Overview of Fertility Medications
by Scott Roseff, M.D.

This paper gives an overview of fertility medications used in the United States.  It is meant to be a guide to what the various available medications are, only, and should never replace the information that should be given to you by your infertility doctor and pharmacist.  Your doctor should discuss the potential risks vs. benefits with you before you begin using any of these medicines.  Specific drug protocols will not be elucidated herein, because what works for one woman may not work for another.  ALL injectable fertility drug treatments should be HIGHLY individualized for each patient in order to maximize success while minimizing side effects.

Since we will focus on injectable medications, clomiphene citrate (Clomid®, Serophene®) will be discussed only briefly, as it is an oral agent and in general is not considered to be a true fertility drug. For more information on Clomid use, please read Clomid Use and Abuse located here: http://www.inciid.org/clomidberger.html .

Clomiphene citrate is a tablet that is typically prescribed to help someone conceive.  While many doctors use it as a “fertility drug”, it often does not enhance fertility per se - A true fertility drug can increase the odds of pregnancy in someone who is already fertile, and Clomid® doesn’t usually do this.  Clomiphene works by “faking the brain out” into thinking there’s no estrogen in the body, and the brain responds by putting out more appropriate amounts of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary in order to stimulate a follicle to grow.  Clomiphene, therefore, works indirectly on the ovaries and depends on your body’s own hormones to cause an egg to grow.  Because this medicine can cause more than one egg to develop about 10% of the time, it increases the odds of a multiple pregnancy.

It’s important to realize that clomiphene causes an egg to grow, but it doesn’t necessarily cause the egg to ovulate.  Therefore, while some women respond to clomiphene by producing a follicle (egg), they don’t ovulate and may therefore need an injection of a drug called hCG to trigger the egg to be released.  We can determine if an egg is produced (but not ovulated) by monitoring clomiphene citrate cycles with blood tests and ultrasound examinations.

Clomiphene is usually started at a dose of 50 mg (one tablet) per day for five days per menstrual cycle, beginning on the third, fourth, or fifth day of the cycle.  Starting the drug earlier tends to induce ovulation somewhat sooner in the cycle, and may also increase the odds of developing more than one egg.  It’s crucial to be monitored while taking clomiphene (rather than simply going home and taking it month after month), so as to determine if it’s doing a proper job.  If you ovulate on a particular dose of clomiphene, there’s generally no benefit to increasing the dosage on a subsequent menstrual cycle.

This medicine can also have some adverse effects on your fertility, and it would be beneficial to assure these haven’t occurred.  Possible negative effects of clomiphene that can interfere with getting and/or staying pregnant include, but aren’t limited to:

• Decreased or “hostile” cervical mucus

• Thin uterine (endometrial) lining

• Disordered uterine lining at a microscopic level

Your doctor can check your mucus around the time of ovulation if intercourse is planned, or intrauterine insemination (IUI) can be scheduled to “bypass” potential mucus problems and optimize the odds of becoming pregnant.  A sonogram can be done to assure the uterine lining isn’t too thin, and an endometrial biopsy can be performed to check the endometrium at a microscopic level to assure it has properly developed for pregnancy implantation and maintenance.

One final note on clomiphene – As I mentioned earlier, it’s generally not a true fertility drug.  There are clear indications for it, and if you’re a clomiphene “candidate” it works quite well.  But, if you don’t “need” this medicine, then it can potentially work against you by preventing you from getting pregnant or causing a miscarriage.  If you don’t “need” clomiphene , it can potentially “throw a wrench into your works” by interfering with your pituitary hormones, creating poor cervical mucus, thinning out your uterine lining, and creating an environment that’s not conducive to getting or staying pregnant.  So, who should not take clomiphene?  If you fulfill the following criteria, then you may want to question whether you should be taking this medicine:

• Regular menstrual cycles every 26-32 days

• Documented or presumed monthly ovulation

• Normal peak progesterone blood level seven days after ovulation

• Normal luteal phase length

• In-phase (normal) endometrial biopsy in the late luteal phase

Human, Urinary-derived Gonadotropins (a.k.a. Menotropins, Human Menopausal Gonadotropins or HMG)

Menotropins approved for usage in the United States are:

• Pergonal®

• Repronex®

• Humegon®

• Bravelle™

This class of injectable fertility drugs has been available and in clinical use for over 30 years.  Since FSH and LH are necessary for follicle development, the menotropin drugs contain either a combination of FSH and LH (Pergonal®, Repronex®, and Humegon®) or FSH alone (Bravelle™).  Menotropins containing FSH alone actually have a very small amount of LH in them, and specialists who use the urinary-derived FSH preparations also depend on your body to produce some LH during your stimulation cycle.  As menopausal women excrete large amounts of FSH and LH in their urine, menotropins are manufactured by obtaining and purifying the urine of postmenopausal women, after which the FSH and LH are extracted and made into a powder for later reconstitution (mixing with a liquid).