Risk evaluation and preimplantation genetic diagnosis in an infertile man with an unbalanced translocation t(10;15) resulting in a healthy baby

Abstract

Balanced chromosome structural rearrangement, including reciprocal translocation, Robertsonian translocation and inversion, is an important cause of male infertility that results in azoospermia, oligozoospermia or asthenozoospermia [1]. Unbalanced translocation between two autosomes, which usually results in mental retardation or multiple congenital anomalies, is rare in infertile patients. To our knowledge, only the t(15;18) unbalanced translocation has been reported, in two healthy infertile brothers. Although fluorescence in situ hybridization (FISH) analysis showed that chromosomal normal sperms existed in their semen, these two brothers and their partners chose donor insemination rather than preimplantation genetic diagnosis (PGD) [2]. Whether patients with this kind of rare karyotype could deliver a healthy baby is unclear. Here, we report a man with severe oligoasthenoteratozoospermia carrying a derivative chromosome 10 resulting from the rare unbalanced translocation t(10;15). Based on risk evaluation by sperm FISH, we performed PGD for the couple and successfully established a normal pregnancy. Our results show that patients with such an abnormal karyotype can produce their own offspring, and emphasize the importance of risk evaluation using sperm FISH for infertile male patients. Patient data A couple presented to our reproduction center due to primary infertility that had persisted for 5 years. The woman showed no obvious cause of infertility on examinations, which included: (1) clinical findings: physical examination and medical history evaluation,such as menstrual history, obstetrical history, sexual history, family history, personal and lifestyle history; (2) biochemical tests: liver and renal function; blood cholesterol, blood triglycerides and blood glucose; and immunologic function; and (3) hormonal assay: estradiol, testosterone, progesterone, follicle stimulating hormone (FSH), luteinizing hormone, prolactin, 17-hydroxypregnenolone and thyroid stimulating hormone (TSH); (4) other diagnosis test such as hysterosalpingography. Her karyotype was also normal. However, the man was found to have severe oligoasthenoteratozoospermia after three routine sperm analyses and one sperm morphology examination following the WHO guidelines (Table 1). Conventional G-banding (G-bands after trypsin and Giemsa, GTG) analysis showed that he had only 45 chromosomes, with one derivative chromosome comprising chromosomes 10 and 15 (Fig. 1). Table 1 Semen analysis Fig. 1 a Partial karyotype of the patient showing normal chromosome 10,15 and der(10). b ideogram of the normal chromosome 10,15 and rearranged chromosome. Red, green and aqua bands show the position and color of the FISH probes used for preimplantation genetic ... The couple then accepted a genetic counseling and asked for further fertility evaluation. Oligoasthenoteratozoospermia might have been the cause of the primary infertility in this couple. The husband carried a rare unbalanced translocation comprising chromosome 10 and chromosome 15 that had not been reported previously. The genetic risk was unclear for this kind of abnormal karyotype. His chromosomal structure was similar to that of a Robertsonian translocation; therefore, the meiosis pattern might also be similar to a Robertsonian translocation. Sperm chromosome constitution can be obtained by sperm FISH analysis and might predict the probability of producing an embryo with normal karyotype. If chromosomally normal sperms are present in semen at a high prevalence, PGD can be performed to select embryos with balanced chromosomes for transfer and deliver a healthy baby. This study was approved by the Institutional Review Board of Central South University and Reproductive and Genetics Hospital of Citic-Xiangya, and the patients’ written informed consent was obtained.