Insulin Resistance and Free Androgen as Predictors for Ovarian Hyperstimulation Syndrome in Non-PCOS Women

Abstract

We evaluated the effect of insulin resistance and free androgen index (FAI) in non-PCOS (polycystic ovary syndrome) infertile women following controlled ovarian hyperstimulation. A prospective study was done on 144 infertile non-PCOS women with regular menstrual cycle. At first, insulin resistance (IR), free androgen index (FAI), PCOM (polycystic ovary morphology), AFC (antral follicle count), and AMH (anti-Müllerian hormone) were assessed. The patients underwent assisted reproductive technology (ART), and then preovulatory follicles and oocytes retrieved were recorded. The variables of the study were compared between two groups of patients with ovarian hyperstimulation syndrome (OHSS) (n=66) and non-OHSS patients (n=78). Of the 9 variables: BMI, HOMA-IR, FAI, AFC, AMH, PCOM, and preovulatory follicles were risk factors, while the age and retrieved oocytes were not. The 7 variables that showed significance in the univariate analyses were determined as independent variables included in the multivariable logistic regression analysis, as a result, a total of 5 risk factors, BMI, HOMA-IR, FAI, PCOM, and preovulatory follicles entered the equation. The maximum contribution was HOMA-IR followed by PCOM, FAI, preovulatory follicles and BMI. Patients with OHSS had higher chance to have ovaries with polycystic morphology (74%), about three times more than patients who did not develop OHSS (29%) (p<0.001). The best cut-points for IR, FAI, AFC, AMH, and preovulatry follicles were 2.36, 3.9, 8, 3.3 ng/ml, and 10, respectively. Patients with a higher value of BMI, FAI, HOMA-IR, and preovulatory follicles and the presence of PCOM are more likely to develop OHSS, which are not confined to PCOS patients.

Key words

infertility - polycystic ovary syndrome - ovarian hormone - assisted reproductive techniques

• References

• 1 Jahromi NB, Parsanezhad ME, Shomali Z. et al. Ovarian hyperstimulation syndrome: A narrative review of its pathophysiology, risk factors, prevention, classification, and management. Iran J Med Sci 2018; 43: 248-260
• 2 Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): A review. Hum Reprod Update 2002; 8: 559-577
• 3 Ashrafi M, Bahmanabadi A, Akhond MR. et al. Predictive factors of early moderate/severe ovarian hyperstimulation syndrome in non-polycystic ovarian syndrome patients: A statistical model. Arch Gynecol Obstet 2015; 292: 1145-1152
• 4 Fatemi HM, Garcia-Velasco J. Avoiding ovarian hyperstimulation syndrome with the use of gonadotropin-releasing hormone agonist trigger. Fertil steril 2015; 103: 870-873
• 5 Asch RH, Li H-P, Balmaceda JP. et al. Severe ovarian hyperstimulation syndrome in assisted reproductive technology: Definition of high risk groups. Hum Reprod 1991; 6: 1395-1399
• 6 Rizk B, Smitz J. Review: Ovarian hyperstimulation syndrome after superovulation using GnRH agonists for IVF and related procedures. Human Reprod 1992; 7: 320-327
• 7 Delvigne A, Demoulin A, Smitz J. et al. Endocrinology: The ovarian hyperstimulation syndrome in in-vitro fertilization: A Belgian multicentric study. I. Clinical and biological features. Hum Reprod 1993; 8: 1353-1360
• 8 Dickerson E, Cho L, Maguiness S. et al. Insulin resistance and free androgen index correlate with the outcome of controlled ovarian hyperstimulation in non-PCOS women undergoing IVF. Human Reprod 2010; 25: 504-509
• 9 Vloeberghs V, Peeraer K, Pexsters A. et al. Ovarian hyperstimulation syndrome and complications of ART. Best Pract Res Clin Obstet Gynaecol 2009; 23: 691-709
• 10 Rotterdam E, ASRM-Sponsored P. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25
• 11 Stanek MB, Borman SM, Molskness T. et al. Insulin and insulin-like growth factor stimulation of vascular endothelial growth factor production by luteinized granulosa cells: Comparison between polycystic ovarian syndrome (PCOS) and non-PCOS women. J Clinic Endocrin Metab 2007; 92: 2726-2733
• 12 Nieman LK, Biller BMK, Findling JW. et al. The Diagnosis of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
• 13 Bonora E, Targher G, Alberiche M. et al. Homeostasis model assessment closely mirrors the glucose clampn technique in the assessment of insulin sensitivity: Studies in subjects with various degrees of tolerance and insulin sensitivity. Diabetes Care 2000; 23: 57-63
• 14 Tso LO, Costello MF, Albuquerque L. et al. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2009; 15: CD006105
• 15 Tummon I, Gavrilova-Jordan L, Allemand MC. et al. Polycystic ovaries and ovarian hyperstimulation syndrome: A systematic review. Acta Obstet Gynecol Scand 2005; 84: 611-616
• 16 Rizk B, Aboulghar M, Smitz J. et al. The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome. Hum Reprod Update 1997; 3: 255-266
• 17 Kamat BR, Brown LF, Manseau EJ. et al. Expression of vascular permeability factor/vascular endothelial growth factor by human granulosa and theca lutein cells. Role in corpus luteum development. Am J Pathol 1995; 146: 157
• 18 Visnova H, Ventruba P, Crha I. et al. Importance of sensitization of insulin receptors in the prevention of ovarian hyperstimulation syndrome. Cesk Gynekol 2003; 68: 155-162
• 19 Salamalekis E, Makrakis E, Vitoratos N. et al. Insulin levels, insulin resistance, and leptin levels are not associated with the development of ovarian hyperstimulation syndrome. Fertil Steril 2004; 82: 244-246
• 20 Muniyappa R, Madam R. Assessing Insulin Sensitivity and Resistance in Humans. 2018. South Dartmouth (MA): MDText.com, Inc.; Available from https://www.ncbi.nlm.nih.gov/books/NBK278954/
• 21 Keskin M, Kurtoglu S, Kendirci M. et al. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005; 115: e500-e503
• 22 Fiedler K, Ezcurra D. Predicting and preventing ovarian hyperstimulation syndrome (OHSS): The need for individualized not standardized treatment. Reprod Biol Endocrinol 2012; 10: 32-41
• 23 Lee TH, Liu CH, Huang CC. et al. Serum anti-Müllerian hormone and estradiol levels as predictors of ovarian hyperstimulation syndrome in assisted reproduction technology cycles. Hum Reprod 2008; 23: 160-167
• 24 Van der Westhuizeen S, Van der Spuy Z. Ovarian morphology as a predictor of hormonal values in polycystic ovary syndrome. Ultrasound Obstet Gynecol 1996; 7: 335-341
• 25 Ocal P, Sahmay S, Cetin M. et al. Serum anti-Müllerian hormone and antral follicle count as predictive markers of OHSS in ART cycles. J Assist Reprod Genet 2011; 28: 1197-1203
• 26 Nardo LG, Gelbaya TA, Wilkinson H. et al. Circulating basal anti-Mullerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization. Fertil Steril 2009; 92: 1586-1592
• 27 Vembu R, Reddy NS. Serum AMH level to predict the hyper response in women with PCOS and Non-PCOS undergoing controlled ovarian stimulation in ART. J Hum Reprod Sci 2017; 10: 91-94
• 28 Papanikolaou EG, Tournaye H, Verpoest W. et al. Early and late ovarian hyperstimulation syndrome: Early pregnancy outcome and profile. Human Reprod 2005; 20: 636-641
• 29 Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clinic Endocrinol Metabol 1999; 84: 3666-3672