Several hormonal medications are used in an IVF cycle. These medicines belong to several categories and each is an important part of the IVF cycle. The types and amounts of medications used vary according to the medication protocol prescribed by your physician. 

Gonadotropins

To increase the likelihood of pregnancy through ART, multiple eggs are made at one time. Stimulation can be achieved with a variety of medication regimens. This is accomplished through the administration of gonadotropins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)), hormonal medications that directly stimulate the ovaries. They provide LH and FSH which are normally produced by the pituitary gland.  Gonadotropin medications come in several forms: Menopur® is a combination of FSH and LH, and Follistim® and Gonal-F® only contain FSH. They are recombinant products, which are made by genetically engineered cells. This process ensures uniform purity and potency. Because the dose of hormones that are used in ART is greater than what the body normally produces, the ovaries typically develop more than one egg.

Gonadotropins act directly on the ovary to stimulate the growth of follicles (the structures in the ovaries that contain eggs). The follicles enlarge and fill with follicular fluid. These developing follicles can be counted and measured using transvaginal ultrasound. As the follicles grow, they produce increasing amounts of estrogen, which can be measured with a laboratory blood test. 

Dosage and Monitoring

Gonadotropins are packaged in pre-mixed injectable vials containing 300-900 International Units (IU).  Multi-dose vials of some medications are also available. Dosage may vary depending on the patient's history. Patients will then have regularly scheduled transvaginal ultrasound examinations and blood estradiol tests. The dose of gonadotropins is then determined by the result of the ultrasound and estradiol tests. Most women require between 8 to 10 days of gonadotropin therapy.  The medications are administered subcutaneously.

GnRH Agonists

Gonadotropin-releasing hormone (GnRH) is a hormone produced in the brain that indirectly stimulates the ovaries. GnRH agonists are synthetic forms of this hormone that do not directly induce follicle development or ovulation but have become very important in IVF treatment.

There are several advantages to using GnRH agonists:

1. They make ovarian stimulation easier to regulate since the patient's own hormones are suppressed.
2. GnRH agonists markedly the risk of cycle cancellation for most patients. 
3. If necessary, GnRH agonists can suspend ovarian function for variable periods of time, which allows for flexibility in cycle scheduling. 
4. If used as a trigger shot, the risk of OHSS (ovarian hyperstimulation syndrome) is greatly reduced

Mechanism Of Action

GnRH agonists (such as Lupron®) initially stimulate the pituitary gland to release gonadotropins (LH and FSH). Over the course of 7 to 10 days, GnRH agonists then suppress the production of any new LH and FSH. This effect appears to prevent the ovaries from receiving mixed signals from the patient's own LH and FSH.  The result for many patients is a more synchronized development of many mature oocytes at one time and prevents ovulation. 

Dosage and Monitoring

The GnRH agonist used most commonly is leuprolide acetate (Lupron®).  Lupron® is not FDA-approved for use in IVF treatment but has been used successfully in IVF for 20 years.  Lupron® must be injected to be active. During IVF, patients use a subcutaneous formulation of Lupron®.

The usual dosage of Lupron® is 0.1 or 0.2 cc daily as a single injection. Menstruation usually occurs 5 to 10 days later. During actual ovarian stimulation, the dosage of Lupron® is halved (e.g., 0.1 cc to 0.05 cc daily). Lupron is usually administered until the day of hCG administration. Some patients, because of their history or condition, are treated with a different dosage or schedule of Lupron®.

In some protocols, a GnRH agonist can be used to trigger ovulation of mature follicles in place of hCG (human chorionic gonadotropin). This is usually reserved for patients at risk for OHSS.

GnRH Antagonists

GnRH antagonists (Cetrotide®, Fyremadel®, and Ganarelix®) are also available. These are started later in the IVF cycle and directly and immediately inhibit FSH and LH production. Protocols that use these medications may require fewer injections. Ultrasound measurements of follicular growth are used to determine when to start these medicines. 

Mechanism of Action

GnRH antagonists bind to the receptor for gonadotropin-releasing hormone on the pituitary, preventing the natural LH surge and ovulation. This is important to the success of an IVF cycle, as premature ovulation could reduce the number of oocytes retrieved. 

Human Chorionic Gonadotropin

Human chorionic gonadotropin (hCG) is an injectable medication that is administered to complete egg maturation. The brand names for hCG are Ovidrel®, Novarel®, and Pregnyl®. 

Mechanism of Action

Human chorionic gonadotropin is structurally similar to the LH  produced by the pituitary gland. It acts on the ovary in a manner similar to the body’s own LH. Human chorionic gonadotropin, like LH, stimulates the final maturation of the oocytes in the follicle. It also stimulates progesterone production from the ovary after egg retrieval. This progesterone is important to prepare the uterus for implantation of the embryo. 

Dosage and Administration

Human chorionic gonadotropin can be administered in several different ways. The commonly administered dose is a single injection of 10,000 or 5,000 units. Ovidel may be 250-500 mcg.  Once hCG is administered, ovulation usually occurs in approximately 36 to 40 hours. Therefore, oocyte retrieval is routinely scheduled at 34-36 hours after hCG. This helps ensure egg maturity, which is important for fertilization and embryo development.

It typically takes 8-10 days for a single injection of 10,000 units of hCG to be cleared from the bloodstream. As hCG is the same hormone that is produced by a developing pregnancy, patients should not have a blood or urine pregnancy test sooner than 10 days following the hCG injection. If a pregnancy test is performed earlier, it may measure the hCG that was given by injection rather than measure the hCG produced by a pregnancy.

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