1 00:00:09,450 --> 00:00:12,740 Progesterone is a key pregnancy hormone with modulating effects 2 00:00:12,740 --> 00:00:15,739 that are essential for successful reproduction. 3 00:00:17,759 --> 00:00:22,989 For patients going through In Vitro Fertilization and other Assisted Reproductive Technologies, 4 00:00:22,989 --> 00:00:26,209 progesterone supplementation is standard practice. 5 00:00:26,929 --> 00:00:32,210 During oocyte retrieval, removal or disruption of the granulosa cells lining the follicle, 6 00:00:32,210 --> 00:00:35,560 can impair progesterone production from the corpus luteum. 7 00:00:36,740 --> 00:00:40,318 Use of GnRH analogues used to prevent early ovulation 8 00:00:40,318 --> 00:00:43,309 can also suppress luteal function. 9 00:00:47,933 --> 00:00:52,213 (First-Generation Progesterone Supplements) 10 00:00:53,253 --> 00:00:59,009 Intramuscular injection of progesterone in an oil-based suspension is one common delivery method. 11 00:01:00,089 --> 00:01:05,249 It is not approved by the FDA for women undergoing IVF or other ART treatments. 12 00:01:06,249 --> 00:01:10,030 Oil-based injections have been associated with a number of side effects, 13 00:01:10,030 --> 00:01:15,820 including pain at the injection site, inflammatory reactions and abscess formation. 14 00:01:16,180 --> 00:01:19,260 The aid of another person is often required. 15 00:01:19,800 --> 00:01:24,969 In 1997, Crinone progesterone gel 8% was approved by the FDA 16 00:01:24,969 --> 00:01:30,859 for vaginal administration during ART treatment for infertile women with progesterone deficiency. 17 00:01:31,499 --> 00:01:37,790 Crinone gel is a water-insoluble Polycarbophil emulsion that contains micronized progesterone. 18 00:01:40,050 --> 00:01:45,630 Crinone is delivered once or twice a day to the vagina via a prefilled disposable applicator. 19 00:01:47,130 --> 00:01:51,358 Once administered, the gel adheres to the vaginal wall through hydrogen bonds. 20 00:01:52,258 --> 00:01:54,470 Vaginal moisture penetrates the emulsion, 21 00:01:54,470 --> 00:01:57,479 beginning a slow process of progesterone release 22 00:01:57,479 --> 00:02:00,100 and absorption by the vaginal epithelia. 23 00:02:01,300 --> 00:02:04,199 Because it is bioadhesive and water insoluble, 24 00:02:04,199 --> 00:02:06,708 the gel can remain adhered to the vaginal wall 25 00:02:06,708 --> 00:02:09,539 even after the progesterone has been absorbed. 26 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. 27 00:02:17,089 --> 00:02:21,079 This may require manual removal prior to embryo transfer. 28 00:02:22,739 --> 00:02:26,480 If gel accumulates, vaginal discharge appearing as white globules 29 00:02:26,480 --> 00:02:30,220 may occur as the gel is discarded and exits the body. 30 00:02:35,278 --> 00:02:39,318 (ENDOMETRIN Vaginal Insert Advancing the ART of Luteal Phase Support) 31 00:02:41,198 --> 00:02:46,488 In 2007, endometrial progesterone vaginal insert was approved by the FDA 32 00:02:46,488 --> 00:02:50,889 as an alternative to vaginal gel for women undergoing ART treatment. 33 00:02:52,969 --> 00:02:55,978 ENDOMETRIN is a 100-milligram vaginal insert 34 00:02:55,998 --> 00:02:58,279 administered two or three times daily 35 00:02:58,279 --> 00:03:00,739 with a sterile disposable applicator. 36 00:03:02,239 --> 00:03:07,478 In a moist environment, the bicarbonate delivery system of the insert is highly soluble. 37 00:03:09,498 --> 00:03:13,730 Vaginal moisture penetrates the insert, causing an acid-based reaction. 38 00:03:14,690 --> 00:03:18,759 The insert breaks down, releasing progesterone into the aqueous environment. 39 00:03:19,199 --> 00:03:24,789 Progesterone, being a hydrophobic molecule, rushes towards the vaginal epithelia, 40 00:03:24,789 --> 00:03:30,330 where it is absorbed by serum proteins and delivered to the endometrium via local circulation. 41 00:03:31,070 --> 00:03:34,509 Unlike crinone, which is dosed 90 milligrams once daily, 42 00:03:34,509 --> 00:03:38,720 ENDOMETRIN is dosed 100 milligrams two or three times daily 43 00:03:38,720 --> 00:03:42,499 due to differences in the pharmacokinetic profile of the two products. 44 00:03:42,779 --> 00:03:48,499 In a randomized open-label pharmacokinetic study with 18 women aged 18-40, 45 00:03:48,719 --> 00:03:54,528 both doses of endometrium reached steady-state progesterone concentrations in about 24 hours, 46 00:03:54,528 --> 00:03:58,489 while the gel did not reach steady state by the end of the fifth day. 47 00:03:58,629 --> 00:04:02,829 Efficacy was not a parameter being examined in this PK study. 48 00:04:05,350 --> 00:04:07,529 because of its bicarbonate formulation, 49 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. 50 00:04:17,509 --> 00:04:21,779 With the introduction of these FDA-approved vaginal progesterone preparations, 51 00:04:21,899 --> 00:04:26,199 relying on painful intramuscular injections is no longer necessary. 52 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. 53 00:04:36,979 --> 00:04:40,780 However, only ENDOMETRIN provides rapid progesterone uptake 54 00:04:40,780 --> 00:04:43,730 while causing no build-up and minimal discharge. 55 00:04:47,430 --> 00:04:50,570 ENDOMETRIN progesterone vaginal insert is indicated to 56 00:04:50,570 --> 00:04:56,939 support embryo implantation and early pregnancy by supplementation of corpus luteum function 57 00:04:56,939 --> 00:05:03,239 as part of an Assisted Reproductive Technology (ART) treatment program for infertile women. 58 00:05:03,799 --> 00:05:05,870 Important Safety Information 59 00:05:06,150 --> 00:05:10,190 ENDOMETRIN should not be used in individuals with any of the following conditions: 60 00:05:10,190 --> 00:05:14,809 previous allergic reactions to progesterone or any of the ingredients of endometrium, 61 00:05:14,809 --> 00:05:18,339 known missed abortion or ectopic pregnancy, liver disease, 62 00:05:18,339 --> 00:05:20,250 known or suspected breast cancer, 63 00:05:20,250 --> 00:05:25,070 active arterial or venous thromboembolism or severe thrombophlebitis, 64 00:05:25,070 --> 00:05:27,029 or a history of these events. 65 00:05:27,209 --> 00:05:31,120 The physician should be alert to the earliest signs of myocardial infarction, 66 00:05:31,120 --> 00:05:35,549 cerebrovascular disorders, arterial or venous thromboembolism 67 00:05:35,549 --> 00:05:38,460 (venous thromboembolism or pulmonary embolism), 68 00:05:38,460 --> 00:05:40,999 thrombophlebitis or retinal thrombosis. 69 00:05:41,079 --> 00:05:44,769 ENDOMETRIN should be discontinued if any of these are suspected. 70 00:05:44,769 --> 00:05:47,750 Patients with a history of depression need to be closely observed. 71 00:05:47,750 --> 00:05:50,429 Consider discontinuation if symptoms worsen. 72 00:05:50,689 --> 00:05:56,150 ENDOMETRIN should not be recommended for use with other vaginal products (such as antifungal products) 73 00:05:56,150 --> 00:06:00,230 as this may alter progesterone release and absorption from the vaginal insert. 74 00:06:00,690 --> 00:06:04,290 The most common adverse reactions reported (greater than 5%) 75 00:06:04,290 --> 00:06:07,260 were post-oocyte retrieval pain, abdominal pain, 76 00:06:07,260 --> 00:06:10,279 nausea, and ovarian hyperstimulation syndrome. 77 00:06:10,699 --> 00:06:13,569 Please see full prescribing information.