Long protocol for IVF: what it is, how it goes, how long it lasts

Every 10th couple suffers from infertility. Standard treatment methods do not always bring the desired result. Therefore, at a certain stage, indications for artificial insemination arise. This is not just an embryo transfer, but also a special preparation of the woman’s body for the upcoming procedure. All these activities taken together constitute an IVF protocol, which can be long or short. Today we’ll talk about what a long protocol for IVF is and what is its difference.

Why choose a long IVF protocol?

The long protocol is the most tested and most researched, because... appeared one of the first in reproductology. It allows you to achieve good results, having many advantages:

good control over the process of growth and maturation of follicles;
absence of unplanned pre-ovulatory hormone surges that can cause premature ovulation;
better quality of mature eggs and obtaining them in sufficient quantity.

However, like any medical intervention, the long protocol has some disadvantages:

a woman has to take hormonal medications for a longer period of time, so at the preparatory stage an assessment of the functional activity of these organs is required;
at the first stage of the protocol, the cyclic activity of the female body is completely blocked, that is, the patient is put into a short-term drug-induced menopause, so symptoms of estrogen deficiency may appear (headache, hot flashes, increased sweating, etc.);
a long protocol uses large doses of tropic hormones, which can lead to ovarian hyperstimulation syndrome. This condition is manifested by the release of fluid from the vascular bed into the intercellular space. As a rule, in most cases, ovarian hyperstimulation syndrome is mild and responds well to drug therapy. According to statistics, only 1-4% of women with this complication require hospitalization.

At SM-Clinic, reproductive specialists carefully assess the gynecological and somatic status of the patient in order to minimize the risk of undesirable consequences and achieve the best therapeutic result.

Side effects of Buserelin

It is worth noting that “Buserelin” for fibroids and other diseases has a number of side effects:

From the gastrointestinal tract: thirst, nausea and vomiting, weight gain or loss;
From the central nervous system: headaches and dizziness, insomnia, constant feeling of weakness and fatigue, depression, anxiety;
From the cardiovascular system: strong heartbeats, increased blood pressure;
From the senses: visual impairment, hearing impairment, tinnitus;
From the endocrine system: hot flashes, severe sweating, decreased libido, pain in the lower abdomen;
Allergic reactions of varying intensity.

Indications for a long protocol

As a rule, the long protocol is preferred in cases where short stimulation failed to obtain the required number of good quality eggs. However, there are also categories of women who are recommended to begin the ART program with long-term stimulation. We are talking about patients with the following diseases and conditions:

uterine fibroids;
endometrioid disease;
poor egg quality;
cystic formations of the ovaries;
overweight and obesity;
elevated levels of luteinizing hormone according to hormonal screening.

Depends on the characteristics of the clinical case, ovarian reserve and general level of health. The optimal ART program will be selected by a reproductologist after a detailed examination of the female body.

Surgery

Today, the only radical way to treat uterine fibroids is surgery. To determine the most effective method, I suggest that each patient undergo a comprehensive examination. Indications for surgical intervention are:

the presence of nodes larger than 4 cm, regardless of size, if the nodes are located submucosal, of atypical localization, subserous nodes on a stalk, centripetal growth of the node;
bleeding and menstrual dysfunction;
anemia;
pain syndrome;
infertility or miscarriage;
dysuric disorders.

Today there are different methods for removing fibroids; when choosing the most suitable one, I take into account, in addition to the number of fibroids and their characteristics, the patient’s age and her desire to maintain fertility or menstrual function.

Long IVF protocol by day

Unlike the short protocol, the long one begins in the previous cycle before stimulation. Approximately 1 week before the upcoming menstruation, the introduction of gonadoliberin analogues begins, which block the production of their own tropic hormones, and, therefore, the functional activity of the ovaries. The duration of the blocking phase is approximately 2 weeks. In reproductology, this phase is called regulatory, because allows you to bring the menstrual cycle to a common denominator.

After this, the reproductologist begins the stimulating phase. Gonadotropin preparations are administered, which cause a state of superovulation, that is, several eggs begin to mature in the ovaries at once. The average duration of this phase is also about 2 weeks. When the follicles reach the required size (about 20 mm) and the endometrium is prepared, doctors perform a puncture. Under ultrasound control, eggs are obtained from the ovaries through the vagina or through the anterior wall of the abdomen with a special needle, which are then combined with sperm in the laboratory, and subsequently implanted into the uterine cavity.

Now let’s tell you in detail what a long protocol looks like day by day:

Approximately on the 20-25th day of the previous cycle, the administration of GnRH analogues begins.
On the 2-4th day of the current menstrual cycle, drugs that stimulate ovulation are administered.
Towards the end of the first phase (on average 15-22 days), when the follicle reaches 18-20 mm in diameter, ovulation inducers (hCG drug) are introduced, which initiate the final maturation of the egg and its preparation for fertilization. After 36 hours, follicular puncture is performed.
After the puncture is performed, the man collects the sperm. The sperm contained in it are combined with the resulting eggs in the laboratory.
“In vitro” embryos grow for 5-7 days. Before replanting, they are tested for various genetic abnormalities.
Three- or five-day-old embryos are introduced into the uterine cavity. To increase the likelihood of implantation, the hatching technique can be used, when notches are made on the blastocyst (they connect more easily with the uterine mucosa).
Support of the second phase with progestin drugs. It usually begins on the day when the follicle puncture is performed. Progestin drugs help prepare the mucosa for embryo implantation. Their use is mandatory, because against the background of initial suppression of ovarian function, inhibition of the production of its own progesterone is observed.

To confirm pregnancy, 2 weeks after embryo transfer, the level of hCG in the blood is determined. If the result is positive, an ultrasound is performed after some time to directly visualize the fetal egg.

Buserelin in the treatment of internal endometriosis and uterine fibroids

Uterine fibroids and endometriosis are the most common reasons why women visit a gynecologist. In more than 60% of cases, the diseases are combined. The issues of etiology and pathogenesis of hyperplastic processes of the uterus remain not fully understood, and as a result, to date there are no effective drug therapy regimens for these pathologies. At the present stage, the most acceptable approach to the treatment of uterine fibroids and endometriosis is the administration of GnRH agonists. Six-month courses of treatment with these drugs lead to a relative regression of the size of the uterus, myomatous nodes and endometriotic formations, as well as to the leveling of symptoms. Currently, the domestic pharmaceutical market offers a wide range of different forms of GnRH agonists produced by Western manufacturers. The latter causes their high cost and, accordingly, leads to a significant limitation in the number of patients able to receive such therapy. However, relatively recently, a domestic analogue of GnRH appeared in our country - Buserelin (Pharm-Sintez CJSC).

Over the past two years, we have conducted clinical trials of this drug in patients with hyperplastic processes of the uterus. The study included 82 patients aged 40 to 51 years. All patients had a combination of uterine fibroids and grade 1 adenomyosis. The initial size of the uterus in women included in the study did not exceed 10 weeks of pregnancy. On average, after 6 months of therapy with Buserelin at a dose of 900-1200 mcg/day administered endonasally, the size of the uterus decreased to 5-6 weeks, and myomatous nodes decreased by 30-80%. This variation in treatment results is explained by the heterogeneity of myomatous nodes, which probably causes their different sensitivity to the drug. The severity of clinical manifestations of endometriosis decreased. Thus, the frequency of pain syndrome decreased by 85%, the manifestation of dysmenorrhea decreased by 81%, dyspaurenia - by 42%, pain on palpation of the pelvic organs - by 30%, induration - by 25%. Ultrasound data: after treatment with Buserelin, in 78% of cases, the disappearance of ultrasound signs of adenomyosis was noted. In addition, the quality of life of patients taking Buserelin, determined by the severity of adverse reactions, suffered slightly and was higher than when using other drugs.

After completion of therapy, 9 patients experienced menopause; After completing therapy with Buserelin, 16 patients were transferred to maintenance therapy with microdose oral contraceptives. According to our experience, the use of other GnRH agonists in a similar group of patients gives similar results with a significant difference in the cost of treatment.

Thus, Buserelin is not inferior in its effectiveness to foreign analogues, but also has significant advantages over them due to its availability and ease of use.

What drugs are used in a long protocol?

The main drugs used in the long protocol are represented by the following groups:

Analogues of gonadoliberins. They block the pituitary gland, which secretes follicle-stimulating and luteinizing hormones. Shutting off the ovaries in advance helps prevent unplanned early ovulation in the next cycle. These drugs are most often administered once a day in the IVF protocol by injection.
Gonadotropic drugs that contain follicle-stimulating hormone. They act as ovulation stimulants, promoting the maturation of several follicles at once. At this stage, doctors perform strict ultrasound control to avoid the development of ovarian hyperstimulation syndrome.
Ovulation inducers, the active ingredient of which is human chorionic gonadotropin. These drugs help the follicle ovulate and prepare the endometrium (uterine lining) for upcoming implantation.
Progesterone drugs. These funds help maintain the functional activity of the corpus luteum and increase the level of progesterone in the blood, providing sufficient conditions for the secretory transformation of the endometrium. These drugs continue to be administered not only to modulate the second phase of the cycle, but also after the fact of pregnancy has been confirmed by laboratory methods.

Myomectomy

This organ-preserving technique is considered the “gold” standard in the treatment of fibroids in clinics in Western Europe and America. During the operation, the myomatous nodes are “husked”, removed, and the body of the uterus is sutured. The presence of a capsule allows the operation to be performed without damaging the myometrium.

But myomectomy can be performed in three ways: using an open technique, laparoscopy or resectoscopy; in any case, the operation allows not only to avoid organ removal, but also preserves the woman’s reproductive abilities.

I always give preference to laparoscopic surgery, among the advantages of which are: minimal tissue trauma, rapid recovery, painlessness and excellent cosmetic results. I have developed and patented a unique technique that has been successfully used for more than 12 years. Using this technique, I am able to remove even large and complexly located myomatous nodes without blood loss, with the formation of a reliable scar on the uterine wall and the absence of adhesions, which is important for future pregnancy and childbirth. Many of my patients who were diagnosed with infertility, after myomectomy performed in our clinic, were able to safely give birth to a healthy child.

Are there any contraindications?

A long IVF protocol may increase ovarian hyperstimulation syndrome. Therefore, it is not recommended for use in patients with excess follicular apparatus, polycystic ovary syndrome, and elevated levels of anti-Mullerian hormone. Other contraindications are:

excess estrogen content in the body;
repeated stimulation schemes;
allergic mood of the body.

There are also general restrictions when assisted reproduction methods are prohibited. These include:

oncological processes in the body;
severe diseases of internal organs;
mental disorders in which pregnancy is undesirable.

How to increase the chances of pregnancy with a long protocol?

There are a number of recommendations that help increase the success of a long IVF protocol. In addition to using medications prescribed by a doctor, a woman should adhere to the following rules:

Avoid drinking coffee and caffeine-containing products. It has been proven that drinking coffee every 5 days or more increases the likelihood of spontaneous miscarriage.
Eat properly and balanced. The diet should be dominated by vegetables and herbs, lean meats, sea fish (heat-treated), cottage cheese, and eggs.
Maintain sexual rest. Intimacy is prohibited for 2 weeks after embryo transfer, so as not to disrupt the implantation process by mechanical and chemical means.
Do not visit baths and saunas, do not take a hot bath. High temperatures can damage the fertilized egg.
You should spend more time outdoors. Bed rest, as it turned out, does not improve the outcome of conception, but on the contrary, it can even be harmful, for example, due to an increased risk of thrombosis.
Try to avoid heavy physical activity and psycho-emotional shocks, because... they can disrupt the delicately regulated endocrine system.

Naturally, before entering the IVF program and at all stages of its implementation, as well as carrying a child, you should stop smoking and drinking alcohol. These factors have been proven to increase the frequency of miscarriages and the formation of placental insufficiency.

To realize your dream of happy motherhood, make an appointment with the fertility specialists of the SM-Clinic clinic. Our center has introduced the most advanced technologies for diagnosing the causes of infertility and the most advanced treatment methods that help cope with even the most severe fertility disorders. Doctors are available at convenient times by appointment.

Mode of application

Side effects can be minimized and positive results can be achieved from taking Buserelin by strictly following the dosage and dosage regimen recommended by your doctor. They directly depend on the form of release of the drug. Thus, a nasal spray is usually used three times a day at equal intervals at a rate of 0.9 mg per day. During treatment, oral contraceptives cannot be used, so it is recommended to replace them with other methods of contraception. Intramuscular injections of Buserelin are given every 28 days, starting 5 days before the start of the cycle. If the product is used as preoperative preparation, then injections are given within three months. As for conservative therapy, its course lasts six months.