In the UK, around 20-25% of IVF treatment cycles result in a birth.
Success rates decrease dramatically in women over 40
Our research seeks to shed light on the factors responsible for reproductive failure. We are also actively engaged in efforts to improve infertility treatments, such as in vitro fertilisation (IVF). Our work aims to simplify treatments and reduce risks, increase success rates and lower costs.
what we do
We carry out clinical trials in Assisted Reproductive Technology (ART) including the development and evaluation of novel infertility treatments. Research teams based at the Nuffield Department of Obstetrics and Gynaecology have been at the forefront of research into techniques such as oocyte in‐vitro maturation (IVM‐ first in the UK), ovarian tissue cryopreservation, and the use of genetic tests to predict embryo viability.
Research into male infertility has focused on sperm DNA integrity, chromosome abnormality, and the molecular mechanisms underlying the activation of oocytes by sperm at the time of fertilisation. Activation of the egg is a fundamental developmental event, associated with a series of characteristic oscillations in the levels of calcium within the oocyte. Current research strongly suggests that the protein responsible for inducing activation is a sperm-specific phospholipase C with distinctive properties, PLCζ.
We investigate how PLCζ, and other sperm proteins interacting with the oocyte at fertilisation, might be related to certain types of male infertility including oocyte activation deficiency, total fertilisation failure, or recurrent intracytoplasmic sperm injection (ICSI) failure, a condition that affects approximately 1200 couples in the UK each year. We are also investigating the potential role of proteins inside the oocyte, which might interact with PLCζ and other sperm proteins, in order to induce activation. This work aims to develop new diagnostic tests and therapeutic strategies.
Not only must sperm activate the oocyte upon fertilisation, but they must also successfully deliver the male genetic contribution to the zygote. In some cases, sperm successfully fertilise the oocyte, but the male genome is degraded and unable to support subsequent embryo development. We have developed novel approaches for detecting this sort of DNA damage in sperm, helping to improve the evaluation of semen quality. It is hoped that such methods will improve IVF treatments.
Additional projects focused on sperm quality, oocyte activation and other aspects of the fertilisation process aim to assess how clinical procedures might influence the function of sperm proteins, optimize the use of infra-red laser technology in assisted reproductive technology, and evaluate how cytoplasmic movements in the oocyte might serve as potential markers of clinical viability.
We also have a strong interest in female infertility and conduct varied research aimed at understanding the process of oocyte formation. Not only does the oocyte contain the female genetic contribution, but it also contains the raw materials needed during the first few days following fertilisation, a time during which the embryo has not yet switched on its own genes. Our research has examined the cells that surround and support the oocyte during its maturation in the ovary (cumulus cells). The cumulus cells play a key role in communicating signals to the oocyte as well as providing it with important resources. We have sort to learn more about the complex interactions between the oocyte and its cumulus cells using transcriptomic approaches, such as RNA sequencing. Not only has this research provided important data concerning the activity of genes in cumulus cells, but it may also reveal potential biomarkers that can be used to predict the likelihood of an oocyte producing a viable embryo.
The single most important factor impacting embryo viability is the presence of chromosome abnormalities. More than half of all the embryos produced using IVF techniques have cells containing the wrong number of chromosomes (a condition known as aneuploidy). The incidence of aneuploidy in embryos is greatly affected by the age of the mother, such that for women over the age of 40 more than 75% of embryos are abnormal. Aneuploidy is almost always lethal to the embryo, usually causing failure of the embryo to implant but also responsible for the loss of embryos later in pregnancy (miscarriage). The high frequency of aneuploidy in embryos produced using IVF means that it is not unusual for an abnormal embryo to be inadvertently transferred to the uterus of the mother during treatment.
Researchers at the Nuffield Department of Obstetrics and Gynaecology have been at the forefront of work to characterise chromosome abnormalities in oocytes and embryos and have developed various novel technologies to assist in their detection. Some of these methods are now widely used around the world in order to help identify non-viable aneuploid embryos and avoid their transfer to the uterus. This strategy, sometimes referred to as preimplantation genetic screening (PGS), typically involves removal of one or more cells from the embryo before implantation, when it is still microscopic in size, composed of just a handful of cells. The cell(s) taken are lysed (burst), releasing their DNA which is then amplified and subsequently tested using a method known as Next Generation Sequencing, or alternatively using a device called a microarray, revealing the number of chromosomes. The intention of PGS is to improve the chances that a chromosomally normal embryo will be transferred to the mother’s uterus, thus improving the chance of a pregnancy and reducing the risk of miscarriage.
In addition to extensive research looking at the chromosomes of oocytes and embryos, we have also been heavily involved in the development of new ways of detecting serious inherited conditions during the first few days of life, before a pregnancy has been established. The concept of testing cells biopsied from early embryos for inherited disorders, with transfer to the uterus of the embryos found to be unaffected is known as preimplantation genetic diagnosis (PGD). The use of PGD by couples at high-risk of transmitting a disorder to their children greatly reduces the probability of having a pregnancy with an affected fetus, making it much less likely that the couple will have to consider pregnancy termination. As well as performing diagnosis of mutations in genes within the nucleus, scientists at the NDOG also have an active research interest in the PGD of disorders caused by mutations in the DNA of mitochondria, the organelles responsible for the production of energy within the cell. This research extends beyond diagnostic considerations and also seeks to improve understanding of the role that mitochondria play in embryo development as well as other aspects of reproduction.
Finally, a wide range of cutting-edge research is also undertaken in the Department aimed at the improvement of other aspects of IVF. These include new technologies that allow oocytes to be matured in vitro, potentially reducing risks and costs associated with traditional IVF treatment, and enhanced methods of embryo culture for the improvement of IVF results.