Insulin-like growth factor–1 gene splice variants as markers of muscle damage in levator ani muscle after the first vaginal delivery Eduardo Cortes, MD, a,b, * Lan F. Wong te Fong, MPhil, b Mahjabeen Hameed, PhD, c,d Stephen Harridge, PhD, d Allan Maclean, FRCOG, MD, b Shi Yu Yang, PhD, c Wendy M. Reid, FRCOG, a,b Geoffrey Goldspink, PhD, Scd c Pelvic Floor Unit, Royal Free Hospital, a Departments of Obstetrics and Gynaecology, b Surgery, c and Physiology, d Royal Free and University College Medical School, London, UK Received for publication September 16, 2004; revised December 16, 2004; accepted December 28, 2004 KEY WORDS Muscle damage Levator ani muscle Objective: Studies in animals and human muscle have demonstrated differential splicing of the insulin-like growth factor–1 gene in response to mechanical strain and damage. We conducted a study on the expression of insulin-like growth factor–1 splice variants in the levator ani muscle after the first vaginal delivery. Study design: Ten women were recruited after the first vaginal delivery. Biopsy specimens were taken vaginally of the pubovisceral component of the levator ani muscle. Five nonpregnant women were recruited as control subjects. Samples were processed with real-time quantitative polymerase chain reaction, with specific primers for the insulin-like growth factor–1 splice variants. Results: Insulin-like growth factor splice variants mechano growth factor and insulin-like growth factor–1Ea were significantly up-regulated (100- and 1000-fold) in the delivery population, compared with control subjects (P = .012 and .04, respectively). Statistical analysis indicated a correlation between the expression of the insulin-like growth factor–1 splice variants and the length of the second stage. Conclusion: These results show that damaged levator ani muscle results from stretch and overload after the first vaginal delivery. Ó 2005 Elsevier Inc. All rights reserved. The relationship between vaginal delivery and its effect on the pelvic floor has been acknowledged re- cently. Studies have covered most aspects that are associated with pelvic floor dysfunction, including histomorphologic changes in the levator ani (LA) muscle and attached fascia, 1,2 collagen variations, 3-5 Supported by grants from the Wellcome Trust and University College London BioMedica (G.G.). * Reprint requests: E. Cortes, MD, Academic Department of Obstetrics and Gynaecology, Royal Free Hospital, 5th Floor, Pond St, London NW3 2QG, UK. E-mail: e.cortes@medsch.ucl.ac.uk 0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.12.088 American Journal of Obstetrics and Gynecology (2005) 193, 64–70 www.ajog.org