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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 a 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 the number of abnormal sperm forms;
  • unexplained infertility.

Step 1

Consultation, preparation for the cycle

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

It is not necessary that the doctor will recommend you exceptionally the procedure of IVF. 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 of the doctor and a couple on the basis of different factors combination:

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

 

For the first consultation the following examinations are required:

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

Step 2

IVF cycle

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

IVF cycle consists of the following etapes:

  • Controlled ovarian hyperstimulation or endometrial preparation for transferring previously frozen/thawed embryos (“cryocycle”);
  • Follicle puncture 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 purpose of protocols enough individually and depends 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 it is hold about 85% of IVF cycles. As usual the protocol begins with injection of Diphereline (Dekapeptil, Zoladex, Buserelin acetate etc.) on 19-24 day of menstrual cycle. The peculiarities of medication are in his action which lasts 28 days. After one injection of medication next cycle starts in usual time.

In 14-16 days after the injection stimulation with gonadotropins begins (Gonal-F, Puregon, Menopur, etc.), the medication causes the follicles growth. 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 clinic for ultrasound examination and 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. 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 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 2nd day of 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 3rd day of the cycle. In certain cases from 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 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.

Ultra short protocol

2.1.3. Antagonist protocol

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

2.1.4. “Natural cycle”

It is usually used for patients with bad evocation of an ovary on controlled hyper stimulation 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 puncturing.

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 puncture. Standard protocol for endometria preparation to the transfer of frozen embryos is similar to a “long” protocol and starts with injection of 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 carrying out. Contrary to the stereotype the efficiency of cryo cycle is such as for a conventional cycle.

 

2.2 Puncture of follicles

Follicle puncture is carrying out in 32-36 hours after HCG administration of medivations (Ovitrel, Pregnil, Horagon). Usually an injection administered at 23-00 to make a puncture in one day in the morning. For the puncture the patient arrives at an empty stomach. Naturally, that husband has to be present in the clinic this day. He is offered to collect semen. If for some reason the husband can not come to the clinic on the day of the puncture, 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 in the day of puncture. Puncture is carried out under intravenous anesthesia, then the patient stay in clinic during 1-2 hours. Immediately after the puncture is not recommended to drive.

In the case of acute pain and any complaints on the first day after follicle puncture is an urgent need 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 an 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 in order 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 puncture. The doctor informs you about this after the husband’s sperm preparation for fertilization.

2.4. Embryos cultivation

In 16-18hours afterartificial insemination it is possible toestimate the possibility of fertilization.Embryos aretransferredto fresh environment for furthercultivation.

Embryo transfer is carried out from 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. When 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.