Clinical trial NCT02238431: Down-regulated Hormonally Controlled Cycles for Vitrification-warmed Blastocyst Transfers
Official title: Down-regulated Hormonally Controlled Cycles for Vitrification-warmed Blastocyst Transfers: Reduces Time to Transfer and Cycle Cancellation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Pregnancy
Keywords: Lucrin depot,
frozen embryo transfer,
artificial cycle,
pregnancy,
cancellation
Lead sponsor: Antalya IVF
Sponsor class: OTHER
First posted: 2014-09-12
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Currently all patients that have freeze-all ICSI treatment cycles have the start of their FET cycle scheduled with the use of OCP. While an excellent pregnancy rate (75%) for the patients that have a blastocyst transfer has been maintained over time, 15% of started FET cycles are being cancelled because of premature luteinization, and the treatment (to transfer) takes approximately 89 days. The use of a Lucrin depot may reduce the number of cycles cancelled and reduce the treatment time to approximately 69 days. The use of no drugs and allowing the normal menstrual cycle to determine the time to start the FET cycle may suit some patients. Whether these benefits can be obtained while still maintaining the current FET pregnancy rate will be the main focus of the trial.

Detailed description: The patients will undergo standard assisted conception procedures; controlled ovarian stimulation (COS), oocyte pickup procedure (OPU), ICSI, embryo culture, blastocyst vitrification and frozen embryo transfer. If sufficient (\>2) viable blastocyst develop from the in vitro culture of their embryos, all viable blastocysts will be cryopreserved using a routine vitrification procedure. This is the eligible patient population. On the day the last blastocyst(s) are frozen the patients will be given a further opportunity to ask questions and if satisfied they will be asked to complete a trial consent. At this point patients will be randomized by numeric code and given a schedule and drug prescription for scheduling the start of their hormone supplemented frozen embryo transfer cycle. During the scheduling period the patients will follow the drug prescription provided . After the completion of their treatment - the transfer of one or two vitrified-warmed blastocyst - the patients from both groups will receive identical luteal support drug schedules and prescriptions. A blood test will be performed on the 15th day of progesterone supplementation, to determine the βhCG blood concentration. Currently at Antalya IVF, approximately 75% of patients who have blastocysts transferred in a frozen embryo transfer cycle have a positive biochemical pregnancy test, \>29 international units per litre (IU/L) of human chorionic gonadotropin (βhCG). If pregnant, patients will continue using estrogen and progesterone supplementation for a further 8 weeks. At 7 weeks of gestation (5 weeks after embryo transfer ) the patients will receive a transvaginal ultrasound scan (TVUS) to check for pregnancy viability (fetal sac with cardiac activity). Thereafter the patients will have regular TVUS to follow fetal development. At 20 weeks of gestation a TVUS will be performed to confirm an ongoing pregnancy (normal fetal development).

All drug packs are delivered to the clinic by the pharmacy after receiving the prescription. A staff member will verify the code on the prescription with randomization code allocated to the patient. The pack will then be given to the patient after verbally confirming patient identity. The packs will also contain a drug use instruction sheet and a trial information sheet.

Eligibility criteria: Inclusion Criteria:

* If patients have \>2 blastocysts vitrified

Exclusion Criteria:

* All patients not willing to participate in the study
* Patients with any known adverse reaction to one or the other of the drugs prescribed
* All patients that have no surviving blastocysts for transfer

Primary outcomes:
measure: Cycle cancellation
timeFrame: On day 14 of estrogen supplementation
Secondary outcomes:
measure: Ongoing pregnancy rate
timeFrame: 20 weeks of gestation
Other outcomes:
measure: Pregnancy
timeFrame: 15 days after start the start of progesterone supplementation
Locations:
city: Antalya
country: Turkey
facility: Antalya IVF
Study officials:
References:
citation: Gelbaya TA, Nardo LG, Hunter HR, Fitzgerald CT, Horne G, Pease EE, Brison DR, Lieberman BA. Cryopreserved-thawed embryo transfer in natural or down-regulated hormonally controlled cycles: a retrospective study. Fertil Steril. 2006 Mar;85(3):603-9. doi: 10.1016/j.fertnstert.2005.09.015.
citation: Hill MJ, Miller KA, Frattarelli JL. A GnRH agonist and exogenous hormone stimulation protocol has a higher live-birth rate than a natural endogenous hormone protocol for frozen-thawed blastocyst-stage embryo transfer cycles: an analysis of 1391 cycles. Fertil Steril. 2010 Feb;93(2):416-22. doi: 10.1016/j.fertnstert.2008.11.027. Epub 2009 Jan 26.
citation: Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2.