In vitro fertilization (IVF), how it works

This fertilization technique is based on the surgical retrieval of mature oocytes (pick-up) and fertilization in the laboratory with the partner’s sperm.

In vitro fertilization is an  assisted fertilization technique   based on the surgical collection of mature oocytes (pick-up) and fertilization in the laboratory with the partner’s sperm. The first IVF in history was obtained in 1978 and since then around 2 million babies have been born with this technique.

When is in vitro fertilization used?

It is recommended for severe endometriosis, severe tubal disease such as obstruction, moderate male fertility problems, failed IUI and unexplained infertility.

In particular IVF (or ICSI) is necessary to achieve pregnancy in case of:

• tuboperitoneal factor: acquired or congenital tubal pathology (previous ectopic pregnancy, previous tubal abortions, history of pelvic inflammation, pelvic surgery);
• moderate male infertility: when medical-surgical treatment or intrauterine inseminations have not given results or have been judged inappropriate;
• endometriosis of III or IV degree;
• endometriosis if surgery or intrauterine inseminations have failed or have been judged inappropriate;
• unexplained infertility if previous treatment (e.g. insemination cycles) did not give results or was judged inappropriate;
• cryopreserved semen in relation to the seminal quality following thawing;
• failure of the low-tech therapeutic pathway.

Procedure

3 different types of protocols are mostly used in this technique:

• On natural cycle
• long protocol: cycle with GnRH agonist
• short protocol: cycle with GnRH antagonist

The procedure will include:

1.  in spontaneous cycle or with induction of follicular growth and maturation of several oocytes by administering drugs that induce ovulation ;
2. control of ovarian response to such therapy by ultrasound monitoring and/or estradiol dosage;
3. transvaginal oocyte retrieval, under ultrasound control, under local anesthesia and/or deep sedation, or laparoscopic or transabdominal retrieval in cases where the trans-vaginal technique is not applicable
4. possible identification of oocytes to be donated (egg sharing) for the purpose of heterologous assisted procreation ;
5. semen sample preparation;
6. choice of oocytes;
7. union and extracorporeal culture of gametes (oocytes and spermatozoa);
8. verification of the fertilization of each oocyte;
9. transfer of embryos to the uterus.

Long protocols are the most commonly used. It involves the administration of a GnRH agonist. The aim of prolonged administration is to obtain the absence of stimulation of the ovary and the suppression of folliculogenesis. In about 3 weeks estradiol levels are similar to those of menopause.

Once ovarian suppression has been verified, ovarian stimulation with gonadotropins can proceed.

Protocols with antagonists are of recent introduction. The advantage is that their action on the pituitary gland is practically immediate, protecting the patient from having a premature LH peak and therefore spontaneous ovulation. The advantages of this short protocol are the absence of side effects (similar menupausal), no risk of cysts, shorter duration of stimulation, lower total gonodatropin dosage per cycle and therefore savings in terms of costs.

As in IUI it is important to constantly monitor follicular growth during stimulation , using transvaginal ultrasound. Scheduled dosages of estradiol can also be used to add information to ultrasound monitoring.

Egg retrieval (pick-up)

To achieve final maturation of the oocyte, hCG is administered. This administration should be done upon reaching one or two dominant follicles with a diameter equal to or greater than 17 millimeters. Usually the administration takes place about 34 hours before the egg retrieval.

The sampling is carried out with modern techniques, through ultrasound-guided transvaginal probes.

The retrieval is usually done under local anesthesia and takes 20 to 30 minutes depending on the number of oocytes to be retrieved. Typically, patients are discharged a few hours after the procedure.

The collected oocytes are fertilized in the laboratory

In a standard in vitro fertilization the oocytes are incubated with a motile sperm concentration of 100,000/ml. Otherwise we proceed with an ICSI .

The incubation must take place under specific conditions of temperature, PH and gas content.

The incubation leads to the formation of the embryos which will have to be transferred to the uterus. By the second day they are in the 4 cell stage, by the third day they are in the 8 cell stage, by the third day they are in the morula stage and by the fifth day they are blastocyst.

The embryo transfer takes place either on the third day after oocyte retrieval or on the fifth day at the blastocyst stage . The advantage of the transfer on the fifth day is that the embryo is placed in the uterus in a phase in which it would physiologically be there. The transfer of the blastocyst also allows a better selection of embryos as between the 2nd and 5th day the abnormal ones stop their development.

The transfer is performed without anesthesia using a special catheter.

When can the pregnancy test be done?

It is advisable to do it no earlier than 12 days after the embryo transfer . In case of a positive test, an ultrasound is performed after 2-3 weeks to evaluate the state of pregnancy. If a beta blood measurement is performed, if the beta hCG value is low, it must be repeated 48 hours later to evaluate its progress.

Success rates

The success of this technique depends a lot on the age of the woman (the older the woman the more the chances of success decrease) and the cause of infertility. Smoking and obesity are also parameters that undermine the success of IVF. Obviously the role of the laboratory is crucial.

From the Italian PMA register:

Table 4.28 shows the pregnancy percentages according to the age groups of the patients with respect to the cycles started, blood samples taken and transfers performed only for fresh IVF and ICSI techniques.

What are the complications associated with IVF?

As with any medical procedure, there are risks involved which mainly include:

• multiple pregnancies (the incidence decreases by transferring a single embryo at a time)
• low birth weight and premature birth
• miscarriage
• ectopic pregnancy
• ovarian hyperstimulation syndrome (OHSS) , a rare condition involving excess fluid in the abdomen and chest

The decision to undergo assisted reproduction treatment, whatever it is, is very important because it requires physical, emotional and even economic commitment.

Always discuss with your doctor not only the best options available, but also if IVF is the right path for you. A support group and/or a couple infertility therapist can also be of great help throughout the process.