PROGESTERONE THERAPY

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Progesterone is a reproductive hormone that is frequently administered to

patients during infertility treatment. It is prescribed for several purposes

and comes in multiple forms, each of which has advantages, disadvantages, and

contexts in which it is most likely to be used.

Progesterone’s Role in Reproduction during an unmedicated cycle, progesterone is

produced by the corpus luteum, a cyst-like structure formed after the oocyte is

released from its ovarian follicle. Progesterone vascularizes the uterine

lining, increasing the blood supply in preparation for potential implantation of

a fertilized egg. In the absence of pregnancy, the corpus luteum’s progesterone

output will normally begin to decrease after about 12 days. In response, the

vascularized lining is shed in the form of a period. Because of these effects,

the primary uses of progesterone in infertility treatment are (1) triggering of

menstruation and (2) luteal phase supplementation.

The Uses of Progesterone

Triggering of Menstruation Women who are anovulatory and do not have periods

frequently undergo the triggering of menstruation at the beginning of a

treatment cycle. During this process, the patient will undergo progesterone

dosing (typically in the form of a single injection or an 8- to 10-day course of

oral medication) which will vascularize the uterine lining. As progesterone

levels begin to fall (as a result of the injection wearing off or stopping the

oral medication), the lining begins to break down, and menstruation is

triggered.

Luteal Phase Supplementation

In luteal phase supplementation, patients begin progesterone after ovulation in

order to augment the progesterone produced by the corpus luteum. In some cases,

supplementation is simply used as insurance. In other cases, a patient’s corpus

luteum may not function properly, and lack of supplementation can cause the

luteal phase to end prematurely and prevent a successful pregnancy. Finally, in

most medicated frozen embryo transfer protocols, patients often produce no

progesterone, and complete supplementation is needed in both the luteal phase

and in early pregnancy. It is also important to note what progesterone *cannot*

do. Some women with shortened luteal phases assume that progesterone

supplementation alone will be adequate for correction of their condition. In

some cases, however, short luteal phases are caused by poor oocyte development

in the follicular phase. This condition cannot be treated by progesterone alone,

and careful testing and accurate diagnosis is therefore needed before any

medication is used.

Types of Progesterone

Synthetic Progesterone (Provera) Synthetic progesterone, which can be

administered orally or via injection, is most commonly used to trigger

menstruation. Because of its chemical makeup, it is less likely to cause some of

the undesirable size effects of natural progesterone, such as sleepiness or

dizziness. Unlike natural progesterone however, synthetic progesterone is

generally *not* considered safe to use during pregnancy, which should be ruled

out prior to its use.

The remaining types of progesterone, described below, are all natural forms

Oral Progesterone Natural oral progesterone, such as Prometrium pills, is used

primarily as a supplement in the luteal phase for patients undergoing natural or

IUI cycles. The primary advantage of oral progesterone is its convenience;

patients do have not have to learn to give themselves injections or deal with

the discharge that may occur with vaginal application. Despite its appeal,

however, oral progesterone has several disadvantages. Most seriously, at least

one study suggests that it may be associated with lower success rates than some

other forms of progesterone; it has been hypothesized that oral progesterone may

be more effective at raising serum progesterone levels than at raising the level

of progesterone within the uterine lining itself,

which is where its true effect occurs. Additionally, oral progesterone is

metabolized by the liver, and the byproducts may cause side effects such as

dizziness or sleepiness. Recently, some doctors have begun to have patients

administer these same progesterone pills vaginally. Few data are yet available

on the efficacy of this approach.

Progesterone Suppositories

Progesterone suppositories are compounded by individual pharmacists and consist

of natural progesterone suspended in a base similar to cocoa butter. Upon

insertion, the warmth of the body causes the suppository to melt and release the

progesterone. Since suppositories are vaginally administered, the liver does

not produce the high number of side effect-causing metabolites that can occur

with natural progesterones taken orally. The vaginal administration also allows

the progesterone to be targeted more specifically to the uterine area. Many

women, however, find the discharge associated with suppositories to be overly

messy or uncomfortable and there is some question as to how long the

progesterone is effective after insertion. Additionally, it can be difficult to

find a pharmacy that will compound the suppositories, and the individualized

process may cause a lower level of dosing accuracy and quality control.

Finally, some women may be sensitive to the suspending substance.

Bioadhesive Gel (Crinone)

Crinone gel is also applied vaginally. In contrast to suppositories, however,

the progesterone is suspended in a bioadhesive gel (sold without progesterone

under the brand name Replens) and is packaged in a tampon-like applicator.

Crinone gel is highly efficient at the uterine level; in fact, the progesterone

stays so concentrated in the uterus that Crinone often has minimal impact on

serum progesterone levels. Crinone is frequently used as a progesterone

supplement in IUI and IVF cycles. This uterine level impact is one of the

primary advantages of Crinone, as is the fact that many patients only need to

apply it once a day. For many women, Crinone is far better at delaying

premature onset of menstruation than are suppositories or oral progesterone.

Some women do, however, find that the suspension gel accumulates in the vagina

and may need to be removed every couple of days; additionally, patients

occasionally experience vaginal irritation as a result of the build-up.

Injectible Progesterone

Injectible progesterone consists of progesterone suspended in an oil, commonly

sesame or peanut. Used most frequently in IVF cycles, progesterone in oil is

normally injected intramuscularly once a day, most commonly in a dose of one

cubic centimeter (cc). Progesterone in oil is highly effective at the uterine

level; many physicians consider it to be the gold standard for progesterone

supplementation, particularly in high stakes in vitro fertilization cycles.

Additionally, unlike Crinone, progesterone in oil supplementation is also

reflected in serum tests, allowing levels to be more easily, albeit indirectly,

monitored. The once a day dosing is convenient for patients, and the cost is

quite low, often only several dollars a day for a patient taking 1 cc.

For many women, the primary disadvantage of progesterone in oil is the manner in

which it is administered. In addition to being intramuscular, progesterone

injections must be performed using a 20 or 22 gauge needle to accommodate the

relatively high viscosity of the oily solution. This gauge is larger than that

used for most other infertility medications, and patients often find the change

intimidating. Additionally, like progesterone suppositories, progesterone in

oil normally has to be compounded by a specialty pharmacy or mail ordered.

Finally, some women may be allergic to the oil in which the progesterone is most

commonly suspended.

What about Progesterone Creams?

In contrast to the above products, progesterone creams are available over the

counter. These products deliver a small amount of supplemental progesterone,

and absorption may vary significantly from person to person. These creams may

provide a bit of “insurance” to a woman with a fairly normal cycle, but the

dosages are not high enough to treat significant hormonal issues. When you are

trying to conceive, it is always a good idea to consult a knowledgeable

professional about the use of any drug that might affect fertility.

What is the Best Form?

As is often the case, there is no one single treatment that is best for all

women. Although oral progesterone may be sufficient for some women, Crinone and

progesterone in oil do appear to be the most effective at the uterine level.

The issue of whether either of these two supplementation forms is superior to

the other remains unresolved. Some preliminary research suggests that

progesterone in oil is superior at preventing bleeding in pregnancy, but that it

may also delay bleeding in some cases where genetically abnormal pregnancies

ultimately result in blighted ova. Definitive research is, however, yet to be

done.

Hart

Wife to Jon, Love of My Life

Mom to 4:

Arianne (16) ~ a(7)

(4) ~ (My TR Baby - born 6/20/02)

Glory to God and Many Thanks to Dr. Levin

http://www.geocities.com/thehartclantx/Thehartclantx.html