Clomid to stimulate ovulation in women - how it works?
Clomid (Clomiphene) is currently one of the most affordable and cheap drugs that are used to stimulate ovulation in women.
Estrogens, which include Clomiphene, play an important role in the process of conception-stimulate the secretion of cervical mucus (a favorable environment necessary for life, movement and nutrition of sperm), stimulate the release of luteinizing hormone (LH), promote regeneration and growth of the endometrium.
Lack of estrogen can lead to the impossibility of ovulation and, consequently, pregnancy.
- When is Clomid used by women?
- What is stimulation, why is it necessary and can you do without it?
- Determining the need for ovulatory stimulation
- What research might be required before...?
- " Side effects " of stimulation
- Trying without medication
- Preparing for stimulation with Clomid
- In what cases should I stop taking Clomid?
- When to use Clomid is not worth it?
- How should women take Clomid?
- Rare but possible side effects
- Research: treatment of hormonal infertility with Clomiphene
- Indicators of the effectiveness of Clomiphene
When is Clomid used by women?
One of the most popular methods of treatment for doctors who do not know how to speed up the pregnancy process in impatient expectant parents is ovulation stimulation. Most of all – the “Clomid”. Often it is prescribed without any reason and any preliminary examination.
Patients, as a rule, trust the opinion of the doctor and agree to any treatment, without first understanding either the need for such treatment, or the conditions and features of its implementation.
What is stimulation, why is it necessary and can you do without it?
In modern medicine, ovulation stimulation can be produced by hormonal drugs in the event that a woman does not have her own ovulation.
At the same time, it is important to remember that a single stimulation of ovulation with hormonal drugs has nothing to do with restoring a woman's own ovulation.
First of all, it should be noted that you can restore natural ovulation only by finding out the reason for its absence and eliminating all adverse factors. And not in all cases, ovulation stimulation can give the desired effect, if the reason for its absence has not been previously established.
Determining the need for ovulatory stimulation
When making a diagnosis of " no ovulation”, it is very important to remember that it should not be based on basal temperature (BT) charts – even for several observation cycles, not to mention a single study cycle.
Basal body temperature is measured in the mouth, rectum or vagina in a state of complete rest. It changes on different days of the menstrual cycle. Usually a woman's indicators are below 37°C before ovulation, that is, until the middle of the cycle.
This is such a wild phenomenon in medical practice that it does not lend itself to any criticism.
This is how a huge number of false diagnoses are made and treatment is prescribed, which is not only unnecessary, but can cause huge harm to a perfectly healthy woman.
ATTENTION!!!the diagnosis of “lack of ovulation” NOT PUT ON THE CHARTS OF BASAL TEMPERATURE
So put aside your schedules and in any case do not even show them to the doctor-God forbid he will start you on them "treat".
The maximum they can help is to encourage additional examinations if there are any doubts about the presence of ovulation. More serious conclusions can be made only after a comprehensive survey.
What research might be required before...?
Special attention should be paid to the hormonal theme.
Often, doctors simply do not know “when”, “why” and “what” hormone tests they prescribe to their patients. And the most common mistake is progesterone. As a result, a woman passes tests completely on the wrong days, gets far from reality “results”, false "diagnoses” and harmful" treatment”, which she not only does not need, but can also be dangerous to health.
But even if you are sure that you passed everything “correctly” and you really have " something wrong”, in this case, all the tests must be retaken several times before making any decision.
It is better to retake them at different times and in different laboratories. However, do not forget that the level of hormones in the body is very unstable, and nutrition, stress and other factors can also affect the results.
And it is not necessary that in another cycle the picture will be similar.
In any case, you should not start stimulation if such hormones as – thyroid hormones, prolactin and male hormones are not normal. Such violations, in themselves, can interfere with ovulation. First, you should bring them back to normal – perhaps no other treatment is required, and ovulation will recover on its own.
Before you start taking the drug it is recommended to investigate the function of the liver.
Before starting treatment, a thorough gynecological examination should be performed. Treatment begins when:
- the total gonadotropin content in the urine is normal or below the lower limit of the norm
- the state of the ovaries on palpation is normal
- thyroid function is normal
- adrenal function is normal
In the absence of ovulation, all other possible forms of infertility should be excluded or treated before starting the drug.
" Side effects " of stimulation
Always remember that any medical treatment is not just a " magic pill” to achieve a one-time(!) result's.
In addition to tempting " pluses”, it can have various negative consequences (both short-term and long-term) for your health - problems of the gastrointestinal tract and CNS, cystic formations, ovarian hyperstimulation, apoplexy (rupture) of the ovary, hormonal disorders, early ovarian depletion (early menopause), excess weight, multiple pregnancy.
Trying without medication
The presence of problems with ovulation indirectly indicates the health of the entire body. This means that over time, the number of problems and "diagnoses" will only grow.
Before you come to terms with your “ill health” and decide on the need for stimulation as the “only and last hope”, consider alternative options for restoring health by natural means. Change your way of life, thinking, nutrition.
There are many ways to improve your health. Start to fight not "with diseases”, but “for health" (feel the difference?). Then the result will not take long to wait.
Preparing for stimulation with Clomid
If you still decide to perform stimulation
The first thing to do before starting stimulation and regardless of what drugs are used for stimulation, it is necessary to have good (or at least – suitable for natural conception) fresh results of the spermogram of the husband on his hands.
Regardless of what results he had in the year before last or how many children there were in the previous marriage, the analysis should be done immediately before planning treatment by stimulation, in order to avoid wasting money on drugs and not expose the woman's health to unnecessary danger.
If the doctor suggests that you examine your husband only after one-two-three or more months of unsuccessful stimulation - go away from such a doctor! Such negligence does not deserve any confidence and can cost you and your health very dearly.
Partner surveys should be conducted every cycle. Otherwise, you can miss a lot of details that affect the overall trend.
Even better – if you have before the start of stimulation will be on hand the results of studies of the fallopian tubes for patency - GSH or laparoscopy, if you do not have IVF/ICSI.
The second thing to remember is that any stimulation should be performed under the strict supervision of a doctor and ultrasound monitoring. Since any stimulation is a serious health risk. Negligent attitude can lead not only to health problems, but also to create a threat to a woman's life.
If the doctor offers you to come to an appointment or ultrasound only " after a couple of months of failures”, “when the schedule becomes two-phase” , etc. - leave this doctor! Such negligence does not deserve any confidence and can cost you and your health very dearly.
The main indicators should be analyzed by your doctor at least once a week before ovulation. In the ovulatory cycle, indicators can be monitored every 12 hours. Dynamics can help the doctor make a decision about changing treatment.
In addition, returning to such a doctor after 3 months of unsuccessful attempts, you will not be able to get a clear answer about even the approximate causes of failure.
In what cases should I stop taking Clomid?
If ovarian enlargement or cystic changes occur while taking the drug, treatment should be discontinued until the size of the ovaries returns to normal. In the future, the reception can be resumed, but at the same time reduce the dose of the drug or the duration of treatment.
In the process of treatment, you need constant supervision of a gynecologist, you should monitor the function of the ovaries, conduct vaginal studies, observe the phenomenon of "pupil". Often during the course of treatment, it is difficult to determine the moment of ovulation, and often there is a deficiency of the yellow body. Therefore, after conception, it is recommended to carry out preventive treatment with progesterone.
Progesterone is an endogenous steroid and progestogenic sex hormone that affects the menstrual cycle, pregnancy, and embryonic development. Its effects are enhanced in the presence of estrogens. Progesterone is sometimes called the "pregnancy hormone" - it has many functions related to the development of the embryo.
When to use Clomid is not worth it?
For each drug and substance there is a certain threshold of acceptability. Each person has their own individual characteristics. In order not to harm yourself you need to get acquainted with the contraindications at the start of taking the drug:
- hepatic and / or renal failure the norm
- ovarian cyst (except for polycystic ovarian syndrome)
- tumor or hypofunction of the pituitary gland
- disorders of the thyroid gland
- disorders of adrenal function
- metrorrhagia of unknown etiology
- long-existing or recently frolicking visual impairment
- neoplasms of the genitals
- insufficiency of ovarian function on the background of hyperprolactinemia
- lactation (breastfeeding)
- galactose intolerance, lactase deficiency or glucose malabsorption
- hypersensitivity to the components of the drug
Pregnancy and lactation
It is contraindicated during pregnancy and breastfeeding.
Application for violations of liver function
Contraindicated in liver failure.
Application for violations of renal function
Contraindicated in renal failure.
How should women take Clomid?
In infertility, the dose and duration of treatment depend on the sensitivity (reaction to the drug) of the ovaries.
Patients with a regular menstrual cycle are recommended to start treatment on the 5th day of the cycle (or on the 3rd day of the cycle with early ovulation or the duration of the follicular phase less than 12 days). With amenorrhea, treatment can be started any day.
Scheme I: 50 mg / day for 5 days with simultaneous control of ovarian reaction using clinical and laboratory studies. Ovulation usually occurs between 11 and 15 days of the cycle. If this treatment does not lead to ovulation, then scheme II should be used.
Scheme II: from day 5 of the next cycle, 100 mg/day is prescribed for 5 days. If at this time ovulation is not observed, then you should repeat the same scheme again (100 mg/day).
For polycystic ovarian syndrome
In polycystic ovarian syndrome, due to the tendency to hyperstimulation, the initial dose of the drug is 50 mg/day.
In post-contraceptive amenorrhea, the drug should be administered at a dose of 50 mg / day daily. As a rule, when using scheme I, a five-day course of treatment is successful.
Men in accordance with the indications, the drug is prescribed 50 mg 1-2 times/day for 6 weeks under the systematic control of the spermogram.
In the case of continued anovulation, the drug should be discontinued for 3 months, and then repeated treatment for 3 months. If the second course is ineffective, subsequent treatment with the drug is also not effective.
The maximum total dose of the drug taken during each course is 750 mg.
Increases the likelihood of twins pregnancies.
The drug is contraindicated in patients with galactose intolerance, lactase deficiency or glucose malabsorption, because each tablet contains 100 mg of lactose.
Influence on the ability to drive vehicles and control mechanisms. Since the drug can cause visual impairment, during treatment, patients should be careful when driving and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
Supply conditions for pharmacies
The drug is produced by prescription.
Rare but possible side effects
Determining the frequency of side effects: often - less than 1%; rarely - more than 1%. For clomid, this figure does not exceed 1%. But they are still possible.
From the digestive system: nausea, vomiting; rarely-gastralgia, flatulence, diarrhea, acute abdominal syndrome, increased appetite.
From the Central nervous system: headache, dizziness, drowsiness; rarely-slowing of mental and motor reactions, increased excitability, depression, insomnia.
From the part of the senses: visual impairment (including impaired perception of light, double vision, blurred contours, photophobia).
From the urinary system: increased urination, polyuria.
From the sexual system: pain in the lower abdomen, dryness of the vagina.
From the endocrine system: breast compaction, dysmenorrhea, abnormal uterine bleeding, increase in the size of the ovary (including cystic); rarely-pain in the chest area.
Dermatological reactions: rarely-alopecia.
From the side of metabolism: rarely-an increase or decrease in body weight.
Allergic reactions: rarely-rash, urticaria, allergic dermatitis, vasomotor disorders.
Other: feeling a rush of blood to the face with a feeling of heat (stop after the end of the drug).
In the treatment of clomiphene increases the likelihood of multiple pregnancy, ectopic pregnancy, endometriosis, growth of existing uterine fibroma.
Possible cystic ovarian enlargement, especially with Stein-Leventhal syndrome. In these cases, the size of the ovaries can reach 4-8 cm. in this case, you should monitor the body temperature and stop treatment as soon as it becomes two-phase.
Research: treatment of hormonal infertility with Clomiphene
You can assign synthetic progestins-3-4 cycles of 2-3 months. It is known that synthetic progestins have a pronounced inhibitory effect on all levels of the hypothalamus-pituitary-ovary system, many times greater than the effect of previous therapy with estrogen and progesterone. Along with this, treatment with synthetic progestins for 2-4 months makes it possible to find out the functional state of the hypothalamic-pituitary-ovarian system and its reserve capabilities, which allows you to choose a more rational method of hormonal therapy, taking into account the age of the patient and the duration of the disease.
Progestins are a class of steroid hormones that get their name because of the gestagenic effects that are important in the occurrence and development of pregnancy. These female sex hormones are produced in the uterus when pregnancy occurs and to preserve it. Due to the fact that the progestogen inhibit ovulation, they are used as components of contraceptive.
The positive result of treatment of endocrine forms of infertility with synthetic progestins is explained by stimulation of the hypothalamus-pituitary-ovary system due to rebound or reflected effect after discontinuation of treatment, since during their reception there is a pronounced inhibitory effect on the hypothalamic-pituitary system.
Indicators of the effectiveness of Clomiphene
The second stage is treatment with direct ovulation stimulators.
Clomiphene has been widely used in the clinic since 1961, when Greenblatt accidentally discovered that it is a strong ovulation stimulant. The literature provides data on the birth of more than 6700 children in women due to the use of clomiphene. Clomiphene is an analog of synthetic non-steroidal estrogen, which has the structure of stilbestrol and part of the TASE molecule.
In the experiment, clomiphene was first described as an effective fertility inhibitor in rats. In the future, it was found that clomiphene in small doses increases, and in large — inhibits the secretion of gonadotropins. Clomiphene has no estrogenic or gestagenic activity and is toxic only with long-term use of large doses: 5-40 mg per 1 kg of animal body weight for 40-50 weeks.
It was found that clomiphene has a different effect depending on the initial level of estrogen in the body. So, with a small number of endogenous estrogens clomiphene gives a moderate effect, resulting in an increase in the mass of the uterus and keratinized epithelium in the vagina. At the same time, with high estrogen saturation, clomiphene acquires a high antiestrogenic activity, which is explained by its ability to replace estradiol in estrogen-sensitive receptors and thereby reduce their physiological effect [Greenblatt]. Along with this, different doses of clomiphene cause ambiguous shifts in the animal's body.
So, it turned out that clomiphene in large doses blocks the action of estrogens on the uterus by inhibiting the synthesis of protein and glycogen, and in small-increases the growth of the uterus and immature animals due to increased glycogen synthesis.
In clinical practice, clomiphene has become widely used in recent years due to the fact that it was an active ovulation stimulant. However, the mechanism of action of clomiphene still remains completely unclear. According to the hypothesis of Roy, Greenblatt, Mahesh and Jundek, clomiphene stimulates ovulation by direct action on the hypothalamic-pituitary system, which causes increased secretion of gonadotropins that stimulate the biosynthesis of steroids in the ovaries, provided their normal enzyme ability to respond to stimulation with gonadotropins.
These authors believe that the antiestrogenic activity of clomiphene leads to disinhibition of FSH-LH in the hypothalamus, which in turn causes a consistent increase in the excretion of FSH, estrogens and LH. This hypothesis is supported by experimental studies by Hisenfeld and Axelrood, which showed that the introduction of clomiphene causes a decrease in the concentration of estradiol. This indicates the possibility of competing effects of clomiphene and estrogens at the hypothalamic level. Data from Kahwanago and co-authors on the ability of clomiphene to exert a inhibitory effect on the" binding " of estradiol by the receptors of the hypothalamus and pituitary also confirm this position.
The explanation of the mechanism of action of clomiphene on the hypothalamus-pituitary system only by competing influence with estrogens is complicated by the data that different doses of clomiphene and its introduction to different parts of the brain cause ambiguous shifts in the secretion and release of FSH and LH by the adenohypophysis. So, Vauag showed that the introduction of small doses of clomiphene (0.3 mg/kg) stimulates the secretion of FSH, and then LH, while increasing the dose of clomiphene 10 times gives the opposite effect.
Based on the introduction of clomiphene in various parts of the brain, it was found that it stimulates the release of FSH, as well as the synthesis and isolation of LH by the adenohypophysis. In this case, clomiphene has a stronger effect on the hypothalamus than on the adenohypophysis.