Relationship of insulin resistance with recurrent pregnancy loss

Asifa Ali Wani, Irfan Gul, Farhat Jabeen, Shiveta Kaul, Farhat Ali Lone, Gulshan Akhter


Background: The recurrent pregnancy loss (RPL) is defined as two and more failed pregnancies as documented by ultrasound and histopathological examination and suggested some assessment after each loss with a thorough evaluation after three or more losses. RPL is one of the most frustrating and difficult areas in reproductive medicine because the aetiology is often unknown and there are few evidence based diagnostic and treatment strategies.

Methods: 150 Non pregnant females were taken as both cases and controls in the study. All the pregnancy losses were documented by ultrasound or histological examination after uterine curettage. The control group consisted of women with no RPL with at least one live birth. These two groups were matched on the basis of age and BMI. All the women underwent following examinations, viz. Hysterosalpingography, karyotype of both partners, serum TSH, FT4, prolactin and antibodies for APLA. In addition blood sample were taken for fasting serum glucose and serum insulin level later insulin resistance was calculate using three parameters Fasting insulin > 20IU/ml. Diagnostic of Insulin Resistance. (2) Fasting glucose / Fasting insulin. A ratio of < 4.5 being diagnostic of insulin resistance. (3) HOMA IR.

        FG (mg/dl) x FPI (IU/ml) FG (mmol/l) x FPI (IU/ml)

------------------------------------ OR -----------------------------------

                                             405 22.5

Where 1 mmol/l = 18mg/dl, A value of > 4.5 being diagnostic of insulin resistance.

Results: 150 patients were enrolled in this study among which 75 were selected as cases and 75 as controls after fulfilling inclusion and exclusion criteria with mean age cases group was28.4+2.37 years and 29.1+2.70 years in control group mean miscarriage rate in study group was 3.17+83 and control group with 0.35+0.48 with statistically significant difference. Mean fasting glucose (96.5+ 7.86) mg/dl, Fasting Insulin (14.1±5.91) IU/ml. Mean Glucose Insulin ratio (8.1±3.39), HOMA-IR (3.4 ±1.51) in the study group and in control group mean fasting glucose was (87.1+11.49) mg/dl, Fasting Insulin (6.9 ± 4.99) IU/ml. Mean Glucose Insulin ratio (17.8 ±11.44), HOMA-IR (1.5 ±1.27) respectively with statistically significant difference.

Conclusions: In women with recurrent pregnancy loss fasting insulin and insulin resistance are higher than those in women without spontaneous abortion. The most sensitive parameter for calculating insulin resistance was found to be fasting insulin followed by HOMA – IR and followed by fasting glucose/fasting insulin ratio. It is therefore important to recommend a fasting insulin and fasting glucose level while evaluating a case of recurrent pregnancy loss to assess for insulin resistance.


Fasting Insulin, HOMA-IR, Mean fasting glucose, Mean glucose insulin ratio, Re-current pregnancy loss

Full Text:



Fox Lee Laura, Schust DJ. RPL in Berek, Jsed and Novak Gynaecology 14th Ed. Phillipedia, Lippincott Williams and Wilkins. 2007;1277-322.

Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss. Fertil Steril 2008;89(6):1603.

Rayah S. Baban A. Al-Moayed. Serum leptin and insulin hormone level in recurrent pregnancy loss. Oman Med J. 2010;25(3):203-07.

Grattan D, Ladyman S. Hormonal induction of leptin resistance during pregnancy. Physiology and Behaviour. 2007;91(4):366-74.

Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss. Fertility and Sterility 2008;90:60.

Kotaniae Maryam. The comparison of insulin resistance frequency in patients with recurrent early pregnancy loss to normal individuals. BMC Research Notes 2012;133.

Celik Nazan. Evaluation of the relationship between insulin resistance and recurrent pregnancy loss. Ginekologia Polska. 2011;82:272-75.

Sudha Salhan. Recurrent pregnancy loss. In: Textbook of Gynaecology. 1st Edition. 2011;184-88.

Lin PC. Reproductive outcome in women with uterine anomalies. Women Health. 2004;13:36-9.

Green IA, Thrombophilia: complication for pregnancy outcome. Thromb Res 2003; 109: 73-81.

Lane DA and Grat P. Role of hemostatin gene polymorphism in women. Thromphia. 2000;95:1517-32.

Management of RPL. Washington DC. The American College of Obstetrics and Gynaecology the ACOG Practice Bulletin No. 2011;24.

Stephenson MD. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril. 1996;66:24-9.

Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2(2):76-83.

Kassie al Genetic considerations in RPL. Cold Spring Harb Perspect Med 2015; 5: a023119.

Fauser BCGM. Contemporary genetic technologics and female reproduction. Humans Reproduction Update. 2011;17(6):829-47.

Legro RS; Strauss JF. Molecular progress in infertility: polycystic ovary syndrome. Fertility and Sterility Sept. 2002;78(3):569-76.

Diamanti-Kandarakis. The role of genes and environment in the etiology of PCOS. Endocrine. 2006;30(1):19-26.

Goldenberg. Medical therapy in women with polycystic ovary syndrome before and during pregnancy and lactation. Minerva Ginecol. 2008;60(1):63-75.

Boomsma CM. Pregnancy complications in women with polycystic ovary syndrome. Semin. Reprod. Med. 2008;26(1):72-84.

Azziz R. The Prevalence and Features of the Polycystic Ovary Syndrome in an Unselected Population. Journal of Clinical Endocrinology and Metabolism. 2004;89(6):2745-9.

H Teede, A. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Medicine J. 2010;8:41.

Wang JX. Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res. 2002;10:551-4.

Gordon MC, Zimmerman PD. Insulin and glucose modulate glucose messenger ribonucleic acid expression and glucose uptake in trophoblasts isolated from first-trimester chorionic villi. Am J Obstet Gynecol. 1995;173:189-97.

Corrina Alina, IS Pasou. High fasting insulin levels and insulin resistance may be linked to idiopathic RPL. Journal of Endocrinology. 2013;3.

Glueck CJ, Wang. Plasminogen activator inhibitor activity: an independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovarian syndrome. Metabolism. 1999;48: 1589-95.

Glueck CJ, Phillips H. Continuing metformin throughout pregnancy in women with polycystic ovarian syndrome appears to safely reduce first-trimester abortion: a pilot study. Fertil Teril. 2001;75:46-52.

Gris JC, Ripart Neeu S. Respective evaluation of the prevalence of haemostasis abnormalities in unexplained primary early recurrent miscarriages. The Nimes Obstetricians and Haematologists (NOHA) Study. Thromb Haemost. 1997;77:1096-103.

Gris JC, Neveu S. Plasma fibrinolytic activators and their inhibitors in women suffering from early recurrent abortion of unknown etiology. J Lab Clin Med. 1993;122:606-15.

DJ Jakubowicz, PA Essah. Reduced serum glycodelin and insulin like growth factor binding protein-1 in women with polycystic ovary syndrome during first trimester of pregnancy. Journal of Clinical Endocrinology and Metabolism 2004;89(2):833-39.

Craig LB, Ke RW. Increased prevalence of insulin resistance in women with a history of recurrent pregnancy loss. Fertil Steril. 2002;78(3):487-90.

K.A. Wahba. Assessment of the Role of Insulin Resistance in Cases of Recurrent Unexplained First Trimesteric Miscarriage. Life Science Journal 2015;12(7):174-81.

Li ZL, Xiang HF. Association between recurrent miscarriages and insulin resistance: a meta-analysis. Zhonghua Fu Chan Ke Za Zhi. 2012;47(12):915-9.

Michael Diejomaoh. Insulin resistance in women with recurrent spontaneous miscarriage of unknown etiology. Med Princ Pract. 2007;16:114-18.

Wang Y, Zhao H. Relationship between recurrent miscarriage and insulin resistance. Gynecol Obstet Invest. 2011;72(4):245-51.