A RCT Comparing Spontaneous Natural Cycles and Human Chorionic Gonadotrophin-induced Natural Cycles in FET
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|ClinicalTrials.gov Identifier: NCT02197208|
Recruitment Status : Completed
First Posted : July 22, 2014
Last Update Posted : December 11, 2015
|Condition or disease||Intervention/treatment||Phase|
|Subfertility Pregnancy||Procedure: Daily monitoring of LH and E2 Procedure: hCG induced natural cycle Device: ultrasound||Not Applicable|
Embryo cryopreservation is essential nowadays. It allows the usage of surplus good quality embryos in frozen-thawed embryo transfer (FET) cycles which avoids embryo wastage and facilitates the adoption of transferring a small number of embryos in the fresh stimulation cycle so as to reduce the risk of multiple pregnancy during in vitro fertilization (IVF) treatment. Elective cryopreservation of all fresh embryos is also required in special circumstances where fresh transfer is undesirable, for example in cases where a high risk of ovarian hyperstimulation syndrome is anticipated. Fresh transfer is not advisable when serum progesterone level is elevated or hydrosalpinx is detected during ovarian stimulation.
The availability of FETs would increase the likelihood of successful pregnancy from a single superovulation and oocyte retrieval cycle. It has been estimated that in modern IVF programmes which incorporates embryo cryopreservation, up to 42% of all conceptions could be derived from FET (Borini et al, 2008).
Although the pregnancy rate in FET is comparable with stimulated IVF cycles, the optimal regimen to prepare the endometrium for implantation is not yet well proven. By a recent Cochrane review, there is no evidence to prove the use of one regimen in preference to another (Ghobara T 2008).
Natural cycles (NC) are considered the best regimen as it is physiological, where natural conception occurs in. However, there are two most commonly employed methods to time the ovulation in natural cycles. One is to use ultrasound (USG) to monitor the follicular growth and endometrial thickness, with the use of human chorionic gonadotrophin (hCG) to trigger ovulation in the presence of a dominant follicle around 17-18mm in diameter. Another is to monitor the blood hormonal concentration to detect the luteinising hormone (LH) surge associated with natural ovulation. There is scarce information in this area as only one randomized controlled trial compared these two approaches. The authors aimed to recruit 240 subjects, but the study was prematurely terminated as significant results were resulted in the first interim analysis when the sample size reached 124. The ongoing pregnancy rate was 31.1% in the group with spontaneous LH surge and 14.3% in the hCG-induced group (Fatemi et al., 2010).
The use of natural LH surge and hCG trigger in intrauterine insemination was compared too. A meta-analysis revealed a significantly higher clinical pregnancy rate in IUI cycles with natural LH surge than that with hCG trigger. However, the data from randomized controlled trial showed no significant difference. Also the data were contradictory when the analysis confined to a specific indication of subfertility (Kosmas et al., 2007). A cochrane review in 2012 also suggested there was no evidence to advise that any regimen was better than another (Cantineau et al., 2012).
This randomized controlled trial aims to compare the ongoing pregnancy rate of FET in spontaneous NC and hCG-induced NC. The hypothesis of this trial is that the ongoing pregnancy rate of FET is similar for spontaneous NC and hCG-induced NC. The advantage of hCG-induced NC is likely a reduction in the duration of monitoring for timing FET when compared with spontaneous NC.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||300 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||A Randomized Controlled Comparison of Spontaneous Natural Cycles and Human Chorionic Gonadotrophin-induced Natural Cycles in Frozen-thawed Embryos Transfer|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||December 2015|
|Actual Study Completion Date :||December 2015|
Active Comparator: Spontaneous NC
Timing by the onset of LH surge as shown daily blood monitoring of serum estradiol and LH levels
Procedure: Daily monitoring of LH and E2
ultrasound scanning would be carried out from 18 days before the expected period to confirm follicular growth, followed by daily blood monitoring of serum E2 and LH levels when the dominant follicle reaches 13-14mm in diameter. Ultrasound scanning can be arranged accordingly if the leading follicle remains less than 10mm in diameter. 5 ml of blood would be taken daily. LH surge is defined as the LH level being double of the average of the previous three days and higher than 20 IU/L. Ultrasound examination will be performed on the next day after the LH surge to measure the endometrial thickness. The transfer will be scheduled three or four days after the LH surge (for cleavage stage embryos) or six days after LH surge (for blastocyst transfer).
Experimental: hCG induced NC
Timing by giving hCG when the dominant follicle reaches >=17mm in diameter on ultrasound monitoring
Procedure: hCG induced natural cycle
ultrasound monitoring would be started from 18 days before the expected period to monitor follicular growth, followed by USG every 2-3 days. hCG, 5,000-10,000 IU will be given when the leading follicle is >/= 17 mm and the endometrium measures >/=8 mm. Serum E2, LH and progesterone levels will be measured on the day of hCG. Embryo transfer would be scheduled on the fourth or fifth days after hCG injection (for cleavage stage embryos) or seventh days (for blastocyst transfer).
- ongoing pregnancy rate [ Time Frame: 12 weeks after embryos transfer ]the ongoing pregnancy rate which is defined as the number of viable pregnancies beyond 10-12 weeks gestation per transfer cycle
- Days of monitoring for timing FET [ Time Frame: 4 weeks after last menstrual period ]The number of days needed for the monitoring for the timing of FET
- Endometrial thickness on day of hCG or the next day after LH surge [ Time Frame: 2-3 weeks after LMP ]The measurement of the endometrial thickness on the day of hCG or the next day after LH surge
- Implantation rate [ Time Frame: 4-6 weeks after embryo transfer ]Implantation rate: number of gestational sacs per number of embryos transferred
- pregnancy rate [ Time Frame: 2-4 weeks after embryo transfer ]number of positive pregnancy rate per transfer
- Clinical pregnancy rate [ Time Frame: 6-8 weeks after embryo transfer ]Number of pregnancy with positive fetal pulsation on scanning at 6 weeks of gestation.
- Miscarriage rate [ Time Frame: 20 weeks after embryo transfer ]rate of pregnancy loss <20 weeks per transfer cycles
- Multiple pregnancy rate [ Time Frame: 20 weeks after embryo transfer ]The rate of multiple pregnancy after ET
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02197208
|Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University|
|Queen Mary Hospital|
|Hong Kong, Hong Kong, 852|
|Principal Investigator:||Vivian CY Lee, MBBS||Queen Mary Hospital / University of Hong Kong.|