In vitro fertilization (IVF)

In vitro fertilization (IVF) – treatment of infertility, in which some or all stages of conception and early embryo development are carried out outside the woman’s body.

The principal indications for assisted reproductive technologies cycle are the following:

  • tubal peritoneal infertility;
  • endometriosis;
  • polycystic ovary syndrome and other hormonal forms of infertility, where you cannot achieve ovulation (release of the egg) with the help of medication;
  • immunological infertility;
  • male infertility – decreasing of quality of one or more sperm indicators: the concentration of spermatozoa in 1 ml of semen, reduction in the frequency of motile sperm, increasing number of abnormal sperm forms;
  • unexplained infertility.

Step 1

Consultation, preparation for the cycle

The first step of personal contact with a patient is the first appointment. During the meeting, you discuss the future plan of treatment with the doctor.

It is not necessary that the doctor recommend you the IVF procedure. However, generally more simple treatments for the majority of patients have already been tried.

The decision of reasonability of IVF cycle is discussed in cooperation with the doctor and the couple on the basis of a combination of different factors:

  • the age of the partners;
  • diagnosis of wife and husband;
  • duration of infertility;
  • results of previous treatment.

After first consultation, the doctor can prescribe additional examinations (hormonal examination, immunogram, karyotype,etc.) or manipulative procedures (hysteroscopy, study of uterine tube patency,etc.).

Step 2

IVF cycle

After a detailed examination and consultation in the case of mutual decision, a patient starts a cycle of treatment.

IVF cycle consists of the following steps:

  • Controlled ovarian hyperstimulation or endometrial preparation for transferring previously frozen/thawed embryos (“cryocycle”);
  • Follicle injection to obtain eggs;
  • Eggs fertilization;
  • Embryo culture;
  • Embryo transfer;
  • Luteal phase support;
  • Diagnosis of pregnancy.
2.1. Controlled ovarian hyperstimulation

This step is carried out according to several common protocols.
With all the standardization process protocols of treatment are calculated individually and depend on many factors (age of the patient, the results of hormonal studies, data from previous cycles of treatment, etc.). The main protocols used are as follows:

2.1.1. “Long protocol”

The main protocol under which about 85% of IVF cycles are undergone. As usual, the protocol begins with the injection of Diphereline (Dekapeptil, Zoladex, Buserelin acetate, etc.) on 19-24 day of menstrual cycle. The peculiarities of medication are in its action which lasts 28 days. After one injection of medication, the next cycle starts at its usual time.
In 14-16 days after the injection stimulation with gonadotropins begins (Gonal-F, Puregon, Menopur, etc.), the medication causes the follicles to grow. For a prescription of gonadotropins, it is necessary to ensure in the efficient impact of the first injection of Diphereline. For this purpose, a patient comes to the clinic for an ultrasound examination and a test of estradiol in the blood.
If ultrasound and estradiol levels in the blood indicate the effective impact of the first injection, then the doctor prescribes gonadotropic stimulation – if not, the patient receives additional medications or an additional intake of gonadotropins delayed for several days. The initial dose of gonadotropins is selected from 150 to 300 units per day, depending on the condition of the ovaries, the results of previous treatments, blood hormones level, age.
The next visit to the clinic is assigned in 5-8 days after the start of intake of gonadotropins. Subsequently, the doctor adjusts the dose of gonadotropins according to the results of ultrasound and serum estradiol level. Upon reaching the “leading” follicle diameter of 16-18 mm, the patient receives medication helping an egg maturation (Ovitrel, Pregnil, Horagon, etc.).
These medications should be injected for 32-36 hours before the expected puncturing of follicles.

2.1.2. “Short protocol”

It is usually used for patients with bad evocation of an ovary. It starts from the 2nd day of the menstrual cycle with an injection of Diphereline for everyday injection (0.1 mg) b continues from 3 days (known as “ultra short protocol”) till the day of HCG medication (Ovitrel, etc.) In this case, the intake of gonadotropins starts from the 3rd day of the cycle. In certain cases from the 10-12th day of the cycle, it is prescribed the medication antagonist LHRH (Centrotid, Orgalutran, etc.) aimed to prevent the premature ovulation of follicles.
At the present moment, the appointment of the “short” protocol using antagonist is considered as critical, the prescription of antagonist for more than 3 days is limited. After reaching the diameter of 16-18 mm by a “leading” follicle, a patient takes medications that promote oocyte maturation (Ovitrel, Pregnyl, Horagon).

These medications should be injected for 32-36 hours before the expected puncturing of follicles.

Ultrashort protocol

2.1.3. Antagonist protocol

Practically it is a variant of short or ultrashort protocol without using antagonists.

2.1.4. “Natural cycle”

It is usually used for patients with bad evocation of an ovary on controlled hyperstimulation of ovaries, but with preserved natural folliculogenesis, it means patients who can produce 1-2 eggs whether using gonadotropins or without it. We do ultrasound and hormone monitoring from 7-8 day of the cycle. In certain cases, it can be prescribed medications aimed to grow a follicle and prevention of premature ovulation.

Medications which promote egg maturing should be injected for 28-32 hours before the expected injecting.

2.1.5. Cryo-cycle

In the case of the presence of cryopreserved embryos obtained in previous cycles, it is advisable to carry out their transfer. Transfer of frozen embryos avoids additional controlled ovarian hyperstimulation and follicular injection. Standard protocol for endometria preparation for the transfer of frozen embryos is similar to a “long” protocol and starts with an injection of an agonist for 19-24 days of the cycle. After menses, medications of estrogen are prescribed (Proginova, Estrofem, Divigel, etc.),and on 3-5th day after prescription of progestin (Progesteron, Utrogestan, Dufaston), the transfer of pre-thawed embryos is carriedout. Contrary to the stereotype, the efficiency of the cryo cycle is such as for a conventional cycle.

2.2. Puncture of follicles

Follicle puncture is carried out in 32-36 hours after HCG administration of medications (Ovitrel, Pregnil, Horagon). Usually, an injection administered at 23-00 to make an injection in one day in the morning. For the injection, the patient arrives with an empty stomach. Naturally, the husband has to be present in the clinic this day. He is offered to collect semen. If for some reason the husband cannot come to the clinic on the day of the injection, it is necessary in advance to inform the doctor. In this situation, you can pre-cryopreserved (collect for storage in liquid nitrogen) the husband’s sperm for the purpose of its use on the day of injection. Injection is carried out under intravenous anesthesia, then the patient stays in the clinic for 1-2 hours. Immediately after the injection it is not recommended to drive.
In the case of acute pain and any complaints on the first day after follicle injection it is required to contact your doctor.

2.3. Fertilization of eggs is produced within 3-8 hours after egg collection.

It is used two types of artificial insemination.

2.3.1. Routine (normal) fertilization

To perform it, you must have at least 10 million active motile sperm in the total ejaculate sperm after special treatment. In the culture plate, the minimum amount of processed sperm is added.

2.3.2. ICSI (Intracytoplasmic sperm introduction)

It is used even with minimal changes in the sperm. Carrying out this manipulation and one selected spermatozoid is injected using a special device (micromanipulator) and micropipette into an egg.
There are additional indications for this manipulation – obtaining small amounts of eggs (5 or less), the failure of the previous cycle, etc. In any case, sometimes doctors are reinsured to achieve the maximum amount of egg fertilization. Naturally, the question of the need for ICSI is desirable to decide at the start of IVF cycles, but sometimes there is a need for the appointment of this procedure, the actual day of the injection. The doctor informs you about this after the husband’s sperm preparation for fertilization.

2.4. Embryos cultivation

In 16-18hours after artificial insemination, it is possible to estimate the possibility of fertilization. Embryos are transferred to a fresh environment for further cultivation.
Embryo transfer is carried out from the 2nd to 5th day. Preferred day of transfer depends on many factors. However, conclusive evidence about the benefits of a development day embryos for transfer to the uterus is not revealed. On the transfer of the 5th day an embryologist has more criteria for the selection of embryos, but only 40% of the embryos survive to the 5th day. Not transferred embryos of good quality shall be cryopreserved for possible use in subsequent cycles of treatment.

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