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.
You have been chosen because you are going through an IVF/ICSI cycle and are likely to undergo an embryo transfer. If you become pregnant you will be asked to take part in the trial. If you agree you will be randomised into one of two treatments, either an extra 8 weeks of progesterone or 8 weeks of a placebo. The placebo will look like the progesterone pessaries but will have no active ingredients and is completely harmless. The chances of you receiving progesterone pessaries or placebo are 50:50.
Do I have to take part?
Participation is voluntary. If you decline participation, the current unit policy is to use progesterone pessaries for two weeks after the embryo transfer. If you do decide to take part, you will be given this information sheet to keep and be asked to sign a consent form. If you decide to take part, you are still free to withdraw at any time without it affecting your future treatment. Withdrawal from the trial will not affect the standard of care you receive or your relationship with your doctor.
What will happen to me if I take part?
Entering into the trial is entirely voluntary. If you agree then:
On the day of your positive pregnancy test (i.e. two weeks after embryo transfer) you should make contact with the Hewitt Centre who will take you through the initial steps to joining the trial. A prescription for the additional pessaries will be prepared for you to collect. The staff on the unit will not know which treatment you are to receive. If you have done your pregnancy test at home you will be required to attend the unit within 24 hours to be recruited and randomised into the DOLS trial. You will be asked to take these pessaries for the following 8 weeks, in exactly the same way as you have done in the last 2 weeks. At the beginning of the trial we perform a blood test to measure your hormone levels, before you have had any additional treatment.
As routine care you will be asked to return to the unit for a pregnancy scan 3 weeks following your positive pregnancy test (you should be seven weeks pregnant by this stage). At this appointment a further blood sample test will be taken to check again for your pregnancy hormone levels.
It is at this point that you will also have your first pregnancy ultrasound scan. This will include a further measurement looking at the blood supply to your womb.
Unique to this trial a further appointment will be arranged for you for five weeks after your first pregnancy scan, again looking at the pregnancy and the blood flow to your womb. A third and final blood test will also be performed. At this stage of your pregnancy you should be twelve weeks pregnant.
This is a research study, we do not yet know the outcome of prolonging the use of your progesterone pessaries, but if you participate and go onto deliver, a routine newborn examination will be performed by your birth hospital and the information returned to us.
Also, if you take part in our research and go onto have a child as a result of the IVF treatment you are currently receiving (again it is not known whether you will or will not), we will ask your permission to find out how your child is progressing. The NHS has a central register (based at the General Register Office), which we would use to find your address and to contact you at this time if required.
What is being tested?
Our primary objective is to determine whether using progesterone pessaries for an extra 8 weeks after the embryo transfer increases the pregnancy rate.
What are the possible benefits of taking part?
The information we collect from the trial will determine whether IVF units should change practice and use the progesterone pessaries for 8 weeks after a positive pregnancy test. This may benefit your treatment and those undergoing IVF in the future. However there may be no direct benefits to you from participating in the trial.
What are the possible side effects of taking part?
Occasionally women may experience some vaginal discharge or irritation, nausea, bloating, fluid retention, weight gain, dizziness, and reduced glucose tolerance.
Will my taking part in this study be kept confidential?
All information collected about you during the course of research study will be kept strictly confidential in your IVF notes. Any information about you which leaves the hospital will have your name and address removed so that you cannot be identified from it.
What if something goes wrong? If you are harmed by taking part in this research project, there are no special compensation arrangements. If you are harmed by someone’s negligence, then you may have grounds for legal action but you may have to pay for it. Regardless of this, if you wish to complain, or have any concerns about any aspect of the way you have been approached or treated during the course of this study, the normal National Health Service complaints mechanisms should be available to you.
What will happen to the results of the research study?
The results will be published in scientific journals and presented at conferences to further our knowledge about assisted conception.
Who is organising the research?
Hewitt Centre for Reproductive Medicine, Liverpool Women’s NHS Foundation Trust.
Who has reviewed the study?
Liverpool Research Ethics Committee