Kisspeptin-54 Triggers Egg Maturation in Women undergoing IVF Treatment

New trigger for ovulation could make IVF safer

This Imperial College London video describes the results of research carried out by Professor Dhillo’s team which has shown for the first time in women with infertility that the novel hormone kisspeptin can be used safely and effectively to stimulate ovulation and mature eggs in IVF treatment.

BACKGROUND

Patients with mutations that inactivate kisspeptin signaling are infertile. Kisspeptin-54, the major circulating isoform of kisspeptin in humans, potently stimulates reproductive hormone secretion in humans. Animal studies suggest that kisspeptin is involved in generation of the luteinizing hormone surge, which is required for ovulation; therefore, we hypothesized that kisspeptin-54 could be used to trigger egg maturation in women undergoing in vitro fertilization therapy.

METHODS

Following superovulation with recombinant follicle-stimulating hormone and administration of gonadotropin-releasing hormone antagonist to prevent premature ovulation, 53 women were administered a single subcutaneous injection of kisspeptin-54 (1.6 nmol/kg, n = 2; 3.2 nmol/kg, n = 3; 6.4 nmol/kg, n = 24; 12.8 nmol/kg, n = 24) to induce a luteinizing hormone surge and egg maturation. Eggs were retrieved transvaginally 36 hours after kisspeptin injection, assessed for maturation (primary outcome), and fertilized by intracytoplasmic sperm injection with subsequent transfer of one or two embryos.

RESULTS

Egg maturation was observed in response to each tested dose of kisspeptin-54, and the mean number of mature eggs per patient generally increased in a dose-dependent manner. Fertilization of eggs and transfer of embryos to the uterus occurred in 92% (49/53) of kisspeptin-54–treated patients. Biochemical and clinical pregnancy rates were 40% (21/53) and 23% (12/53), respectively.

CONCLUSION

This study demonstrates that a single injection of kisspeptin-54 can induce egg maturation in women with subfertility undergoing in vitro fertilization therapy. Subsequent fertilization of eggs matured following kisspeptin-54 administration and transfer of resulting embryos can lead to successful human pregnancy.

Sources:

  • New trigger for ovulation could make IVF safer, Imperial College London, news_18-7-2014-11-49-26, 18 July 2014.
  • Full Study – Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization, J Clin Invest. doi:10.1172/JCI75730, view/75730, July 18, 2014.

IVF Possibly Safer : New Method to Stimulate Ovulation and Effectively Mature Eggs

New trigger for ovulation could make IVF safer

Researchers have successfully used a new and potentially safer method to stimulate ovulation in women undergoing IVF treatment.

Twelve babies have been born after their mothers were given an injection of the natural hormone kisspeptin to make their eggs mature.

Doctors normally administer another hormone, hCG, for this purpose, but in some women, there is a risk that this can overstimulate the ovaries, with potentially life-threatening consequences.

Scientists at Imperial College London and clinicians at Imperial College Healthcare NHS Trust tested the new method in 53 healthy volunteers at Hammersmith Hospital in London. The study, funded by the Medical Research Council, the National Institute for Health Research and the Wellcome Trust, is published today in the Journal of Clinical Investigation.

One in six couples in the UK experiences infertility, and 48,147 women underwent IVF treatment in 2011.

Ovarian hyperstimulation syndrome (OHSS) affects around a third of IVF patients in a mild form, causing symptoms such as nausea and vomiting. Less than 10 per cent of patients experience moderate or severe OHSS, which can cause kidney failure.

Professor Waljit Dhillo, from the Department of Medicine at Imperial College London, who led the study, said: “OHSS is a major medical problem. It can be fatal in severe cases and it occurs in women undergoing IVF treatment who are otherwise very healthy. We really need more effective natural triggers for egg maturation during IVF treatment, and the results of this trial are very promising.”

Kisspeptin is a naturally occurring hormone that stimulates the release of other reproductive hormones inside the body. Unlike hCG, which remains in the blood for a long time after an injection, kisspeptin is broken down more quickly, meaning the risk of overstimulation is lower.

The women in the study had a single injection of kisspeptin to induce ovulation. Mature eggs developed in 51 out of 53 participants. Forty-nine women had one or two fertilised embryos transferred to the uterus, and 12 became pregnant, which is a good outcome compared to standard conventional IVF therapy.

The researchers will now carry out a second study in women with polycystic ovary syndrome, who have the highest risk of OHSS.

Our study has shown that kisspeptin can be used as a physiological trigger for egg maturation in IVF therapy,” said Professor Dhillo. “It’s been a joy to see 12 healthy babies born using this approach. We will now be doing more studies to test whether kisspeptin reduces the risk of OHSS in women who are most prone to developing it, with a view to improving the safety of IVF therapy.”

Alison and Richard Harper had a baby boy, Owen, in October 2013 after taking part in the trial in January.

We took part because we wanted to pay it forward in return for the people who made it possible for us to have a child through IVF,” Alison said.

“I went through several cycles of IVF previously but the one in the trial was the least uncomfortable – it was less painful and I felt less swollen. The staff we dealt with were incredible.”

Sources:

  • New trigger for ovulation could make IVF safer, Imperial College London, news_18-7-2014-11-49-26, 18 July 2014.
  • Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization, J Clin Invest. doi:10.1172/JCI75730, view/75730, July 18, 2014.