Back to resultsThe Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment
Primary Purpose
Infertility
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Kisspeptin 1.6nmol/kg
Kisspeptin 3.2nmol/kg
Kisspeptin 6.4nmol/kg
Kisspeptin 9.6nmol/kg
Kisspeptin 12.8nmol/kg
Kisspeptin 9.6 nmol/kg double
Kisspeptin 9.6 nmol/kg + saline
Sponsored by
About this trial
This is an interventional treatment trial for Infertility focused on measuring kisspeptin, infertility, in vitro fertilisation
Eligibility Criteria
Inclusion Criteria:
- Aged 18 - 34 years
- Body mass index between 18 and 29 kg/m2
- Stable body weight for at least 3 months
- Normal early menstrual cycle follicular phase serum FSH concentration
- Serum anti-Mullerian hormone (AMH) > 40pmol/L
- No more than one previous IVF treatment cycle
- Both ovaries intact
Exclusion Criteria:
History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer
- Without access at home to a telephone, or other factor likely to interfere with ability to participate reliably in the study
- Treatment with an investigational drug within the preceding 2 months
- Donated blood during the preceding 3 months or intention to do so before the end of the study
- Previous poor response to IVF treatment
Sites / Locations
- Hammersmith Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Kisspeptin-54, 1.6 single
Kisspeptin-54, 3.2 single
Kisspeptin-54, 6.4 single
Kisspeptin-54, 12.8 single
Kisspeptin-54 OHSS, 3.2 single
Kisspeptin-54 OHSS, 6.4 single
Kisspeptin-54 OHSS, 9.6 single
Kisspeptin-54 OHSS, 12.8 single
Kisspeptin-54 OHSS, 9.6 + 9.6
Kisspeptin-54 OHSS, 9.6 + saline
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg
Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg
Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg
Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later
Outcomes
Primary Outcome Measures
Percentage of Oocyte Maturation
This was assessed by oocyte yield (percentage of mature [metaphase 2; M2] oocytes collected from the number of follicles ≥ 14 mm on final ultrasound scan prior to kisspeptin-54 trigger administration
Secondary Outcome Measures
Biochemical Pregnancy
Number of participants achieving biochemical pregnancy by serum βhCG > 10 mIU/mL
Occurrence of OHSS
Women were routinely screened for the development of early OHSS and late OHSS. Women were screened by symptoms, blood analysis, and ultrasound parameters
Fertilization Rate
Percentage of M2 oocytes that fertilize to form two pronuclear [2PN] zygotes following intracytoplasmic injection with sperm [ICSI]
Embryo Formation
All embryos were graded at day 3 by an independent embryologist, blinded to doses of kisspeptin administered, using the British Fertility Society and Association of Clinical Embryologist embryo grading scheme for cleavage stage embryos, which describes embryos based on cell number, blastomere size, and fragmentation
Number of Participants With Clinical Pregnancy
Intrauterine gestational sac with heartbeat on ultrasound at 6 weeks' gestation
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01667406
Brief Title
The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment
Official Title
The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
June 1, 2012 (Actual)
Primary Completion Date
October 11, 2016 (Actual)
Study Completion Date
October 11, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
We want to find out if kisspeptin is successful in stimulating oocyte maturation when it is used as a 'trigger' injection during IVF therapy for infertility.
Detailed Description
Participants in the study will have a standard Gonadotrophin Releasing Hormone (GnRH) antagonist IVF cycle, but instead of having a trigger injection of hCG (human chorionic gonadotrophin) they will be randomised to receive one of 4 doses of kisspeptin injection.
Oocytes will be retrieved and graded by an embryologist to see whether or not they have matured.
The reproductive hormones Luteinising hormone, follicle stimulating hormone, oestradiol and progesterone will also be measured
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
kisspeptin, infertility, in vitro fertilisation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Different dose for each volunteer
Masking
ParticipantCare Provider
Masking Description
participants and IVF physicians were blinded.
Allocation
Randomized
Enrollment
175 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Kisspeptin-54, 1.6 single
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg
Arm Title
Kisspeptin-54, 3.2 single
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg
Arm Title
Kisspeptin-54, 6.4 single
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg
Arm Title
Kisspeptin-54, 12.8 single
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg
Arm Title
Kisspeptin-54 OHSS, 3.2 single
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg
Arm Title
Kisspeptin-54 OHSS, 6.4 single
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg
Arm Title
Kisspeptin-54 OHSS, 9.6 single
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg
Arm Title
Kisspeptin-54 OHSS, 12.8 single
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg
Arm Title
Kisspeptin-54 OHSS, 9.6 + 9.6
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later
Arm Title
Kisspeptin-54 OHSS, 9.6 + saline
Arm Type
Experimental
Arm Description
Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later
Intervention Type
Drug
Intervention Name(s)
Kisspeptin 1.6nmol/kg
Other Intervention Name(s)
kisspeptin-54
Intervention Description
single kisspeptin dose 1.6 nmol/kg subcutaneously
Intervention Type
Drug
Intervention Name(s)
Kisspeptin 3.2nmol/kg
Other Intervention Name(s)
kisspeptin-54
Intervention Description
single kisspeptin dose 3.2 nmol/kg subcutaneously
Intervention Type
Drug
Intervention Name(s)
Kisspeptin 6.4nmol/kg
Other Intervention Name(s)
kisspeptin-54
Intervention Description
single kisspeptin dose 6.4 nmol/kg subcutaneously
Intervention Type
Drug
Intervention Name(s)
Kisspeptin 9.6nmol/kg
Other Intervention Name(s)
kisspeptin-54
Intervention Description
single kisspeptin dose 9.6 nmol/kg subcutaneously
Intervention Type
Drug
Intervention Name(s)
Kisspeptin 12.8nmol/kg
Other Intervention Name(s)
kisspeptin-54
Intervention Description
single kisspeptin dose 12.8 nmol/kg subcutaneously
Intervention Type
Drug
Intervention Name(s)
Kisspeptin 9.6 nmol/kg double
Other Intervention Name(s)
kisspeptin-54
Intervention Description
kisspeptin dose 9.6 nmol/kg given twice 10hrs apart subcutaneously
Intervention Type
Drug
Intervention Name(s)
Kisspeptin 9.6 nmol/kg + saline
Other Intervention Name(s)
kisspeptin-54
Intervention Description
kisspeptin dose 9.6 nmol/kg subcutaneously and saline subcutaneously, 10hrs apart
Primary Outcome Measure Information:
Title
Percentage of Oocyte Maturation
Description
This was assessed by oocyte yield (percentage of mature [metaphase 2; M2] oocytes collected from the number of follicles ≥ 14 mm on final ultrasound scan prior to kisspeptin-54 trigger administration
Time Frame
36 hours post Kisspeptin-54 trigger injection
Secondary Outcome Measure Information:
Title
Biochemical Pregnancy
Description
Number of participants achieving biochemical pregnancy by serum βhCG > 10 mIU/mL
Time Frame
11 days after embryo transfer
Title
Occurrence of OHSS
Description
Women were routinely screened for the development of early OHSS and late OHSS. Women were screened by symptoms, blood analysis, and ultrasound parameters
Time Frame
11 days following embryo transfer
Title
Fertilization Rate
Description
Percentage of M2 oocytes that fertilize to form two pronuclear [2PN] zygotes following intracytoplasmic injection with sperm [ICSI]
Time Frame
3 days after oocyte retrieval
Title
Embryo Formation
Description
All embryos were graded at day 3 by an independent embryologist, blinded to doses of kisspeptin administered, using the British Fertility Society and Association of Clinical Embryologist embryo grading scheme for cleavage stage embryos, which describes embryos based on cell number, blastomere size, and fragmentation
Time Frame
3 days after oocyte retrieval
Title
Number of Participants With Clinical Pregnancy
Description
Intrauterine gestational sac with heartbeat on ultrasound at 6 weeks' gestation
Time Frame
6 weeks after embryo transfer
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
woman undergoing IVF treatment
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
34 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 18 - 34 years
Body mass index between 18 and 29 kg/m2
Stable body weight for at least 3 months
Normal early menstrual cycle follicular phase serum FSH concentration
Serum anti-Mullerian hormone (AMH) > 40pmol/L
No more than one previous IVF treatment cycle
Both ovaries intact
Exclusion Criteria:
History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer
Without access at home to a telephone, or other factor likely to interfere with ability to participate reliably in the study
Treatment with an investigational drug within the preceding 2 months
Donated blood during the preceding 3 months or intention to do so before the end of the study
Previous poor response to IVF treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Waljit S Dhillo, PhD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hammersmith Hospital
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Data will be presented in anonymised groups
Citations:
PubMed Identifier
25036713
Citation
Jayasena CN, Abbara A, Comninos AN, Nijher GM, Christopoulos G, Narayanaswamy S, Izzi-Engbeaya C, Sridharan M, Mason AJ, Warwick J, Ashby D, Ghatei MA, Bloom SR, Carby A, Trew GH, Dhillo WS. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest. 2014 Aug;124(8):3667-77. doi: 10.1172/JCI75730. Epub 2014 Jul 18.
Results Reference
result
PubMed Identifier
28854728
Citation
Abbara A, Clarke S, Islam R, Prague JK, Comninos AN, Narayanaswamy S, Papadopoulou D, Roberts R, Izzi-Engbeaya C, Ratnasabapathy R, Nesbitt A, Vimalesvaran S, Salim R, Lavery SA, Bloom SR, Huson L, Trew GH, Dhillo WS. A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial. Hum Reprod. 2017 Sep 1;32(9):1915-1924. doi: 10.1093/humrep/dex253.
Results Reference
result
PubMed Identifier
26192876
Citation
Abbara A, Jayasena CN, Christopoulos G, Narayanaswamy S, Izzi-Engbeaya C, Nijher GM, Comninos AN, Peters D, Buckley A, Ratnasabapathy R, Prague JK, Salim R, Lavery SA, Bloom SR, Szigeti M, Ashby DA, Trew GH, Dhillo WS. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy. J Clin Endocrinol Metab. 2015 Sep;100(9):3322-31. doi: 10.1210/jc.2015-2332. Epub 2015 Jul 20.
Results Reference
result
PubMed Identifier
29446481
Citation
Abbara A, Islam R, Clarke SA, Jeffers L, Christopoulos G, Comninos AN, Salim R, Lavery SA, Vuong TNL, Humaidan P, Kelsey TW, Trew GH, Dhillo WS. Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment. Clin Endocrinol (Oxf). 2018 Jun;88(6):920-927. doi: 10.1111/cen.13569. Epub 2018 Mar 6.
Results Reference
derived
PubMed Identifier
29206944
Citation
Owens LA, Abbara A, Lerner A, O'floinn S, Christopoulos G, Khanjani S, Islam R, Hardy K, Hanyaloglu AC, Lavery SA, Dhillo WS, Franks S. The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function. Hum Reprod. 2018 Feb 1;33(2):292-302. doi: 10.1093/humrep/dex357.
Results Reference
derived
Learn more about this trial
The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment
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