Ask us about IVF

In vitro fertilisation (IVF)

In vitro fertilisation is a widely used fertilisation technique worldwide effectively resolving a number of current infertility issues. In brief, female ovaries are fertilised under laboratory conditions and then placed in the endometrium. The treatment objective is to achieve pregnancy by transferring one or more embryos to the future mother’s uterus.

When to select this treatment

IVF is mostly used in cases where there is fallopian tube obstruction or dysfunction, hormonal disorders, polycystic ovary syndrome, endometriosis, male reproductive system problems and various other known or unknown infertility causes.

The IVF cycle consists of the following stages:

  • Ovarian suppression and stimulation –drug-induced ovulation


At the initial stage of treatment, ovaries are stimulated by hormonal drugs to produce many ovaries. Should one consider that normally the female body grows and releases only one mature egg monthly, the development of more ovarian follicles is possible by administering hormones (a combination of GnRH and FSH analogues) inducing controlled ovarian stimulation to develop multiple ovarian follicles.Monitoring stimulation with a series of sonograms and hormonal determinations

  • During ovarian stimulation treatment, the female undergoes systematic sonographic tests to assess whether the ovarian follicles in which eggs are found have achieved the desired size and maturation.ν


Sonographic and hormonal determination is required to monitor stimulation and administer chorionic gonadotropin (hCG). Ovulation is induced by a midnight injection approximately 36 hours prior to the egg collection and completes the medication in the treatment protocol followed.

  • Egg collection


The egg collection follows (collecting developed eggs); during this process, the gynaecologist performs an ultrasound-guided transvaginal paracentesis of ovarian follicles using precise and fine movements. The ovarian fluid is immediately tested by an embryologist under the microscope to confirm an egg has been collected and the process is repeated for all mature eggs in ovaries. The embryology lab will then let us know of the final number of collected eggs. Egg collection is carried out under intravenous sedation and it is practically a painless and brief process.

  • Sperm collection


Approximately two hours before the egg collection, a sperm sample is collected from the wife’s husband. This samples is subjected to a special activation process, where the most mobile and healthy spermatozoa are selected. They remain in the lab in a nutrient until they are placed with the eggs. In case where no spermatozoa are found in the fluid, a testicular biopsy is performed.


Testicular biopsy (MESA /TESA)

In cases of azoospermia (where there are no spermatozoa at ejaculation), a testicular biopsy is performed to take spermatozoa from the testicle or the epididymis for fertilisation.
There are two ways to collect semen: from the head of the epididymis under local anaesthetic using paracentesis (MESA), or by a small testicular incision or using full sedation and biopsy (TESA). The process is performed by an expert urologist on the same day as the egg collection or one day earlier.


ICSI Microfertilisation

In case of male or unknown infertility suspected to result from the semen’s difficulty to normally enter the egg, ICSI (Intra-Cytoplasmic Sperm Injection) is used. Following the egg collection, microfertilisation is performed using special equipment and a spermatozoon is placed in each egg to be fertilised.

This technique is recommended in cases of semen quality-related issues (reduced number, low mobility, abnormal morphology etc) since it practically overrides almost all male-related infertility issues. Provided that spermatozoa are viable, over 50% of ovaries are normally fertilised, regardless of semen quality. ICSI combined with IVF is currently the most effective method to treat male infertility.


Fertilisation

This stage in treatment takes place in laboratories by experienced embryologists. A specific number of spermatozoa is placed with eggs in plates (special tubes) containing a culture nutrient to be fertilised under laboratory conditions, where they will remain for approximately 16-20 hours.

The following morning, eggs are examined using a microscope and it is verified whether or not fertilisation has occurred. The embryologist records the number of eggs normally fertilised and monitors their normal development for the next 2-3 days during which fertilised eggs remain in the lab and continue to grow.


Standard IVF

In standard IVF, eggs are placed in a high concentration of spermatozoa, come in contact with the egg by themselves, and one of them enters the egg and fertilises it. In cases of male infertility, this is the stage where ICSI microfertilisation is applied, i.e. placing a spermatozoon inside the egg using a micropipette (see ICSI microfertilisation).


Embryo transfer

The fourth stage of treatment is embryo transfer, i.e. the transfer of embryos developed in the lab in the uterine cavity. This is a painless procedure performed two or three days after the egg collection or the fifth and sixth day at the blastocyst stage. The embryologist selects the best embryos, which are transferred to the uterine using an ultrasound-guided fine catheter. The number of embryos transferred depends on many factors, but usually two to four embryos are transferred. If there are also other high-quality embryos, they may be cryopreserves. As in normal conception, embryos are implanted in the uterine mucous membrane, the endometrium, by themselves. If there is an implant, there will be a pregnancy. The first pregnancy test is performed approximately 13 days after embryo transfer.


Blastocyte culture

Recently, the development of more ideal culture means resulted in performing the embryo transfer at the blastocyte stage. The term blastocyte refers to a specific stage of embryonic development after 5-6 days of culture. It is essentially the final embryonic development stage prior to its implantation in the endometrium to induce pregnancy. The blastocyte transfer process is similar to the embryo transfer process except it is performed on the 5th or 6th day after the egg process.

This method regards couples who eventually have a number of embryos available for transfer. In these cases, embryon transfer of a few blastocytes (embryos), one or tow, may be carried out to avoid multiple pregnancies without reducing the success rate.

Embryo transfer at the blastocyte stage allows the selection of better-quality embryos (most healthy, morphologically intact, and most developed embryos) since only genetically healthy and potentially capable of implantation embryos will reach this stage (20-40%). Moreover, it mimics the normal reproductive process and offers a better synchronisation of embryos-endometrium.

If the amount of embryos to survive this stage is zero, embryo transfer may not take place.


Stimulation protocols

There is a large variety of ovarian stimulation protocols, but IVF usually uses three, the long, the short, and the antagonist ones. The choice of protocol is at the doctor’s discretion and depends on the particular features of each woman. The duration of the administration of the GnRH analogue is the key difference in the therapeutic protocol to be followed; however, based on each body’s drug response, the protocol may be changed during treatment.

  • Long protocol


The long protocol has two stages, ovarian suppression and stimulation. The first stage, in a woman having a regular 28-day menstrual cycle, suppression will begin on the 2nd or 21st day by administering GnRH agonist analogues (Arvekap, Daronda, Suprefact). Administration of these drugs will last for approximately 10-15 days. A uterine and ovarian sonogram, as well as blood estradiol measurement will be performed to check pituitary and ovarian suppression at the Unit. If suppression is adequate, instructions will be given to take gonadotropins in stage two.   

Ovarian stimulation will begin once deemed that suppression is adequate and pharmaceutically manufactured gonadotropins (Puregon, Gonal-F, Altermon, Merional, Menopur) will be administered under continuous pituitary suppression, i.e. by taking an analogue until the end of treatment at a dosage recommended by the doctor. The duration of stage two is approximately 10-14 days i.e. the long protocol will last approximately one month.

  • Antagonist protocol


Using antagonists, treatments will not last more than 10-12 days. Antagonist effectiveness in achieving pregnancy has been confirmed by recent scientific data and although they are always given considering the particular features of each woman, they are a treatment of choice in major reproduction centres in Europe.

In the gonadotropin-antagonist protocol, stimulation with gonadotropins will begin on the 2nd or 3rd day of the cycle and it will be followed by administration of an antagonistic GnRH analogue to prevent ovulation. Initiation of antagonist administration may take place on the 6th day of gonadotropin stimulation or based on sonographic and hormonal criteria during IVF treatment.

  • Short protocol


The short protocol (flare-up GnRH agonist protocol) is mostly chosen for women with a poor ovarian response to the induced development of multiple ovarian follicles or of an older age. It takes almost half the time it takes the long protocol (10-15 days) since suppression and stimulation phases take place almost concurrently. The GnRH agonist usually begins on the 1st-2nd day of the cycle and pharmaceutical gonadotropins begin on the 2nd-3rd day of the cycle. During treatment, often sonograms and estradiol measurements are performed at the Unit to monitor ovarian response and proper drug dosage. Once found that ovarian follicles have grown (have obtained a diameter over 17 mm) and that the estradiol value has reached the desired rates, ovaries will be matured using a midnight injection (Pregnyl, Ovitrelle) and two days later, egg collection will take place. Other drug administration is stopped (analogues, gonadotropins)

  • Normal Cycle


It is recommended to young women, in cases of male infertility or women with a poor response to medicinal treatment. During the cycle, ovarian follicular progress is systematically monitored with a series of sonograms and hormonal determinations. In the normal cycle, there is only one ovarian follicle producing an egg to be fertilised and finally an embryo to be transferred.


Drug treatment in IVF

Proper drug treatment is one of the key stages for IVF success. In recent years, a major part of reproduction research is focused on the development of new pharmaceutical substances to improve treatment in women. Used drugs increase pregnancy success rates and are considered harmless. They are administered given that in IVF there is an effort to mandate the ovary to produce more than one ovarian follicles to produce enough ovaries to be fertilised and create good-quality embryos to be transferred to the uterus.

Therapeutic protocols used in IVF apply depending on the particularities of each woman’s cycle, age, ovarian response to previous attempts etc.

  • GnRH analogues (agonists and antagonists)


Pharmaceutical GnRH analogues temporarily suspend pituitary function thus preventing an undesired ovarian follicular rupture prior to egg collection. To achieve multiple ovarian follicular development, the doses of pituitary gonadotropins (Follicle-stimulating hormone, FSH/Luteinising hormone, LH) should be under total control better achieved when the pituitary gland will not produce these hormones on its own but with the help of medicinal GnRH analogues.

They are separated in “agonists” marketed under the names Superfact, Daronda, Arvecap and "antagonists” under the names Orgalutran and Cetrotide. Their active ingredients are similar. They are marketed as nasal sprays or subcutaneous injections for daily administration or as 4-week slow-release injections. Depending on the pharmaceutical protocol, the type of GnRH analogue, administration method, and dosage will be selected.

  • Gonadotropins


Ovarian stimulation to develop and mature multiple ovarian follicles takes place by administering pituitary gonadotropins marketed under the names Puregon, Gonal-F, Altermon, and Menopur.  Since these hormones are proteins, they may be administered only by injection, either subcutaneous or intramuscularly using a special pen device.

  • Chorionic gonadotropin (hCG)


This is the last injectable treatment drug. It is administered at a specific time when ovarian follicular maturation is satisfactory since this drug induces ovulation 32-36 hours after its administration, and then egg collection will take place. These drugs are marketed as solution for injection or powder mixed with a special solvent or in a pen syringe under the names Ovitrelle, Pregnyl, and Profasi.

  • Progesteron


Progesteron preparations properly prepare the uterine environment to accommodate the embryo. It is administered after embryo transfer. It is marketed under the name Utrogestan – a product which may be used as oral tablet or vaginal supplement – and the vaginal gel Crinone.

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ASK US ABOUT IVF

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