Naturally the ovary continuously recruits and develops the eggs. The egg develops over 60-90 days but only the last 14 days are in the menstrual cycle and when we can make changes. Normally the ovary recruits a group of eggs and the number allocated each month vary with the ovarian reserve of eggs and certain conditions such as polycystic ovaries. In older women or when ovaries have been affected by a past illness/treatment, the total number of eggs in the ovary goes down and hence the number it can allocate per month also reduces.
From the number allocated normally one follicle is visibly larger by the 4th-5th day of the menstrual cycle and has started to grow ahead of others. This dominant follicle prevents other follicles from growing that month. By giving you stimulating drugs however we can allow more than one egg to develop. Naturally the glands interact and prepare for ovulation as the hormone levels rise. Normally this would only happen when the single follicle reaches a mature stage. However when more than one follicle is growing, the hormone levels go up faster and to higher levels which can confuse the Interacting glands to send messages related to ovulation prematurely. This will affect the quality of egg development. Hence we give medication to inactivate these glands. Often this will start before the stimulating hormones as in the long protocol’ but we can also use other hormones with similar effects but during the stimulation phase as in the ‘short protocol’.
Fertilisation represents a complex series of changes and interaction between the sperm and the egg. Normally the egg matures within the growing ‘follicle’, which is a small fluid filled sac like structure with in the ovary. The follicle stimulating hormone (FSH) allows development and maturation of the follicle and its egg. The luteinising hormone (LH/hCG) allows the mature follicle to prepare the egg for fertilisation. In natural cycles, only one follicle and egg develops fully. By contrast in an IVF cycle, the ovary is stimulated with hormones to allow multiple eggs to develop simultaneously. At the appropriate time these eggs are removed after they have completed their maturation in the ovary. The egg is surrounded by a shell called the `zona pellucida’ and a group of cells called the `cumulus oophorus’.
Naturally after the sperm are ejaculated in the vagina, they swim upwards, through the womb and into the fallopian tubes where they expect to meet the egg. On the other hand in an IVF cycle, the sperm meets the egg within the laboratory dish approximately 3 to 7 hours after the egg collection. The sperm then has to dissolve the cumulus cells to reach and fertilise the egg. Once the sperm reach the zona pellucida, it undergoes a series of changes before entering and fertilising the egg. Immediately after this the egg undergoes a complex reaction that will stop any more sperm from entering except when it is not of a good quality when this may happen. In couples with very low sperm counts or other defects of sperm function, a single sperm is injected into the egg to assist fertilisation. This procedure is called ICSI (Intracytoplasmic Sperm Injection). This is described in detail elsewhere in this booklet.
After fertilisation, the egg forms a single-cell embryo which will then undergo a series of divisions. On the second day the embryo would have reached the 2 to 4-cell stage. By day 3 the embryos have 5-8 cells within. This is when the embryos are usually transferred. After culture to day 3-5 and with continued development, the embryo will become a tight ball of cells, `the morula’ by day 4 and a `blastocyst’ by day 5 or 6. At this stage, the embryo is ready to implant. If further development continues within the body after implantation, the embryo will release the hCG that can be detected with a pregnancy test.
In nature only 1 in 4 embryos implant and carry on development to be recognised as a pregnancy. Nearly 40-50% embryos are genetically abnormal both in nature and also when formed in the laboratory. The risk of abnormal embryos increases progressively with the age of both the female and the male partner.
When more than one embryo is transferred, your chance of becoming pregnant is increased but your chance of multiple pregnancy is also higher. The law permits a transfer of a maximum of 3 embryos in women >40 years in age because the risk of multiple pregnancy is very low in this group. In suitable patients, prolonged culture to day 3 or day 5 improves the selection of embryos for transfer when a single embryo may achieve the same success rate as two but without a high risk of a twin or a triplet pregnancy.