Replacement of Fresh Embryo Transfers (ETs) by Frozen Embryo Transfers (FETs) Using Vitrification

In Vitro Fertilization Clinical Trial

Official title:

Can Fresh Embryo Transfers be Replaced by Cryopreserved-thawed Embryo Transfers in Assisted Reproductive Cycles?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00823121
• Other study ID #: 654YazdRCCI
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: January 14, 2009
• Last updated: January 19, 2010
• Start date: August 2008
• Est. completion date: December 2009

Study information

• Verified date: April 2009
• Source: Yazd Research & Clinical Center for Infertility
• Contact: homa oskouian, Dr
• Phone: 3518247085
• Email: homaoskouian[@]gmail.com
• Is FDA regulated: No
• Health authority: Iran: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Cryopreservation of all embryos and transferring them subsequently in assisted reproductive technology (ART) cycles to improve outcome.

Description:

All patients in the initial cohort were treated with long protocol for ovarian stimulation. For pituitary down-regulation, patients were treated with daily administration of 0.5 mg buserelin (suprefact, Aventis, Frankfurt, Germany) from day 21 of menstrual cycle. Buserelin was reduced to 0.25 mg daily when ovaries were quiescent on ultrasound, and COH was initiated with recombinant FSH (Gonal F, Serono, Aubnne, Switzerland) 150 IU/day on day 2 of withdrawal bleeding. Serial ultrasound examinations and evaluation of serum E2 levels were used to assess ovarian response, and then gonadotropin dose adjustments were done as required. Human chorionic gonadotropin (pregnyl, Organon, Oss, the Netherlands ) 10,000 IU was administered when at least two follicles reached a mean diameter of 18 mm.

Oocyte retrieval was performed 34-36 hours after hCG administration and conventional insemination or ICSI was performed as clinically appropriate.

In 187 patients allocated to fresh ET group, ET were performed on the day 2. Embryos were transferred under ultrasound guidance, with a C.C.D. embryo transfer catheter (Laboratory C.C.D., Paris, France). Luteal support with progesterone in oil (Progesterone, Aburaihan Co., Tehran, Iran) 100 mg daily IM was started on the day of oocyte retrieval and continued until the documentation of fetal heart activity on ultrasound.

In 187 patients allocated to FET group, cryopreservation of all embryos were undertaken with vitrification by Cryotop method and after two months, embryos were transferred.

The protocol for the Cryotop vitrification of embryos was described previously (Kuwayama et al., 2005; Kuwayama, 2007).

After a two-step loading with equilibration solution containing 7.5% (v/v) ethylene glycol and 7.5% (v/v) dimethyl sulfoxide, and vitrification solution containing 15% (v/v) ethylene glycol, 15% (v/v) dimethyl sulfoxide and 0.5 mol/L sucrose, embryos were loaded with a narrow glass capillary onto the Cryotop in a volume of < 0.1 µL . After loading, almost all the solution was removed to leave only a thin layer covering the embryos, and the sample was quickly immersed into liquid nitrogen (LN). Subsequently, the plastic cap was pulled over the film part of the Cryotop, and the sample was stored under LN. At warming, the protective cap was removed from the Cryotop while it was still submerged in LN and the Cryotop was immersed directly into a 37˚C medium containing sucrose. The embryos were then sequentially incubated in diluents solution before further in vitro culture for transfer.

Patients were prepared for ET with oral E2 to attain endometrial thickness ≥ 8 mm and triple line pattern on ultrasound scans. At that time, patients were given 100 mg of IM progesterone in oil daily and ET was preformed three days later under abdominal ultrasound guidance as described earlier. Oral E2 and progesterone were continued until documentation of fetal heart activity by ultrasonography.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 38 Years

Eligibility

Inclusion Criteria:

• age < 38

• normal day 3 FSH

• classified as high risk for OHSS

• has = 15 follicles with a mean diameter = 12 mm per each ovary

• E2 levels on the day of hCG administration > 3000 pg/mL

• undergoing her first assisted reproduction treatment cycle

Exclusion Criteria:

• who does not have good-quality embryos appropriate for cryopreservation

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• In Vitro Fertilization

Intervention

Procedure:
• freezing embryos by vitrification
vitrification by Cryotop method
• fresh embryo transfers
fresh embryo transfers

Drug:
• buserelin
Daily administration of 500 µg subcutaneous buserelin from day 21 of menstrual cycle; reduce to 250 µg daily when ovarian suppression is confirmed.
• recombinant FSH
gonadotropin stimulation with rFSH 150 IU/day from day 2 of menstrual cycle
• human chorionic gonadotropin (pregnyl)
hCG 10,000 IU is administered when at least 2 follicles reach a mean diameter of 18 mm.

Locations

Country	Name	City	State
Iran, Islamic Republic of	: Research and clinical center for infertility	Yazd

Sponsors (1)

Lead Sponsor	Collaborator
Yazd Research & Clinical Center for Infertility

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	implantation rate		4 weeks	Yes
Secondary	on going pregnancy rate		3 months	Yes