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Drug Therapy

Overview

Some people compare starting fertility treatments to a journey to a new and foreign land. You have to adjust to a new language and a new environment, as well as new routines and, of course, emotions. The ups and downs of medical treatments can be draining, but the journey will be easier if you are well prepared and informed, and can count on support. By this stage, you probably already have a good idea of what you are undertaking. But, because the future is still full of many unknown factors, it is very easy to feel that you are not in control. By discussing treatment openly with your partner, you can set up a schedule for your treatment plans including such considerations as how many stages of the treatments you are willing to undergo, and how many cycles. This type of planning helps you to introduce some certainty into the process and help regain a sense of control. In this section, you will find advice on what you and your partner can do in terms of preparing for treatment. In this way, the treatment process will become a  less of a mystery.

The prospect of drug therapy can be daunting. You naturally want to know as much as possible about the medicine. For every medicine administered you should know what the possible adverse effects may be so that you and your partner know exactly what to expect, as well as why it is being used. Side effects are possible with fertility drugs - as with any other medicine - but they are not a certainty. Never feel shy about questioning your doctor. Pose as many questions as are necessary for you to understand your treatment and all the unknown medical terms related to it. Try to be patient, it can be some time before you fully understand everything. This section contains detailed information regarding general drug therapies for reduced fertility for both males and females. You will learn how each of these drugs work, how they are administered and what you can expect as far as side effects and results are concerned. It is important to remember that you have a very important reason for using these medicines. A certain amount of discomfort due to side effects must, to some extent, be taken in your stride. However, if the side effects cause you a great deal of discomfort, then it is obviously important to inform your doctor and to consider whether there are other options available that are suitable for you.

01. Ovulation Induction Therapy
02. Clomiphene Citrate
03. Gonadotropins
04. GnRH
05. Drug Therapy For Endometriosis
06. GnRH Agonists
07. GnRH antagonists
08. Human Choriongonadotrofine (HCG)
09. Progesterone Capsules

Ovulation Induction Therapy

The absence of ovulation (egg release) is one of the most common causes of female infertility. Without ovulation, pregnancy cannot occur. Ovulation problems can be apparent if the woman’s cycle is generally irregular or absent (no menstruations). Fortunately, even if an ovum (egg) is not normally released from the ovaries on a monthly basis, it is often possible to induce it with ovulation stimulating drugs. This is called ovulation induction. Ovulation induction is a fundamental part of many fertility treatments. Ovulation stimulating drugs are often used alone or in combination with fertility stimulating treatments  (ovarian hyperstimulation) to stimulate more follicles to mature increasing the numbers of eggs released for subsequent assisted reproductive techniques such as intrauterine insemination (IUI) or in vitro fertilisation (IVF). A number of different types of ovulation stimulating drugs are available.

Ovulation Induction:
The goal of this treatment is to stimulate or induce ovulation (egg release) through drug therapy. The drugs used can be administered in the form of tablets, injections or a pump. This depends on a range of factors including the underlying reason for the ovulation problem. Your doctor will consider the best approach for you individually. In most cases, tablets – clomiphene citrate - are the first-line option. During treatment, the reaction of the ovaries is monitored at the clinic. If ovulation has not been induced one month, then the dosage may be increased for the next cycle.

If clomiphene citrate fails, an ovulation is still not induced at the maximum dosage (“clomiphene resistant”), then various other treatments can be used.  In women with polycystic ovaries, another medicine (metformin) may be added to clomiphene or surgical intervention proposed.

The next step is usually the injection of follicle stimulating drugs containing gonadotropins. Sometimes injections are used straight away. Here too, the necessary dosage for each individual will have to be determined. The age of the woman and her ovary ‘reserve’ play a role in the chances of success: in general, at a later age a slightly higher dosage is necessary to induce an ovulation.

Pumps are used to administer the hormone gonadatrophin releasing hormone (GnRH) usually in cases where the women has hypothalamic amenorrhoea disorder – the lack of menstruation/ovulation as a consequence of reduced GnRH production.

Ovarian Hyperstimulation:
Aside from prescribing these medicines in order to induce an ovulation, these medicines are also often used by women who are receiving fertility treatments for other reasons. Their use in combination with other fertility stimulating techniques, such as intrauterine insemination (IUI) or in vitro-fertilisation (IVF), is however substantially different from their use in ovulation induction. Instead of one ovum (egg), the goal is now to stimulate multiple ova to mature.  A distinction is made between mild ovarian hyperstimulation for IUI in which the aim is to obtain just a few follicles and controlled ovarian hyperstimulation for IVF procedures.

In order to follow the growth of the follicles and because therapies can sometimes have side effects, you will undergo regular check-ups at the clinic. It is not only important to monitor whether an ovulation occurs, but also to prevent a situation where too many eggs mature at the same time. For instance in the case of IUI this may mean there is an unacceptable risk of a multiple pregnancy. The maximum acceptable number of eggs depends on the type of treatment. The occurrence of ovulation can be monitored in various ways. Your doctor will discuss the options with you.

General Risks:
Aside from the fact that the drugs themselves may have side effects, there may also be risks connected with treatment. For example, one general risk of treatments in which ovarian hyperstimulation is employed is the occurrence of over-stimulation. The chance of this occurring is greater during controlled ovarian hyperstimulation (IVF/ICSI) than during mild ovarian hyperstimulation (IUI); and higher with gonadotropins than with clomiphene, but the principle remains the same. Additionally, ovarian hyperstimulation increases the risk of multiple pregnancy. This chance also varies for each type of treatment and can be partially overcome through control and, in IVF, replacing fewer embryos.

Clomiphene Citrate

Clomiphene citrate, tablets designed to induce ovulation. When fertility problems are caused by either irregular ovulation or an absence of ovulation, clomiphene citrate can be the first fertility treatment undertaken. Moreover, as clomiphene citrate is relatively safe and cheap, some doctors prescribe a course after the first series of infertility tests, before moving onto somewhat more complicated investigations.

As a rule though, at least a vaginal ultrasound will have been performed in order to assess the ovaries, check if ovarian cysts are present (sacs filled with fluid) and measure the thickness of the endometrium (womb lining). A semen analysis will also have been undertaken to identify possible sperm abnormalities. Additionally, tests may have been carried out to check for disorders of the pituitary gland (hyperprolactinemia), the thyroid gland or the adrenal gland.

If treatment does not meet with success, and another course is advised, another ultrasound must be performed. This is because in approximately 5% of the cases, cysts can occur after the use of clomiphene.


If clomiphene does not succeed, some doctors combine it with other treatments. When an ovulation still does not occur using the highest dosage of clomiphene, women with polycystic ovarian disease (PCO), for example, may also be prescribed the insulin-regulating drug, metformin. This drug influences the glucose levels and appears to have beneficial effects in stimulating ovulation in combination with clomiphene.

How does it work:
Clomiphene works in the opposite way to the female hormone oestrogen. The drug thus behaves like an “anti-oestrogen” and convinces the body the oestrogen level is low. In response, the body produces all the necessary hormones needed for the follicle growth. It stimulates the brain to release follicle stimulating hormone (FSH) and luteinizing hormone (LH), the hormones that are essential for ovulation. Clomiphene actually stimulates ovulation indirectly. It works at the level of the hypothalamus and thereby ensures an increased release of gonadotrophin releasing hormone (GnRH). At the same time, the pituitary gland becomes more sensitive to GnRH, resulting in an increased production of FSH and LH increasing the chances of ovulation. The anti-oestrogen properties of clomiphene can also have an influence upon other organs. Some women notice that their cervical mucus doesn’t become thin and elastic, as it normally would around the time of ovulation. The womb lining (endometrium) may also not be sufficiently prepared to receive an embryo. In order to monitor this, the thickness of the endometrium is also monitored at every check-up.

How is it used :
Clomiphene is taken orally in tablet form over a five-day period, generally starting on day 3-7 of your cycle (day 1 is the first day of complete menstrual bleeding). You can, in some cases, monitor its effect yourself by keeping a record of your basal body temperature. However, your doctor will decide on the best strategy for monitoring taking into account the reasons why you have been prescribed clomiphene and the aim of treatment.


Doctors mostly prefer patients to visit them in their practice. The first clomiphene is often very carefully monitored until ovulation has occurred. If the correct dosage for you is identified, then check-ups in the following cycles can be more relaxed. However, because multiple follicles can develop in reaction to clomiphene, ultrasound of the ovaries is often carried out in order to follow the development of the follicles.

If clomiphene is only being used for ovulation induction, then couples are advised to have intercourse every second day for a week, starting a few days after the last day therapy is taken. There is no perfect formula for predicting the correct daily dose for each woman. Treatment normally begins with a 50 milligram tablet once a day for five days. There is a connection between body weight and dosage. If the first course does not cause ovulation, the daily dose is raised by one tablet for the second course. The dosages are increased by 50 milligrams until 150 milligrams (3 tablets) is reached. It is rare to achieve success at 200 milligram or 250 milligram and so these dosages are not used. If ovulation has not occurred at 150 milligrams, the clomiphene course is viewed as having failed and other treatments used.

Possible Side Effects:
In principle, every drug can cause side effects, of varying degrees of severity. However, not everyone will experience side effects with a particular drug. Because clomiphene works as an anti-oestrogen, there may be side effects that are caused by a relative insufficiency of the female hormone (a situation that in some respect can be compared to menopause).

  • Approximately 10% of patients report experiencing hot flushes.
  • Over 5% of patients report a swollen abdomen, a puffy feeling, pain and sensitivity.
  • Approximately 2% of patients report feeling discomfort in their breasts, nausea and vomiting.
  • Less than 2% of patients report symptoms relating to eyesight, headaches or hear loss.
  • 5% of patients develop cysts.
  • Clomiphene causes tough cervical mucus, because the body thinks that the oestrogen level is low, which can hinder the success of fertilisation.
  • An increased (but controllable) chance of multiple pregnancy.

The use of clomiphene has also been associated with an increased risk of ovarian cancer - although such a link has never been proved. It is known that women without children, who have always had problems with their cycle and who have used clomiphene have a slightly higher chance of ovarian cancer than other women. However, this could also be caused by the underlying disorder in the ovaries rather than drug therapy. A relationship between infertility and ovarian cancer was apparent before the introduction of these drugs. Nevertheless, it is still always a good idea to avoid using this unnecessarily for too long.

Results:
Clomiphene is used in a number of different treatments. As such, the chance of success depends on the reasons for its use. In terms of ovulation induction: “With well-selected patients, 80% can expect to ovulate while 40% can expect to become pregnant”, according to Speroff, et al, authors of the textbook Clinical Gynecologic Endocrinology and Infertility. Approximately 75% of pregnancies occur within the first three treatment cycles. The percentage of pregnancies per ovulation cycle lies around 15%. Almost 5% of the pregnancies are multiple  (nearly all twins).


Couples must not be discouraged if the use of clomiphene does not result in pregnancy. This is the mildest of a diverse range of fertility treatments. If the treatment does not result in a successful pregnancy, doctors may combine clomiphene with other drug therapies, or opt for another approach.

The diagram below represents the cumulative or running percentage of successful pregnancies for women who do not regularly ovulate and have used multiple courses of clomiphene citrate.

Gonadotropins

Gonadotropins - follicle stimulating hormone (FSH) and luteinzing hormone (LH) - play an essential role in a woman’s natural cycle. Both are produced by the pituitary gland; FSH stimulates the follicles to grow and produce the female hormone oestrogen. The ova (eggs), which develop within the follicles, start to mature at the same time. During the average cycle, on day 14, the pituitary releases a quantity of LH (the LH peak). LH stimulates the final maturation of the eggs and triggers ovulation - the release of one mature egg from the dominant follicle into the fallopian tube.

  • Gonadotropins are also used in various fertility treatments: 
    Ovulation induction.
  • Mild ovarian hyperstimulation in combination with intrauterine insemination.
  • Controlled ovarian hyperstimulation in combination with IVF or ICSI.

Treatment with gonadotrophins - which are administered by injection is a more  - intensive form of ovulation induction than treatment with tablets (clomiphene). The reasons for switching from from clomiphene to gonadotropin injections are:

  • Ovulation does not occur even after the maximum dosage of clomiphene tablets;
  • Severe side effects with clomiphene;
  • Failure to become pregnant;
  • The absence of quality cervical mucus at the time of ovulation;
  • If only small amount of hormones are released by the pituitary.

The risks associated with gonadotrophin ovulation induction are also somewhat greater than with clomiphene, and include a greater chance of multiple pregnancy and overstimulation of the ovaries. Consequently, patients are therefore carefully evaluated before embarking on treatment with gonadotropins. Women are tested for ovarian suitability and for abnormalities of the fallopian tubes and uterus (womb) perhaps via laparoscopy or hysteroscopy. A semen analysis is also performed in the male partner and possible hormonal problems are checked.

How does it work:
Gonadotropins stimulate ovulation in a direct manner, because they contain the same hormones - FSH and LH - that, in a natural scenario, are responsible for the stimulation of the growth of the follicles and ovulation induction. They must be administered by injection, because they would be immediately destroyed in the gut if they were given orally (by tablet). Fortunately, methods have been developed which make it easier for women to administer these injections themselves.

Traditionally, these hormones are extracted from the urine of postmenopausal women, which contains high concentrations of FSH and LH. This is called human menopausal gonadotropin or HMG. Aside from FSH, menopausal gonadotropins contain a small amount of LH. These have to be injected into the muscle.

Nowadays, gonadotrophins can also be produced in the laboratory through the use of biotechnological (recombinant DNA) techniques. In this manner, a ‘factory’ of cells is able to produce highly purified human FSH. (As the administration of LH is rarely necessary, most women only need purified FSH.) Recombinant FSH is purer than urinary products, but due to the complicated method of production, they are somewhat more expensive. An added advantage of these recombinant FSH products is that these drugs can be administered through a highly efficient and patient-friendly hypodermic system, allowing injection just under the skin - subcutaneously - rather than into the muscle. It is a sort of adapted insulin pen (Puregon Pen®) with which the patient can finely adjust the dosage delivered according to her needs.

How is it administered :
Treatment with gonadotrophins is more complicated than with tablets. Gonadotropins are administered using hypodermic injections. Usually, a nurse at the clinic will teach the person who is to administer the injections how to do this. These days, there are increasingly user-friendly administration methods, which make it easier and less painful for the woman to inject herself. An example is the use of a sort of insulin pen, which can be filled with special cartridges and in which the exact quantity of the injection can be set.

A woman must administer the injection at least once a day over a period of between one to two weeks. (This is one difference with treatment using tablets, where the tablets have to be ingested for five consecutive days every cycle.) The duration of the gonadotropin treatment will vary from woman to woman and depends on how quickly the follicles mature. It may be that the woman will have to visit her doctor relatively frequently. The formation of follicles on the ovaries is carefully monitored using ultrasound and sometimes also through blood tests. If it appears that the ovaries are not reacting, then the doctor can increase the dosage.

Couples who are receiving treatment for ovulation induction may be advised to have intercourse on the day of the subsequent hCG injection (used to stimulate actual ovulation), and once a day for the next two days. (For IVF and IUI treatments, separate instructions follow.) If three to six courses still produce no results, the following next step would be assisted reproductive techniques such as IUI or IVF ICSI.

Possible Side Effects:
It is important to distinguish between the side effects of the drug and the risks associated with the treatment for which they are being used.
POTENTIAL SIDE EFFECTS OF GONADOTROPHINS:

  • Swollen breasts.
  • Rash at the site of injection.
  • Mood swings.
  • Possible stomach ache and a bloated feeling as a result of overstimulation (hyperstimulation syndrome).

POTENTIAL SIDE EFFECTS OF THE TREATMENT:

  • Increased risk of multiple pregnancy  (careful dosing and check-ups can significantly lower this risk).
  • Higher risk of ectopic pregnancy (where the pregnancy occurs outside of the womb, normally in a fallopian tube).

Results:
Gonadotropins can increase pregnancy rates to such an extent that they are even higher than in naturally fertile couples. The chance of pregnancy depends on, amongst other things, the type of treatment being undertaken. 

GnRH

Gonadotropin releasing hormone (GnRH) is normally produced by the hypothalamus in the brain. It ‘instructs” the pituitary to release the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), which in turn instruct the follicles on the ovaries to develop (FSH) and mature/ovulate (LH). GnRH is most likely to be used for the treatment of hypothalamic amenorrhoea disorder - when a woman does not menstruate as a consequence of reduced GnRH production. It is a safe and relatively cheap method of treatment. GnRH must, just as it is in a natural state, be administered in small “pulses”. This is achieved using a small pump that is worn 24 hours a day. The pump is attached to a belt and a needle is inserted generally under the skin of the abdomen. Test for disorders in the pituitary gland, the thyroid gland or the adrenal gland are conducted. A semen analysis can also be performed beforehand to check for sperm disorders.

How does it work :
GnRH is normally produced by the hypothalamus, and is released in pulses. The drug functions in the same way as the GnRH that is produced naturally. It thus mimics the action of the hypothalamus gland by releasing GnRH during the day, at 90-minute intervals. It stimulates the pituitary to produce FSH and LH, which starts the ovulation process.

How is it administered :
GnRH is administered 24 hours a day (even during sleeping and bathing) at 90-minute intervals through a pump with a needle, which is introduced under the skin of the abdomen (subcutaneous). The pump can also be attached via a thin hose into a vein in the lower arm (intravenous). The pump is the biggest disadvantage of the treatment. During treatment, regular monitoring of the ovaries occurs to see if follicle maturation occurs. Because it imitates the natural hormonal events of the body, intensive check ups are not necessary during every cycle. The most difficult part of the treatment is knowing when to have intercourse. Ovulation can occur at any moment between day 10 and day 22 of treatment, but normally happens around day 14. Ultrasound, LH levels in the blood or predictor sets for identifying ovulation can help in pinpointing ovulation.

Possible Side Effects:

  • Discomfort (due to the pump)
  • Headaches
  • Nausea
  • Sometimes a superficial skin or vein infection may occur where the needle is inserted.

Results:
The percentage of pregnancies for hypothalamic (hypogonadotropic) amenorrhoea stands at 20 to 30 percent per treatment cycle, which is similar to the pregnancy rate of normally fertile couples. Perseverance in the form of repeated use increases the chance of success. About 80 % of couples become pregnant after six cycles and 93 % after 12 cycles. (This is known as the cumulative pregnancy rate.)

Drug Therapy For Endometriosis

There is much to discuss in relation to endometriosis. As the information provided here is only brief you should ask your doctor for further details if you are affected. A diagnosis of endometriosis varies from mild to serious, and diagnosis may or may not contribute to infertility. The disorder could certainly cause a mechanical problem in the reproductive system, but this is not always the case. With the help of a laparoscopy, the seriousness of the condition can be assessed, and sometimes surgery can be used to minimise it. Drug therapies - usually gonadotrophin releasing agonists (GnRH agonists) - can also be used in some cases.

How does it work :
The rationale behind drug therapy is to try to lower oestrogen levels in order to reduce the amount of endometrial tissue outside the womb. For this reason, you will normally NOT be able to become pregnant if you use these medicines and you should probably also not try to become pregnant. This is normally achieved with a GnRH agonist. The dosage and timing of therapy is decided upon by the doctor and depends on the body of the woman and the seriousness of the endometriosis. If the treatment is stopped, the endometriosis can, in many cases, return.

How is it administered :
GnRH agonists are administered as injections. Because these hormones must be used over a longer period, there are special long acting preparations available (so-called depot preparations), which work over a period of 1 to 3 months.

Possible Side Effects:

  • Weight gain
  • Retention of moisture
  • Lethargy
  • Acne
  • Facial hair
  • Cramps
  • Hot flushes
If GnRH is used for a prolonged time, osteoporosis can occur.

GnRH Agonists

GnRH agonists can be prescribed for a number of different reasons including the treatment of endometriosis and fibroids. This section however concentrates on the use of GnRH agonists in fertility treatments, especially assisted reproduction techniques. Ironically, the naturally occurring hormones (oestrogen, androgen and gonadotropins) that are so important for fertility can themselves interfere with fertility treatments. As a result during in vitro fertilisation (IVF) and associated procedures, it is important to avoid the possibility of a premature (spontaneous) ovulation resulting in the loss of the ova (egg) needed for the IVF treatment. To avoid premature ovulation, your own hormonal factory is therefore suppressed or shut down during hormonal stimulation. This can be achieved with the administration of GnRH agonists. An agonist is a drug that mimics a naturally occurring hormone. GnRH agonists halt the natural hormonal activity of a woman so that the gonadotropin treatment can run as appropriately as possible. They are administered by injection. The newer GnRH antagonists also prevent premature ovulation in a more direct manner.

How does it work :
GnRH agonists mimic the effects of natural GnRH. At first, they stimulate the pituitary gland to produce FSH and LH (the so-called flare-up effect). However, with continued use, they lead to a suppression of these hormones, due to exhaustion and tolerance of the pituitary (This is referred to as a down-regulation.) The second part of their actions - that is the suppression of FSH and LH - is the one that is important. Natural ovulation is stimulated by a rise of LH (LH peak) so suppressing natural LH production minimises the chance of a premature ovulation.

How is it administered :
GnRH agonists are administered as injections. Because these hormones must be used over a longer period, there are special long acting preparations available (so-called depot preparations), which work over a period of 1 to 3 months.

Possible Side Effects:

  • Local reaction where the injection took place.
  • Headache, nausea, dizziness, depression, allergic reactions.
  • Loss of bone density (if used for long periods).

GnRH antagonists

Just like the GnRH agonists, the GnRH antagonists can also be used in order to prevent premature ovulation during fertility treatments such as in vitro fertilisation (IVF). Whereas an agonist works in the same way as naturally produced GnRH, an antagonist has the opposite effect.

How does it work :
GnRH antagonists have a more rapid effect than agonists because they directly block LH and FSH production at the level of the pituitary. This means they only have to be administered just before premature ovulation is expected. GnRH antagonists can, as a result, be administered for a much shorter time than agonists. The necessary dosage is also lower than for the GnRH agonists. Experience with GnRH antagonists, however, is still limited.

How is it administered :
GnRH antagonists must, just like most agonists, be administered by injection under the skin at a certain point in the cycle. This generally happens on the fifth to seventh day of the FSH cycle.

Possible Side Effects:

  • Local reaction where the injection took place.
  • Headaches and nausea (> 1%).
  • Dizziness, lethargy, malaise (< 1%).

Human Choriongonadotrofine (HCG)

The pregnancy hormone human Chorionic Gonadotropin (hCG) may be prescribed to ensure that an egg is actually released, that is to stimulate the actual ovulation. It can be administered to women whose follicles do not mature or whose ovulation does not occur during fertility treatment in order to better assess the moment of ovulation(s). There is therefore a difference between the hormones that ensure that the follicles grow - the ovulation stimulating medicines - and this hormone that is administered to stimulate the final maturation and the ovulation itself. hCG is often used in combination with the ovulation stimulating medicines. The hormone is prepared from the urine of pregnant women.

How does it work :
hCG stimulates the final maturation of the follicles and the subsequent ovulation, thereby replacing the LH peak, which normally has this role under natural conditions. Additionally, hCG can also be prescribed to support the luteal phase (as a substitute for your own LH). Ovulation takes place approximately 40 hours after the injection.

How is it administered :
hCG is administered as a one-off subcutaneous injection. When insemination is planned, the timing of the hCG injection is critical. Your doctor will indicate when you must administer the injection. For IVF, it is also of the utmost importance to administer the injection at the exact time that your specialist indicates, because the timing of the puncture is synchronised to this; the ova must be sufficiently matured, but cannot yet have ovulated.

Possible Side Effects:

  • Local reaction where the injection takes place.
  • Sometimes, allergic reactions.
  • Rarely, general rashes and fever.
  • In combination with ovulation stimulating medicines, overstimulation can occur.

Progesterone Capsules

Progesterone capsules can be prescribed for specific cyclical disorders characterised by a shortage of progesterone in the second half of the cycle. In addition, it is often prescribed as a component of in vitro fertilisation (IVF) treatment. This section is limited to its use in fertility treatments. A woman’s natural hormone production is usually suppressed during an IVF cycle (by the use of GnRH agonists or antagonists). This also prevents natural progesterone production during the second half of an IVF cycle after egg collection ( the puncture). This must be rectified because progesterone is necessary for preparing the womb lining for the implantation of a fertilised egg (embryo). Consequently, progesterone capsules are prescribed after the puncture. (Alternatively, hCG injections can be given.)

How does it work :
Progesterone works in exactly the same way as naturally occurring progesterone to prepare the lining of the womb for pregnancy.

How is it administered:
Progesterone capsules are licensed for oral use. In order to limit the chances of potential side effects, in practice you are often advised to put them into your vagina. (The progesterone is absorbed across the vaginal wall and into the blood circulation.) A normal dosage is two tablets twice a day, starting on the day of the puncture and for at least fifteen days.

Possible Side Effects:
When these pills are taken vaginally, they cause a vaginal secretion and they can also delay the start of menstruation for a few days. It is particularly important you are aware of this so you don’t immediately view a delay in your period as a sign of pregnancy.

Acknowledgement: Organon India Ltd., a subsidiary of Schering-Plough Corp.For further information:

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