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

Sponsor

Cairo University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03832894

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: Estradiol Valerate	Phase 3

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

2 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Randomization will be held by using the computer generated randomization codes, which will then be placed in the sealed envelopes by a third party (nurse). Each patient will choose a sealed envelope containing randomization number either group A or B. Both participant and health provider will be blinded to patients grouping

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Dec 1, 2018

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Jan 1, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Implantation rate [4 weeks after embryo transfer of each enrolled patient]
Number of gestational sacs per number of embryos transferred per cycle

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 38 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

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

Exclusion criteria:

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