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 ~ Moderator

TR 6-4-01 ~ 8cm R ~ 9cm L

~ Mom to 4 Great Children ~

Arianne (17) ~ a (8)

(5) ~ Bean (1)

Glory to God and Many Thanks to Dr. Levin!

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

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