0:00:09.450,0:00:12.740
Progesterone is a key pregnancy hormone with modulating effects

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that are essential for successful reproduction.

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

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progesterone supplementation is standard practice.

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

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can impair progesterone production from the corpus luteum.

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Use of GnRH analogues used to prevent early ovulation

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can also suppress luteal function.

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(First-Generation Progesterone Supplements)

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

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

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

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

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The aid of another person is often required.

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

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

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

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

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

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Vaginal moisture penetrates the emulsion,

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beginning a slow process of progesterone release

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and absorption by the vaginal epithelia.

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Because it is bioadhesive and water insoluble,

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the gel can remain adhered to the vaginal wall

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even after the progesterone has been absorbed.

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

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This may require manual removal prior to embryo transfer.

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If gel accumulates, vaginal discharge appearing as white globules

0:02:26.480,0:02:30.220
may occur as the gel is discarded and exits the body.

0:02:35.278,0:02:39.318
(ENDOMETRIN Vaginal Insert[br]Advancing the ART of Luteal Phase Support)

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

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

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ENDOMETRIN is a 100-milligram vaginal insert

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administered two or three times daily

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with a sterile disposable applicator.

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

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

0:03:14.690,0:03:18.759
The insert breaks down, releasing progesterone into the aqueous environment.

0:03:19.199,0:03:24.789
Progesterone, being a hydrophobic molecule, rushes towards the vaginal epithelia,

0:03:24.789,0:03:30.330
where it is absorbed by serum proteins and delivered to the endometrium via local circulation.

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Unlike crinone, which is dosed 90 milligrams once daily,

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ENDOMETRIN is dosed 100 milligrams two or three times daily

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

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

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

0:03:54.528,0:03:58.489
while the gel did not reach steady state by the end of the fifth day.

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

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because of its bicarbonate formulation,

0:04:07.529,0:04:14.769
The majority of each ENDOMETRIN vaginal insert ends up as water and carbon dioxide, resulting in minimal discharge.

0:04:17.509,0:04:21.779
With the introduction of these FDA-approved vaginal progesterone preparations,

0:04:21.899,0:04:26.199
relying on painful intramuscular injections is no longer necessary.

0:04:27.719,0:04:36.499
Both FDA-approved vaginal preparations have been proven as efficacious as IM delivery of progesterone in randomized prospective trials.

0:04:36.979,0:04:40.780
However, only ENDOMETRIN provides rapid progesterone uptake

0:04:40.780,0:04:43.730
while causing no build-up and minimal discharge.

0:04:47.430,0:04:50.570
ENDOMETRIN progesterone vaginal insert is indicated to

0:04:50.570,0:04:56.939
support embryo implantation and early pregnancy by supplementation of corpus luteum function

0:04:56.939,0:05:03.239
as part of an Assisted Reproductive Technology (ART) treatment program for infertile women.

0:05:03.799,0:05:05.870
Important Safety Information

0:05:06.150,0:05:10.190
ENDOMETRIN should not be used in individuals with any of the following conditions:

0:05:10.190,0:05:14.809
previous allergic reactions to progesterone or any of the ingredients of endometrium,

0:05:14.809,0:05:18.339
known missed abortion or ectopic pregnancy, liver disease,

0:05:18.339,0:05:20.250
known or suspected breast cancer,

0:05:20.250,0:05:25.070
active arterial or venous thromboembolism or severe thrombophlebitis,

0:05:25.070,0:05:27.029
or a history of these events.

0:05:27.209,0:05:31.120
The physician should be alert to the earliest signs of myocardial infarction,

0:05:31.120,0:05:35.549
cerebrovascular disorders, arterial or venous thromboembolism

0:05:35.549,0:05:38.460
(venous thromboembolism or pulmonary embolism),

0:05:38.460,0:05:40.999
thrombophlebitis or retinal thrombosis.

0:05:41.079,0:05:44.769
ENDOMETRIN should be discontinued if any of these are suspected.

0:05:44.769,0:05:47.750
Patients with a history of depression need to be closely observed.

0:05:47.750,0:05:50.429
Consider discontinuation if symptoms worsen.

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

0:05:56.150,0:06:00.230
as this may alter progesterone release and absorption from the vaginal insert.

0:06:00.690,0:06:04.290
The most common adverse reactions reported (greater than 5%)

0:06:04.290,0:06:07.260
were post-oocyte retrieval pain, abdominal pain,

0:06:07.260,0:06:10.279
nausea, and ovarian hyperstimulation syndrome.

0:06:10.699,0:06:13.569
Please see full prescribing information.