Hormonal Monitoring and Progesterone Adjustment in Frozen Embryo Transfer Cycles

Female Infertility Clinical Trial

Official title:

A Prospective Randomized Study of the Impact of Hormonal Monitoring and Progesterone Supplementation Adjustment on Outcome of Programmed Thawed Embryo Transfer Cycles

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05189145
• Other study ID #: 0201269
• Status: Completed
• Phase: N/A
• Start date: October 1, 2019
• Est. completion date: October 1, 2021

Study information

• Verified date: December 2021
• Source: Alexandria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: October 1, 2021
• Est. primary completion date: March 15, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 42 Years

Eligibility

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).

Related Conditions & MeSH terms

• Female Infertility
• Infertility
• Infertility, Female

Intervention

Drug:
• 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

Other:
• 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.

Diagnostic Test:
• 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

Drug:
• Progesterone 400 Mg Vaginal Suppository
Progesterone supplements given in form of daily two vaginal prontogest suppositories400 mg each

Other:
• 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

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

Locations

Country	Name	City	State
Egypt	Infertility Center	Alexandria

Sponsors (1)

Lead Sponsor	Collaborator
Alexandria University

Country where clinical trial is conducted

Egypt, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: J Assist Reprod Genet. 2016 Mar;33(3):431. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	clinical pregnancy rate	the number of clinical pregnancies (defined as the presence of a gestational sac with positive heart beat detected by transvaginal ultrasound scan 2 weeks after positive pregnancy test) divided by the number of embryo transfer procedures	assessed 4 weeks after embryo transfer