Hormonal Monitoring and Progesterone Adjustment in Frozen Embryo Transfer Cycles

NCT05189145 | Completed

• 1 other identifier: 0201269
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Hormonal monitoring impact on overall pregnancy rate in frozen embryo transfer (FET)cycles and hence progesterone supplement adjustments remain debatable in current literature. This prospective randomized study aims to investigate the effect of monitoring and follow-up of serum progesterone, estradiol \& luteinizing hormone (LH) levels and progesterone supplement adjustments on pregnancy outcomes for FET in programmed hormonal replacement therapy cycles in comparison with ultrasound only in control group

Conditions

Female Infertility

Keywords

Hormonal monitoring; Frozen embryos; Progesterone; estradiol

Outcome Measures

Primary Outcomes (1)

• live birth rate

  the number of live births (defined as at least one live born after 28 weeks of gestation) divided by the total number of patients who performed pregnancy tests

  assessed 26-40 weeks after embryo transfer

Secondary Outcomes (1)

• clinical pregnancy rate

  assessed 4 weeks after embryo transfer

Study Arms (2)

Group I (control)

ACTIVE COMPARATOR

All patients given 8 mg estradiol valerate orally on daily basis for 13 days beginning with the first day of either a spontaneously or induced menstrual cycle. Patients examined using transvaginal ultrasonography on day 13 of exogenous estrogen supplementation to measure endometrial thickness and to detect signs of escape ovulation. In all Patients progesterone supplements in form of two vaginal prontogest suppositories 400 mg each. Transfer of frozen embryo will be done on day 5 after progesterone supplementation.

Drug: estradiol valerate; Diagnostic Test: transvaginal ultrasound examination; Drug: Progesterone 400 Mg Vaginal Suppository

group II (experimental)

EXPERIMENTAL

All patients given 8 mg estradiol valerate orally on daily basis for 13 days beginning with the first day of either a spontaneously or induced menstrual cycle. Patients examined using transvaginal ultrasonography on day 13 of exogenous estrogen supplementation to measure endometrial thickness and to detect signs of escape ovulation. In all Patients progesterone supplements in form of two vaginal prontogest suppositories 400 mg each. Transfer of frozen embryo will be done on day 5 after progesterone supplementation. progesterone (P4) and estradiol assessed and Progesterone supplement adjustments based on serum level of P4 on day of embryo transfer dividing Group II (Cases) into 3 groups: * Group II A: If P4 levels \< 5ng/dl, one progesterone supplement in form of 100 mg intramuscular injection daily added * Group II B: If P4 levels 5-10ng/dl, dydrogesterone three times daily added * Group II C: If P4 levels \>10ng, continue on 400 mg prontogest suppositories twice daily

Drug: estradiol valerate; Other: Hormonal monitoring progesterone, estradiol, luteinizing hormone; Diagnostic Test: transvaginal ultrasound examination; Drug: Progesterone 400 Mg Vaginal Suppository; Other: Hormonal monitoring progesterone and estradiol; Drug: Progesterone

Interventions

estradiol valerate DRUG

8mg orally on daily basis for 13 days beginning with the first day of either a spontaneously or induced menstrual cycle then assess by ultrasound

Also known as: Progenova

Group I (control); group II (experimental)

Hormonal monitoring progesterone, estradiol, luteinizing hormone OTHER

Serum Progesterone, estrogen \& LH measured on day 13 after priming endometrium with 8mg estradiol valerate on a daily basis beginning as early as the first day of menstrual cycle.

Also known as: P4, E2, LH

group II (experimental)

transvaginal ultrasound examination DIAGNOSTIC_TEST

Patients examined using transvaginal ultrasonography on day 13 of exogenous estrogen supplementation to measure endometrial thickness and to detect signs of escape ovulation

Group I (control); group II (experimental)

Progesterone 400 Mg Vaginal Suppository DRUG

Progesterone supplements given in form of daily two vaginal prontogest suppositories400 mg each

Also known as: prontogest 400 mg vaginal suppository

Group I (control); group II (experimental)

Hormonal monitoring progesterone and estradiol OTHER

Measuring the serum Progesterone \& Estradiol in the early morning on the day of embryo transfer an progesterone supplementation adjusted as follows: Group II A: If P4 levels \< 5ng/dl, one 100 mg intramuscular injection daily added, Group II B: If P4 levels 5-10ng/dl, dydrogesterone three times daily added. Group II C: If P4 levels \>10ng, continued on 400 mg prontogest suppositories twice daily

Also known as: P4 and E2

group II (experimental)

Progesterone DRUG

group II A: 100 mg intramuscular injection daily Group II B: If P4 levels 5-10ng/dl dydrogesterone added

Also known as: prontogest Intramuscular injection, duphaston tab

group II (experimental)

Eligibility Criteria

• Age: 20 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age of female patient 42 years or less
• Normal uterine cavity
• All embryos are day 5 or day 6 frozen blastocysts

You may not qualify if:

• History of recurrent implantation failure
• Previously known major thrombophilia factors
• Non-compliance to given protocol
• Endometrial thickness \< 7mm after 13 days of priming with estradiol valerate
• pre-existing metabolic diseases (Diabetes Mellitus \& Hypertension).

Sponsors & Collaborators

• Alexandria University: lead

Study Sites (1)

Infertility Center

Alexandria, Egypt

Location

Related Publications (7)

• Kang HJ. Programmed versus natural frozen embryo transfer: which is the best nest? Fertil Steril. 2018 Sep;110(4):636-637. doi: 10.1016/j.fertnstert.2018.06.020. No abstract available.

  PMID: 30196954 BACKGROUND

• Zeilmaker GH, Alberda AT, van Gent I, Rijkmans CM, Drogendijk AC. Two pregnancies following transfer of intact frozen-thawed embryos. Fertil Steril. 1984 Aug;42(2):293-6. doi: 10.1016/s0015-0282(16)48029-5. No abstract available.

  PMID: 6745463 BACKGROUND

• Zheng Y, Li Z, Xiong M, Luo T, Dong X, Huang B, Zhang H, Ai J. Hormonal replacement treatment improves clinical pregnancy in frozen-thawed embryos transfer cycles: a retrospective cohort study. Am J Transl Res. 2013 Dec 1;6(1):85-90. eCollection 2013.

  PMID: 24349625 BACKGROUND

• Kofinas JD, Blakemore J, McCulloh DH, Grifo J. Serum progesterone levels greater than 20 ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. J Assist Reprod Genet. 2015 Sep;32(9):1395-9. doi: 10.1007/s10815-015-0546-7. Epub 2015 Aug 4.

  PMID: 26238390 BACKGROUND

• Dong Z, Sun L, Zhang H, Chen Z, Jian Y. The frozen-thawed embryo transfer timing determined by serum progesterone level: a retrospective follow-up study. Eur J Obstet Gynecol Reprod Biol. 2014 Oct;181:210-3. doi: 10.1016/j.ejogrb.2014.07.012. Epub 2014 Jul 30.

  PMID: 25171265 BACKGROUND

• Griesinger G, Weig M, Schroer A, Diedrich K, Kolibianakis EM. Mid-cycle serum levels of endogenous LH are not associated with the likelihood of pregnancy in artificial frozen-thawed embryo transfer cycles without pituitary suppression. Hum Reprod. 2007 Oct;22(10):2589-93. doi: 10.1093/humrep/dem207. Epub 2007 Jul 25.

  PMID: 17652451 BACKGROUND

• El-Toukhy T, Taylor A, Khalaf Y, Al-Darazi K, Rowell P, Seed P, Braude P. Pituitary suppression in ultrasound-monitored frozen embryo replacement cycles. A randomised study. Hum Reprod. 2004 Apr;19(4):874-9. doi: 10.1093/humrep/deh183. Epub 2004 Mar 11.

  PMID: 15016780 BACKGROUND

MeSH Terms

Conditions

Infertility, Female

Interventions

Estradiol; Luteinizing Hormone; Progesterone; Suppositories; Dydrogesterone

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners; Dosage Forms; Pharmaceutical Preparations; Pregnadienes

Study Officials

• Sherif Hebisha, phD

  Alexandria University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: January 12, 2022
• Study Start: October 1, 2019
• Primary Completion: March 15, 2021
• Study Completion: October 1, 2021
• Last Updated: February 2, 2024

Record last verified: 2021-12

Locations

EG (1)