Hormonal Monitoring and Progesterone Adjustment in Frozen Embryo Transfer Cycles

NCT ID: NCT05189145

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-01
• Study Completion Date: 2021-10-01

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

Detailed Description

Progesterone (P4) is a steroidal hormone that is required for successful embryo implantation and maintenance of the pregnancy in natural cycles, fresh in vitro fertilization cycles, and frozen embryo transfer (FET) cycles. Women undergoing FET in programmed cycle are unable to provide adequate endogenous P4 and require progesterone supplementation to initiate and maintain the secretory endometrium and pregnancy. There has been previous research into luteal phase support in frozen cycles, which has demonstrated that supplementation of progesterone does impact outcome in FET. Despite this evidence for the role of progesterone, there is surprisingly little data on the optimal values for serum P4 during the luteal phase and specifically on the day of embryo transfer in frozen cycles. Following years of a prevalent belief that the higher values of P4 are better, it seems that there may be an optimal window for P4 values during the luteal phase in bovine IVF. Though progesterone levels on the day of transfer have not yet been studied extensively in humans, tailoring the time of transferring a frozen embryo based on serial P4 values rather than cycle day number alone results in higher pregnancy rates. By direct action on the endometrium, a rise of LH might interfere with endometrial receptivity during a FET cycle, in which no pituitary suppression is used. The significance of LH level on the day before addition of progesterone is not yet well defined. The aim of this study is to investigate the effect of monitoring and follow-up of serum progesterone, estradiol & luteinizing hormone levels on day of embryo transfer on pregnancy outcomes for FET in programmed HRT cycles in comparison with ultrasound only in control group and to evaluate the effect of progesterone supplements adjustments depending on serum progesterone levels on day of FET in affecting clinical pregnancy rate.

Conditions

Female Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group I (control)

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.

Group Type: ACTIVE_COMPARATOR

estradiol valerate

Intervention Type: 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

transvaginal ultrasound examination

Intervention Type: 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

Progesterone 400 Mg Vaginal Suppository

Intervention Type: DRUG

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

group II (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

Group Type: EXPERIMENTAL

estradiol valerate

Intervention Type: 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

Hormonal monitoring progesterone, estradiol, luteinizing hormone

Intervention Type: 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.

transvaginal ultrasound examination

Intervention Type: 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

Progesterone 400 Mg Vaginal Suppository

Intervention Type: DRUG

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

Hormonal monitoring progesterone and estradiol

Intervention Type: 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

Progesterone

Intervention Type: DRUG

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

Interventions

estradiol valerate

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

Intervention Type: DRUG

Hormonal monitoring progesterone, estradiol, luteinizing hormone

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.

Intervention Type: OTHER

transvaginal ultrasound examination

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

Intervention Type: DIAGNOSTIC_TEST

Progesterone 400 Mg Vaginal Suppository

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

Intervention Type: DRUG

Hormonal monitoring progesterone and estradiol

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

Intervention Type: OTHER

Progesterone

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

Intervention Type: DRUG

Other Intervention Names

Progenova; P4, E2, LH; prontogest 400 mg vaginal suppository; P4 and E2; prontogest Intramuscular injection, duphaston tab

Eligibility Criteria

Inclusion Criteria

1. Age of female patient 42 years or less

2. Normal uterine cavity

3. All embryos are day 5 or day 6 frozen blastocysts

Exclusion Criteria

1. History of recurrent implantation failure

2. Previously known major thrombophilia factors

3. Non-compliance to given protocol

4. Endometrial thickness < 7mm after 13 days of priming with estradiol valerate

5. pre-existing metabolic diseases (Diabetes Mellitus & Hypertension).

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Alexandria University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sherif Hebisha, phD

Role: PRINCIPAL_INVESTIGATOR

Alexandria University

Locations

Infertility Center

Alexandria, , Egypt

Countries

Egypt

References

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.

Reference Type: BACKGROUND

PMID: 30196954 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 6745463 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24349625 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26238390 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25171265 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17652451 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15016780 (View on PubMed)

Other Identifiers

0201269

Identifier Type: -

Identifier Source: org_study_id