Assessment of Endometrial and Sub-endometrial Vascularity Before and After PRP Infusion in Frozen Embryo Transfer Cycles

3D Power Doppler Ultrasound Assessment of Endometrial and Sub-endometrial Vascularity Before and After PRP Infusion in Frozen-thawed Embryo Transfer Cycles: a Pilot Study.

A good quality embryo and receptive endometrium are important aspects in achieving optimal outcomes in assisted reproductive treatment (ART). Endometrial thickness is an important marker of uterine receptivity. A thin endometrium defined by an endometrial thickness ≤7mm was reported as a poor factor associated with significantly lower implantation and pregnancy rates as well as a higher risk of miscarriage.

Nowadays, platelet-rich plasma (PRP) intrauterine infusion is a promising approach for the treatment of refractory thin endometrium in patients undergoing frozen-thawed embryo transfer. This is based on its ability to stimulate proliferation and angiogenesis with a large number of growth factors and cytokines i.e. the endometrium becomes thicker, with higher vascularity. PRP is easily prepared from an autologous blood sample that eliminates the risk of immunological reactions and transmission infections at low cost.

Endometrial blood flow is another important marker reflective of uterine receptivity. Although publications are increasing concerning the efficacy of PRP intrauterine infusion on endometrial expansion and proliferation in frozen-thawed embryo transfer cycles, yet its angiogenetic effects have not been evaluated so far in either thin endometrium or normal endometrium thickness.

Our study aims to evaluate endometrial and sub-endometrial vasculature patterns before and after PRP infusion in frozen-thawed embryo transfer cycles with normal endometrium thickness.

Study Overview

• Status: Unknown
• Conditions: Frozen Embryo Transfer
• Intervention / Treatment: Biological: Platelet-rich plasma intrauterine infusion

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subfertile women undergoing frozen-thawed embryo transfer with at least previously failed one ICSI cycle.
• Age between 20-35 years.
• Women with endometrium thickness between 8-14 mm on D15 of the frozen embryo transfer cycle

Exclusion Criteria:

• Women with a thin endometrium (≤ 7 mm) on day 15 of the cycle.
• Women with known hematological or immunological disorders
• Women with uncontrolled endocrine or other medical conditions, such as hyperprolactinemia or thyroid diseases.
• Women with uterine abnormalities e.g. Asherman syndrome, myomas, uterine septum, bicornuate uterus.
• Women who refuse to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Platelet-rich plasma (PRP) intrauterine infusion

Biological: Platelet-rich plasma intrauterine infusion; For all women, basic transvaginal sonography will be done in the 2nd day of frozen embryo transfer (FET) cycle and they will receive standard hormone replacement therapy (HRT) in the form of estradiol valerate tablets (white tablets of Cyclo-Progynova; Bayer Schering Pharma AG, Germany) at a dose of 4mg for 7 days then 6mg for 6 days. Endometrial assessment will be done on day 15 of FET cycle. Those with endometrial thickness between 8-14 mm will be evaluated for endometrial and sub-endometrial vasculature pattern by 3D power Doppler analysis. Then 1 ml of PRP (prepared from autologous blood) will be infused in the uterine cavity and vaginal progesterone 400 mg twice daily will be prescribed for 3 days. Subsequently, D3 embryos will be transferred. Endometrial, sub-endometrial and uterine arterial vascularity pattern will be re-evaluated on the day of ET. Both estradiol valerate tablets and vaginal progesterone will be continued up to 12th week of gestation in case of pregnancy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascularization index of the endometrial region	Vascularization index of the endometrial region will be measured by a researcher using the built-in VOCAL (Virtual Organ Computer-Aided Analysis) software for 3D power Doppler analysis.	Day 15 to 18 of the frozen embryo transfer cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow index of the endometrial region	Flow index of the endometrial region will be measured by a researcher using the built-in VOCAL (Virtual Organ Computer-Aided Analysis) software for 3D power Doppler analysis	Day 15 to 18 of the frozen embryo transfer cycle
Vascularization flow index of the endometrial region	Vascularization flow index of the endometrial region will be measured by a researcher using the built-in VOCAL (Virtual Organ Computer-Aided Analysis) software for 3D power Doppler analysis	Day 15 to 18 of the frozen embryo transfer cycle
Vascularization index of the sub-endometrial region	Vascularization flow index of the sub-endometrial region will be measured by a researcher using the built-in VOCAL (Virtual Organ Computer-Aided Analysis) software for 3D power Doppler analysis	Day 15 to 18 of the frozen embryo transfer cycle
Flow index of the sub-endometrial region	Flow index of the sub-endometrial region will be measured by a researcher using the built-in VOCAL (Virtual Organ Computer-Aided Analysis) software for 3D power Doppler analysis	Day 15 to 18 of the frozen embryo transfer cycle
Vascularization flow index of the sub-endometrial region	Vascularization flow index of the sub-endometrial region will be measured by a researcher using the built-in VOCAL (Virtual Organ Computer-Aided Analysis) software for 3D power Doppler analysis	Day 15 to 18 of the frozen embryo transfer cycle

Collaborators and Investigators

• Sponsor: Hatem AbuHashim
• Investigators: Principal Investigator: Mohamed Taman, MD, Faculty of Medicine, Mansoura University

Publications and helpful links

General Publications

• Nandi A, Martins WP, Jayaprakasan K, Clewes JS, Campbell BK, Raine-Fenning NJ. Assessment of endometrial and subendometrial blood flow in women undergoing frozen embryo transfer cycles. Reprod Biomed Online. 2014 Mar;28(3):343-51. doi: 10.1016/j.rbmo.2013.11.004. Epub 2013 Nov 22.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 8, 2020
• Primary Completion (Anticipated): August 31, 2020
• Study Completion (Anticipated): October 5, 2020

Study Registration Dates

• First Submitted: January 24, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: R.20.01.711

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No