List of medications that help to carry out in vitro fertilization is rather wide. Only the basic ones are listed below.
Please note:
The following medications, which are used for IVF programs, can be used only on physician's order. Be sure to carefully read a data sheet of every drug. The information presented here is intended for reference only. That is the reason why dosages of medications are not specified.
I. Blocking agents
1. Agonists (analogues) of gonadotropin releasing hormone
Gonadotropin releasing hormone (GnRH) is produced by the hypothalamus. It is characterized by a strongly pronounced specificity. GnRH creates rather stable complexes by interacting mostly with only relevant receptors, which are located in the anterior pituitary, and also with some proteins. After the first phase of hypophysis activation passes (typically in 7-10 days), GnRH sensitivity to stimuli begins to decrease.
This leads to reduction of LH, FSH levels, and suspension of ovaries stimulation. The amount of estrogen decreases, and its level drops below 100pmol/l. Such characteristics are observed in postmenopausal women. The amount of testosterone and progesterone produced by the ovaries also reduces.
Agonists of gonadotropin releasing hormone increase the probability of fertilization through the IVF programs.
There are several side effects of gonadotropin agonists’ application. Usually there are unpleasant symptoms, which are due to a lack of estrogen, and developing hypoestrogenic state accompanied by headache, sweating, hot flashes, feeling of vaginal dryness, mood swings and depression.
The effect of agonists on bone tissue is the most dangerous, as its density may be reduced due to prolonged use of these drugs. There is data showing that certain bone remodeling is observed throughout the year after the completion of treatment with agonists.
List of manufacturers:
(Ferring Arzeimittel, Germany)
(Beaufour Ipsen International, France)
(Astra Zeneca, Great Britain)
Preparations:
Diferelin
Artificial decapeptide, an analogue of the natural GnRH
Decapeptyl
A sterile kit for depot injections, as well as for daily administration, which is completely ready for use. Consists of: 1) syringe containing a suspending formulation 2) conventional syringe 3) microcapsules containing Triporelin 4) injection needles, connecting element.
Triptorelin, composing the active basis of medication, is a synthetic analogue of GnRH. It has a longer half-life period and is used during in vitro fertilization.
Drug concentration in the blood decreases to a minimum in 44 days after intramuscular injection, after subcutaneous - in 64 days.
Lucrin depot - Leuprorelin
Has anti-estrogenic, anti-androgenic effect; area of application - treatment of endometriosis, hormone-dependent tumors, which include prostate cancer and uterus fibromyoma. Lucrin depot reduces concentration of estradiol in women, testosterone levels in men, moreover, inhibits FSH and LH incretion by the pituitary gland.
Intramuscular injection creates a depot, which can maintain an effective concentration of the substance for 30 days. Indicator of bioavailability is about 90%.
After the drug treatment is stopped, the physiological hormone secretion is gradually recovering.
Goserelin, Synarel, Buserelin
These preparations are represented by nasal sprays.Zoladex
The drug is a synthetic analogue of the natural luteinizing hormone (LH) releasing factor. It is often used during artificial fertilization. The drug intake helps to reduce estradiol concentration in blood serum, and is the result of suppression of anterior pituitary LH secretion. It is represented by capsules, which get inside and slowly dissolve, resulting an even release of substance contained inside. Concentration maintains for four weeks.
New generation:
2. Antagonists of gonadotropin-releasing hormone
These drugs more effectively suppress the LH secretion, and the pituitary gland activity recovers much faster after cessation of the medication administration. It is often used in treatment of infertility.
Pharmacodynamics:
after the drug is delivered inside the organism, the level of blood gonadotropins significantly decreases, and LH, different from FSH, is more susceptible to the process. For example, single administration of 0.25 mg of the medicament causes the reduction of FSH concentration by 32%, LH - 74%. Duration of suppression is then 4 - 16 hours. If the drug is administered repeatedly, the concentration will remain unchanged for 2-3 days.
So, its pharmacokinetics is characterized by direct blocking effect on gonadotropes' receptors and good bioavailability; the drug starts to act very quickly. Level of gonadotropins is very quickly restored after discontinuation of the drug administration. Due to the fact that the substance is rapidly eliminated, the impact on the receptors is characterized by immediate reversibility.
Main pharmacokinetic and pharmacodynamic characteristics of the drug:
- half-life period of the drug is 13 hours;
- aftereffect period is maximum 3 days;
- pharmacokinetics is proportional to the dose of the drug needed for the pituitary function suppression;
- pituitary functions are quickly restored after the treatment cessation.
Main differences from the GnRH analogues (clinical studies were carried out by leading clinical centers of in vitro fertilization):
- duration of stimulation is reduced by 1-2 days;
- first days after stimulation with recombinant FSH - follicle size increases much faster;
- a smaller dose of gonadotropins is necessary for the ovulation stimulation;
- the final number of follicles differs by a smaller quantity, however, the production of estradiol is also slightly reduced, number of egg cells is reduced by 1-2 pcs;
- high quality artificial fertilization demonstrates high results of embryos number and fertilization rate;
- good clinical outcome, which is composed of the quantity and quality of oocytes and embryos, frequency of implantation, fertilization, pregnancy, and its progression.
Another important difference of the GnRH stimulation - support of the corpus luteum function after the implementation of artificial fertilization, is optional.
The most commonly used medications – Orgalutran and Cetroride (Cetrorelix), differ from each other only by the manufacturer (Organon, Serono). Both formulations are characterized by good tolerability, high safety, and have a low probability of side reactions occurrence.
II. Direct stimulators of ovulation
These drugs are used in such operations as medications that can replace natural gonadotropins, having an effect on ovaries, causing growth, maturation of the follicles and subsequent ovulation.
The drugs are represented by two groups: urinary gonadotropins, recombinant gonadotropins. They are produced by several companies: Ferring Arzeimittel (Germany), Aeras-Serono (Switzerland), Organon (Netherlands).
There are produced several analogues of the drugs for the operations, which have a similar composition and method of exposure.
1. Urinary gonadotropins
They include Menogon, Pergonal, Humegon.
Pergonal
The drug contains an active substance - menotropin, containing human menopausal gonadotropin. The content of LH and FSH hormone substance has a ratio of 1:1.
Pergonal is used during artificial fertilization, it contributes to stimulation of growth and maturation of follicles, increases concentration of blood estrogen, and also results in endometrial proliferation. The drug should be administered intramuscularly.
There are some contraindications for Pergonal. Sharply pronounced sensitivity to menotropins, abnormal development of reproductive organs, gynecological bleedings of unknown etiology, persistent ovarian enlargement, ovarian cyst that occurred not for the reason of polycystic ovary, hysteromyoma, primary ovarian failure.
Treatment with gonadotropins can cause multiple pregnancy and miscarriage.
Menogon
The drug is used for stimulation of superovulation in IVF. Menogon contains an active substance - menotropin, produced from the urine of postmenopausal women. It contains FSH and LH, in the ratio of 3:1. Gonadotropic pharmacological action.
Contributes to stimulation of follicular maturation.
Metrodin
The drug is used for treatment of infertility in extracorporal fertilization programs. It is a follicle-stimulating hormone, which is produced from the urine of postmenopausal women. The drug contributes to stimulation of growth and maturation of follicles, as well as increases estrogen blood level and endometrial proliferation. No luteinizing action is observed.
Humegon
Preparation of pituitary gonadotropin-releasing hormones, helps to activate the maturation of follicles and egg cell (before the preovulatory period), compensating for the lack of FSH and LH. Steroid hormones production by the gonads significantly increases due to the action of the drug. Physicians often prescribe it for infertility treatment.
2. Recombinant gonadotropins
(Puregon, Gonal-F)
Puregon
- Follitropin beta
The drug is a pure follicle-stimulating hormone, the result of genetic engineering. Due to its more powerful effect, smaller doses of Puregon are used for stimulation of follicles during IVF, in comparison with urinary preparations. One major difference is the lack of ovarian hyperstimulation effect.
3. Indirect ovulation stimulants
(it is frequently used for stimulation of ovulation in egg donors)
Clostilbegyt (Egis, Hungary)
Antiestrogen preparation containing an active substance - clomiphene, which is non-steroidal anti-estrogen. The drug is able to selectively block the binding of estradiol with receptors of ovaries and pituitary gland.
Effectiveness of the drug depends on the content of estrogen hormones in the organism. Due to the low concentration there can be observed a moderate estrogenic effect. High concentration of estrogen contributes to an anti-estrogenic effect. Small doses of the drug can increase the secretion of gonadotropins (FSH, LH, prolactin).
Clostilbegyt contributes to ovulation stimulation; application of high doses of the drug causes inhibition of gonadotropin secretion. Androgenic, progestogenic activity is absent.
The drug is used to stimulate ovulation in patients with anovulatory ovarian dysfunction, which is the cause of infertility. Indications for use also include dysfunctional uterine bleedings, and other pathologies caused by endocrine system disorders. The drug is characterized by good absorption in the gastrointestinal tract.
There are several contraindications for application of Clostilbegyt. It cannot be used by pregnant women with kidney or hepatic insufficiency, tumors of genital organs, metrorrhagia of unknown etiology, endometriosis, tumors, pituitary insufficiency, ovarian failure proceeding on the background of hyperprolactinemia, and increased sensitivity to the drug. Application of Clostilbegyt is often accompanied by multiple pregnancy.
The highest efficacy of the drug is observed when the level of endogenous estrogen is high - low level reduces the effectiveness of the medication. Low level of gonadotropic hormones reduces the effect of the drug to zero.
III. Ovulation triggers
Ovulation triggers are medications imitating or stimulating the release of LH. There effect causes egg maturation and ovulation. Indications for application - treatment of infertility (some forms).
Manufacturers: Ferring, Aeras-Serono, Arzeimittel,Organon
Preparations:
In vitro fertilization is carried out using the following preparations containing human chorionic gonadotropin: Horagon, Profasi, Pregnyl.
There are also drugs that have not been practically applied, but well enough described by the theory:
- recombinant hCG (ovidrel);
- recombinant FSH;
- recombinant LH (LHadi);
- GnRH, GnRH agonists,;
- antagonists of GnRH.
Profasi
Contains an active substance - chorionic gonadotropin, produced from the urine of pregnant women. Contributes to the stimulation of gonads steroidogenesis, production of estrogen, progesterone - post ovulation period. It is prescribed when in vitro fertilization is being performed.
Caution should be exercised when prescribing Profasi to women with kidney diseases, heart insufficiency, hypertension, migraine and epilepsy.
Sometimes application of the drug may trigger the development of ovarian hyperstimulation syndrome. In this case the drug application should be discontinued. Treatment with gonadotropins is often accompanied by the development of multiple pregnancy, and it also increases the risk of miscarriage.
Horagon
The drug helps to stimulate the production of progesterone and estrogen in women in the post-ovulatory period, and of testosterone - in men. In addition, Horagon provokes enhancement of gonadal steroidogenesis. It is recommended as a stimulator of ovulation during IVF.
There are several side effects: simultaneous use with clomiphene citrate and menogon can provoke occurrence of ovarian hyperstimulation syndrome. This may cause their breakage.
IV. Corpus luteum function support (second phase)
Utrogestan
Manufacturer: Besins-Iscovesco Laboratories, France
Active substance - corpus luteum hormone, natural micronized progesterone.
The drug is used as a stimulant of secretory endometrium formation in female patients, who need in vitro fertilization. Its effect results in production of sufficient amount of secretory endometrium contributing to the normal implantation of the egg. After the drug intake, uterine mucous membrane enters the secretory phase. After the in vitro fertilization occurs, the condition of mucosa becomes appropriate for normal development of the fertilized egg. The drug inhibits ovulation without having androgenic activity.
Possible side effects: allergic reactions, insignificant drowsiness, occasional dizziness that usually ceases in 2-3 hours after the medication intake.
Vaginal use of the drug is in common practice.
Duphaston
Manufacturer: Solvay Pharmaceuticals B.V., Netherlands
Active substance - dydrogesterone.
The drug selectively affects the endometrial mucosa, promoting onset of the endometrium secretory phase.
Indications for use: lack of native endogenous progesterone. The drug is prescribed for luteal phase support after the embryo transfer.
Progesterone
Has the form of an oily solution. Injections (1%, 2.5%).
Manufacturer: Russia.
The preparation is used for intramuscular administration.
Progesterone injections are very painful; prolonged treatment may contribute to the appearance of lumps.
Horagon
Horagon injections - 3rd, 6th, 9th day of the post-ovulation period. Corpus luteum is being stimulated.
Additional drugs, which can be prescribed to the patient before, during and after the implementation of in vitro fertilization
DIPRIVAN PROPOFOL ZENECA
Has the form of emulsion. Intravenous administration. Used for short-term narcosis in order to implement puncture of oocytes.
1 ml of the substance contains 10 mg of propofol.
Pharmacological action:
Propofol is a substance used for general anesthesia. The result of its application - patient falls asleep pretty fast - in 30 seconds, but it does not last long.
Pharmacokinetics:
Propofol has the ability to be rapidly excreted from the body, metabolism occurs mostly in the liver.
Indications:
It is used for induction and maintenance of general anesthesia, and in order to achieve sedative effect of adult patients, carrying out intensive therapy or artificial lung ventilation. Diprivan is also used for some diagnostic and surgical procedures when the patient is fully conscious.
Side effects:
Induction of anesthesia with the use of Diprivan is carried out smoothly, signs of patient excitation are minimal.
Sometimes there are temporary apnea and blood pressure lowering. Other side effects are very rare.
Epileptoid movements (opisthotonus, convulsions) are observed very rarely. There are reports about the occurrence of pulmonary edema. After awakening the minimum number of patients report headache, nausea and vomiting. Prolonged application may result in change of the urine color. Postoperative fever is extremely rare. Phlebitis and thrombosis are also observed only occasionally.
Contraindications:
Presence of allergic reactions, active substance of Diprivan - Propofol.
Special instructions:
Diprivan is often used in conjunction with analgesics. It is not recommended for children under the age of 3 years.
Diprivan should be prescribed with caution to severely weakened patient, as well as to the patients who have a history of respiratory and cardiovascular system diseases, epilepsy, hypovolemia, liver and kidneys disorders.
Special attention is required by patients with disorders of lipid metabolism. If the patient has a risk of excessive fats accumulation, it is recommended to monitor blood lipids level in case of Diprivan prescription. If there is insufficient elimination of fats from the organism, Diprivan dose has to be adjusted.
Patients for whom Diprivan was prescribed should be careful during driving, as well as in other situations that require increased attention.
It is undesirable to prescribe the drug to pregnant women, as it is able to pass through the placental barrier, causing neonatal depression. Diprivan application is allowed when the pregnancy is aborted, if the term is less than 12 weeks.
Regarding lactating women, there is no information on the drug safety for child. Therapeutic doses of Diprivan do not contribute to the suppression of adrenocortical hormones synthesis.
Medical workers who do not have an appropriate training for intensive care performance are not allowed to use Diprivan as an anesthetic. Physician that performs a surgical or a diagnostic procedure has no right to administer an anesthetic; this should be done by a particular specialist.
Application of the medication should be accompanied by monitoring of the patient's state. It is required to have special equipment, which can be used for resuscitation.
Diprivan must be stored at the temperature of +2 - +25 degrees. It is strictly forbidden to freeze the medicine. Shake before use. Drug residues inside the syringe and vial have to be immediately disposed.
Overdosage:
Drug overdosage can cause depression of respiration and cardiac activity. In the first case it is recommended to perform mechanical ventilation with oxygen, in the second case the patient has to be injected with angiotonic drug, plasma substitute.
Drug interaction:
Diprivan is well combined with drugs for epidural and spinal anesthesia, as well as with drugs that are used for premedication (analgesics and muscle relaxants).
In practice, no cases of Diprivan pharmacological incompatibility have been observed.
Estrofem (estradiol) 2 mg
Manufacturer: NOVO NORDISK A/S Denmark
The drug contains an active substance estradiol.
Estrofem is a hormonal medicament contributing to compensation for the lack of endogenous estrogen, which can occur after artificial fertilization, and also to appearance of proliferative changes in endometrium. It is used as a stimulant of uterus development. Estrofem enhances libido, maintenance of normal bone structure.
Side effects:
There can be observed breast tenderness, headache, nausea, swelling, uterine bleeding, exacerbation of gallstone disease. All side effects are usually temporary, and pass independently after a while. Consult your doctor if discomfort persists for a long period of time.
Proginova - estradiol valerate.
Manufacturer: Schering - Germany
The drug contributes to replenishment of the endogenous estrogen deficit, to the development of proliferative changes in the endometrium, and to the maintenance of normal bone structure. It is prescribed after performance of the artificial fertilization.
Side effects:
The drug application is sometimes accompanied by headaches and nausea; there can also be observed a very rare weight change, breast tenderness and uterine bleeding.
Metypred (methylprednisolone)
Manufacturer: ORION CORPORATION, Finland.
It is a hormonal drug that is used as an immunosuppressive substance, preventing the rejection of grafted embryo.
General indications for use:
Rejection reactions after tissues and organs transplantation operations, which include artificial fertilization; some liver and kidneys functional disorders, allergic diseases and nonspecific ulcerative colitis.
Side effects:
Endocrine disorders: weight gain, suppression of the hypothalamic-pituitary-adrenal function, hirsutism, reduced resistance to carbohydrates.
Immune system disorders: hypersensitivity, reduced resistance to infectious diseases, immunosuppression.
Neuropsychological disorders: insomnia, depression.
Eye disorders: cataract, exacerbation of fungal and viral diseases of eyes, increased intraocular pressure.
Furthermore, application of the drug may cause nausea, appetite changes, and liability to thromboembolism.
Dexamethasone
Manufacturer: Weimer Pharma - Germany.
The preparation is a strong glucocorticoid drug. It is characterized by immunosuppressive, anti-inflammatory, anti-shock, anti-allergic and antitoxic action.
When prescribing glucocorticoids, the following fact has to be considered: the cortisol level reaches its maximum early in the morning. If the drug is used for the suppression of androgen level (in case of the adrenal cortex dysfunction), it is recommended to take it in the evening. In case of autoimmune disorders it is better to take glucocorticoids in the morning, then the risk of side effects is minimal.
Application of any medications should be discussed with the attending physician!
