Procedure for conventional IVF (in vitro fertilisation/test tube fertilisation)
1. Initial treatment with medications
In conventional IVF, initial treatment with medications is used to generate a relatively high number of egg cells. For this purpose, patients are usually given daily subcutaneous injections of 150 225 IU of FSH (Gonal-F or Puregon) or an FSH/LH mixture (Menogon). Depending on the stimulations protocol, various additional medications will be required to prevent premature ovulation (Synarel spray, Zoladex, Enantone, Decapeptyl).
If enough follicles (egg vesicles) have grown, the so-called “ovulation injection” (Brevactid, Pregnesin, Ovitrelle) is administered to end the egg cell maturation phase. At this point, egg retrieval must be performed.
2. Egg retrieval
Ultrasound-guided transvaginal follicular aspiration (puncture) generally requires the patient to be under anaesthesia for a short amount of time. This procedure takes place 32 to 36 hours after the hCG injection.
During this procedure an aspiration needle in a guide sheath is inserted into the vagina on the ultrasound transducer head. The ovary is only a few millimetres away. The needle is then advanced through the vaginal wall and directly into the individual follicle. The liquid is drawn out and passed directly to the biologist so that it can be determined immediately whether the follicle contains an egg cell.
The egg cells are placed in a nutrient solution in the laboratory and coated with approximately 50,000 to 100,000 sperm with good motility. The dishes are incubated (cultured) in an incubation cabinet overnight.
After it has been determined 19 – 21 hours later how many cells have reached what is known as the pronucleus (PN) stage, a maximum of 3 PN-stage cells (this is the case in Germany, at least) must be selected to complete the fertilisation process. The pronuclei each contain the chromosomes of the egg cell and the sperm cell.
On day 2 or 3 after the sperm has been introduced, when one or more embryos have developed, the embryo(s) are transferred into the uterine cavity. A transfer on day 5 is also possible and is advisable if one or more blastocysts have developed.
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4. Embryo transfer
Embryo transfer is performed on day 2, 3 or 5 after the sperm has been introduced. This is an entirely pain-free procedure which involves a catheter being advanced into the uterine cavity, if necessary with ultrasound guidance. The embryo(s) are carefully positioned there.
To prepare for the transfer, the woman can take medications to relax the muscles in the uterus. Over the next 14 days, progesterone (luteinising hormone: Crinone-Gel, Utrogest) should be added to achieve optimal conditions in the mucous lining for implantation (nidation) of the embryo.
During the time following embryo transfer, patients should avoid excitement and excessive activity. They should also avoid cardiovascular exertion such as sports and severe increases in temperature (such as saunas or hot baths). Otherwise, there are no specific recommendations. Even sex is more likely to have a positive effect.
12 to 14 days after fertilisation, a urine pregnancy test or a blood test can be performed to determine whether the woman is pregnant.
One advantage of this method is that in most cases “sufficient” (partially) inseminated eggs are “left over”. These can then be used in later “cryo cycles” However, more recent studies indicate that the percentage of “good” egg cells appears to be higher if fewer follicles are cultured. This would mean that the frozen cells (obtained from conventional IVF) would include fewer cells capable of development than expected and hoped for.
The risks of IVF are as follows:
- Damage to organs
- Multiple pregnancy
- Tubal (ectopic) pregnancy
OHSS (Ovarian Hyper-Stimulation Syndrome) – overstimulation of the ovaries
With every type of hormonal stimulation of the ovaries, such as the treatment performed prior to in vitro fertilisation and intracytoplasmic sperm injection, there is a risk of the ovaries being overstimulated. The higher the stimulation dose selected, the higher the risk of hyperstimulation. The risk is especially high for women with polycystic ovary syndrome (PCOS).
The goal of ovarian stimulation for IVF is to have multiple egg cells mature to ensure that it is sufficiently likely that enough embryos will be available for embryo transfer. The target of 10 – 15 follicles will grow under the commonly selected standard dose of 150 – 225 IU per day. However, particularly during the first stimulation cycle, it is not yet known exactly how the woman will react to the hormone administration. An excessive reaction may result in OHSS. OHSS often involves 20 – 50 follicles growing, which due to their size alone causes problems with compression. Just imagine that a mature follicle has a diameter of 2 cm. An additional problem is posed by the oestrogen produced by the follicles. The higher the blood oestrogen level, the more pronounced the changes in the walls of blood vessels and there can in some cases be a shift of fluids (from the blood vessels into the abdominal cavity), which in turn causes the compression problems to worsen. This accumulation of fluid (ascites) may be so severe that the patient may feel very unwell and may be at risk of thrombosis due to a relative shortage of water in the blood. If severe, the accumulated fluid can be aspirated transvaginally (through the vagina, in a manner similar to follicular aspiration) or percutaneously (through the skin) in order to achieve rapid improvement of symptoms. Unfortunately, this will usually need to be performed over several days as the walls of the blood vessels will continue to be permeable.
In extreme cases, patients may require treatment on the intensive care unit.
Follicular aspiration – egg retrieval
Follicular aspiration is performed with the aid of vaginal ultrasound and can be performed with or without anaesthesia. The use of a local anaesthetic is also possible, but requires some time and effort.
The aspiration involves a long needle that is advanced through a guide sheath mounted on the ultrasound transducer. Under visual guidance, the needle is then advanced through the vaginal wall (2 -3 mm), directly into the follicle, which contains a fluid that holds the egg cell. If the ovary is in an unfavourable position or if there are other technical problems, it is conceivable that the bowel, blood vessels and bladder could be injured.
Because access is via the vagina, there is in principle a risk of infection, even if local disinfection is performed.
Risk of multiple pregnancy
In order to achieve pregnancy rates of 30 – 35 % in Germany, an average of at least 2 embryos need to be transferred. The multiple pregnancy rate in Germany is approximately 20 – 25 %, with a rate of triplet pregnancies of up to 4 %. The problem lies in the increased incidence of pregnancy complications – premature births and the associated problems.
For years, unwanted multiple pregnancy was regarded to be the fault of reproductive medicine. There are various options for reducing this risk. However, many of these are prohibited in Germany. In countries with far more liberal laws, comparable pregnancy rates are achieved with the transfer of just one “top quality” embryo.
Given a liberal legal framework and the appropriate expertise on the part of the IVF laboratory, SET (single embryo transfer) represents the best strategy for avoiding multiple pregnancy.
Even IVF may result in ectopic (tubal) pregnancies. This is because embryos will continue to shift back and forth in the uterine cavity for a few days (due to muscle contractions). As a result, in up to 4 % of cases the embryo may migrate into the fallopian tube, resulting in an ectopic pregnancy with its associated complications. Depending on when it is diagnosed, this problem is treated with either medications or surgery. Only early diagnosis is capable of protecting the patient from life-threatening complications.
— Diagrams: © Professor Herrero, Barcelona