Hormonal Monitoring and Progesterone Adjustment in Frozen Embryo Transfer Cycles

Not Applicable

Completed

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

• Registration Number: NCT05189145
• Lead Sponsor: Alexandria University

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.

Study Timeline

• Study Start: 2019-10-01
• Primary Completion: 2021-03-15
• Study Completion: 2021-10-01
• Status Verified: 2021-12
• Study First Submitted: 2021-12-27
• Study First Submitted QC: 2021-12-27
• Study First Posted: 2022-01-12
• Last Update Submitted: 2024-02-01
• Last Update Posted: 2024-02-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 600

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

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (control)	transvaginal ultrasound examination	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 I (control)	Progesterone 400 Mg Vaginal Suppository	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 II (experimental)	Hormonal monitoring progesterone, estradiol, luteinizing hormone	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 II (experimental)	transvaginal ultrasound examination	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 II (experimental)	Hormonal monitoring progesterone and estradiol	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 II (experimental)	Progesterone 400 Mg Vaginal Suppository	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 I (control)	estradiol valerate	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 II (experimental)	estradiol valerate	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 II (experimental)	Progesterone	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

Primary Outcome Measures

Name	Time	Method
live birth rate	assessed 26-40 weeks after embryo transfer	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

Secondary Outcome Measures

Name	Time	Method
clinical pregnancy rate	assessed 4 weeks after embryo transfer	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

Trial Locations

Locations (1)

Infertility Center; 🇪🇬 Alexandria, Egypt