Meriofert, lyophilizate 75 me fsg+75 me lg

Meriofert is a highly purified human menopausal gonadotropin (hMG) preparation. It belongs to the group of menotropins. The ratio of the biological activity of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is 1:1. The drug is obtained from the urine of postmenopausal women.

The specific receptors for gonadotropins are present only in the tissues of the genital organs. In the ovaries, LH binds to receptors on the surface of theca cells and the corpus luteum, as well as to granulosa cells of large follicles.

FSH binds to receptors on the surface of granulosa cells of small follicles in the ovaries and Sertoli cells in the testes.

In women, Meriofert stimulates growth and maturation of ovarian follicles, increases the concentration of estrogens, and stimulates endometrial proliferation. In men, it stimulates spermatogenesis in azoospermia and oligoasthenospermia.

Indications

In women:

– Anovulation (including polycystic ovarian syndrome (PCOS) when clomiphene therapy is ineffective).

– Controlled ovarian hyperstimulation for the induction of multiple follicle growth in assisted reproductive technology (ART).

In men:

Stimulation of spermatogenesis in azoospermia and oligoasthenospermia caused by congenital or acquired hypogonadotropic hypogonadism (in combination with human chorionic gonadotropin (hCG) preparation).

Active ingredient

Composition

1 vial of lyophilizate contains:

The active ingredient – highly purified human menopausal gonadotropin hMG (menotropin) 75 IU FSH+75 IU LH, 150 IU FSH+150 IU LH

Ancillary Component – lactose monohydrate 10.00 mg

Interaction

Pharmacodynamic

Meriofert may be administered alone or in combination with gonadotropin-releasing hormone (GnRH) agonists or antagonists./p>

The combined use of Meriofert with other drugs used for ovulation stimulation (e.g. hCG, clomiphene) may increase follicular response. Co-administration with GnRH agonists may require increasing the dose of menotropin.

Pharmaceutical

Meriofert should not be mixed with other medications in the same syringe.

Directions for use

Meriofert is administered intramuscularly or subcutaneously with periodic change of injection site. Subcutaneous method of administration is preferred because it provides the greatest absorption of the drug substance. Therapy with Meriofert should only be carried out under the supervision of a physician with appropriate specialization and experience in the treatment of infertility.

The solution is prepared immediately prior to injection using the solvent provided. The doses described below are for FSH and are the same for both subcutaneous and intramuscular administration.

In women, the dose of the drug is set individually depending on the ovarian response. This requires monitoring the response of the ovaries to therapy by ultrasound examination (USG) in combination with determination of plasma estradiol concentrations.

Anovulation (including PCOS when clomiphene therapy is ineffective).

The drug Meriofert may be administered daily. The drug should be started within the first 7 days of the menstrual cycle. The recommended initial dose is 75-150 IU/day. If the ovaries do not react sufficiently, the dose is gradually increased. The recommended interval for increasing the dose should be at least 7 days. The recommended increasing dose is 37.5 IU, but no more than 75 IU.

The maximum daily dose usually does not exceed 225 IU. If the therapeutic effect is not achieved within 4 weeks of treatment, Meriofert injections are stopped and then a new cycle is started with a higher dose of the drug. The patient is recommended to use barrier methods of contraception or abstain from sexual intercourse until the onset of menstruation.

If an adequate ovarian response is achieved on the day after the last Meriofert injection, 5000-10000 IU of hCG is administered once to induce ovulation. The patient is recommended to have sexual intercourse on the day of hCG injection and the day after the injection. Intrauterine insemination is an alternative method.

If the ovaries overreact, Meriofert should be stopped and hCG injections should be discontinued.

The treatment should be resumed in the next cycle at a lower dose than in the previous cycle.

Controlled ovarian hyperstimulation for the induction of multiple follicle growth in assisted reproductive technology (BPT).

The commonly used protocol for hyperstimulation involves administering 150-225 IU of Meriofert daily starting on day 2 or 3 of the menstrual cycle and continuing until sufficient follicle size is achieved. The daily dose is adjusted according to the patient’s response to therapy. The daily dose of the drug should not exceed 450 IU of FSH.

24-48 hours after the last injection of Meriofert, one injection of hCG is administered at a dose of 5000 IU-10000 IU to induce final follicle maturation.

To prevent the release of endogenous LH, gonadotropin-releasing hormone (aGnRH) agonists are now widely used. In this case, Meriofert should be started about two weeks after starting GnRH agonist treatment. Thereafter, both drugs continue to be used together until adequate follicle development is achieved. The dose of Meriofert is adjusted according to the patient’s ovarian response.

In male hypogonadotropic hypogonadism for stimulation of spermatogenesis, Meriofert is prescribed if the previous therapy with hCG drugs caused only an androgenic response without signs of increased spermatogenesis. In this case, treatment is continued by administering 2000 IU of hCG 2 to 3 times a week along with injections of Meriofert (75 IU or 150 IU) 2 to 3 times a week. This regimen should be continued for at least 3 months.

If there is no positive effect during this time, treatment may be continued for up to 18 months.

Special Instructions

The treatment should be supervised by a physician experienced in treating infertility.

Pending administration of Meriofert, an examination for hypothyroidism, adrenal insufficiency, hyperprolactinemia, pituitary or hypothalamic tumors; and appropriate specific treatment is recommended.
SGN
SGN is a syndrome distinct from uncomplicated ovarian enlargement whose manifestations vary in severity. It includes significant ovarian enlargement, high serum estrogen concentrations, and increased vascular permeability, which may lead to fluid accumulation in the abdominal, pleural and, rarely, pericardial cavities (in severe SGF). In moderate CGY, the following symptoms are observed: abdominal pain, abdominal bloating, significant ovarian enlargement, weight gain, shortness of breath, oliguria, and gastrointestinal symptoms, including nausea, vomiting, and diarrhea.

Hypovolemia, hemoconcentration, electrolyte disturbances, ascites, hemoperitoneum, hydrothorax, acute respiratory distress syndrome and thromboembolic complications develop in severe SUI.

The overreaction of the ovaries to gonadotropin administration rarely leads to the development of SVF unless hCG is administered to stimulate ovulation. Therefore, in cases of ovarian hyperstimulation, hCG should not be injected and the patient should be warned to abstain from intercourse or use barrier methods of contraception for at least 4 days.

HCG can progress rapidly (within 24 hours to several days), becoming a serious medical complication, so patients should be monitored for at least 2 weeks after HCG injection. Adherence to recommended doses of Meriofert, the administration regimen, and close monitoring of therapy can minimize cases of ovarian hyperstimulation and multiple pregnancies. In ART, aspiration of all follicle contents before ovulation can reduce the risk of SVF.

SGF can be more severe and prolonged in the development of pregnancy. Most commonly, SGY develops after discontinuation of gonadotropin treatment and peaks in severity within 7-10 days of the end of treatment. Typically, SGN passes spontaneously after the onset of menstruation.

In moderate to severe SGN the patient is hospitalized and specific therapy is initiated.
SGN occurs with high frequency in patients with polycystic ovarian syndrome.
Multiple pregnancies.

In multiple pregnancies, there is an increased risk of adverse maternal and perinatal outcomes. Multiple pregnancies are more common with the use of menotropins than with natural conception. In the case of in vitro fertilization (IVF), the likelihood of a multiple pregnancy depends on the number of embryos injected, their quality and the age of the patient. The patient should be warned about the potential risk of multiple pregnancies before starting treatment.
Complications of pregnancy.

The incidence of spontaneous abortions in pregnancies that occurred after treatment with Meriofert is higher than in healthy women.
Ectopic pregnancy.

Women with a history of fallopian tube disease, whether they conceive naturally or are treated for infertility, have a high risk of ectopic pregnancy. The prevalence of ectopic pregnancy after IVF is 2 to 5% compared with 1 to 1.5% in the general population.

Novoplasms of the reproductive system.
There have been reports of neoplasms of the ovaries and other reproductive organs, both benign and malignant, in women who have been treated for infertility with multiple ART techniques. It has not yet been determined whether gonadotropin treatment increases the baseline risk of these tumors in women with infertility.

Congenital malformations
The prevalence of congenital fetal malformations with ART is slightly higher than with natural conception. It is believed that this could be due to the individual characteristics of the parents (age of the mother, characteristics of the sperm) and multiple pregnancies.

Thromboembolic complications
Women with known risk factors for thromboembolic complications, such as individual or familial predisposition, obesity (body mass index > 30 kg/m2) or thrombophilia may have an increased risk of venous or arterial thromboembolic complications during or after gonadotropin treatment. In such cases, the benefits of their use should outweigh the risks. Note that pregnancy itself also increases the risk of thromboembolic complications.

In men with high FSH concentrations in the blood (indicative of primary hypogonadism), Meriofert is usually ineffective.

Impact on the ability to drive and operate vehicles

Meriofert does not affect the ability to drive and operate vehicles.

Features

The biological efficacy of hMG is mainly due to the follicle-stimulating component. The pharmacokinetic properties of hMG when administered intramuscularly and subcutaneously have high individual variability.

Intravenous absorption

According to studies of Meriofert, after a single subcutaneous and intramuscular administration of the drug at a dose of 300 IU, the time of reaching the maximum concentration of the drug in plasma (Tmax) is 22 and 19 hours, respectively.

The bioavailability of the drug by subcutaneous administration is higher than by intramuscular administration.

Elimination

Elimination is mainly excreted by the kidneys. The elimination half-life of Meriofert (300 IU FSH) is approximately 45 hours when administered intramuscularly and 40 hours when administered subcutaneously.

Contraindications

– Hypersensitivity to menotropin and other components of the drug.

– Tumors of the pituitary gland or hypothalamus.

– Decompensated thyroid disease, insufficiency of the adrenal cortex, hyperprolactinemia.

– Age less than 18 years.

In women:

– Persistent ovarian enlargement, ovarian cysts (not caused by polycystic ovary syndrome).

– Genital abnormalities incompatible with pregnancy.

– Uterine fibroid incompatible with pregnancy.

– Vaginal bleeding of unclear etiology.

– Estrogen-dependent tumors (ovarian cancer, uterine cancer or breast cancer).

– Primary ovarian insufficiency.

– Pregnancy and breastfeeding.

In men:

– Prostate cancer, testicular tumor, androgen-dependent tumors.

– Primary testicular insufficiency.

With caution

The presence of risk factors for thromboembolic complications, such as individual or familial predisposition, severe obesity (body mass index >30 kg/m2) or thrombophilia, as there is an increased risk of venous or arterial thrombosis and thromboembolism during or after gonadotropin use. In this case, the benefits of gonadotropin treatment should outweigh the risks of gonadotropin use.

Pregnancy and lactation The drug is contraindicated in pregnancy and lactation.

Side effects

The undesirable adverse reactions observed while taking the drug were mostly mild and transient.

The most common adverse reactions were ovarian cyst formation, injection site reactions, and headache (up to 10% frequency). The most serious adverse reactions were SUI and complications associated with this syndrome.

The main adverse reactions are shown in the table below:

The adverse adverse reactions were classified as follows:

Very frequent (>1/10); frequent (>1/100 to <1/10); infrequent (> 1/1000 to <

1/100); rare – (> 1/10000 to < 1/1000); very rare – (< 1/10000).

Bodies and systems

Frequency

Side-reaction

Gastrointestinal tract disorders

Often

Gastrointestinal syndrome, including nausea, vomiting, diarrhea, intestinal colic and bloating, abdominal pain

Gastrointestinal syndrome including nausea, vomiting, diarrhea, colic and abdominal pain/p>

General disorders and disorders at the site of administration

Very common

Pain, redness, bruising, swelling, and/or irritation at the injection site

/p>

Nervous system side

Very often

Headache

Genital and breast disorders

Very often

Frequent

Rarely

Ovarian enlargement and formation of ovarian cysts

Ovarian hyperstimulation syndrome, gynecomastia (in men)

Twisted ovary

Cardiovascular system side

Very rare

Overdose

In case of an overdose, SLE and thromboembolic complications are possible. Symptoms of SUI are ovarian enlargement, lower abdominal pain, nausea, vomiting, diarrhea, weight gain, oliguria, ascites, hydrothorax, hemoperitoneum, hemoconcentration, shortness of breath (for more information, see “Special Precautions”).

The symptoms of mild to moderate SGN usually do not require additional treatment and go away on their own within 2-3 weeks.

Heavier CGY requires hospitalization in the intensive care units of specialized gynecological hospitals for comprehensive treatment.