Progesterone is a key pregnancy hormone with modulating effects

that are essential for successful reproduction.

For patients going through In Vitro Fertilization and other Assisted Reproductive Technologies,

progesterone supplementation is standard practice.

During oocyte retrieval, removal or disruption of the granulosa cells lining the follicle,

can impair progesterone production from the corpus luteum.

Use of GnRH analogues used to prevent early ovulation

can also suppress luteal function.

(First-Generation Progesterone Supplements)

Intramuscular injection of progesterone in an oil-based suspension is one common delivery method.

It is not approved by the FDA for women undergoing IVF or other ART treatments.

Oil-based injections have been associated with a number of side effects,

including pain at the injection site, inflammatory reactions and abscess formation.

The aid of another person is often required.

In 1997, Crinone progesterone gel 8% was approved by the FDA

for vaginal administration during ART treatment for infertile women with progesterone deficiency.

Crinone gel is a water-insoluble Polycarbophil emulsion that contains micronized progesterone.

Crinone is delivered once or twice a day to the vagina via a prefilled disposable applicator.

Once administered, the gel adheres to the vaginal wall through hydrogen bonds.

Vaginal moisture penetrates the emulsion,

beginning a slow process of progesterone release

and absorption by the vaginal epithelia.

Because it is bioadhesive and water insoluble,

the gel can remain adhered to the vaginal wall

even after the progesterone has been absorbed.

With each additional dose, 1.125 grams of gel are delivered and can contribute to build up.

This may require manual removal prior to embryo transfer.

If gel accumulates, vaginal discharge appearing as white globules

may occur as the gel is discarded and exits the body.

(ENDOMETRIN Vaginal Insert
Advancing the ART of Luteal Phase Support)

In 2007, endometrial progesterone vaginal insert was approved by the FDA

as an alternative to vaginal gel for women undergoing ART treatment.

ENDOMETRIN is a 100-milligram vaginal insert

administered two or three times daily

with a sterile disposable applicator.

In a moist environment, the bicarbonate delivery system of the insert is highly soluble.

Vaginal moisture penetrates the insert, causing an acid-based reaction.

The insert breaks down, releasing progesterone into the aqueous environment.

Progesterone, being a hydrophobic molecule, rushes towards the vaginal epithelia,

where it is absorbed by serum proteins and delivered to the endometrium via local circulation.

Unlike crinone, which is dosed 90 milligrams once daily,

ENDOMETRIN is dosed 100 milligrams two or three times daily

due to differences in the pharmacokinetic profile of the two products.

In a randomized open-label pharmacokinetic study with 18 women aged 18-40,

both doses of endometrium reached steady-state progesterone concentrations in about 24 hours,

while the gel did not reach steady state by the end of the fifth day.

Efficacy was not a parameter being examined in this PK study.

because of its bicarbonate formulation,

The majority of each ENDOMETRIN vaginal insert ends up as water and carbon dioxide, resulting in minimal discharge.

With the introduction of these FDA-approved vaginal progesterone preparations,

relying on painful intramuscular injections is no longer necessary.

Both FDA-approved vaginal preparations have been proven as efficacious as IM delivery of progesterone in randomized prospective trials.

However, only ENDOMETRIN provides rapid progesterone uptake

while causing no build-up and minimal discharge.

ENDOMETRIN progesterone vaginal insert is indicated to

support embryo implantation and early pregnancy by supplementation of corpus luteum function

as part of an Assisted Reproductive Technology (ART) treatment program for infertile women.

Important Safety Information

ENDOMETRIN should not be used in individuals with any of the following conditions:

previous allergic reactions to progesterone or any of the ingredients of endometrium,

known missed abortion or ectopic pregnancy, liver disease,

known or suspected breast cancer,

active arterial or venous thromboembolism or severe thrombophlebitis,

or a history of these events.

The physician should be alert to the earliest signs of myocardial infarction,

cerebrovascular disorders, arterial or venous thromboembolism

(venous thromboembolism or pulmonary embolism),

thrombophlebitis or retinal thrombosis.

ENDOMETRIN should be discontinued if any of these are suspected.

Patients with a history of depression need to be closely observed.

Consider discontinuation if symptoms worsen.

ENDOMETRIN should not be recommended for use with other vaginal products (such as antifungal products)

as this may alter progesterone release and absorption from the vaginal insert.

The most common adverse reactions reported (greater than 5%)

were post-oocyte retrieval pain, abdominal pain,

nausea, and ovarian hyperstimulation syndrome.

Please see full prescribing information.