Aim :
To improve chance of pregnancy following In Vitro Fertilisation (IVF) treatment.
Background :
Infertility affects one in six couples in the UK. Each year 65,000 IVF cycles are carried out in
the UK resulting in the birth of ~18,000 babies. IVF is a costly procedure, relying on the
expertise of a team of health professionals in order for eggs to be retrieved, fertilised with
sperm in the laboratory to form embryos, before an embryo is selected to be put back into the
womb in order to lead to pregnancy. However less than a third of IVF cycles result in the
birth of a baby.
In order to improve the chance of pregnancy, more than half of patients having IVF treatment
in the UK have at least two embryos put back into the womb simultaneously. However this
will increase the risk of twin and triplet pregnancy. Multiple pregnancy increases the risks of
complications to mother and baby during pregnancy. Therefore increasingly only one embryo
is put back into the womb to reduce these risks, but this strategy will further reduce the
chance of pregnancy occurring during a single IVF cycle.
Current IVF protocols :
There are two main types of medications used to prepare the eggs for collection from the
ovary (also known as 'maturing' eggs) in IVF treatment:
1. human Chorionic Gonadotrophin (hCG)
2. Gonadotrophin Releasing Hormone (GnRH)
hCG is the most commonly used medication to mature eggs for collection in IVF cycles, but
hCG can result in a dangerous side effect termed 'Ovarian Hyperstimulation
Syndrome'(OHSS). OHSS can lead to sickness, abdominal pain, kidney failure, fluid on the
lungs and rarely even death.
GnRH is safer with regards to the risk of this dangerous side effect. GnRH is also more
convenient for patients (treatment courses are shorter and do not induce menopausal
symptoms as a side effect) and produces at least as many eggs as cycles using hCG to mature
eggs. The main disadvantage of using GnRH is that chance of pregnancy is lower than those
observed following hCG use. Some doctors suggest adding a small dose of hCG to GnRH
cycle to improve pregnancy rates, but this will also increase the risk of the dangerous side
effect OHSS.
Luteal Phase is important for chance of pregnancy :
One of the major factors which determines the likelihood of pregnancy are the changes in sex
hormones (such as oestrogen and progesterone) during the latter part of IVF cycles before a
pregnancy is established (this is called the 'luteal phase'). These hormones prepare the womb
for implantation of the embryo and help determine whether a pregnancy will be established.
The production of these hormones is disordered in all IVF cycles due to the high levels of
hormonal stimulation required to generate enough eggs for IVF treatment. Almost all women
having IVF treatment are given progesterone (and sometimes also oestrogen) to improve the
chance of pregnancy, which is termed 'luteal phase support'.
Hypothesis:
Studying the luteal phase will benefit patients by improving pregnancy rates :
A recent literature review of 'luteal phase support' by the Cochrane group described the
quality of available evidence as predominantly 'very low quality' with 'significant risk of
bias'. Developing a better understanding of the hormonal changes in the luteal phase will
allow us to optimise pregnancy rates following IVF treatment, such that patients may fall
pregnant sooner, saving the NHS money on the number of IVF cycles required to have a
baby. Although NICE guidelines recommend that each couple be offered three cycles on the
NHS, many areas in the UK are unable to afford to adhere to this recommendation and thus
many couples are only offered one cycle of IVF treatment.
Furthermore improving the pregnancy rates following a GnRH cycle will increase the
proportion of patients having GnRH cycles, thereby reducing the risk of OHSS (which is
more common following hCG cycles) thus improving the safety of IVF treatment.
Research plan :
I shall collect data on reproductive hormone levels during the luteal phase of IVF cycles to
identify the optimal timing and levels of hormones for pregnancy, to be achieved by 'luteal
phase support' regimens.