Clinical trial NCT00823121: Replacement of Fresh Embryo Transfers (ETs) by Frozen Embryo Transfers (FETs) Using Vitrification
Official title: Can Fresh Embryo Transfers be Replaced by Cryopreserved-thawed Embryo Transfers in Assisted Reproductive Cycles?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: In Vitro Fertilization
Keywords: Fresh embryo transfer
frozen- thawed embryo transfer
vitrification
endometrial receptivity
implantation rate
pregnancy
ART
Lead sponsor: Yazd Research & Clinical Center for Infertility
Sponsor class: OTHER
First posted: 2009-01-15
Enrollment: 500
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: implantation rate
timeFrame: 4 weeks
Secondary outcomes:
measure: on going pregnancy rate
timeFrame: 3 months
Other outcomes:
Locations:
city: Yazd
country: Iran, Islamic Republic of
facility: : Research and clinical center for infertility
Study officials:
affiliation: Research and Clinical Center for Infertility
name: abbas aflatoonian, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Research and Clinical Center for Infertility
name: homa oskouian, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aflatoonian A, Oskouian H, Ahmadi S, Oskouian L. Can fresh embryo transfers be replaced by cryopreserved-thawed embryo transfers in assisted reproductive cycles? A randomized controlled trial. J Assist Reprod Genet. 2010 Jul;27(7):357-63. doi: 10.1007/s10815-010-9412-9. Epub 2010 Apr 6.