Clinical trial NCT03832894: Oestradiol Supplementation in Luteal Long Agonist Fresh In Vitro Fertilization/Intra Cytoplasmic Sperm Injection ( IVF/ICSI) Cycle .
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Infertility
Keywords: IVF
ICSI
oestradiol
long protocol
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2019-02-06
Enrollment: 2
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Implantation rate
timeFrame: 4 weeks after embryo transfer of each enrolled patient
Secondary outcomes:
measure: Chemical pregnancy rate
timeFrame: Two weeks after embryo transfer of each enrolled patient
measure: Clinical pregnancy rate
timeFrame: 4 weeks after embryo transfer of each enrolled patient with positive pregnancy test or 6 weeks from IVF cycle beginning in pregnant patients
measure: Ongoing pregnancy rate
timeFrame: 10 weeks after embryo transfer of each enrolled patient or 12 weeks from starting IVF cycle in pregnant patients
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Art Unit/ Obatetrics and Gynecology Department
state: Cair0
Study officials:
References: