Preimplantation genetic diagnosis in female and male carriers of reciprocal translocations: clinical outcome until delivery of 312 cycles

Abstract

Carriers of reciprocal translocations (rcp) are known to be at risk for reproductive difficulties. Preimplantation genetic diagnosis (PGD) is one of the options these carriers have to try in order to fulfil their desire to have a child. In the present study, we retrospectively looked at the results of 11 years (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007) of PGD for rcp in our center to improve the reproductive counseling of these carriers. During this period 312 cycles were performed for 69 male and 73 female carriers. The mean female age was 32.8 years, the mean male age 35.8 years. Most carriers were diagnosed with a translocation because of fertility problems or recurrent miscarriages, and most of them opted for PGD to avoid these problems. In 150 of the 312 cycles, embryo transfer (ET) was feasible and 40 women had a successful singleton or twin pregnancy. This gives a live birth delivery rate of 12.8% per started cycle and of 26.7% per cycle with ET. Owing to the large number of abnormal embryos, PGD cycles for rcp often lead to cancellation of ET, explaining the low success rate when expressed per cycle with oocyte pick-up. Once ET was feasible, the live birth delivery rate was similar to that of PGD in general at our center. PGD is therefore an established option for specific reciprocal translocation carriers.

Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

“…[39][40][41][42] However, these findings will reduce the number of embryos available for transfer by detecting abnormalities, which may not persist during embryo development, or may be clinically insignificant. The data we present here demonstrate that reciprocal translocation couples are likely to have relatively few normal/balanced embryos; rejecting embryos with apparent 30 Keymolen et al 31 Ko et al 24 Harper et al 6 Outcome measure per cycle Calculated % (95% CI) Calculated % (95% CI) Calculated % (95% CI) Calculated % (95% CI) Calculated % (95% CI)…”

“…28 Our study also confirms that mosaicism resulting from mitotic anaphase lag is the predominant plausible mechanism. 29 Data from multiple centres carrying out PGD are collected by the ESHRE PGD Consortium; 6 these data for reciprocal translocations and for three large single-centre studies 24,30,31 are shown in Table 3. The overall pregnancy and live birth rates for our couples are slightly higher than in these previous studies.…”

Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy

“…Balanced chromosomal translocations are a known cause of RPL [18]. For men with reciprocal chromosomal translocations, pre-implantation genetic screening (PGS) is recommended, as this has increased the live birth rate from 4.9 % to more than 80 % in some studies [19][20][21]. PGS utilizes either FISH or array-based analysis to detect chromosomal abnormalities or genetic defects in embryos undergoing IVF/ICSI [5].…”

Reproductive outcomes in men with karyotype abnormalities: Case report and review of the literature

“…2 Studies have shown that for couples in whom the male has a reciprocal translocation, 75% of natural pregnancies will result in a spontaneous abortion, with a live birth rate of only 4.9%. 3,4 Increased frequency of male infertility in men with reciprocal translocations is due to abnormal meiosis during spermatogenesis. 5 Abnormal segregation during meiosis can result in sperm with unbalanced translocations (i.e., chromosomal duplications and deletions).…”

“…For couples in whom one or more partners have a reciprocal translocation, preimplantation genetic diagnosis (PGD) reduced the frequency of spontaneous abortions to 12.5% and increased the live birth rate to more than 80%. 3,4 Due to the complexity of translocations and the high incidence of chromosomal aneuploidy with similar phenotypes, a review of the existing literature was critical (Table 1). Most patients with chromosomal abnormalities, with the notable exception of patients with 45,X/46,XY including those with complex chromosomal rearrangements, can still achieve pregnancies.…”