Oestradiol Supplementation in Luteal Long Agonist Fresh In Vitro Fertilization/Intra Cytoplasmic Sperm Injection ( IVF/ICSI) Cycle .

Effects of Adding Oestradiol Supplementation in Luteal Phase in Patients Undergoing in Vitro Fertilization/ Intra Cytoplasmic Sperm Injection (IVF/ICSI ) Long Agonist Fresh Embryo Transfer Cycles

Whether oestradiol administration affects the pregnancy rate in long agonist fresh IVF/ICSI cycles. Oestradiol level will be measured the day of HCG trigger to assess whether oestradiol level affects cycle outcome results.

Study Overview

• Status: Unknown
• Conditions: Infertility
• Intervention / Treatment: Drug: Estradiol Valerate

Detailed Description

6. Background and Rationale: Progesterone is essential for successful implantation and maintenance of early pregnancy . Although the oestrogen is not essential, it is important to maintain the progesterone level during the pregnancy and promote the transformation of the endometrium from the secretory to proliferative phase.

Compromised granulosa cells luteinisation could cause infertility or early miscarriage. In assisted reproductive technologies (ART) cycles, curettage of the granulosa cells during oocyte retrieval is thought to reduce corpora lutea function and thus progesterone production, resulting in a decrease in pregnancy rate.

Therefore, luteal support is routinely performed in ART cycles. Consensus has been reached on the supplementation of progesterone after the day of oocyte retrieval, which was performed in approximately 80% of the cycles and significantly improved clinical outcomes.However, the efficacy of oestradiol supplementation in luteal support remains controversial.

Previous studies have shown that the lower the serum estrogen level was at 4, 7 and 9 days following transplantation, the lower the clinical pregnancy rate. Previous studies showed that in patients with long or short duration ovulation induction, luteal support with oestradiol supplementation led to an increased serum estrogen level and an improved pregnancy rate . It was also found that patients having luteal support with estrogen (4 mg per day) had a significantly higher clinical pregnancy rate (40.6% vs 21.6%) and a significantly lower abortion rate (12.8% vs 38%) than those treated with progesterone alone.

In contrast, other investigators have failed to show any benefit of oestradiol supplementation during the luteal phase and a Cochrane review published in 2015 reported no differences in rates of live birth or ongoing pregnancy between the progesterone group and progesterone add oestrogen group. Hence, it remains unclear whether the addition of estrogen to progesterone for luteal support is associated with higher pregnancy rate and live birth rate.

In this study, the investigators will evaluate outcomes of patients undergoing IVF/ICSI-ET with oestradiol supplementation in addition to progesterone for luteal support. The investigators also report on the efficacy implications of oestradiol supplementation for patients undergoing IVF/ICSI-ET.

• Study Type: Interventional
• Enrollment (Anticipated): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cair0
    • Cairo, Cair0, Egypt, 11542
      • Recruiting
      • Art Unit/ Obatetrics and Gynecology Department
      • Contact: Sherine H Hosny; Phone Number: 01097665573

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 38 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion criteria:

1. Age group 20-38 years old.
2. Patients Undergoing gonadotropin Releasing Hormone (Gn RH) long agonist protocol, with fresh embryo transfer.
3. Day 3 Grade 1 embryos.
4. Trilamellar endometrium with ranging endometrial thickness from 8 mm to 14 mm.

Exclusion criteria:

1. Karyotypic abnormalities in either partner.
2. Patients with uterine abnormalities.
3. G3-G4 quality embryos.
4. Estradiol level 10,000 or more at time of trigger.
5. Cases of egg donation/sperm donation/embryo donation.
6. Polycystic ovary syndrome (PCOS )patients.
7. Poor responders (maternal age >40, Antral follicle counts (AFC )<5, Anti Mullerian Hormone (AMH )<1 and previous trial <5 oocyte retrieved ) (bologna criteria 2011)
8. Those with 3 or more implantation failure.
9. Endometrial thickness <8 or >14mm.
10. Severe male factor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group receiving oestradiol tablets in addition to progesterone; Group A :Will receive 400mg progesterone in the form of vaginal or rectal suppositories in addition to estradiol valerate oral tablets in a dose of 4mg/day(2x2), for luteal phase support. Starting from the day of ovum pickup and for 14 days after embryo transfer. Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer.	Drug: Estradiol Valerate; Oestradiol supplementation starting from day of trigger through out the luteal phase; Other Names: Progynova; Progesterone vaginal suppositories
PLACEBO_COMPARATOR: Group not receiving oestradiol tablets.; Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer	Drug: Estradiol Valerate; Oestradiol supplementation starting from day of trigger through out the luteal phase; Other Names: Progynova; Progesterone vaginal suppositories

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	Number of gestational sacs per number of embryos transferred per cycle	4 weeks after embryo transfer of each enrolled patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemical pregnancy rate	Quantitative Beta Human Chorionic Gonadotropin (BHCG)	Two weeks after embryo transfer of each enrolled patient
Clinical pregnancy rate	Intrauterine gestational sac with fetal pole with positive pulsation	4 weeks after embryo transfer of each enrolled patient with positive pregnancy test or 6 weeks from IVF cycle beginning in pregnant patients
Ongoing pregnancy rate	12 weeks gestation and more	10 weeks after embryo transfer of each enrolled patient or 12 weeks from starting IVF cycle in pregnant patients

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2018
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): January 1, 2020

Study Registration Dates

• First Submitted: February 4, 2019
• First Submitted That Met QC Criteria: February 5, 2019
• First Posted (ACTUAL): February 6, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 7, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: IVF; ICSI; long protocol; oestradiol
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins; Estradiol; Progesterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: MD IVF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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