G. Karlikaya

In vitro Fertilization in Normoresponder Patients with Endometriomas : Comparison with Basal Simple Ovarian Cysts

Objective: To investigate whether the space-occupying effect of an endometrioma, rather than endometriosis itself, affects results in in vitro fertilization (IVF) using women with simple ovarian cysts as the control group. Methods: 85 normoresponder patients with endometriomas of 10–50 mm who underwent IVF treatment directly without initial removal were compared with 83 normoresponder patients with simple ovarian cysts of 10–35 mm detected at the beginning of stimulation and initiated treatment without aspiration. Results: Gonadotropin consumption was higher in the endometrioma group (3,013 vs. 2,451 IU; p = 0.001), although significantly fewer numbers of oocytes were retrieved (13.9 vs. 16.4; p = 0.03). However, oocyte maturation rates were similar. The transferred grade I embryos ratio was evaluated and found to be better in the cyst group (79.7 vs. 70.7%; p = 0.03). Consequently, the implantation rate was found to be significantly higher in the cyst group (28 vs. 19%; p = 0.02), although pregnancy and ongoing pregnancy rates were similar. Conclusion: The presence of an endometriotic cyst during the IVF cycle was demonstrated to be associated with a lower embryo quality and implantation rate, although pregnancy success was unaffected. This adverse effect is suggested to be the result of the disease itself, not the presence of a cystic mass.

Clinical aspects of preimplantation genetic diagnosis for single gene disorders combined with HLA typing

Preimplantation genetic diagnosis (PGD) for single gene disorders combined with human leukocyte antigen (HLA) matching has recently emerged as a therapeutic tool for stem cell transplantation in couples bearing an affected offspring. There may exist, however, several patient- or cycle-specific limitations for certain couples. This article documents data regarding experience of single gene disorders combined with HLA matching obtained at Istanbul Memorial Hospital, Turkey. The data were obtained from 20 couples undergoing 26 PGD-HLA cycles for thalassaemia (n = 23), Wiscott-Aldrich syndrome (n = 1) and acute lymphoblastic leukaemia (n = 2). A total of 206 embryos was biopsied on day 3 of embryo development and subsequently analysed. After the analysis, 26 (12.6%) of them were found to be both healthy and HLA compatible. In 16 embryo transfers performed, seven (43.7%) clinical pregnancies were obtained, one of which resulted in miscarriage. Ten of the 26 cycles started (38.4%) were cancelled due to a lack of suitable (mutation-free and/or HLA-compatible) embryos. The data suggest that application of PGD in combination with HLA typing is a promising therapeutic tool for an affected sibling.

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.

The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial

We compared the efficiency of progesterone vaginal gel (PVG) with intramuscular progesterone (IMP) supplementation for luteal phase support after in vitro fertilization and embryo transfer in gonadotropin-releasing hormone (GnRH) antagonist cycles. The treatment outcomes were similar for PVG and IMP for luteal support in GnRH-antagonist protocols. With its ease of use, high tolerability by patients, and fewer side effects, PVG can be a successful alternative to IMP.

Serum oestradiol and β-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome

The aim of this study was to assess the clinical value of serum oestradiol concentration 8 days after embryo transfer (D8E2) and beta-human chorionic gonadotrophin (HCG-beta) concentration 12 days after embryo transfer (D12HCG-beta) in the prediction of pregnancy and the outcome of pregnancy following assisted reproduction, taking into account the day of transfer, which was either day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by giving quantitative and reliable predictive information instead of non-specific uncertainties. A total of 2035 embryo transfer cycles performed between January 2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic pregnancy and first-trimester abortions were classified as non-viable pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing pregnancies (OP). Significantly higher D8E2 and D12HCG-beta were obtained in D5 transfers compared with D3 transfers with regard to pregnancy and OP (P<or=0.001). For D3 embryo transfers, the cut-off value of D8E2 in predicting OP was 130 pg/ml (sensitivity 80%, specificity 72%), compared with 98 mIU/ml (sensitivity 89%, specificity 69%) for D12HCG-beta. For D5 embryo transfers, the values were 179 pg/ml (sensitivity 79%, specificity 84%) and 257 mIU/ml (sensitivity 78%, specificity 81%) respectively. It appears that serum post-embryo transfer D8E2 and D12HCG-beta concentrations provided clear information regarding pregnancy and the outcome of pregnancy following IVF-embryo transfer.

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.