Overcoming ovarian hyperstimulation syndrome via kisspeptin
Pioneering a safer way of preparing eggs for use in IVF
Ovarian hyperstimulation syndrome (OHSS)
Mild symptoms are common in women having IVF treatment. As many as one in three (33%) women develop mild OHSS. 1,2 About one in 10 (10%) women develop moderate or severe OHSS. However women at risk of OHSS such as women with polycystic ovaries (PCOS) are five times more likely to develop OHSS. 2,3 In these women, severe OHSS can occur in up to a quarter of women.3
Key Imperial researchers
- Professor Waljit Dhillo
- Mr Geoffrey Trew
- Dr Ali Abbara
- Dr Sophie Clarke
- Dr Rumana Islam
Imperial College researchers are pioneering a safer way of preparing eggs for use in IVF. To date, more than forty babies have been born using the naturally occurring hormone kisspeptin to gently stimulate women's ovaries to produce eggs.
A hormone, hCG, is normally used to produce eggs during standard IVF treatment. However, the ovaries can go into overdrive and produce too many eggs leading to a dangerous side effect called ‘Ovarian Hyperstimulation Syndrome’ (OHSS). OHSS affects around a third of IVF patients in a mild form, causing symptoms such as nausea and vomiting. Approximately 10% of patients experience moderate or severe OHSS, which can cause more serious complications such as kidney failure.
In 2003, researchers discovered kisspeptin. Kisspeptin is a naturally occurring hormone that stimulates the release of other reproductive hormones inside the body. It is physiologically involved in the menstrual cycle and people without the hormone will not go through puberty. The team at Imperial College London believe kisspepin can stimulate the ovaries in a gentler, more natural way that would prevent OHSS.
The first human trial using kisspeptin in IVF treatment took place on 53 volunteer couples at Hammersmith Hospital IVF unit in London. Eggs were successfully collected from 51 women (96%) and 12 healthy babies were born. A further trial was carried out in 60 women at high risk of OHSS, such as those with polycystic ovaries (PCOS). Despite being at high risk of OHSS, none of the women in the trial developed moderate or severe OHSS. Interestingly, pregnancy rates in the trial were at least as good as standard IVF with 30 being babies being born.
Professor Dhillo’s research suggests that kisspeptin will prevent ovarian hyperstimulation syndrome (OHSS). His team will now carry outlarger trials to fully assess how kisspeptin compares with current treatments.
This work was supported by grants from the Medical Research Council (MRC), Wellcome Trust, and the National Institute for Health Research (NIHR).
This study was registered in ClinicalTrials.gov as trial number NCT01667406.
1) Kawwass JF, Kissin DM, Kulkarni AD, et al. Safety of assisted reproductive technology in the United States, 2000–2011. JAMA. 2015;313(1):88–90.
2) Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): A review. Hum Reprod Update. 2002;8(6):559–577.
3) Wada I, Matson PL, Troup SA, Lieberman BA. Assisted conception using buserelin and human menopausal gonadotrophins in women with polycystic ovary syndrome. Br J Obstet Gynaecol. 1993;100(4):365–369.
4) 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.
5) 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.