Tarek El Toukhy’s research while affiliated with King's College London and other places

Study question Does the literature suggest that high sperm DNA damage affect IVF and ICSI outcome? Summary answer High sperm DNA damage detected with SCSA, TUNEL or COMET assays has been shown to be associated with lower clinical pregnancy rates in IVF cycles. What is known already Sperm DNA damage is found in infertile as well as fertile men. The relationship between sperm DNA damage and fertilization rate, embryo quality, pregnancy and miscarriage rates has been evaluated in the literature. It has been demonstrated that DNA damaged sperm have the capacity to fertilize oocytes but could be associated with an increase in the miscarriage rate following ART (assisted reproductive technique). Study design, size, duration A systematic review and meta-analysis of studies on the effect of high sperm DNA fragmentation rate on IVF/ICSI outcome was undertaken. Medline, Embase and Cochrane library databases were searched from database inception to January 2013. The search was limited to studies published in English language. Participants/materials, setting, methods Study selection and data extraction were conducted independently by two reviewers. We used 'sperm DNA damage', 'DNA fragmentation', 'IVF','ICSI', 'outcome', 'pregnancy' to generate the relevant citation. Studies with clinical pregnancy outcome (gestational sac or fetal heart on USS) were included. Revman 5 statistical software was used for analysis. Main results and the role of chance The search identified 25 studies involving 3360 couples. For SCSA assa Y : Meta-analyses of 14 studies (n = 1621) showed a significantly higher clinical pregnancy rate (CPR) in the group who had a DNA fragmentation index (DFI) score of <30% (Relative risk (RR) 1.17, 95% CI 1.05-1.30; P = 0.004) compared to the group who had a DFI >30%. For TUNEL assa Y : Meta-analyses of 8 studies (n = 1233) showed a significantly higher CPR in the group who had a low DNA fragmentation compared to the group who had a high DNA fragmentation (RR 0.69, 95%CI 0.52-0.90, P= 0.006). For Comet assay : Meta-analyses of 3 studies (n= 506) showed a significantly higher CPR in the group who had a low DNA fragmentation compared to the group with high DNA fragmentation (RR 1.16, 95%CI, 1.03-1.30, P = 0.01). Limitations, reason for caution There has been several assays described in the literature to define low and high DNA fragmentation. The diagnostic accuracy of these assays has been widely debated. There is inconsistency in defining the threshold for high DNA fragmentation test. The studies included were heterogeneous and not adequately powered. Wider implications of the findings Increased sperm DNA fragmentation may have a detrimental effect on IVF outcome. Adequately powered studies with strict inclusion criteria to further evaluate the effect of DNA fragmentation testing in IVF and the role of antioxidants as well as IMSI (intracytoplasmic morphologically selected sperm injected) as treatment options are needed. Study funding/competing interest(s) none Trial registration number none

The European Union Tissues and Cells Directive requires screening of tissue and cell donors for infective organisms to prevent inter-patient transmission. The Directive includes the unique term partner donation, which refers to "donation of reproductive cells between a man and a woman who declare that they have an intimate physical relationship". In line with the Directive, partners undergoing Assisted Reproductive Technology (ART) now require screening before each treatment, regardless of the time interval between consecutive cycles. Evidence to support this recommendation is lacking. Therefore, we conducted a retrospective study of all virology screening tests undertaken over a three year period for individuals attending an assisted conception unit serving a high risk inner city population. We ascertained prevalence and seroconversion rates for HIV, hepatitis B and C and estimated the additional cost of implementing the Directive fully in our unit. With more than 3910 ART individuals screened between January 2007 and December 2009, the prevalence of HIV, hepatitis B and C was 0.6, 1.7 and 0.4%, respectively. A total of 422 individuals had a second screening test during the three year period and none seroconverted. This study suggests that increasing the frequency of screening individuals undergoing ART to less than 12 months would not confer added benefit and has significant cost implications.

Approximately 15% of couples are affected with subfertility, of which up to 20% remain unexplained. Uterine cavity abnormalities can be a contributing cause of subfertility and recurrent implantation failure. Uterine cavity assessment has been suggested as a routine investigation in the evaluation of subfertile women. Traditionally, hysterosalpingography has been the most commonly used technique in the evaluation of infertility. Transvaginal ultrasound scan allows visualization of the endometrial lining and cavity, and has been used as a screening test for the assessment of uterine cavity. Abnormal uterine findings on a baseline scan can be further evaluated with saline hysterosonography, which is highly sensitive and specific in identifying intrauterine abnormalities. Hysteroscopy is considered as the definitive diagnostic tool to evaluate any abnormality suspected on hysterosalpingography, transvaginal ultrasound scan or saline hysterosonography during routine investigation of infertile patients. Minimally invasive hysteroscopes have minimized the pain experienced by patients during the procedure and made it feasible to use hysteroscopy as a routine outpatient examination. Following recurrent IVF failure there is some evidence of benefit from hysteroscopy in increasing the chance of pregnancy in the subsequent IVF cycle, both in those with abnormal and normal hysteroscopic findings. Various possible mechanisms have been proposed for this beneficial effect, but more randomized controlled trials are needed before its routine use in the general subfertile population can be recommended.

Objectives. To assess the outcomes of ovulation induction (OI) using the anti-oestrogen, clomiphene citrate (CC) in a Nurse led service in tertiary referral fertility centre. Methods. A consecutive series of 131 cycles of OI using CC were included. Outcomes included the assessment of clinical pregnancy rates in relation to patient characteristics and the dose of treatment. Results. A total of 87 women underwent 131 cycles of OI with CC during a 7 month period. The mean (SD) age was 33 (4.69) years, while the age range was 20–45 years. The mean (SD) BMI and number of treatment cycles per woman was 24.8 (3.86) and 1.7 (1.17) cycles, respectively. A total of 121 (92.4%) women were under the age of 38 years. A total of 28 (21%) cycles required a dosage of 100 mg CC, while 10 (7.6%) required 150 mg. Seven (5%) women had laparoscopic ovarian drilling, of which two were resistant to CC. A total of 32 (24.4%) cycles had a positive pregnancy test, while 26 (19.8%) had a fetal heart noted on ultrasound scan. All these were singleton pregnancies. The majority of pregnancies (91%) occurred in the first two cycles of CC treatment. Of these 19 (59%) occurred in the first treatment cycle, while 10 (31%) became pregnant in the second treatment cycle. All pregnancies occurred in women under the age of 38 years. Two (1.5%) cycles were cancelled for over-response, while two (1.5%) women experienced symptoms of mild ovarian hyperstimulation. Conclusion. The majority of pregnancies occurred within two treatment cycles of CC, while the best prognosis was for women under the age of 38 years. A lower threshold to proceeding to IVF treatment needs to be considered for women of 38 years and above.

Objective. To assess the success rates of PGD cycles performed in a 2-day egg collection (EC) week programme compared to those with IVF/ICSI cycles performed in a 5-day EC week programme. Methods. Analysis of all conventional IVF/ICSI and PGD cycles in a tertiary referral centre between January 2006 and March 2009. Results. A consecutive series of 2772 IVF/ICSI cycles and 311 PGD cycles were included in the analysis. Female age and the number of previous treatment attempts were adjusted for in the analysis, and the following are the results for women up to the age of 38 years in both groups. The mean (SD) number of days of FSH stimulation for IVF/ICSI was 10.5 (1.8) and for PGD 10.2 (1.3) [Difference between means 0.25, 95%CI for the difference in means: 0.03 to 0.48, p ¼ 0.03]. The mean (SD) number of oocytes collected for IVF/ICSI was 12.0 (7.1), while that for PGD was13.4 (7.4) [Means difference 1.33, 95%CI for difference between means: 0.42 to 2.24, p 50.01]. The mean (SD) number of oocytes fertilised for IVF/ICSI was: 6.7 (4.7) and for PGD 7.8 (5.1) [Means difference 1.05, 95%CI for difference between means: 0.43 to 1.68, p5 0.01]. The fertilisation rate for IVF/ICSI was: 56% and for PGD: 58% [OR: 0.92, 95%CI: 0.51 to 1.68, p ¼ 0.89]. The pregnancy rate per embryo transfer for IVF/ICSI was 49% and for PGD 46% [OR: 1.13, 95%CI: 0.62 to 2.04, p ¼ 0.78], while the clinical pregnancy rate per embryo transfer in the IVF/ICSI group was 40% compared with 37% for the PGD group [OR: 1.14, 95%CI: 0.62 to 2.09, p ¼ 0.77]. Conclusions. PGD cycles scheduled to a 2-day EC week had similar outcomes when compared to conventional IVF/ICSI cycles. Scheduling PGD cycles to a 2-day EC week did not seem to compromise outcomes when compared to a 5-day EC programme.

Introduction Since its first clinical use, pre-implantation genetic testing (PGT) has become increasingly available as a method of detecting genetic disorders before pregnancy is established. Based on a difference of purpose, PGT can be classified as either pre-implantation genetic diagnosis (PGD) or pre-implantation genetic screening (PGS). PGD was established in the early 1990s as an alternative to prenatal diagnosis (PND) and termination of pregnancy. PGD describes the testing of oocytes or embryos from patients who have a significant risk of conceiving a pregnancy affected by a known recurrent genetic disorder, in order to preselect for transfer only those embryos found not to carry the disorder. PGS, on the other hand, aims to improve the outcome of assisted reproductive technology (ART) treatment for the subfertile by testing for a number of the more frequent chromosome aneuploidies in an attempt to improve implantation and reduce the incidence of miscarriage. It is estimated that worldwide, more than 1000 children have been born following PGT. The clinical application of PGT is expanding into new areas, creating novel ethical and practical dilemmas. In order for a pre-implantation genetic test to be performed, a representative sample of the embryo is required. A single cell can be removed from a late cleavage stage embryo (8-16 cells), or a few cells may be taken from the trophectoderm of a blastocyst, or one or both of the polar bodies can be removed from the unfertilised egg or early zygote.