Hormonal Monitoring and Progesterone Adjustment in Frozen Embryo Transfer Cycles

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Female Infertility

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of female patient 42 years or less Normal uterine cavity All embryos are day 5 or day 6 frozen blastocysts Exclusion Criteria: 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).

Ages Eligible for Study
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Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group I (control)<br>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<br>* 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<br>* Other names: Progenova;Diagnostic Test: transvaginal ultrasound examination<br>* Patients examined using transvaginal ultrasonography on day 13 of exogenous estrogen supplementation to measure endometrial thickness and to detect signs of escape ovulation<br>Drug: Progesterone 400 Mg Vaginal Suppository<br>* Progesterone supplements given in form of daily two vaginal prontogest suppositories400 mg each<br>* Other names: prontogest 400 mg vaginal suppository;|
| Experimental: group II (experimental)<br>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<br>* 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<br>* Other names: Progenova;Other: Hormonal monitoring progesterone, estradiol, luteinizing hormone<br>* 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.<br>* Other names: P4, E2, LH;Diagnostic Test: transvaginal ultrasound examination<br>* Patients examined using transvaginal ultrasonography on day 13 of exogenous estrogen supplementation to measure endometrial thickness and to detect signs of escape ovulation<br>Drug: Progesterone 400 Mg Vaginal Suppository<br>* Progesterone supplements given in form of daily two vaginal prontogest suppositories400 mg each<br>* Other names: prontogest 400 mg vaginal suppository;Other: Hormonal monitoring progesterone and estradiol<br>* 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<br>* Other names: P4 and E2;Drug: Progesterone<br>* group II A: 100 mg intramuscular injection daily Group II B: If P4 levels 5-10ng/dl dydrogesterone added<br>* Other names: prontogest Intramuscular injection, duphaston tab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormonal monitoring; Frozen embryos; Progesterone; estradiol