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Study · Randomized controlled trial · n = 62 · 2017

4 results

A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

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 and 6 more

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Salim R, Lavery SA, Bloom SR, Huson L, Trew GH, Dhillo WS

Human reproduction (Oxford, England)1 Sept 2017Cited by 49 (Europe PMC)

PMID28854728 (opens in a new tab)PMCIDPMC5850304 (opens in a new tab)DOI10.1093/humrep/dex253 (opens in a new tab)PepBankPUB-28854728
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Summary

Study questionCan increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)?Summary answerA second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS.What is known alreadyKisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS.Study design, size, durationPhase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016. Following controlled ovarian stimulation, all patients (n = 62) received a subcutaneous injection of kisspeptin-54 (9.6 nmol/kg) 36 h prior to oocyte retrieval. Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter. Patients, embryologists, and IVF clinicians remained blinded to the dosing allocation.Participants/materials, setting, methodsStudy participants: Sixty-two women aged 18-34 years at high risk of OHSS (antral follicle count ≥23 or anti-Mullerian hormone level ≥40 pmol/L). Setting: Single centre study carried out at Hammersmith Hospital IVF unit, London, UK. Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%. Secondary outcomes: Reproductive hormone levels, implantation rate and OHSS occurrence.Main results and the role of chanceA second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration. A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2-50%, P = 0.042). Patients receiving two doses of kisspeptin-54 had a variable LH-response following the second kisspeptin dose, which appeared to be dependent on the LH-response following the first kisspeptin injection. Patients who had a lower LH-rise following the first dose of kisspeptin had a more substantial 'rescue' LH-response following the second dose of kisspeptin. The variable LH-response following the second dose of kisspeptin resulted in a greater proportion of patients achieving an oocyte yield ≥60%, but without also increasing the frequency of ovarian over-response and moderate OHSS (Single: 1/31, 3.2%, Double: 0/31, 0%).Limitations, reasons for cautionFurther studies are warranted to directly compare kisspeptin-54 to more established triggers of oocyte maturation.Wider implications of the findingsTriggering final oocyte maturation with kisspeptin is a novel therapeutic option to enable the use of fresh embryo transfer even in the woman at high risk of OHSS.Study funding/competing interest(s)The study was designed, conducted, analysed and reported entirely by the authors. The Medical Research Council (MRC), Wellcome Trust & National Institute of Health Research (NIHR) provided research funding to carry out the studies. There are no competing interests to declare.Trial registration numberClinicaltrial.gov identifier NCT01667406.Trial registration date8 August 2012.Date of first patient's enrolment10 August 2015.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In women at high risk of OHSS, a second dose of kisspeptin‑54 raised the proportion with an oocyte yield of at least 60% from 45% to 71% (P = 0.042).

    In plain wordsIn women at high risk of ovarian overstimulation, a second kisspeptin‑54 dose led to a good egg yield in more women than one dose.

    Peptide
    Kisspeptin-54 (metastin)
    Outcome
    IncreasePatients with oocyte yield of at least 60%
    Study

    n = 62

    Comparator
    Saline instead of a second dose
    Analysis
    Primary
    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    9.6 nmol/kg first dose, second dose 10 h later · subcutaneousAs given in this study (human).

    Measurements

    Patients with oocyte yield >=60%
    71%
    Double dose
    Patients with oocyte yield >=60%
    45%
    Single dose

    Source sentences

    Summary
    A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2-50%, P = 0.042).
    3 context sentences
    Summary · context
    Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%.
    Summary · context
    Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016.
    Summary · context
    Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter.
  2. 02HumanRandomized controlled trialActivity measurement

    In women at high risk of OHSS, a second dose of kisspeptin‑54 at 10 h induced further LH secretion at 4 h after administration.

    In plain wordsIn women at high risk of ovarian overstimulation, a second kisspeptin‑54 dose caused another rise in luteinising hormone.

    Peptide
    Kisspeptin-54 (metastin)
    Outcome
    IncreaseLH secretion after the second kisspeptin-54 dose
    Study

    n = 62

    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    9.6 nmol/kg first dose, second dose 10 h later · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    A second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration.
    2 context sentences
    Summary · context
    Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016.
    Summary · context
    Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter.
  3. 03HumanRandomized controlled trialSafety outcome

    In women at high risk of OHSS, a second dose of kisspeptin‑54 did not increase ovarian over-response or moderate OHSS (single dose 1/31, double dose 0/31).

    In plain wordsIn women at high risk of ovarian overstimulation, a second kisspeptin‑54 dose did not raise rates of overstimulation compared with one dose.

    Peptide
    Kisspeptin-54 (metastin)
    Outcome
    No significant changeOvarian over-response and moderate OHSS
    Study

    n = 62

    Comparator
    Saline instead of a second dose
    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    9.6 nmol/kg first dose, second dose 10 h later · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    The variable LH-response following the second dose of kisspeptin resulted in a greater proportion of patients achieving an oocyte yield ≥60%, but without also increasing the frequency of ovarian over-response and moderate OHSS (Single: 1/31, 3.2%, Double: 0/31, 0%).
    2 context sentences
    Summary · context
    Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016.
    Summary · context
    Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter.
  4. 04HumanRandomized controlled trialMechanism

    In women at high risk of OHSS, patients with a lower LH rise after the first kisspeptin‑54 dose had a more substantial rescue LH response after the second dose.

    In plain wordsIn women at high risk of ovarian overstimulation, those with a smaller first LH rise had a larger LH rise after the second dose.

    Peptide
    Kisspeptin-54 (metastin)
    Outcome
    Not applicableLH response to the second dose by LH response to the first dose
    Study

    n = 31

    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    9.6 nmol/kg first dose, second dose 10 h later · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Patients who had a lower LH-rise following the first dose of kisspeptin had a more substantial 'rescue' LH-response following the second dose of kisspeptin.
    2 context sentences
    Summary · context
    Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016.
    Summary · context
    Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2Results postedNCT01667406

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

Imperial College Londonn = 1751 Jun 2012 to 11 Oct 2016

Infertility

Trial pageClinicalTrials.govUpdated 8 Jun 2021

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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