Ovulation Induction

Ovulation induction medications, often referred to as fertility drugs, are used to stimulate the
follicles in your ovaries resulting in the production of multiple eggs in one cycle. The medications
also control the time that you release the eggs, or ovulate, so sexual intercourse, intrauterine
inseminations, and in vitro fertilization procedures can be scheduled at the most likely time to
achieve pregnancy.

There are risks associated with the use of ovulation induction medications including an increase in
the chance for high order multiple births and the development of ovarian cysts. A rare side effect
that can occur is ovarian hyperstimulation syndrome (OHSS); symptoms include severe pain in the
pelvis, abdomen and chest, nausea, vomiting, bloating, weight gain and difficulty breathing.

The medications most commonly used in fertility treatment are clomiphene citrate, gonadotropins,
Metformin and Parlodel.

Clomiphene Citrate (Clomid, Serophone) - This medication comes in a tablet form and is used for
women who have infrequent periods or long menstrual cycles. Common side effects include
headaches, blurred vision and hot flashes.

Gonadotropins (Repronex, Follistim, Bravelle, Pergonal and GonalF)- This is an injectable

medication that is used to induce the release of the egg once the follicles are developed and the
eggs are mature. Side effects may include abdominal distention/discomfort, bloating sensation,
mood swings, fatigue or restlessness. In most cases, the side effects are relieved by follicular
aspiration.

Glucophage (Metformin) - Metformin is given to patients as an insulin lowering medication. Most

commonly used in PCOS patients, the medication has been shown to reverse the endocrine
abnormalities seen with polycystic ovary syndrome within two or three months. The use of
Metformin can result in decreased hair loss, diminished facial and body hair growth, normalization
of elevated blood pressure, regulation of menses, weight loss and normal fertility.

Parlodel - Parlodel is a medication used to lower prolactin levels. It will also reduce pituitary tumor
size, should one be present. An oral medication taken with meals, Parlodel has few side effects and
is relatively inexpensive.

There are different levels of ovulation induction commonly used to treat infertility related to
ovulation disorders, male factor or unknown causes. One method of treatment involves clomiphene
citrate (Clomid or Serophene) taken in pill form for 5 days at the beginning of a cycle. For women
whose only infertility problem is anovulation, up to 80% of patients will ovulate using this
medication and 50% of those will conceive . Clomiphene may be combined with intrauterine
insemination to boost the success of the medication by placing the sperm and egg in closer
proximity to each other.

The more aggressive level of ovulation induction is called superovulation. This treatment uses
gonadotropins or sometimes a combination of clomiphene and gonadotropins to stimulate the
production of multiple eggs. Patients undergoing superovulation must be closely monitored by blood
tests and ultrasounds. Monitoring ensures that the patient does not hyperstimulate and also helps
the physician administer the correct dosage of medication so that only a few follicles develop. This is
a critical step to keeping the multiple pregnancy rates low. At the end of the superovulation
treatment process, a low dose HCG (human chorionic gonadotropin) may be prescribed to stimulate
ovulation. Ovulation will occur between 24-36 hours after HCG. The patient is instructed to either
have intercourse during this time or to come in for an intrauterine insemination. Depending on the
cause of infertility, the success rate per superovulation treatment cycle is approximately 10-20%
based on the woman's age.

Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome affects women taking injectable hormone medications to
stimulate the development of eggs in the ovaries. This may occur in women undergoing in vitro
fertilization (IVF), ovulation induction or intrauterine insemination.

Too much hormone medication in your system can lead to ovarian hyperstimulation syndrome
(OHSS), in which your ovaries become swollen and painful. A small number of women may develop
severe OHSS, which can cause rapid weight gain, abdominal pain, vomiting and shortness of breath.

Less often, OHSS happens during fertility treatments using medications you take by mouth, such as
clomiphene (Clomid, Serophene). Occasionally OHSS occurs spontaneously, not related to fertility
treatments.

Symptoms

Symptoms of ovarian hyperstimulation syndrome often begin within 10 days after using injectable
medications to stimulate ovulation. Symptoms can range from mild to severe and may worsen or
improve over time.

Mild to moderate OHSS

With mild to moderate ovarian hyperstimulation syndrome, symptoms can include:

Mild to moderate abdominal pain

Abdominal bloating or increased waist size
Nausea
Vomiting
Diarrhea
Tenderness in the area of your ovaries
Sudden weight increase of more than 6.6 pounds (3 kilograms)
Some women who use injectable fertility drugs get a mild form of OHSS, which goes away
after about a week. If pregnancy occurs, however, symptoms of OHSS may worsen and last
several days to weeks.

Severe OHSS

With severe ovarian hyperstimulation syndrome, you might have:

Rapid weight gain such as 33 to 44 pounds (15 to 20 kilograms) in five to 10 days

Severe abdominal pain
Severe, persistent nausea and vomiting
Blood clots in legs
Decreased urination
Shortness of breath
Tight or enlarged abdomen
Causes

The cause of ovarian hyperstimulation syndrome isn't fully understood, although having a high level
of human chorionic gonadotropin (HCG) a hormone usually produced during pregnancy
introduced into your system plays a role. Ovarian blood vessels react abnormally to HCG and begin
to leak fluid. This fluid swells the ovaries, and sometimes large amounts move into the abdomen.

During fertility treatments, HCG may be given as a "trigger" so that a mature follicle will release its
egg. OHSS usually happens within a week after you receive an HCG injection. If you become
pregnant during a treatment cycle, OHSS may worsen as your body begins producing its own HCG in
response to the pregnancy.

Injectable fertility medications are more likely to cause OHSS than is treatment with clomiphene, a
medication given as a pill you take by mouth.

Risk factors

Factors that increase your risk of OHSS include:

Polycystic ovary syndrome a common reproductive disorder that causes irregular

menstrual periods, excess hair growth and unusual appearance of the ovaries on ultrasound
examination
Large number of follicles
Age under 30
Low body weight
High or steeply increasing level of estradiol (estrogen) before an HCG trigger shot
Previous episodes of OHSS
In some cases, OHSS affects women who have no risk factors at all.

Complications

About 1 to 2 percent of women undergoing ovarian stimulation develop a severe form of ovarian
hyperstimulation syndrome. Severe OHSS can be life-threatening. Complications may include:

Fluid collection in the abdomen and sometimes the chest

Electrolyte disturbances (sodium, potassium, others)
Blood clots in large vessels, usually in the legs
Kidney failure
Twisting of an ovary (ovarian torsion)
Rupture of a cyst in an ovary, which can lead to serious bleeding
Breathing problems
Pregnancy loss from miscarriage or termination because of complications
Rarely, death

Diagnosis

For ovarian hyperstimulation syndrome, your doctor may make a diagnosis based on:

A physical exam. Your doctor will take note of any weight gain, increases in your waist size
and abdominal pain you may have.
 An ultrasound. If you have OHSS, an ultrasound may show that your ovaries are bigger than
normal, with large fluid-filled cysts where follicles developed. During treatment with fertility
drugs, your doctor regularly evaluates your ovaries with a vaginal ultrasound.
A blood test. Certain blood tests allow your doctor to check your blood concentration and
whether your kidney function is being impaired because of OHSS.

Treatment

Ovarian hyperstimulation syndrome generally resolves on its own within a week or two or somewhat
longer if you're pregnant. Treatment is aimed at keeping you comfortable, decreasing ovarian
activity and avoiding complications.

Mild to moderate OHSS

Mild OHSS typically resolves on its own. Treatment for moderate OHSS may involve:

Anti-nausea medication, prescription painkillers or both

Frequent physical exams and ultrasounds
Daily weigh-ins and waist measurements to check for drastic changes
Measurements of how much urine you produce each day
Blood tests to monitor for dehydration, electrolyte imbalance and other problems
Adequate fluid intake
Drainage of excess abdominal fluid using a needle inserted in your abdominal cavity
Support stockings, to help prevent blood clots

Severe OHSS

With severe OHSS, you may need to be admitted to the hospital for monitoring and aggressive
treatment, including IV fluids. Your doctor may give you a medication called cabergoline to lessen
your symptoms. In some cases, your doctor may also give you another medication known as a
gonadotropin-releasing hormone (Gn-RH) antagonist to help suppress ovarian activity.

Serious complications may require additional treatments, such as surgery for a ruptured ovarian cyst
or intensive care for liver or lung complications. You may also need anticoagulant medications to
decrease the risk of blood clots in your legs.

Unexplained Infertility
Couples should undergo a semen analysis, ovulation testing, assessment of ovarian reserve, and
imaging to assess for tubal and uterine factors before a diagnosis of unexplained infertility is made.

The principal treatments for unexplained infertility include expectant observation with timed
intercourse and lifestyle changes, clomiphene citrate and intrauterine insemination (IUI), controlled
ovarian hyperstimulation with IUI, and in vitro fertilization (IVF).

Although expectant management is associated with the lowest cost, it results in the lowest cycle
fecundity rates. It may provide an option for a couple with unexplained infertility in whom the
female partner is young and the problem of oocyte depletion is not an immediate concern.

The most expensive, but also most successful treatment of unexplained infertility consists of the
spectrum of assisted reproductive technology including IVF, with or without intracytoplasmic sperm
injection. IVF is the treatment of choice for unexplained infertility when the less costly, but also less
successful treatment modalities have failed.

The optimal treatment strategy needs to be based on individual patient characteristics such as age,
treatment efficacy, side-effect profile such as multiple pregnancy, and cost considerations.

Assisted Reproductive technology (ART)

Assisted Reproductive technology (ART) is the umbrella term given to describe a number of different
treatments that can be performed to help achieve pregnancy. There is no single definition of
Assisted Reproductive Technology, it is usually illustrated in contrast to sexual intercourse as the
method of reproduction. Hence, it covers a wide range of different fertility treatments.

There is a long history of Doctors trying to provide ART to help couples start a family. John Hunter,
the famous Scottish surgeon, carried out the first documented artificial insemination in the 1770s.
Since then, there have been many new techniques introduced and new advances have brought
better chances of success.

Here we go through an outline of each of these fertility treatments:

IUI Intra-Uterine Insemination

IUI is one of the simplest forms of Assisted Reproductive Technology. It involves collection of the
sperm, preparing the sperm in the lab and then inserting the prepared sperm into the uterus
(womb) of the woman close to the time of ovulation. Before this takes place tests of tubal patency
will have to be performed. A cycle of IUI can be undertaken with or without fertility drugs for the
woman, depending on what is medically recommended. The success rate is generally lower
compared with other forms of ART, and so it is usually only suitable for select couples and those
without fertility problems, such as single women and same-sex couples.

IVF In Vitro Fertilisation

IVF is probably the best known form of ART. In essence, it is the collection of sperm from the male
and eggs from the woman, which are then placed together in a petri dish in the laboratory. The
embryologists then observe if fertilization takes place and following this if the embryo undergoes cell
division (cleavage). Good quality embryos are inserted back into the uterus of the woman at any
time from day 2 to day 5.

Contrary to popular conception, there are in fact several different ways of doing IVF, which differ
depending on the amount of stimulation that is given during an IVF cycle.

The first ever IVF baby, Louise Brown, was born following Natural Cycle IVF. This means that her
mother was given no drugs during fertility treatment.

Then, there is Conventional IVF, which is performed by most IVF clinics. The ovaries are usually
suppressed (downregulated) about 10 days before the womans natural menstrual cycle and this is
followed by high dosages of fertility drugs in order to stimulate the growth of multiple follicles and
embryos and embryos. The theory behind this treatment is to increase quantity and thereby
increase success.

Finally, there is Mild IVF, which is the latest stage in the improvement of IVF. Rather than shutting
down the womans menstrual cycle, Mild IVF is performed in a womans natural cycle. Only small
dosages of Fertility drugs are given with the aim to produce high quality eggs, not high quantity. The
success rates of Mild IVF are comparable to conventional IVF, but the cost is reduced, there are
fewer risks, and much fewer side effects.

IVM In Vitro Maturation

IVM is one of the most exciting forms of ART. The inventor of IVF, Sir Robert Edwards, used to
describe IVM as the future of ART. IVM is the process by which we collect immature eggs from a
womans ovaries during a natural (unstimulated) cycle. We then mature these eggs in the laboratory
and when they have reached sufficient maturity, we perform ICSI to achieve fertilization. Hence,
without giving any fertility drugs, we are able to create multiple embryos.

Vitrification The Fast-freezing Method

Vitrification is the method to freeze eggs, sperm and embryos,. Previously, the freezing of gametes
and embryos was a risky process with an uncertain thawing success rate. However, after the
invention of Vitrification, all of that has changed and thawing success rate for embryos is over 95%.
Essentially, in this ART, the cells are frozen much more quickly than they were in the old methods,
and thereby avoid the creation of damaging ice-crystals.

ICSI Intra-Cytoplasmic Sperm Injection

If youve ever watched the news item about IVF, chances are you were actually looking at ICSI! ICSI is
the ART, which is used to achieve normal fertilisation where there is a male factor problem. It
involves an embryologist selecting a single sperm, removing the tail and then injecting it into the
egg.