Clinical trial NCT02254577: Vaginal Compared to Intramuscular Progesterone for Frozen Embryo Transfer
Official title: A Randomized, Three-armed, Non-Inferiority Study of Vaginal Progesterone (Endometrin®) Compared to Intramuscular Progesterone in Oil (PIO) in Infertile Subjects Undergoing Frozen Embryo Transfer (FET)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Keywords: Infertility
Progesterone
ART
IVF
FET
FBT
Frozen Embryo Transfer
Lead sponsor: Shady Grove Fertility Reproductive Science Center
Sponsor class: OTHER
Collaborators: name: Ferring Pharmaceuticals
First posted: 2014-10-02
Enrollment: 1139
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine whether the of vaginal progesterone replacement for frozen embryo transfer results in equivalent live birth rates to intramuscular injection progesterone replacement.

Detailed description: The purpose of this ongoing study is to look at whether Endometrin® (vaginal micronized progesterone tablets) supplemented by intramuscular injection of progesterone in oil (PIO) work as well as PIO alone for women undergoing transfer of frozen-thawed blastocyst(s). Another goal of the study is to determine whether patients prefer Endometrin or PIO. Endometrin® has been approved by the United States Food and Drug Administration, or FDA, "to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women." (FDA New Drug Approval Letter, Endometrin®, 2007). The use of Endometrin® (vaginal micronized progesterone tablets) in this study is investigational. An investigational use is one that is not approved by the U.S. Food and Drug Administration (FDA).

Approximately 1170 women between the ages of 18-48 who are having difficulty becoming pregnant and wish to undergo frozen embryo transfer will be asked to participate. The participants will be recruited from among patients of Shady Grove Fertility.

One-half of the participants who qualify and wish to take part in the ongoing study will be randomized (assigned by chance, like the flip of a coin) to receive Endometrin® and an intramuscular injection of PIO every third day. One-half will be randomized to receive an intramuscular injection of PIO every day. This study is a type of study called an "open label," assessor-blind study. This means that you and your doctor will know which treatment you are assigned and receive; however, the person analyzing the information obtained from the study will not know which patients received which study treatments.

Patients enrolling in the study will receive the medications for their frozen embryo transfer cycle free of charge.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent
2. Female age between 18 and 48 years
3. Having available blastocyst(s) frozen by vitrification method at our center (Shady Grove Fertility).
4. Standard eligibility criteria to undergo frozen blastocyst transfer at Shady Grove Fertility.

Exclusion Criteria:

1. Requires fresh embryos or surrogate carrier
2. Embryos from frozen oocytes and embryos frozen more than once
3. Any embryo cryopreserved by slow freeze method and/or prior to blastocyst stage
4. Presence of any clinically relevant systemic disease contraindicated for ART
5. History of more than 3 failed cycles in previous ART attempts and/or more than 3 recurrent pregnancy losses after ET
6. Surgical or medical condition or requirement for medication, which may interfere with absorption, distribution, metabolism, or excretion of the drugs to be used
7. Subjects with a body mass index (BMI) of \<18 or \>38 kg/m2 at screening
8. Current or recent substance abuse, including alcohol and tobacco. (Note: Subjects who stopped tobacco usage at least 3 months prior to screening visit will be allowed)
9. Currently breast feeding, pregnant, or having (a) contraindication(s) to pregnancy
10. Refusal or inability to comply with the requirements of the protocol for any reason, including scheduled clinic visits and laboratory tests
11. Trophectoderm or blastomere biopsy of the blastocyst(s) to be transferred.
12. Documented intolerance or allergy to any of the medications used, including the study medication
13. Participation in any experimental drug study within 60 days prior to screening
14. If a subject undergoes more than two frozen blastocyst transfers meeting study criteria, she will only be eligible to enroll in the study for two of these.

Primary outcomes:
measure: Live Birth
timeFrame: ~40 weeks post Frozen Embryo Transfer
Secondary outcomes:
measure: Ongoing Implantation Rate
timeFrame: 7-8 weeks after embryo transfer
measure: Implantation rate
timeFrame: 5-6 weeks post embryo transfer
measure: Biochemical pregnancy
timeFrame: ~10 days following embryo transfer
measure: Clinical pregnancy
timeFrame: 5-6 weeks following embryo transfer
measure: Serum progesterone level
timeFrame: ~10 days following embryo transfer
measure: Patient satisfaction with Endometrin® vs. intramuscular progesterone in oil
timeFrame: between 0 and 10 days following embryo transfer
Other outcomes:
Locations:
city: Washington
country: United States
facility: Shady Grove Fertility Center
state: District of Columbia
city: Washington
country: United States
facility: Shady Grove Fertility Center
state: District of Columbia
city: Annapolis
country: United States
facility: Shady Grove Fertility Center
state: Maryland
city: Baltimore
country: United States
facility: Shady Grove Fertility Center
state: Maryland
city: Bel Air
country: United States
facility: Shady Grove Fertility Center
state: Maryland
city: Columbia
country: United States
facility: Shady Grove Fertility Center
state: Maryland
city: Frederick
country: United States
facility: Shady Grove Fertility Center
state: Maryland
city: Rockville
country: United States
facility: Shady Grove Fertility Center
state: Maryland
city: Towson
country: United States
facility: Shady Grove Fertility Center
state: Maryland
city: Camp Hill
country: United States
facility: Shady Grove Fertility
state: Pennsylvania
city: Chesterbrook
country: United States
facility: Shady Grove Fertility Center
state: Pennsylvania
city: Annandale
country: United States
facility: Shady Grove Fertility Center
state: Virginia
city: Leesburg
country: United States
facility: Shady Grove Fertility Center
state: Virginia
city: Woodbridge
country: United States
facility: Shady Grove Fertility Center
state: Virginia
Study officials:
References:
citation: Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014 Aug;29(8):1706-11. doi: 10.1093/humrep/deu121. Epub 2014 May 20.
citation: Feinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2013 Jan;99(1):174-178.e1. doi: 10.1016/j.fertnstert.2012.09.019. Epub 2012 Nov 6.
citation: Paulson RJ, Collins MG, Yankov VI. Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab. 2014 Nov;99(11):4241-9. doi: 10.1210/jc.2013-3937. Epub 2014 Feb 25.
citation: Devine K, Richter KS, Jahandideh S, Widra EA, McKeeby JL. Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: a randomized clinical trial. Fertil Steril. 2021 Sep;116(3):633-643. doi: 10.1016/j.fertnstert.2021.04.013. Epub 2021 May 13.
citation: Devine K, Richter KS, Widra EA, McKeeby JL. Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomized controlled noninferiority trial. Fertil Steril. 2018 Feb;109(2):266-275. doi: 10.1016/j.fertnstert.2017.11.004. Epub 2018 Jan 17.