In Vitro Fertilisation (IVF)

The IVF process involves:

  • Stimulating multiple follicles and eggs to develop
  • Egg retrieval to get the eggs
  • Fertilizing the eggs in the laboratory
  • Embryo transfer to the uterus

Who should be treated with in vitro fertilization?

IVF can be used as an effective treatment for infertility of all causes except for women with infertility caused by an anatomic problem with the uterus, such as severe intrauterine adhesions.

It is generally used in couples who have failed to conceive after at least one year of trying who also have one or more of the following:

  1. Blocked fallopian tubes or pelvic adhesions with distorted pelvic anatomy. Women that have had tubal ligation and are considering tubal reversal surgery as well as men that are considering vasectomy reversal surgery might also consider IVF.
  2. Male factor infertility (low sperm count or low motility). ICSI is an IVF procedure that can fertilize eggs even with poor sperm quality.
  3. Failed 2-4 cycles of ovarian stimulation with intrauterine insemination
  4. Advanced female age – over about 38 years of age. In vitro fertilization and advanced maternal age is discussed in detail on the female age page.
  5. Reduced ovarian reserve, which means lower quantity (and sometimes quantity) of eggs. A day 3 FSH and estradiol test, antral follicle counts and AMH hormone levels are often done as screening tests for egg quantity. Reduced egg quantity and quality is usually treated with either IVF, or with IVF with egg donation.
  6. Severe endometriosis
  7. Unexplained infertility when inseminations have failed. Unexplained infertility means standard fertility tests have not found the cause of the fertility issue.

How does IVF improve fertility?

In vitro fertilization increases the efficiency of human reproduction, which is often not very efficient naturally.

  • Essentially, it is a numbers game that worsens as the female partner ages
  • With IVF we remove multiple eggs – and after careful culture for 3-5 days of the eggs that fertilize, we transfer one or more of the “prettiest” embryos back to the uterus.
  • Any remaining embryos (if there are any) can be frozen for future use by the couple

In a sense, we compress many months of “natural” attempts into one menstrual cycle. By transferring the fertilized embryo(s) directly to the uterine cavity, fertility is improved for many couples that have sperm issues (fertilization defects), or issues on the female side related to egg pickup from the ovary, or tubal transport of the embryo to the uterus.

Therefore, with IVF:

  1. We stimulate with medications to produce multiple follicles and eggs (only one follicle with one egg inside develops in a natural menstrual cycle)
  2. We retrieve the eggs from the ovaries when they’re ready (release and tubal pickup of the egg can be inefficient naturally)
  3. We coerce fertilization in the lab (sperm or egg issues can cause fertilization problems in a natural situation)
  4. We culture the embryos for several days and then pick the best one (or more) for transfer to the woman – selection of the best one(s) increases success.
  5. We transfer the embryos to the best location in the middle of the uterine cavity (tubal transport of the embryo to the uterus is bypassed)

 

The Natural versus The IVF cycle

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.

 Steps of IVF

 

Risks of In Vitro Fertilisation (IVF)

There are no treatments that are completely free of risk. In an IVF cycle there are the following risks:

Ovarian hyperstimulation syndrome

If your ovaries have shown an excessive response then you are at risk of Ovarian Hyperstimulation Syndrome. Everybody receiving drugs for ovarian stimulation in order to produce multiple eggs is at risk. However the risk is not the same in everybody and we have developed clinical tools with which we assess your individual risk. This can vary between mild, moderate, severe and very severe. Young and overweight women with polycystic ovaries are especially ‘at risk’.

 

Miscarriage

The risk of miscarriage after a positive pregnancy test alone is approximately 10-20%. This is no different to that after a normal conception. Once the pregnancy sac has been seen and the fetal heart action identified then the risk of miscarriage is substantially less. The risk of a congenital or genetic abnormality in babies born after IVF has not been higher than that in spontaneously conceived pregnancies. Your personal risk is more likely to relate to your age, your family history and whether or not you have a multiple pregnancy. Please see the section on multiple pregnancies for further detail.

Risk of an ectopic pregnancy

The embryos are not ready to implant at the time of their replacement. At that time they are in a very small volume of fluid which we expect to spread like a thin film on the surface of the lining of your womb. The embryo may sit in a fold of the lining of the uterus until it reaches the stage of implantation. The risk of embryo floating away in the direction of the fallopian tube exists in all patients. In normal circumstances we expect that the fine hair in the tube that beat in the direction of the womb will prevent such a migration. However in some cases this may not happen and the embryo enters the tube. Unable to return to implant in the uterus and especially in women with damaged tubes, it may attach itself to the tube and thus a tubal pregnancy occurs. If left undiagnosed, the tube may rupture and internal bleeding may take place.

 

Risks of the Egg Collection Procedure

At the time of an egg collection a needle is carefully passed through the wall of your vagina into the ovary under ultrasound vision. The risks include those of an infection, bleeding and damage to an internal organ requiring surgery and repair.

Infection

  1. The needle can transfer germs from your vagina into the pelvis and lead to an infection. The risk of this is greater:
  • if you have chronically infected tubes, an active vaginal or pelvic infection, your tubes are swollen or distended with fluid that may still contain bacteria.
  • if you have endometriosis and especially if you have Endometriomas that have to be entered during the egg collection.
  • If you have extensive adhesions incorporating the bowel the risk of bowel injury is increased also.

2. Its  advise that both partners undergo screening for genito-urinary infections before they undergo a treatment cycle at least once but it could be prudent that you have screening done before each cycle. It can easily be done via your GP and requires the nurse to take a swab and check your early morning urine samples for NAAT analysis for chlamydia in particular.

 

Bleeding or internal injury

Potentially the needle can also enter a blood vessel leading to internal bleeding or perforate a loop of the small or the large bowel leading to internal infection, need for major surgery and further treatment as appropriate. The risk of this complication is quite remote and less than 0.001%.

Risk of a multiple pregnancy

Most assisted conception procedures carry with them the risk of a multiple pregnancy. Please read the section on the number of embryos to be transferred and multiple pregnancies where this risk has been discussed in greater detail.

Other risks

  1. Although some have raised alarm over the risk of ovarian cancer with the use of hormones, these preparations have been used in treatment since early 1960’s without any notified cases that can be directly liked to the use of these hormones. The available evidence suggests that there is no increase in your risk over and above that exists naturally. Infertility per se, delay in first pregnancy, and failure to breast feed, family history, obesity and smoking are known risk factors for the cancer of the ovary and the breast.
  2. There have been no cases of complications with protein impurities in the urinary preparations. Theoretically some have worried that external proteins when injected could transfer viruses or prions that could lead to an illness like CJD at a later date.