Genetic Reproductive Risk And The Value Of PGD In INV(9) Or Balanced Translocation Carriers

Chapter1Genetic reproductive risk and the value of preimplantation genetic diagnosis in inv(9) carriersBackground The pericentric inversion of chromosome9has been considered as a normal variant of human karyotype, however, some studies seem to reveal associations of inv(9) with increased congenital abnormalities, chromosomal instability, and cancer. Many reports raised conflicting viewpoints regarding the chromosomal association of inv(9) with abnormal clinical consequences such as infertility, recurrent pregnancy loss. To date, many studies have investigated the meiotic segregation of pericentric inversion carriers using sperm-FISH (Fluorescence In-Situ Hybridization) and several laboratories have reported their experience with preimplantation genetic diagnosis (PGD) for pericentric inversion, but few about inv(9). The aim of this study was to reveal the genetic reproductive risk of inv(9) and validate PGD with FISH for patients carrying pericentric inversion in chromosome9.Methods33couples prepared to undergo PGD for either male or female partners carrying pericentric inversion of chromosome9, including32cases were infertility (25cases were primary infertility),2cases had histories of spontaneous abortion, and2cases had history of histories of abnormal pregnancy. Blastomeres or blastocysts from these couples were analyzed by FISH. Results A total of152embryos were analyzed. Fluorescence In-Situ Hybridization analysis revealed a45.39%(69/152) of abnormal embryos (54were unbalanced embryos and15were aneuploidy) and a54.61%frequency of balanced chromosome9(normal or inverted). For various types of inv(9),75%were inv(9)(p12q13). At the time this article goes to press, the pregnancy rate per embryo transfer has been66.67%(22/33) and the ongoing pregnancy rate has been54.55%(18/33).Conclusions The percentage of unbalanced embryos was close to the theoretical prevalence for pericentric inversion and carriers with inv(9) obtained high pregnancy rate. This study verified the value of Fluorescence In-Situ Hybridization analysis in PGD for pericentric inversion of chromosome9, and we should not ignore the risk resulting from the inverted segment involved<30%of the chromosome9length. Chapter2Patterns of ovarian response to controlled ovarian hyperstimulation and the value of preimplantation genetic diagnosis in balanced translocation carriersBackground Ovarian response to controlled ovarian hyperstimulation (COH) is a critical factor which influence the outcomes of assisted reproductive technology, however, the effect of chromosomal autosomal balanced translocations on ovarian response is still controversial. Many researches have shown that PGD for translocation carriers has the potential to reduce the risk of conceiving a chromosomally abnormal baby or recurrent spontaneous abortions. The aim of this study was to reveal the effect of chromosomal autosomal balanced translocations on the ovarian response to COH and the value of PGD in balanced translocation carriers.Methods In this retrospective study,121PGD cycles from patients with autosomal translocations were analyzed. Ovarian response parameters and PGD outcomes were examined and compared between two groups:63cycles in56women with autosomal balanced translocations (study group) compared with58cycles in53women whose male partner had an autosomal balanced translocation (control group).Results The study group did not significantly from the control group in female age, BMI, basal hormone or AFC. COH parameters, such as the total dose of Gn, estradiol level on day of hCG administration, the number of retrieved oocytes and embryos on Day3, balanced and transferred embryos were not significantly different between the study group and the control group. For carriers with Robertsonian translocation or reciprocal translocation, patient characteristics and COH parameters were not significantly different between the two groups. Females with diseases which might have influence on the outcome of ovarian response to COH were excluded and only cycles with long protocol were included, both patient characteristics and COH parameters were also not significantly different between the two groups. The pregnancy rate per embryo transfer was48.1%and the ongoing pregnancy rate per embryo transfer was40%. For the two groups, no differences were observed for pregnancy rate, early abortion rate and ongoing pregnancy rate.Conclusions This study suggested that female carriers with autosomal balanced translocations, including Robertsonian or reciprocal translocation, didn’t influence the ovarian response to COH in PGD. We should consider female carriers of balanced translocations as normal responders and in clinical practice, use the standard doses of gonadotropins for COH. This study highlighted that PGD had the potential to improve clinical pregnancy rate and the sex of the carriers had no effect on the outcomes of PGD.