Preimplantation genetic screening (PGS) has been proposed as a method to improve the success rates of assisted conception in certain indications. Most commonly the technique involves analysing part of the karyotype of one or two biopsied blastomeres by fluorescence in situ hybridisation and thus detecting aneuploid embryos which are then not transferred into the uterus. Proposed indications include advanced maternal age, repeated IVF failure and recurrent miscarriage. While there are a considerable number of reports of the use of this technique, there are only two randomised controlled trials reported at present, both for the indication of advanced maternal age. Neither show an increase in live birth rate, and indeed the more recent (using a relatively low age cut-off of 35 years) suggests that live birth rate is reduced by the use of PGS. Methodological aspects of both studies are discussed. It remains possible that PGS may be of benefit under certain circumstances. However at present patients should be informed that there is no robust evidence that PGS for advanced maternal age improves live birth rate per cycle started, and PGS should preferably be offered within the context of robustly designed randomised trials performed in suitably experienced centres.

Purpose To evaluate the role of Anti-mullerian hormone (AMH) in predicting cumulative pregnancy outcome during in-vitro fertilization (IVF) treatment. Methods Serum AMH levels on day 6 of ovarian stimulation were taken from 180 women undergoing IVF with or without intracytoplasmic sperm injection (ICSI). The main outcome measures were ongoing pregnancy in the fresh cycle, cumulative ongoing pregnancy and ovarian response.Results There was a trend of higher median AMH levels in subjects achieving ongoing pregnancy in the fresh IVF cycle. The median AMH levels were significantly higher in subjects attaining ongoing pregnancy cumulatively and in subjects showing ovarian hyper-response in the stimulated cycle. Areas under the ROC curves were 0.606 and 0.792 for the prediction of cumulative ongoing pregnancy and ovarian hyper-response respectively. Conclusions Serum AMH concentration on day 6 of stimulation was significantly higher in subjects who achieved cumulative ongoing pregnancy in IVF compared to those who did not. Serum AMH is a reasonably good predictor of ovarian hyper-response.

Azoospermia is a rare, irreversible complication in the UK resulting from heavy infection of schistosomiasis of the male genital tract. Adequate anti-bilharzial treatment and close follow-up with urological assessments should reduce the risk of chronic ill health. This patient contracted schistosomiasis following swimming in lakes in Uganda, Africa, which resulted in azoospermia and reversible loss of libido. The couple underwent treatment at our assisted conception programme with testicular sperm extraction and intracytoplasmic sperm injection (ICSI). The female partner conceived in her second stimulated ICSI cycle and had a spontaneous vaginal delivery at term.

Elucidating the underlining mechanisms underpinning successful fertilisation is imperative in optimising IVF treatments, and may lead to a specific diagnosis and therefore potential treatment for some infertile couples. One of the critical steps involves paternal chromatin reprogramming, in which compacted sperm chromatin packed by protamines is removed by oocyte factors and new histones, including histone H3.3, are incorporated. This step is critical for the formation of the male pronucleus, without which the zygote contains only 1 pronucleus (1PN), in contrast to normally fertilised zygotes with two-pronuclei (2PN). 1PN zygotes are a frequently observed phenomenon in IVF treatments, therefore aberrant mechanism of action controlling paternal chromatin repackaging may be an important cause of abnormal fertilisation. Hira is the main H3.3 chaperone that governs this protamine-to-histone exchange. In this study, we investigated the maternal functions of two other molecules of the Hira complex, Cabin1 and Ubn1 in the mouse. Loss-of-function Cabin1 and Ubn1 mouse models were developed: their zygotes displayed abnormal 1PN zygote phenotypes, similar to the phenotype of Hira mutants. We then studied human 1PN zygotes, and found that the Hira complex was absent in 1PN zygotes which were lacking the male pronucleus. This result confirms that the role of the Hira complex in male pronucleus formation has coherence from mice to humans. Furthermore, rescue experiments showed that the abnormal 1PN phenotype derived from Hira mutants could be resolved by overexpression of Hira in the mouse oocytes. In summary, we have provided evidence of the role of Hira complex in regulating male pronucleus formation in both mice and humans, that both Cabin1 and Ubn1 components of the Hira complex are equally essential for male pronucleus formation, and that this can be rescued. We present a proof-of-concept experiment that could potentially lead to a personalised IVF therapy for oocyte defects.