WEBVTT 00:00:09.450 --> 00:00:12.740 Progesterone is a key pregnancy hormone with modulating effects 00:00:12.740 --> 00:00:15.739 that are essential for successful reproduction. 00:00:17.759 --> 00:00:22.989 For patients going through In Vitro Fertilization and other Assisted Reproductive Technologies, 00:00:22.989 --> 00:00:26.209 progesterone supplementation is standard practice. 00:00:26.929 --> 00:00:32.210 During oocyte retrieval, removal or disruption of the granulosa cells lining the follicle, 00:00:32.210 --> 00:00:35.560 can impair progesterone production from the corpus luteum. 00:00:36.740 --> 00:00:40.318 Use of GnRH analogues used to prevent early ovulation 00:00:40.318 --> 00:00:43.309 can also suppress luteal function. 00:00:47.933 --> 00:00:52.213 (First-Generation Progesterone Supplements) 00:00:53.253 --> 00:00:59.009 Intramuscular injection of progesterone in an oil-based suspension is one common delivery method. 00:01:00.089 --> 00:01:05.249 It is not approved by the FDA for women undergoing IVF or other ART treatments. 00:01:06.249 --> 00:01:10.030 Oil-based injections have been associated with a number of side effects, 00:01:10.030 --> 00:01:15.820 including pain at the injection site, inflammatory reactions and abscess formation. 00:01:16.180 --> 00:01:19.260 The aid of another person is often required. 00:01:19.800 --> 00:01:24.969 In 1997, Crinone progesterone gel 8% was approved by the FDA 00:01:24.969 --> 00:01:30.859 for vaginal administration during ART treatment for infertile women with progesterone deficiency. 00:01:31.499 --> 00:01:37.790 Crinone gel is a water-insoluble Polycarbophil emulsion that contains micronized progesterone. 00:01:40.050 --> 00:01:45.630 Crinone is delivered once or twice a day to the vagina via a prefilled disposable applicator. 00:01:47.130 --> 00:01:51.358 Once administered, the gel adheres to the vaginal wall through hydrogen bonds. 00:01:52.258 --> 00:01:54.470 Vaginal moisture penetrates the emulsion, 00:01:54.470 --> 00:01:57.479 beginning a slow process of progesterone release 00:01:57.479 --> 00:02:00.100 and absorption by the vaginal epithelia. 00:02:01.300 --> 00:02:04.199 Because it is bioadhesive and water insoluble, 00:02:04.199 --> 00:02:06.708 the gel can remain adhered to the vaginal wall 00:02:06.708 --> 00:02:09.539 even after the progesterone has been absorbed. 00:02:10.679 --> 00:02:16.729 With each additional dose, 1.125 grams of gel are delivered and can contribute to build up. 00:02:17.089 --> 00:02:21.079 This may require manual removal prior to embryo transfer. 00:02:22.739 --> 00:02:26.480 If gel accumulates, vaginal discharge appearing as white globules 00:02:26.480 --> 00:02:30.220 may occur as the gel is discarded and exits the body. 00:02:35.278 --> 00:02:39.318 (ENDOMETRIN Vaginal Insert Advancing the ART of Luteal Phase Support) 00:02:41.198 --> 00:02:46.488 In 2007, endometrial progesterone vaginal insert was approved by the FDA 00:02:46.488 --> 00:02:50.889 as an alternative to vaginal gel for women undergoing ART treatment. 00:02:52.969 --> 00:02:55.978 ENDOMETRIN is a 100-milligram vaginal insert 00:02:55.998 --> 00:02:58.279 administered two or three times daily 00:02:58.279 --> 00:03:00.739 with a sterile disposable applicator. 00:03:02.239 --> 00:03:07.478 In a moist environment, the bicarbonate delivery system of the insert is highly soluble. 00:03:09.498 --> 00:03:13.730 Vaginal moisture penetrates the insert, causing an acid-based reaction. 00:03:14.690 --> 00:03:18.759 The insert breaks down, releasing progesterone into the aqueous environment. 00:03:19.199 --> 00:03:24.789 Progesterone, being a hydrophobic molecule, rushes towards the vaginal epithelia, 00:03:24.789 --> 00:03:30.330 where it is absorbed by serum proteins and delivered to the endometrium via local circulation. 00:03:31.070 --> 00:03:34.509 Unlike crinone, which is dosed 90 milligrams once daily, 00:03:34.509 --> 00:03:38.720 ENDOMETRIN is dosed 100 milligrams two or three times daily 00:03:38.720 --> 00:03:42.499 due to differences in the pharmacokinetic profile of the two products. 00:03:42.779 --> 00:03:48.499 In a randomized open-label pharmacokinetic study with 18 women aged 18-40, 00:03:48.719 --> 00:03:54.528 both doses of endometrium reached steady-state progesterone concentrations in about 24 hours, 00:03:54.528 --> 00:03:58.489 while the gel did not reach steady state by the end of the fifth day. 00:03:58.629 --> 00:04:02.829 Efficacy was not a parameter being examined in this PK study. 00:04:05.350 --> 00:04:07.529 because of its bicarbonate formulation, 00:04:07.529 --> 00:04:14.769 The majority of each ENDOMETRIN vaginal insert ends up as water and carbon dioxide, resulting in minimal discharge. 00:04:17.509 --> 00:04:21.779 With the introduction of these FDA-approved vaginal progesterone preparations, 00:04:21.899 --> 00:04:26.199 relying on painful intramuscular injections is no longer necessary. 00:04:27.719 --> 00:04:36.499 Both FDA-approved vaginal preparations have been proven as efficacious as IM delivery of progesterone in randomized prospective trials. 00:04:36.979 --> 00:04:40.780 However, only ENDOMETRIN provides rapid progesterone uptake 00:04:40.780 --> 00:04:43.730 while causing no build-up and minimal discharge. 00:04:47.430 --> 00:04:50.570 ENDOMETRIN progesterone vaginal insert is indicated to 00:04:50.570 --> 00:04:56.939 support embryo implantation and early pregnancy by supplementation of corpus luteum function 00:04:56.939 --> 00:05:03.239 as part of an Assisted Reproductive Technology (ART) treatment program for infertile women. 00:05:03.799 --> 00:05:05.870 Important Safety Information 00:05:06.150 --> 00:05:10.190 ENDOMETRIN should not be used in individuals with any of the following conditions: 00:05:10.190 --> 00:05:14.809 previous allergic reactions to progesterone or any of the ingredients of endometrium, 00:05:14.809 --> 00:05:18.339 known missed abortion or ectopic pregnancy, liver disease, 00:05:18.339 --> 00:05:20.250 known or suspected breast cancer, 00:05:20.250 --> 00:05:25.070 active arterial or venous thromboembolism or severe thrombophlebitis, 00:05:25.070 --> 00:05:27.029 or a history of these events. 00:05:27.209 --> 00:05:31.120 The physician should be alert to the earliest signs of myocardial infarction, 00:05:31.120 --> 00:05:35.549 cerebrovascular disorders, arterial or venous thromboembolism 00:05:35.549 --> 00:05:38.460 (venous thromboembolism or pulmonary embolism), 00:05:38.460 --> 00:05:40.999 thrombophlebitis or retinal thrombosis. 00:05:41.079 --> 00:05:44.769 ENDOMETRIN should be discontinued if any of these are suspected. 00:05:44.769 --> 00:05:47.750 Patients with a history of depression need to be closely observed. 00:05:47.750 --> 00:05:50.429 Consider discontinuation if symptoms worsen. 00:05:50.689 --> 00:05:56.150 ENDOMETRIN should not be recommended for use with other vaginal products (such as antifungal products) 00:05:56.150 --> 00:06:00.230 as this may alter progesterone release and absorption from the vaginal insert. 00:06:00.690 --> 00:06:04.290 The most common adverse reactions reported (greater than 5%) 00:06:04.290 --> 00:06:07.260 were post-oocyte retrieval pain, abdominal pain, 00:06:07.260 --> 00:06:10.279 nausea, and ovarian hyperstimulation syndrome. 00:06:10.699 --> 00:06:13.569 Please see full prescribing information.