Induction of Ovulation for IVF

IVF is performed very rarely in natural cycles, meaning the woman is almost always given fertility drugs to produce as many healthy eggs as possible, and to control the timing of ovulation so the eggs can be retrieved.

‘Superovulation’ is when drugs are used to make a woman ovulate more than one egg. ‘Controlled ovarian hyperstimulation’ is ‘superovulation’ with the addition of a hormonal response that aids in the creation of the optimal implantation environment. These terms are also sometimes referred to as simply ‘stimulation’, although the catch-all phrase does not properly emphasize the differences between them.

Estrogen (E2, or, Estradiol) is the hormone secreted into the blood by the growing follicles. It is checked to measure the maturation and health of the developing eggs in the ovaries. This is also done via ultrasound.

Egg retrieval must be scheduled before ovulation actually occurs, otherwise the eggs will be ovulated and lost.

Ovulation induction usually involves daily injections of a fertility drug, and regular blood and ultrasound tests to monitor progress. It should also be expected that this part be quite emotional, for both partners! These drugs have quite the effect on most women. Dosages and choice of drugs are determined on an individual basis in accordance with each specific couples situation.

Fertility Drugs

Clomiphene Citrate (Clomid, Serophene)

This is the most popular drug for ovulation induction. It is also used to stimulate follicle growth.
It makes the body think estrogen levels are too low. This makes the hypothalamus release GnRH (gonadotropin releasing hormone) which then makes the pituitary release FSH (follicle stimulating hormone). This causes excessive follicle growth and ultimately ovulation.
Clomiphene is usually started very early in the menstrual cycle (day 2-5) and induces ovulation approx. 12 days later.
Clomiphene should not be taken for more than 3 months consecutively or the result may be opposite to the desired,…a decreased possibility of conception. Women over the age of 40 respond quite poorly to the use of this drug.

Side Effects When used alone, if the response is poor, a luteal phase defect may result. This means the endometrium will not react appropriately to the progesterone. It can also have a similar effect with estrogens influence on the uterine lining.
It can also cause swelling of the ovaries, visual disturbances and hot flashes as a result of too rapid development of the follicles creating cysts.
It can also dry up cervical mucus and decrease the thickness of the endometrium.
It should also be noted that other methods of ‘controlled ovarian hyperstimulation’ most often produce a higher pregnancy rate.

Human Menopausal Gonadotropin (hMG, Pergonal, Repronex, Menogon)

The urine of menopausal women is high in LH and FSH because the body is trying to stimulate the ovaries to once again produce estrogen in the amounts it used to. Purifying this urine is quite expensive.
hMG acts directly on the ovaries to stimulate follicle growth, as opposed to Clomiphene which influences the pituitary. It also does not inhibit the function of estrogen.
The egg retrieval rate with hMG is usually between 6-10.
hMG is an injection that is taken early in the cycle for 6-10 days (+/-).
Although, the administration of an injection of hCG is needed to induce ovulation with the use of this therapy.

Side Effects Breast tenderness, backaches, headaches, insomnia, bloating, and increased vaginal discharge. Luteal phase defects are also reported, although, hMG stimulates lining growth quicker, which is good when the follicles are growing faster. This balance is a positive for implantation.
Other possibilities are ovarian ‘weeping’ of fluid into the abdominal cavity which can cause swelling, and difficult breathing. Rarely, the Liver and Kidneys may shut down which is life threatening.
Most side effects with hMG will only happen once the shot of hCG is given.
Hyperstimulation and excessively high estrogen levels may also occur, although this would usually be found with routine tests.
If no response happens with this therapy, a break of a couple of months is taken and the calculated adjustments in dosage are made for the next try. Many women respond very differently to the use of this drug.

Recombinant FSH (Fertinex, Follistim, Gonal F, Puregon)

This is pure FSH (free of LH) produced by bacteria through genetic engineering.

Gonadotropin-releasing Hormone Agonist (GnRHa, Lupron, Synarel, Nafarelin, Buceleron)

In about 25% of cases where women receive hMG and FSH alone or in combination, a premature release of the hormone LH causes the follicle to stop develping and damages the eggs. This results in a fall in the plasma estradiol concentration and mandates cancellation of the treatment cycle.
It is also used to delay the body from ovulation so that more stimulation can take place if it is needed.
It is quite possible that regulating the amount of LH released into the womans body will help to understand how to regulate her fertility drug treatments.
GnRH agonists inhibit the release of LH. This is why they are used prior and during the treatment with hMG and/or FSH.
They are available in nasal spray or injection.
It should also be noted that women who do not take GnRH agonists generally respond better to the stimulation drugs.

Evaluating Follicular Development

To know when to schedule optimal retrieval, blood-estrogen tests and ultrasounds are done to evaluate the development of the follicles. Between day 9-14 of stimulation the date of retrieval is determined.

Ultrasound

This is used to clearly identify, count, and measure the follicles so as to monitor the progress of stimulation and best determine when ovulation may occur. It should be noted that small size does not necessarily mean poor quality. The smallest mature follicles commonly produce healthy eggs.

Blood-estrogen

This helps determine how many eggs may be developing. High levels generally means more eggs. It also helps determine whether LH has been released the day after the stimulation has stopped. This situation would display a drop in estrogen levels which compromises the health of the follicles and eggs.

hCG Injection (Pregnyl, Novarel, Profasi, Ovidrel)

If it is safe to do so, an injection of hCG (human chorionic gonadotropin) is administered. This induces ovulation to occur within 38-42 hours. hCG is structured like LH, therefore when it is administered it acts like an LH surge, thus inducing ovulation.

When a woman has been successfully stimulated the next step is Egg Retrieval.

The woman moves on to Egg Retrieval once blood estrogen levels have been sustained or have risen after the stopping of the stimulation drugs.

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