (409,410,412–415).
Preservation of Fertility in Cancer Patients
Improved cancer treatments such as chemotherapy, surgery, and radiotherapy have greatly enhanced survival, such that many cancer survivors contemplate parenthood. Unfortunately, those life-saving treatments can diminish fertility potential in both men and women. Cancer itself does not usually affect oocytes, but certain chemotherapeutic drugs or radiation damage may adversely affect ovarian reserve and uterine function, particularly in older women (416). Ovarian transposition prior to radiation therapy seems to be effective in preserving ovarian function (417). It is unclear whether ovarian suppression with GnRH analogues or oral contraceptives before or during chemotherapy or radiation is beneficial. If time allows prior to commencement of cancer treatment, women can undergo IVF with embryo cryopreservation (oocyte and ovarian tissue preservation are not routine). In women with cervical cancer, radical trachelectomy allows for retention of the uterus, those with uterine cancer may respond to progestin therapy in lieu of hysterectomy, and some ovarian tumors are amenable to unilateral oophorectomy if future fertility is desired. In men, cancer directly affects gametogenesis, and cancer treatments cause more fertility damage when given at younger ages. Semen and sperm cryopreservation prior to cancer treatment are often recommended for fertility preservation in men (416) .
1.
World Health Organization. Manual for the standardised investigation and diagnosis of infertile couple. Cambridge, UK: Cambridge University Press, 2000.
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