SubfertilityNCT02197208
A RCT Comparing Spontaneous Natural Cycles and Human Chorionic Gonadotrophin-induced Natural Cycles in FET
A study testing Daily monitoring of LH and E2, hCG induced natural cycle and ultrasound in people with Subfertility and Pregnancy, run by The University of Hong Kong at 2 sites in 2 countries.
Trial summary
This is a randomized controlled trial on the comparison of the ongoing pregnancy rate in frozen-thawed embryo transfer cycles with spontaneous ovulation and hCG-induced natural cycles. Read more about this study
- Who is it for?
- Ages 18 to 43 years, women only
- Conditions the study is for
- Subfertility, Pregnancy
- What is being tested?
- Daily monitoring of LH and E2, hCG induced natural cycle and ultrasound
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Oct 2014to Dec 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 43 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age of women <43 years
- Regular menstrual cycles ranging from 21-35 days with not more than 4 days variation between cycles
- Undergoing FET in natural cycles
- Normal uterine cavity as shown on saline sonogram performed before the IVF cycle or normal uterine cavity shown on pelvic scanning during the stimulated IVF cycle
- Endometrial thickness >=8mm in both stimulated IVF and FET cycles
Who cannot join
- >3 previous IVF cycles
- >6 embryos replaced without pregnancy
- Irregular menstrual cycles
- Subjects requiring clomid-induced cycles and hormonal replacement (HRT) cycles
- History of previous FET cycles within the study period
- Blastocyst transfer
Show all 12Show fewer
- Preimplantation genetic diagnosis treatment
- Use of donor oocytes
- Presence of hydrosalpinx not corrected surgically prior to FET
- Recurrent miscarriage
- Serum progesterone level on the day of LH surge or day of hCG >5 nmol/L or 1.5 pg/L (these patients will be retrospectively excluded)
- Refusal to join the study
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
China1 site
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University
Guangzhou
About this study
Official title: A Randomized Controlled Comparison of Spontaneous Natural Cycles and Human Chorionic Gonadotrophin-induced Natural Cycles in Frozen-thawed Embryos Transfer
This is a randomized controlled trial on the comparison of the ongoing pregnancy rate in frozen-thawed embryo transfer cycles with spontaneous ovulation and hCG-induced natural cycles.
Read the detailed description
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.
- Conditions
- Subfertility, Pregnancy
- Being tested
- Daily monitoring of LH and E2, hCG induced natural cycle, ultrasound
- Keywords
- Frozen-thawed embryo transfer, natural cycle, spontaneous ovulation, hCG induced natural cycles
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daily monitoring of LH and E2Procedure or surgery
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).
hCG induced natural cycleProcedure or surgery
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).
ultrasoundDevice
| Study group | Role | What they receive |
|---|---|---|
| Spontaneous NC | Active comparator | Timing by the onset of LH surge as shown daily blood monitoring of serum estradiol and LH levels Receives: Procedure: Daily monitoring of LH and E2; Device: ultrasound |
| hCG induced NC | Experimental | Timing by giving hCG when the dominant follicle reaches >=17mm in diameter on ultrasound monitoring Receives: Procedure: hCG induced natural cycle; Device: ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
ongoing pregnancy rate
the ongoing pregnancy rate which is defined as the number of viable pregnancies beyond 10-12 weeks gestation per transfer cycle
Measured: 12 weeks after embryos transfer
Secondary outcomes (7)
Days of monitoring for timing FET
The number of days needed for the monitoring for the timing of FET
Measured: 4 weeks after last menstrual period
Endometrial thickness on day of hCG or the next day after LH surge
The measurement of the endometrial thickness on the day of hCG or the next day after LH surge
Measured: 2-3 weeks after LMP
Implantation rate
Implantation rate: number of gestational sacs per number of embryos transferred
Measured: 4-6 weeks after embryo transfer
pregnancy rate
number of positive pregnancy rate per transfer
Measured: 2-4 weeks after embryo transfer
Clinical pregnancy rate
Number of pregnancy with positive fetal pulsation on scanning at 6 weeks of gestation.
Measured: 6-8 weeks after embryo transfer
Miscarriage rate
rate of pregnancy loss <20 weeks per transfer cycles
Measured: 20 weeks after embryo transfer
Multiple pregnancy rate
The rate of multiple pregnancy after ET
Measured: 20 weeks after embryo transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SubfertilityStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vivian CY Lee, MBBS, Principal investigator, Queen Mary Hospital / University of Hong Kong.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02197208
- Sponsor's protocol ID
- HKU-VL-NChCGFET
- Status last verified
- Dec 2015
- First submitted
- 20 Jul 2014
- Last updated
- 11 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Comparison of Spontaneous Natural Cycles and Human Chorionic Gonadotrophin-induced Natural Cycles in Frozen-thawed Embryos Transfer
- ClinicalTrials.gov ID
- NCT02197208
- Acronym / sponsor ID
- HKU-VL-NChCGFET
- Conditions
- Subfertility, Pregnancy
- Keywords
- Frozen-thawed embryo transfer, natural cycle, spontaneous ovulation, hCG induced natural cycles
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 22 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized controlled trial on the comparison of the ongoing pregnancy rate in frozen-thawed embryo transfer cycles with spontaneous ovulation and hCG-induced natural cycles.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spontaneous NC | Active comparator | Procedure: Daily monitoring of LH and E2, Device: ultrasoundTiming by the onset of LH surge as shown daily blood monitoring of serum estradiol and LH levels |
| hCG induced NC | Experimental | Procedure: hCG induced natural cycle, Device: ultrasoundTiming by giving hCG when the dominant follicle reaches >=17mm in diameter on ultrasound monitoring |
Who may qualify
- Ages
- 18 to 43 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age of women <43 years
- Regular menstrual cycles ranging from 21-35 days with not more than 4 days variation between cycles
- Undergoing FET in natural cycles
- Normal uterine cavity as shown on saline sonogram performed before the IVF cycle or normal uterine cavity shown on pelvic scanning during the stimulated IVF cycle
- Endometrial thickness >=8mm in both stimulated IVF and FET cycles
Key exclusion criteria (12 listed)
- >3 previous IVF cycles
- >6 embryos replaced without pregnancy
- Irregular menstrual cycles
- Subjects requiring clomid-induced cycles and hormonal replacement (HRT) cycles
- History of previous FET cycles within the study period
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daily monitoring of LH and E2ultrasound 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). | Procedure or surgery | Spontaneous NC |
| hCG induced natural cycleultrasound 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). | Procedure or surgery | hCG induced NC |
| ultrasound | Device | Spontaneous NC, hCG induced NC |
Primary outcome
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
7 secondary outcomes
Days of monitoring for timing FET
Time frame: 4 weeks after last menstrual period
Endometrial thickness on day of hCG or the next day after LH surge
Time frame: 2-3 weeks after LMP
Implantation rate
Time frame: 4-6 weeks after embryo transfer
pregnancy rate
Time frame: 2-4 weeks after embryo transfer
Clinical pregnancy rate
Time frame: 6-8 weeks after embryo transfer
Miscarriage rate
Time frame: 20 weeks after embryo transfer
Multiple pregnancy rate
Time frame: 20 weeks after embryo transfer
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vivian CY Lee, MBBS principal investigator
Queen Mary Hospital / University of Hong Kong.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Daily monitoring of LH and E2, hCG induced natural cycle and ultrasound in people with Subfertility and Pregnancy, run by The University of Hong Kong at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ongoing pregnancy rate (time frame: 12 weeks after embryos transfer). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2015.