Vaginal Compared to Intramuscular Progesterone for Frozen Embryo Transfer

Infertility Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02254577
• Other study ID #: 13-0028
• Secondary ID: SUSTAIN
• Status: Completed
• Phase: Phase 4
• Start date: October 2014
• Est. completion date: April 27, 2018

Study information

• Verified date: July 2018
• Source: Shady Grove Fertility Reproductive Science Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1139
• Est. completion date: April 27, 2018
• Est. primary completion date: April 27, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 48 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Endometrin® plus Progesterone in Oil (PIO)

• Progesterone in Oil (PIO) Only

Locations

Country	Name	City	State
United States	Shady Grove Fertility Center	Annandale	Virginia
United States	Shady Grove Fertility Center	Annapolis	Maryland
United States	Shady Grove Fertility Center	Baltimore	Maryland
United States	Shady Grove Fertility Center	Bel Air	Maryland
United States	Shady Grove Fertility	Camp Hill	Pennsylvania
United States	Shady Grove Fertility Center	Chesterbrook	Pennsylvania
United States	Shady Grove Fertility Center	Columbia	Maryland
United States	Shady Grove Fertility Center	Frederick	Maryland
United States	Shady Grove Fertility Center	Leesburg	Virginia
United States	Shady Grove Fertility Center	Rockville	Maryland
United States	Shady Grove Fertility Center	Towson	Maryland
United States	Shady Grove Fertility Center	Washington	District of Columbia
United States	Shady Grove Fertility Center	Washington	District of Columbia
United States	Shady Grove Fertility Center	Woodbridge	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Shady Grove Fertility Reproductive Science Center	Ferring Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (3)

Feinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2013 Jan;99(1):174-8. doi: 10.1016/j.fertnstert.2012.09.019. Epub 2012 Nov 6. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live Birth	Live born infant at 23 weeks' estimated gestational age or greater.	~40 weeks post Frozen Embryo Transfer
Secondary	Ongoing Implantation Rate	maximum # fetal heartbeats divided by total number of embryos transferred	7-8 weeks after embryo transfer
Secondary	Implantation rate	Maximum number of gestational sacs, divided by total number of embryos transferred	5-6 weeks post embryo transfer
Secondary	Biochemical pregnancy	detection of beta hCG (pregnancy hormone) above 5 IU/L	~10 days following embryo transfer
Secondary	Clinical pregnancy	Presence of gestational sac(s) at 5-6 weeks post ET	5-6 weeks following embryo transfer
Secondary	Serum progesterone level	blood draw	~10 days following embryo transfer
Secondary	Patient satisfaction with Endometrin® vs. intramuscular progesterone in oil	As assessed by brief, optional online survey	between 0 and 10 days following embryo transfer