The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment

Study Overview
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Brief Summary
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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
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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

Official Title
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The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment

Conditions
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Infertility

Intervention / Treatment
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* Drug: Kisspeptin 1.6nmol/kg
* Drug: Kisspeptin 3.2nmol/kg
* Drug: Kisspeptin 6.4nmol/kg
* Drug: Kisspeptin 9.6nmol/kg
* Drug: Kisspeptin 12.8nmol/kg
* Drug: Kisspeptin 9.6 nmol/kg double
* Drug: Kisspeptin 9.6 nmol/kg + saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Different dose for each volunteer
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kisspeptin-54, 1.6 single<br>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg | Drug: Kisspeptin 1.6nmol/kg<br>* single kisspeptin dose 1.6 nmol/kg subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54, 3.2 single<br>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg | Drug: Kisspeptin 3.2nmol/kg<br>* single kisspeptin dose 3.2 nmol/kg subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54, 6.4 single<br>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg | Drug: Kisspeptin 6.4nmol/kg<br>* single kisspeptin dose 6.4 nmol/kg subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54, 12.8 single<br>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg | Drug: Kisspeptin 12.8nmol/kg<br>* single kisspeptin dose 12.8 nmol/kg subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54 OHSS, 3.2 single<br>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 | Drug: Kisspeptin 3.2nmol/kg<br>* single kisspeptin dose 3.2 nmol/kg subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54 OHSS, 6.4 single<br>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 | Drug: Kisspeptin 6.4nmol/kg<br>* single kisspeptin dose 6.4 nmol/kg subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54 OHSS, 9.6 single<br>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 | Drug: Kisspeptin 9.6nmol/kg<br>* single kisspeptin dose 9.6 nmol/kg subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54 OHSS, 12.8 single<br>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 | Drug: Kisspeptin 12.8nmol/kg<br>* single kisspeptin dose 12.8 nmol/kg subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54 OHSS, 9.6 + 9.6<br>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 | Drug: Kisspeptin 9.6 nmol/kg double<br>* kisspeptin dose 9.6 nmol/kg given twice 10hrs apart subcutaneously<br>* Other names: kisspeptin-54;|
| Experimental: Kisspeptin-54 OHSS, 9.6 + saline<br>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 | Drug: Kisspeptin 9.6 nmol/kg + saline<br>* kisspeptin dose 9.6 nmol/kg subcutaneously and saline subcutaneously, 10hrs apart<br>* Other names: kisspeptin-54;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 36 hours post Kisspeptin-54 trigger injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical Pregnancy | Number of participants achieving biochemical pregnancy by serum βhCG > 10 mIU/mL | 11 days after embryo transfer | 
| 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 | 11 days following embryo transfer | 
| Fertilization Rate | Percentage of M2 oocytes that fertilize to form two pronuclear [2PN] zygotes following intracytoplasmic injection with sperm [ICSI] | 3 days after oocyte retrieval | 
| 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 | 3 days after oocyte retrieval | 
| Number of Participants With Clinical Pregnancy | Intrauterine gestational sac with heartbeat on ultrasound at 6 weeks' gestation | 6 weeks after embryo transfer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kisspeptin, infertility, in vitro fertilisation