The Impact of Endometrial Compaction on Assisted Reproductive Technology Outcome

Study Overview
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Brief Summary
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Absence of endometrial compaction on the day of ET has adverse effects on success of ART outcome.

Detailed Description
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Implantation is a complex process which requires coordination and interaction between a blastocyst and the endometrium. Impaired embryo quality or impaired endometrial receptivity may negatively affect this interaction that in turn results in implantation failure (Diedrich et al., 2007). . Successful implantation entails a process of strict synchronization of endometrial and blastocyst development. (Maged et al., 2018). Despite advancements made since the introduction of assisted reproductive technology (ART), fewer than 40% of ART treatment cycles result in a live birth. Endometrial receptivity remains a crucial rate-limiting step affecting the success of ART treatment. Embryos are thought to be responsible for one-third of implantation failures, whereas the remaining two-thirds result from sub-optimal endometrial receptivity or abnormal embryo-endometrium dialogue.(Craciunas et al., 2019). There are 3 main methods used to assess endometrial receptivity: endometrial biopsy, hormone profile, and ultrasound imaging.(Lawrenz and Fatemi, 2017). Ultrasound has been established as an appreciated, simple, and non-invasive technique in evaluation of endometrial preparation before embryo transfer in IVF cycles. Several sonographic parameters have been assessed that include endometrial thickness (Ent), endometrial pattern (EnP) and sub-endometrial blood flow.(Kader et al., 2016). Endometrial thickness (EMT) is the most used prognostic factor for endometrial receptivity during ART (Kasius et al., 2014). Both clinical pregnancy and live birth rates decreased significantly for each millimeter below 8 mm in fresh IVF-ET cycles and below 7 mm frozen ET cycles (Liu et al 2018). Regarding endometrial patterns (Yuan et al., 2016) and vascularization (Ng et al., 2007) data are still contradictory. Increased frequency of contractility prior to embryo transfer was inversely related to clinical pregnancy in fresh and frozen embryo transfer cycles. (Zhu et al., 2014). Currently, there is an emphasis on a new endometrial parameter called endometrial compaction, which is the decrease in endometrial thickness on the day of ET. In a Study of 274 frozen embryo transfer cycles, patients whose endometrium compacted had a significantly higher ongoing pregnancy rate than patients whose endometrium became thicker or did not change.(Haas et al., 2019). On the other hand, a large-scale cohort study revealed that an increased endometrium thickness after progesterone administration in FET was associated with better pregnancy outcome.(Bu et al., 2019). The role of endometrial compaction in fresh ART cycles is not yet studied. So, it's better to test its effect on fresh cycles ART outcome.

Official Title
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The Impact of Endometrial Compaction on Assisted Reproductive Technology Outcome

Conditions
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Embryo Implantation, ART

Intervention / Treatment
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* Diagnostic Test: blood sampling & ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All women should have the following: Aged from 18 - 37 years old. Undergoing fresh ICSI cycles. A normal uterus with no anomalies or pathologies. At least one good-quality embryo/blastocyst available for transfer (3 BB and more according to Gardner and Schoolcraft grading system). Easy mockup embryo transfer (i.e. the catheter is smoothly inserted without touching the fundus, no cervix tenaculum is used and the catheter is clean of blood). Exclusion Criteria: - Younger than 18 or older than 37 years old. Congenital uterine abnormality or pathology. Presence of a hydrosalpinx. Chronic diseases which are not suitable for pregnancy. ICSI cycles with fresh or frozen TESE samples.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 356 case will be enrolled<br>Pituitary suppression will be achieved by long or antagonist protocol. For long protocol, GnRH agonist will be administered for 10-14 days starting from mid-luteal phase of preceding cycle. After confirmation of down regulation, gonadotropins will be given from second or third day of cycle in a daily dose of (150-300 IU). Gonadotropins therapy will be tailored according to age, BMI, antral follicle count, antimullerian hormone and previous response. In antagonist protocol, gonadotropins will be given from second or third day of cycle in a daily dose of (150-300 IU). GnRH antagonist will be adjusted according to patient response. On the 5th -6th day of stimulation, sonography will be performed and repeated every 1-3 days with regular estradiol assessment. When at least 3 follicles reach ≥ 17 mm in mean diameter, trigger will be given. Oocytes pick up will be performed 34-36 hour after triggering. | Diagnostic Test: blood sampling & ultrasound<br>* Blood sampling: Serum P4 & estradiol will be performed on the day of triggering and on the day of embryo transfer. Progesterone/ Estradiol (P4/E2) ratio will be calculated Ultrasound: On triggering day, at time of ovum pick up and on ET day, we will measure Endometrial thickness Endometrial pattern Endometrial compaction: the difference in measurement of endometrial thickness between the day of embryo transfer and the day of triggering. Junctional zone thickness Uterine contraction (peristalsis). Blood flow of uterine vessels: PI of the uterine arteries will be calculated also Endometrial - sub endometrial blood flow<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| whether the occurrence of endometrial compaction on the day of embryo transfer has a role in optimizing ongoing pregnancy rate in ART cycles | Percent of endometrial compaction will be calculated as the difference in measurement of endometrial thickness between the day of embryo transfer and the day of triggering. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ART, Endometrial Compaction, endometrial receptivity