IVF treatment cycle - key stages see also the general glossary
Stage 1 - Pituitary down-regulation
This is achieved by the use of GnRH analogues. There are 2 main reasons for this down-regulation:
This prevents the spontaneous release of LH from the pituitary, which can interfere with egg development and induce ovulation before the eggs have been collected. It allows for precise control of the treatment cycle - cycle programming and gonadotrophin stimulation can then be started on any day, according to a fixed schedule.
At this stage you can differentiate between "long", "short" and "ultrashort" IVF protocol.
Stage 2 - Ovarian stimulation
Multiple follicular growth is encouraged because multiple embryos greatly improve the success rate.
IVF is still performed in natural cycles - it avoids the risks of multiple births and is cheaper (because the use of ovulatory drugs is avoided), but the success rates of natural cycle IVF are less, simply because fewer embryos are produced and available for transfer.
In the past, stimulation protocols have used clomiphene alone, clomiphene + gonadotrophins, or gonadotrophins alone. Currently, most treatments rely on the use of gonadotrophins, in isolation, but usually in higher doses than those used in simple ovulation induction.
Ongoing monitoring with ultrasound is essential to avoid OHSS.
The response is considered adequate when the largest follicle is 16-20mm in diameter, with several follicles greater than 14mm.
Final maturation of the oocytes is then promoted by a single intramuscular injection of hCG.
Stage 3 - Egg collection
Egg collection is performed 34-48 hours after the hCG injection, before ovulation occurs. Oocyte retrieval is achieved by aspirating the follicles, either laparoscopically or transvaginally, using a fine needle attached to a vaginal ultrasound probe
The fluid from each follicle is examined under a microscope for an egg, and the egg is then kept in a controlled nutrient culture in an incubator.
Stage 4 - In vitro fertilisation
The partner's sperm is prepared in a similar way to that for IUI, and approximately 100,000 motile sperm are added to each egg and fertilisation awaited.
If fertilisation is successful, 2 pronuclei are seen after 12-18 hours and subsequent cell division occurs.
The proportion of oocytes that fertilise varies and may be lower where there are severe abnormalities of the semen sample. However, recent developments have enabled the fertilisation of an egg by a single sperm (ICSI, intracytoplasmic sperm injection, is an example of such a technique). This allows IVF treatment to proceed even in cases of severe male factor infertility.
After fertilisation is confirmed, the zygotes are cultured in vitro for a further 24-48 hours before being placed in the uterus.
Stage 5 - Embryo transfer
A maximum of 3 embryos are replaced, when they are at the 4-8 cell stage.
Embryo transfer is a straightforward procedure - a fine catheter containing the embryos in a small volume of culture fluid, is passed through the cervix and the embryos are deposited in the uterine cavity (see Figure 45.)
Embryo transfer in IVF
Patients need careful counselling about the risks of multiple pregnancies when they consider the number of embryos to transfer , for instance in Europe the maximum is 3. If the unit has the facilities, some embryos or zygotes can be frozen (cryopreserved), using special chemicals to prevent the freezing process damaging the embryo's cells, and these may be used in future unstimulated thaw-replacement cycles.
Stage 6 - Luteal support
Following embryo transfer, most IVF units give patients extra luteal support.
The pituitary down-regulation at the start of the treatment cycle means that there is little endogenous support for the luteal phase. Exogenous hCG or progesterone provides the hormonal balance necessary to prepare the uterus for any pregnancy.
Pregnancy testing is performed 2 weeks after embryo transfer.