IVF protocols: long, short, good, feeling

Protocol selection IVF is not an easy step for the reproductive system and requires the highest level of professionalism It is considered a priority of assisted reproductive technologies, along with diagnostic completeness infertility.

stages of IVF

Methods of treatment of male and female infertility, in which individual or all stages of fertilization and early embryo development take place outside the body, is called assisted reproductive technology (ART).

ART include:

• fertilization of an egg by sperm outside the woman's body - in vitro (IVF);
• embryo transfer good or excellent quality in the uterus or freezing;
• injection of sperm into the egg and ancillary techniques (ICSI, IMSI, pix);
• surrogacy;
• the use of donor material.

in vitro fertilization procedure comprises several consecutive steps:

• conduct diagnostic procedures in order to find the cause of infertility in men and women;
• pre-treatment and correction of pathology with medication and surgical procedures;
• induction of superovulation in long or short protocol;
• monitoring the growth and follicle puncture;
• in vitro fertilization and embryo culture;
• embryo transfer into the uterine cavity;
• drug support after the transfer to the diagnosis and after pregnancy.

For the follicles using a number of ways, reflected in the various techniques of IVF:

• natural (No drug stimulate ovulation);
• short (Covering one menstrual cycle);
• long (Comprising two or more);
• krioprotokolWhich takes place with the purpose of obtaining and freezing embryos for future use.

Protocol selection IVF It carried out individually and depends on the cause of female infertility.

Types of protocols and how they differ

In the framework of assisted reproductive technology experts appointed women to different methods depending on the IVF infertility diagnosis. One woman can apply different protocols in different IVF attempts. After an unsuccessful IVF physician analyzes the existing problems and can apply a different methodology for the next time.

Long and short

The indications for IVF short protocol are:

• inadequate ovarian reserve (low AMH, ovarian failure, resection history);
• age over 35 years;
• multifollikulyarnye ovaries.

Indications for the long protocol IVF consider:

• the woman's age under 35 years;
• endometriosis;
• hyperestrogenia and endometrial hyperplasia;
• PCOS;
• tubo-peritoneal infertility;
• no pipes.

Long pharmacological approach involves regulation of the female menstrual cycle in order to maximize the number of mature, high-quality eggs.

Long protocol is different from the short the following parameters:

• It lasts 2 months or more;
• completely takes control of the growth and maturation of follicles;
• It makes it possible to get the maximum number of follicles;
• obtained follicles characterized by the same degree of maturity;
• follicles in the long protocol IVF grow synchronously;
• risk of immature oocytes is lower than when using short protocol;
• prevents premature ovulation;
• It provides an adequate response to the endometrium.

The main difference between the long protocol Short is ovarian preceding blockade with long procedure.

Long protocol involves disabling pituitary function, followed by stimulation of ovulation, while short IVF protocol begins with the stimulation or blockade with simultaneous stimulation.

When using a long protocol IVF experience a temporary suppression of gonadotropin secretion drugs, resulting in marked positive aspects of methodology:

• obtaining a large number of follicles, which significantly increases the chances of successful IVF outcome. A considerable number of embryos allows for replanting, and the remaining freeze, having chances in the near future to carry out retry IVF with less material investments, as well as to minimize the stress on the body due to lack of women need hormone stimulation;
• preventing sudden LH peak, which allows to control spontaneous ovulation;
• possibility to vary the time of receipt of follicles for IVF;
• protocol flexibility (long and super-long).

The downside of using a long protocol IVF It is a high likelihood of developing ovarian hyperstimulation syndrome.

Hyperstimulation growth is the result of a large number of follicles. Since the follicular wall actively produce estrogen, their level of excess leads to the corresponding reactions in the blood: blood clots, appearance of the liquid in the cavities (thoracic, peritoneal).

Short IVF protocol offers the following features:

• small number of mature follicles;
• asynchronous follicular growth;
• lower chance of developing ovarian hyperstimulation syndrome.

Rule IVF protocol, the observance of which is considered to be a success on the stage of ovulation stimulation is an increase in the follicle diameter is 2 mm daily and endometrial - 1 mm.

At the end of 4-5 days from the start of the stimulation carried ultrasound for the evaluation of ovarian response and endometrial. Further, the multiplicity of ultrasound every 2-3 days, after reaching the follicles of 15-16 mm - every day.

For follicle maturation HCG administered drugs which promote detachment of the egg from the inner follicle wall, whereby it is located freely in the fluid, when subjected to the fence puncture.

HCG preparations which are administered in the final stages of ovulation induction, are crucial for the following parameters:

• of the receipt of eggs;
• timeliness of the cells;
• ability to fertilize oocytes, caused quality;
• the outcome of the IVF.

Criteria for the introduction of hCG in a long protocol IVF:

• average diameter of any three follicles greater than 20 mm;
• Endometrial thickness greater than 8 mm.

Criteria for the injection of hCG in a short protocol:

• achievement follicle size of 18 mm in the main cohort;
• Endometrial thickness greater than 8 mm;
• a threefold increase in the progesterone level in comparison with the initial level.

After the puncture, the course of events in the short and long IVF protocol is virtually the same. Some women to support the luteal phase is introduced 5000 units of HCG several times. In general support is the use of progesterone drugs, blood thinners. After 14 days from the date of replanting prescribe a blood test for hCG. If positive, progesterone continues to support up to 16-20 weeks with gradual withdrawal.

If an ultrasound before replanting mismatch endometrial structure, the woman offered to freeze embryos and start krioprotokol a few months.

Krioprotokol

Method of treatment of infertility by IVF in which the uterus is transferred previously thawed embryos called krioprotokolom.

The method may be used in these cases:

• replanting thawed embryos is carried out after the previous IVF failure;
• replanting previously frozen embryos for the purpose of the birth of the second and subsequent children.

Benefits:

• no need for reception stimulating hormone preparations and blockers;
• the natural state of the endometrium in natural cycle, which increases the chance of successful implantation;
• krioprotokola lower cost by eliminating the need to purchase hormone blockade and stimulation;
• possibility to choose the time of the procedure on the basis of personal capabilities.

Options for:

• krioprotokol in a natural cycle;
• krioprotokol with hormone replacement therapy in the presence of or without blockade;
• with stimulation of the ovaries.

In the natural thawed embryos embodiment replanting is carried women with regular menstruation with precise timing of ovulation. To implement this technique doctor using ultrasound assesses the state of the dominant follicle women in a natural cycle, the structure and the rate of growth of the endometrium. The study begins with 3-5 day cycle and are held at intervals of 2-3 days, uchaschayas the time of ovulation.

Sometimes ovulation provocation injected with hCG. After the doctor sees the picture ultrasound ovulation occurred, replanting is carried thawed embryos (approximately 2-3 days after injection or LH peak in the blood).

The disadvantage krioprotokola IVF in the natural cycle is a high probability of incorrect identification of the time of ovulation in women and the choice of replanting time. This type of protocol IVF requires a high level of experience and skill of reproduction.

Minutes of IVF with frozen embryos on hormone replacement therapy is available in two versions:

• the use of the blockade of the pituitary and ovaries using agonists pituitary releasing hormones;
• without blockade.

Most often, the blockade is used in the presence of endometriosis in women. Doctor modulates the cycle, thereby providing a reliable ground for a successful outcome. As in the long protocol, krioprotokole also begin blocking drugs administration on day 20 of the cycle. After the abolition of monthly and wait 2-3 days menstruation a woman starts using estrogen drugs for the growth of the endometrium. 12-14 days estrogens allow normal growth of the inner layer of the mother providing implantation. Then progesterone drugs are used. 3-4 days of receiving is carried out replanting thawed embryos. Progesterone support to continue.

Krioprotokol on HRT without the blockade by the absence of the introduction at the end of the cycle agonist. When a woman begins next month, appointed by the estrogen until the middle of the cycle. Next follow a similar pattern.

Krioprotokol the stimulation means including a procedure minimum stimulating hormone doses. This method is used for the failures in previous protocols frozen embryos. Main objective: to ensure the normal growth of the endometrium. After reaching the required thickness of the endometrium may conduct hCG for ovulation provocation and create more natural conditions for replanting thawed embryos.

In the natural cycle,

As close as possible to natural conditions IVF protocol, which does not require hormonal support of the first phase. In this case, the follicle grows spontaneously without hormonal intervention. In the middle of the cycle when it reaches 18-20 mm wire size puncture and IVF. Before puncture, some experts use in an injection protocol Tsetrotida and hCG.

All stages of the protocol followed by ultrasound. Progesterone support is assigned at the discretion of the attending physician.

The protocol in the natural cycle prescribed to women with tubal infertility, cervical factor in immunoassay, male infertility, when the function of the ovaries and endometrium is not broken.

In some cases, use a modified natural cycle with the use of analogs of pituitary releasing hormones and gonadotropins in minimal dosages of hCG for short circuit.

Testimony to a modified natural cycle are:

• insufficient ovarian response in response to stimulation in IVF previous protocols;
• Relative contraindications for ovarian superovulation;
• women's fear of superovulation.

Also, a modified natural protocol used in the need to use a natural cycle of estrogen in order to obtain the proper thickness of the endometrium.

Driving on days

of the IVF cycle schemes are different, determines the diagnosis of infertility. Reproductologist picks protocol individually.

Long protocol IVF consists of several stages.

1. "Disable" pituitary through a medicament for the possibility of manipulating growth cycle and the maximum number of follicles in the next cycle. It held from 19-25 of the menstrual cycle using agonists (analogues), gonadotropin releasing pituitary hormones.
2. Superovulation using gonadotropins with 2-5 days of the menstrual cycle.
3. An injection of human chorionic gonadotropin - ovulation trigger to complete the maturation of follicles 32-36 to puncture the ovary.
4. Conducting a puncture on the 12-22 day from the beginning of superovulation induction.
5. Fertilization IVF using ICSI, pix, IMSI indicated.
6. Transfer of embryos into the uterus 3-5 days after the puncture.
7. Medicinal support the second phase of the cycle for 14-21 days after the transfer. Starting supplementation corresponds puncture day, but may be up to 3 days from its holding.
8. Performing diagnosis of pregnancy through the analysis on the HCG, and further medical support for a positive result.

The average duration of the long protocol IVF 40-50 days.

In some pathologies such as endometriosis, long IVF protocol may take several months for the purpose of blocking the growth of endometriotic lesions, alignment hormonal levels.

Short protocol can be carried out with agonists or antagonists of the pituitary releasing hormones.

Scheme short IVF protocol with agonists were as follows:

• 2-3 days of the menstrual cycle beginning to apply agonists for the purpose of the blockade's own hormone production, continue to receive up to follicle puncture;
• 3-5 day cycle beginning to stimulate ovulation rate;
• 14 to 20 day ovarian punctures performed;
• culturing embryos lasts 3-5 days, followed by a time of transfer into the uterus;
• for 14-21 days there is medication to support the diagnosis of pregnancy by a blood test for hCG.

The total duration of a short protocol with agonists of IVF is 28-35 days.

Driving short protocol with antagonists of pituitary releasing hormones as follows:

• 2-5 days of the menstrual cycle, ovulation stimulation begins, which lasts about 12-14 days;
• from 10 to 14 day performed a puncture of the ovaries;
• after three or five day culturing embryo transfer is performed;
• diagnosis of pregnancy is carried out 14 days after the transfer.

IVF protocol with antagonists call ultrashort and it lasts 25-31 days.

Thus, a short protocol IVF agonist different from the ultra simultaneous blockade of the pituitary gland and the stimulation of the ovaries.

used drugs

In IVF protocols used drugs to achieve the same goal: to grow follicles, having matured, egg quality, suitable endometrium ensuring successful implantation. Formulations for different protocols in total identical but are assigned different sequences and combinations, depending on the diagnosis of infertility and initial data. All assignments are exclusively physician, dosages are chosen strictly individually after diagnosis.

pituitary lock draw analogies releasing hormones.

By analogues of gonadotropin-releasing pituitary hormone (GnRHa) include:

• buserelin (Suprefakt as injections, nasal spray, depot);
• Lyuprorelin (Enanton Depot injectable depot form);
• goserelin (Zoladex implant shaped);
• triptorelin (Dekapeptil shaped daily and depot injections);
• nafarelin (Sinarella as a nasal spray).

The most popular drug for long IVF protocol is Dekapeptil.

Stimulation of follicular growth in the short or long protocol IVF is accompanied by the use of exogenous gonadotropins, which are at the same time releasing antagonists of pituitary hormones:

• urinary menopausal gonadotropins (combination of FSH and LH): Humegon, Pergonal, menogon, hysterodynia, Menopur;
• recombinant gonadotropins (FSH) Puregon, Gonal-F.

Stimulation in IVF protocol may be carried out using a combination of recombinant and menopausal gonadotropins, but most commonly used menopausal.

Since the length of the protocol involves the blockade of the work gonads women, which means a lack of estrogen, after the abolition of analogs of pituitary releasing hormones estrogen preparations are appointed:

• Divigel;
• Estrozhel;
• estrofem;
• Proginova.

For maturation oocytes before puncture, when the size of follicles reach 18-20 mm administered hCG preparations: Pregnil, Ovitrel. These funds modulate the conditions of the natural cycle, when ovulation occurs before the increase in the level of LH.

To prevent premature ovulation Tsetrotid used.

Support luteal phase - after the stimulation period, and a puncture in the short and long protocol IVF - accompanied designation progesterone drugs, both natural and synthetic. apply:

• utrozhestan;
• Kraynon;
• Duphaston;
• Norkolut;
• Progesterone in oil.

Reproduction can prescribe progesterone combination preparations. And to support the long and short protocol often used preparations of hCG.

Long and short of IVF protocols are accompanied by not only taking hormonal preparations. Depending on the diagnosis of infertility may be used low molecular weight heparins (Clexane, Fraksiparin), adrenocortical hormones (dexamethasone, metipred).

Advantages and disadvantages

Short IVF protocols differ from each other using agonists or antagonists of the pituitary hormones. Short protocol with analogues releasing hormone promotes alignment of the endometrium in relation to the ovarian response, which means the internal structure corresponds to the time of the mother layer transfer. Follicles grow synchronously endometrium acquires three-layer structure by the time of implantation.

Such a short protocol is suitable for women with tubal infertility, cervical factor, the lack of pipes, with unexplained infertility. In other words, when the blockage is not contraindicated, use short IVF protocol analogues (agonists), releasing pituitary hormones.

When using a short protocol IVF without the use of gonadotropin agonists differ milder interference with the hormonal system of women. Blockade does not occur, which means the absence of illness, recovery cycle. Pituitary gland and the ovaries are restored quickly, the cysts are not formed, the likelihood of hyperstimulation is minimal. It is noted asynchrony follicular growth, a small number, the possible mismatch endometrial structure to transfer torque. Such a protocol IVF often used in women whose age has reached 35-40 years or more, when the blockade is undesirable. Ultrashort protocol saves money, since the number of purchased products is minimal.

It is this kind of a short protocol cryopreservation of embryos often ending that definitely increases the chances of success Subsequently krioprotokole when replanting is carried out at the optimum structure of the endometrium is not affected by hormonal artificial impacts.

Long protocol IVF characterized by the highest probability of success. Can not get a lot of embryos of the plant, and the rest is frozen. A major shortcoming of the long development of techniques considered hyperstimulation syndrome on the background of the growth of a large number of follicles.

Long and super-long protocol IVF allows women with endometriosis significantly increase the chances of pregnancy.

possible complications

The most common complication of IVF using a long protocol include hyperstimulation syndrome.

Since for long embodiment ART matures, usually more than 10 follicles estrogen level rises to a significant amount. This leads to the characteristic pathology for:

• increasing the size of the ovaries;
• increase the size of the stomach and the emergence of pain;
• accumulation of fluid in the abdominal and thoracic cavities;
• disruption of the heart and lungs - shortness of breath, choking, loss of consciousness, tachycardia, weakness;
• thickening of the blood, the risk of thrombosis and thromboembolism.

This pathology causes freezing of embryos and krioprotokola in the future.

At the time of application of blockers of ovarian hormone production women experiencing symptoms of menopause: hot flashes, alternating with chills, nervousness, decreased libido, dryness of mucous membranes. These clinical signs observed in a long manner. After this species ART ovaries harder to restore its function due to the blockade.

Ectopic pregnancy IVF registers is 5%. Bond formation of cancerous ovarian tumors and IVF is currently not scientifically proven.

Given that the reason for seeking ART is heavy, often combined, infertility, the risk of miscarriage, missed abortion IVF increases.

Effectiveness and Statistics

According to world statistics, birth of live full-term baby with the first IVF attempt occurs in 40-45% of cases. The success of IVF completely determined quality of the diagnosis of infertility and fidelity of the selected treatment strategy. Objectively selected protocol IVF - the basis of the success of the procedure.

The older the woman the lower her chances of success of IVF.

Describes the following statistics on the results of the use of different protocols of IVF:

• natural cycle - 11% success rate;
• krioprotokol – 23-25%;
• with donor eggs – 47%;
• long protocol ECO - 36%;
• short – 25%.

Equate all women to single statistical data is incorrect, as is not always exaction tactics and diagnosis of the causes of infertility was carried out in full.

In women with infertility, age younger than 35 years, recorded better results when using the long version of ART.

In women older than 40 years have seen the results of such IVF:

• in the long protocol from the first pregnant manages 16% of patients;
• in short - 57%
• naturally - 13%
• in krioprotokole - 19%.

The chances of a successful pregnancy in the protocol in the natural cycle determined by the accuracy and adjusted time of replanting, infertility diagnosis, assessment of endometrial parameters and correctly received by the physician solutions.

survival percentage thawed embryos averages 70%.

If the couple has frozen embryos of lower quality, and replanting in fresh protocol implemented with high quality embryos, the chances of success are reduced. If long or short protocol were accompanied by IVF to obtain and freeze embryos to plant them in the future, the chances of success increase as much as possible, especially if frozen embryos are subjected to high class.

The highest chances of success in IVF observed at a young age with tubal infertility, as well as using donor material.