High FSH Info

If you choose to pursue Assisted Reproduction Techniques (ART) – i.e., IUI or IVF, it is important to learn as much as you can about the medications and protocols used so that you can work with your doctor to be your best advocate. I apologize for the length of this page, but it seemed better to keep the information one page rather than arbitrarily split it up. This article from Sher Institutes also provides a good overview of some of the medications used in IVF.

Note: Much of the information in this section below was derived from “How to Get Pregnant” by Sherman Silber (c) 2005 (listed on Welcome Page).

There are generally four main types of medications utilized in ART: 1) medication to stimulate the ovaries into producing more eggs than normal – “stims”, 2) medication to suppress ovulation so that ovulation doesn’t happen too early, 3) medication to trigger ovulation at the appropriate time, and 4) medications to promote implantation and support pregnancy. Typical protocols involve using at least one medication from each of the first three categories and medications from the fourth category as needed.

1. Stim medications: There are two main types of stims – Mild Stimulation Medications and Gonadotropins.
   • Mild Stimulation Medications. There are two primary medications that fall into this category - Clomiphene Citrate (brand names are Serophene and Clomid) and Letrozole (brand name Femara).
     • These medications provide mild ovarian stimulation, generally producing a small increase in the number
       of follicles ovulated.
     • Are safe to use with timed intercourse or IUI because of the mild stimulation involved.
     • Can be used in conjunction with Gonadotropins (see below) and they may allow a smaller dose of Gonadotropins to be required.
     • Clomiphene Citrate can have an adverse affect on the uterine lining and cervical mucous in some women and this affect can last for six to eight weeks.
     • Letrozole does not appear to have adverse affects on the lining and mucous and is cleared from the body more quickly.
     • Clomiphene Citrate and Letrozole are similar but operate in somewhat different manners and RE’s will choose a particular medication on a case by case basis.
   • Gonadotropins. Purified preparations of FSH – they work as an additive affect to the FSH your body is already producing (endogenous FSH) and further stimulate the ovaries. There are two types of gonadotropins: Human Menopausal Gonadotropin (HMG) and recombinant FSH products (r-FSH). The two types of gonadotropin can be used individually or can be mixed together – in a so-called “mixed protocol” - to result in an optimal level of LH.
     • Human Memopausal Gonadotropin(HMG)(aka menopausal gonadotropins)
       • Derived from the urine of menopausal women which is high in FSH and contains a small amount of LH which is necessary for follicle development
       • Some brand names – Pergonal, Humegon, Menogon, Repronex, Menopur, and Bravelle.
     • Recombinant FSH (r-FSH)
       • Created using DNA technology
       • Original products contained no LH which was detrimental to follicular development. Some products now have added LH, but the amount of LH can be too much because it is an additive to endogenous LH.
       • Some brand names – Gonal-F, Follistim
       • A low dosage of r-FSH would be 1 or 2 ampules, a high dose would be 6 ampules
       • Costs more than HMG
2. Medication to suppress ovulation: There are two main types: GnRH agonists and GnRH antagonists.  It should also be noted that the mild stimulation medications can also be used to suppress ovulation if they are taken up until the time of desired ovulation.

• • GnRH Agonists
    • GnRH is a hormone produced by the brain that triggers the pituitary to release FSH and LH. Lupron (brand name) is a GnRH agonist which means that it stimulates the pituitary to release lots of FSH and LH, then the pituitary is depleted so it can then no longer release FSH and LH. This process of depleting the pituitary is referred to as “down regulation”. Down regulation takes about five days after Lupron is started.
    • In the US, Lupron can be known as leuprolide, in Europe, Lupron can be known as buserelin, lucrin or suprefact.
    • There are several protocols for using Lupron – Long phase, Short phase and Mini-dose:
      • Long-phase Lupron is started during the luteal phase of the preceding cycle. The normal dosage is .2ml / 1mg. This approach means that by the time the IVF cycle is started there will be no endogenous LH or FSH to interfere with the stims. Long phase results in better pregnancy rates for patients with normal FSH.
      • Short-phase Lupron is started on CD3, then 2 days later HMG or FSH is started. The Lupron provides an early stimulating affect (before down regulation kicks in) which allows the usage of less HMG/FSH. The normal dosage is .2ml / 1mg. Short phase is often used for patients w/ DOR because some patients w/ DOR do not respond well to Lupron.
      • Mini-dose (aka Micro-dose or Flare protocol).  Same as the short phase protocol but 1/4 to 1/10 of the normal dosage is used. Mini-dose is often used for patients w/ DOR because some patients w/ DOR do not respond well to Lupron.  The theory is that it is meant to suppress endogenous FSH and LH less vigorously, thus allowing endogenous FSH and LH to work in combination with the stims to affect the ovary. Sometimes, however, it can result in too much LH which is bad.
  • GnRH antagonists
    • Makes the pituitary think that there is no GnRH which is its trigger to produce LH and FSH, so the pituitary immediately ceases production of LH and FSH
    • LH and FSH drops instantly so there’s no need for a long phase to “prime the system”.
    • There are a few disadvantages: 1) it’s expensive, 2)it drops the LH even lower than Lupron, 3) 1 missed dose of medication can cause a premature LH surge and early ovulation.
    • One way to overcome the extremely low LH is to start it later – when the lead follicle is 13-14mm
    • GnRH antagonists are preferable for DOR because some patients w/ DOR do not respond well to Lupron
    • Two brand names are Cetrotide and Antagon

3. Medication to trigger ovulation: There are two main types: Human Chorionic Gonadotropin (HCG) and Lupron

• Human Chorionic Gonadotropin (HCG) – Is the equivalent of LH and when applied will mimic the natural LH surge which triggers ovulation. Some brand names are Pregnyl, Profasi, and Novarel.
• Lupron – When used in conjunction with an ovulation suppression protocol that does not involve Lupron, Lupron can actually be used to trigger ovulation because of its action as a GnRH agonist.

4. Medication to promote implantation and support pregnancy: In an IVF cycle, the body’s natural ability to produce hormones such as progesterone and estrogen is compromised due to the aspiration of the corpus luteum (mature follicle). For this reason, hormones are taken to supplement or replace the body’s natural hormones. In some cases, hormones are also taken with cycles involving either timed intercourse or IUI if the RE feels that the hormones need to be supplemented.