H. Karagozoglu

Embryo aneuploidy screening for repeated implantation failure and unexplained recurrent miscarriage

Among other factors, chromosomal abnormalities that originate from gametogenesis and preimplantation embryonic development are thought to be one of the major contributing factors for early embryonic death and failure of pregnancy. However, so far, no non-invasive technique exists that allows the detection of the chromosomal complement of an oocyte or a developing embryo as a whole. Rather, by removing polar bodies/blastomeres, recent developments on preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) have paved the way to detect and possibly eliminate the majority of chromosomally abnormal embryos, thereby increasing the chance of a healthy pregnancy. This article summarizes the origin and impact of chromosomal abnormalities on human reproduction in cases with repeated implantation failure (RIF) and unexplained recurrent miscarriage. It also discusses recent advances regarding the possible benefits of PGD-AS in such cases.

Preliminary FISH studies on spermatozoa and embryos in patients with variable degrees of teratozoospermia and a history of poor prognosis.

The aim of this study was to analyse to what extent sperm aneuploidy is associated with sperm morphology and subsequently with embryo aneuploidy. Fifty-nine men with variable degrees of teratozoospermia and previously poor assisted reproduction prognosis were included in the study. Samples from 10 normozoospermic men with proven fertility were used as controls. Individual spermatozoa were scored for chromosomes 13, 21 and for 18, X, Y separately. Compared with controls, 23 out of 59 cases (39.0%) were found to have increased sperm aneuploidy for at least one of the chromosomes analysed in a treatment cycle. Fifty-two patients underwent a treatment cycle and were documented according to the pregnancy and spermatozoa fluorescence in-situ hybridization results. A total of 121 previous unsuccessful assisted reproduction cycles of the cases were then retrospectively reviewed. In 23 of the latest cycles, preimplantation genetic diagnosis was applied to 106 cleavage stage embryos and 47 of 94 embryos analysed (50.0%) were found to be chromosomally abnormal. Furthermore, 16 of 47 (34.0%) embryos with chromosomal abnormality were carrying complex chromosomal defects. The results imply that increased aneuploidy is present in both spermatozoa and embryos in couples with severe male infertility with a history of repeated unsuccessful attempts. Therefore, proper genetic counselling should be considered in these cases.

A genetic survey of 1935 Turkish men with severe male factor infertility

Male factor infertility is the sole reason in approximately 25% of couples who suffer from infertility. Genetic factors such as numerical and structural chromosomal abnormalities and microdeletions of the Y chromosome might be the cause of poor semen parameters. The results of karyotype analyses and Y-chromosome microdeletions of 1935 patients with severe male factor infertility, which is the largest series from Turkey, were assessed retrospectively. The frequency of cytogenetic abnormalities among 1214 patients with non-obstructive azoospermia (NOA) and 721 patients with severe oligoasthenoteratozoospermia (OAT) were 16.40 and 5.83% respectively. The overall incidence of Y-chromosome microdeletion was 7.70%. The incidence of Y chromosome microdeletion in patients with NOA and OAT was 9.51 and 1.86% respectively. The abnormality rate increased with the severity of infertility. Some patients (n = 22) were carriers of both chromosomal abnormalities and Y-chromosome microdeletions. Results suggest the need for genetic screening and proper genetic counselling before initiation of assisted reproduction treatment.

Young patients with diminished ovarian reserve undergoing assisted reproductive treatments: a preliminary report

Young assisted-reproduction patients with diminished ovarian reserve (DOR) are one of the most challenging issues for IVF specialists. A retrospective study of 70 assisted reproduction patients younger than 35 years with DOR determined based on antral follicle count was conducted, investigating: (i) correlation of day 3 FSH measurement with antral follicle count; and (ii) cycle outcome of young DOR patients compared with 53 young assisted reproduction patients with normal ovarian reserve (NR). DOR was considered as antral follicle count of <6 per ovary. Day 3 FSH in the DOR group was significantly higher than in the NR group (8.3 and 6.6 mIU/ml respectively; P < 0.05). Implantation rates between the groups were similar (15% in DOR and 18% in NR). Pregnancy rate was 35.8% in the DOR group, significantly lower than that of the NR group, which was 54.7% (P = 0.028). Although the pregnancy rate was significantly lower in the DOR group compared with the NR group, the statistically insignificant difference in implantation rates demonstrated that the problem in young DOR patients was mainly the number of retrieved oocytes. Therefore, such couples should be informed that lower oocyte numbers will result in statistically lower, but still encouraging, pregnancy rates. Basal FSH should also be measured during evaluation as an adjunct to antral follicle count.

A prospective, randomized, controlled study to compare two doses of recombinant human chorionic gonadotropin in serum and follicular fluid in woman with high body mass index

This prospective, randomized, controlled study compares the efficiency of 250 microg or 500 microg of recombinant hCG in serum and follicular fluid (FF) levels and pregnancy rates (PR) in women with high body mass index (BMI) (>or=26 kg/m(2)) undergoing assisted reproduction treatment (ART). Treatment outcomes are similar between the two groups.

Ovarian stimulation in women with high and low body mass index: GnRH agonist versus GnRH antagonist.

This study evaluated women with a high body mass index (BMI) (>40 kg/m(2)) and low BMI (<18 kg/m(2)) undergoing assisted reproduction treatment and determined whether the type of gonadotrophin-releasing hormone (GnRH) analogue used has an impact on cycle parameters and outcome. The study analysed 65 women with high BMI and 118 with low BMI. In the former group, polycystic ovarian syndrome was significantly more prevalent in the agonist long protocol (ALP) group (P=0.01) and gonadotrophin consumption was lower, peak oestradiol concentrations and total number of oocytes retrieved were higher in the ALP group compared with the antagonist (ANT) group. Implantation rate (IR), pregnancy rate (PR) per embryo transfer and early pregnancy loss rate (EPLR) were similar in both stimulation groups, with overall rates of 21.6%, 55.4% and 44.4%, respectively. In women with low BMI, peak oestradiol concentrations, total oocytes retrieved, mature oocytes and transferred embryos were higher in the ALP group compared with ANT group. IR, PR/embryo transfer and EPLR were similar in both groups, with overall rates of 24.3%, 52.5% and 16.1%, respectively. In all patients, no difference was found between ALP and ANT protocols concerning treatment outcome. Contrary to the reasonable EPLR observed in women with low BMI, the high rate found in women with high BMI is remarkable.