Consultant Gynaecologist

The potential role of paternal sperm derived white blood cells and soluble factors in activating non-pregnant endometrial NK cells

What is the purpose of this study?

The successful outcome of a pregnancy requires, amongst other things, that the placenta grows well so that it can supply the developing foetus. If placental growth is insufficient this can lead to a number of problems, for example babies that are small when born (intrauterine growth retardation) or high blood pressure and kidney problems in the mother (pre-eclampsia). The reason(s) why the placenta fails to develop in some pregnant women are poorly understood. However, recently it has been shown that certain cells in the pregnant womb, so called uterine NK cells, produce chemicals that help the development of blood vessels in the placenta. These uterine NK cells are present in very large numbers in the womb during a healthy pregnancy. However, we don’t know where these cells come from.

In the non-pregnant womb there is an accumulation of another type of NK cell, called the endometrial NK cell. While somewhat similar to the cells seen in pregnancy these endometrial NK cells do not support the development of the placental blood vessels. One theory suggests that these endometrial NK cells receive a “signal” during the very early stages of the pregnancy, and this changes them to uterine NK cells. While this is possible the nature of the “signal” initiating this shift is not known.

During sexual intercourse apart from the sperm, which is necessary for the fertilization of the egg, a number of the male partner’s white blood cells and various chemicals also enter the womb. This study aims to find out if either the white blood cells or some of the chemicals present in the sperm could turn endometrial NK cells to uterine NK cells.

What is the purpose of this study?

During pregnancy the foetus develops in the womb attached to the mother’s blood supply. This is a unique situation when a tissue, which is substantially different from that of the mother, survives for a long period without rejection. The mechanisms that allow this process to happen are far from understood.

Recently a specific type of cell in the human immune system, so called Natural Killer (NK) cell, have received attention both in the scientific community and in the media. Small studies claim that increased numbers or increased activity of NK cells in the mother’s blood may result in the failure of a fertilised egg being implanted in the lining of the uterus, potentially causing infertility or poor outcome in vitro fertilisation (IVF).

To the contrary, NK cells present in the lining of the womb have been claimed to be beneficial for the development of pregnancy, by supporting the development of the placenta. A lack of such cells in experimental animals causes abortions or results in small babies.

There are several treatment options offered to women wishing to become pregnant via assisted fertility, such as IVF or intrauterine insemination. However, the scientific justification of these treatments is weak while the risks could be substantial.

The purpose of this study is to investigate further whether measuring the characteristics of NK cells either in the blood or the womb of non pregnant women could be used to identify individuals who are likely to experience problems in conceiving.

Women who have a history of failed pregnancies or failed IVF attempts. And those with a number of successful pregnancies without complications (controls) are include in the study. Individuals in these two groups (controls vs patients with miscarriages/failed IVF attempts will be compared to see whether there are differences in the number, characteristics or functional activity in the blood or womb-derived NK cells between the two groups.

Participation is entirely voluntary. If patients agree to take part in the research study during their surgery a small amount of tissue from the lining of your womb is sampled.

What is the purpose of this study?

In endometriosis, cells that detach from the lining of the womb find their way to the surface of the other organs in the abdomen. Here these cells will take hold, grow and die according to the menstrual cycle of the affected women. This is a debilitating condition that leads to pain, accumulation of blood in the abdomen and other complications.

Why endometriosis develops in some women but not in others is not clear. In theory during the menstrual period cells from the lining of the womb could find their way into the abdomen in all women. In theory, there are two main possibilities:

1. In affected women the cells from the lining of the womb could be more invasive enabling them to establish a "colony" in the abdomen (or, tummy area).

2. The cells of the abdominal lining (inside the tummy area) show less resistance than normal in affected individuals allowing colonies to be formed. This proposed study aims to distinguish between these two possibilities and to therefore find out why endometriosis affects some women, but not others.

TO IMPROVE THE SUCCESS RATES IN ASSISTED CONCEPTION- A RANDOMISED CONTROLLED TRIAL (DOLS Trial).

Purpose of the study. Progesterone is a reproductive hormone that is administered to patients during infertility treatment. This hormone is produced naturally in the body to ensure a thick lining of the womb which helps the embryo implant and also maintains the pregnancy. As part of the egg collection process, progesterone producing cells are removed along with the follicular fluid and eggs, making the ovaries unable to produce progesterone sufficiently. The amount of progesterone produced by the remaining follicles is usually not enough to support the lining of the womb. Hormone supplements are usually given for two weeks or longer to assist implantation especially if you were given medication to shut down your hormonal system. Progesterone is vital for making the lining of the womb thick and provides continued embryo support.

We currently use progesterone pessaries for two weeks after the embryo transfer i.e. up to the positive pregnancy test. The aim of our study is to evaluate whether or not prolonged use of progesterone up to 10 weeks post embryo transfer increases the pregnancy rate. If we are successful in improving our success rates then it is likely that progesterone pessaries will be used for longer duration and the rest of the country will adopt it as the new standard.