Infertility: Novel Egg Maturation Method Shows Promise

Mary Beth Nierengarten

July 22, 2014

A single injection of kisspeptin-54 can induce egg maturation in women undergoing in vitro fertilization therapy, according to a study published online July 18 in the Journal of Clinical Investigation.

Eggs matured using this novel method can be fertilized in vitro and transferred to the uterus to result in a successful pregnancy for couples who are infertile, the investigators report.

Kisspeptin signalling is necessary for fertility in humans, and patients with inactivating mutations of kisspeptin signalling are infertile, according to Channa N. Jayasena, PhD, from the Department of Investigative Medicine, Imperial College London, and Hammersmith Hospital, London, United Kingdom, and colleagues. A potent stimulant to reproductive hormone secretion in humans is kisspeptin-54, the major circulating isoform of kisspeptin in humans. Data from animal studies suggest that endogenous kisspeptin is required to activate the reproductive system in humans.

"The kisspeptin signalling pathway is…a novel mechanism, which can be therapeutically exploited to trigger egg maturation in patients," the authors write.

In this proof-of-concept study, the investigators tested the hypothesis that administration of kisspeptin can trigger ovulation in humans by looking at the effects of administration of kisspeptin-54 on an objective marker of ovulation (egg maturation) in women undergoing in vitro fertilization therapy.

The researchers gave 53 women a single subcutaneous injection of kisspeptin-54 to trigger egg maturation by inducing a surge in luteinizing hormone. The researchers first treated all of the women with follicle-stimulating hormone to induce superovulation and gonadotropin-releasing hormone antagonist to prevent premature ovulation.

They tested 4 doses of kisspeptin-54: 1.6 nmol/kg (n = 2), 3.2 nmol/kg (n = 3), 6.4 nmol/kg (n = 24), and 12.8 nmol/kg (n = 24). The researchers randomly assigned most of the participants to the higher doses because egg collection was more difficult at the lower doses (1.6 and 3.2 nmol/kg).

After injection of kisspeptin-54, the researchers retrieved the eggs transvaginally and assessed them for maturation (the primary outcome of the study). They then fertilized the eggs with an injection of intracytoplasmic sperm and transferred 1 or 2 embryos to the uterus.

The researchers observed egg maturation after each dose of kisspeptin-54, with similar rates of egg maturation seen after all doses in 75% to 85% of women.

However, the number of mature eggs appeared to increase with the increasing doses of kisspeptin-54, as did the proportion of eggs recovered compared with the expected number (oocyte yield).

In 49 (92%) of 53 women, egg fertilization and transfer of embryos to the uterus was successful with a 40% biochemical pregnancy rate and a 23% clinical pregnancy rate.

According to the investigators, further studies are needed to determine the clinical use of kisspeptin-54 during in vitro fertilization therapy compared with established drug therapies currently used to trigger egg maturation.

This work was funded by the Medical Research Council, National Institute of Health Research (NIHR), and Wellcome Trust. Dr. Jayasena and a coauthor are supported by NIHR Clinical Lectureships, another coauthor is supported by a Wellcome Clinical Research Training Fellowship, another coauthor is supported by a Wellcome Translational Medicine Research Fellowship, another coauthor is supported by an NIHR Academic Clinical Fellowship, and another coauthor is supported by an NIHR Career Development Fellowship. The authors have disclosed no other relevant financial relationships.

J Clin Invest. Published online July 18, 2014. Full text

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