Clinical trial NCT04013438: Luteal Phase Support During Frozen Embryo Transfer Cycle
Official title: Duration of Estrogen for Luteal Phase in Pregnant Women Undergone Frozen Embryo Transfer Cycles- Randomized Controlled Trials Phase III
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility, Female
Frozen Embryo Transfer
Keywords: Ongoing pregnancy rate
Estrogen
Frozen embryo transfer
Luteal phase support
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
First posted: 2019-07-09
Enrollment: 60
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We aimed to decrease quantity of exogenous estrogen and evaluated the success rate of ongoing pregnancy in women undergone artificial FET who have a surplus embryos at previous fertility treatment cycles.

In this study, endometrial prepared with standard long GnRH protocol and for luteal phase support patients received 6 mg oral E2 and intramuscularly P 100 mg/d and embryos on day 2-3 were transferred. Control group continued E2 until 12 week of pregnancy, while for cases after identify gestational sac with heart beat (the 6 week of pregnancy) by vaginal ultrasonography, E2 will discontinued.

Detailed description: Approval Status: Confirmed Approval reference Number: IR.ACECR.ROYAN.REC.1395.70 Board Name: Ethics committee of Royan infertility institute Board Affiliation: Reza Samani Phone: +982122305236 Email: samani@royaninstitute.org

Yes Health, Treatment and Medical Education Ministry: Iran

Hormones replace therapy (Artificial) is a method for endometrium preparation and embryo transfer. In this protocol for decrease of spontaneous ovulation, exogenous estrogen began in 2-3 days on follicular phase of the menstrual cycle which continue about 10 to 14 days. In the following luteal phase support by progesterone begins on 14 to 16 days of cycles. The luteal phase is supported with different dose and duration of estradiol (E2) and progesterone (P) until 8-12 week of pregnancy. Studied reported a higher risk of thromboembolism in pregnant women that using exogenous estrogen. Also, excess estrogen might be resulted fetus congenital anomalies, low birth weight and increased susceptibility to breast cancer in female fetuses. On the other hands, it seems placenta in early pregnancy duration synthesize estrogen and this time estrogen sufficient as a product of progesterone metabolism. We aimed to decrease quantity of exogenous estrogen and evaluated the success rate of ongoing pregnancy in women undergone artificial FET who have a surplus embryos at previous fertility treatment cycles.

In this study, endometrial prepared with standard long GnRH protocol and for luteal phase support patients received 6 mg oral E2 and intramuscularly P 100 mg/d and embryos on day 2-3 were transferred. Control group continued E2 until 12 week of pregnancy, while for cases after identify gestational sac with heart beat (the 6 week of pregnancy) by vaginal ultrasonography, E2 will discontinued.

The level of maternal estrogen and progesterone measured at progesterone days (day 15), the day of embryo transfer, 6 and 12 weeks of pregnancy.

This study is a randomized clinical trial to investigate the duration of estrogen for luteal phase in pregnant women undergone frozen embryo transfer cycles- Randomized controlled trials phase III. The study protocol is approved by the Ethics Committee (Institutional Review Board) of Royan institute and all participants provide informed consent.

Eligibility criteria: Inclusion Criteria:

1. Patients with surplus embryos undergone infertility treatment cycles (e.g. OHSS, inadequate endometrium, surplus frozen embryo from any cause)
2. Age 21-37 years
3. Normal BMI (18.5 \<BMI \<30)
4. IVF / ICSI or IVF or ICSI cycles with antagonists or agonists protocols
5. Frozen embryos on 2-3 days

Exclusion Criteria:

1. Endometrial thickness ≤7mm
2. Egg Donors
3. Surrogacy
4. Male factor infertility with azoospermia
5. Age \<37 years old
6. Hydrosalpinx
7. Uterine anomalies
8. Myoma with a compression effect or submocusa myoma
9. PGD
10. Blastocyst embryo transfer, ZIFT and GIFT

Primary outcomes:
measure: Ongoing pregnancy rate after frozen embryo transfer
timeFrame: ≥20 weeks of gestational age
Secondary outcomes:
measure: Maternal serum estrogen level
timeFrame: The start day of using progesterone for luteal support in FET cycle (day 15 after onset estradiol), the day of embryo transfer (approximately 17-18 days after onset estradiol), 6 and 12 weeks of gestational age
measure: Maternal serum progesterone level
timeFrame: The start day of using progesterone for luteal support in FET cycle (day 15 after onset estradiol), the day of embryo transfer (approximately 17-18 days after onset estradiol), 6 and 12 weeks of gestational age
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
References:
citation: Ghaffari F, Chekini Z, Vesali S. Duration of estradiol supplementation in luteal phase support for frozen embryo transfer in hormone replacement treatment cycles: a randomized, controlled phase III trial. Arch Gynecol Obstet. 2022 Mar;305(3):767-775. doi: 10.1007/s00404-021-06173-w. Epub 2021 Sep 24.