Abstract Study question Is insulin resistance ( IR) a confounding variable in infertile women, other than those those having polycystic ovarian syndrome (PCOS) Summary answer IR was identified in 20.5% of infertile women. The presence of IR did not affect response to ovulation induction but reduced chances of conception What is known already Obesity is strongly correlated with insulin resistance. Obesity also has an adverse effect on fertility. In 2008 Steeg et al reported 5% reduction in chances of spontaneous conception with each unit increase in body mass index (BMI). Tetsurou Sakumoto et al (2010) reported hyperinsulinemia to affect granulose cells in small follicles inducing early response to luteinising hormone and anovulation. Adverse effect on endometrial function and implantation was also postulated. Insulin resistance has been studied in cases of PCOS but has not been studied in infertile women not fulfilling criteria for diagnosis of PCOS . So the present study was planned Study design, size, duration A prospective cohort study was conducted in infertility unit, King George Medical University, Lucknow, India over a period of one year from August 2018 to July 2019. Total 102 women with unexplained infertility were enrolled. Ethical clearance was obtained from institutional ethical committee Participants/materials, setting, methods Women with PCOS; diminished ovarian reserve documented by antral follicle count <7 and anti Mullerian hormone < 1.1ng/ml; bilateral tubal block; abnormal semen analysis; untreated hypothyroidism, hyperprolactinaemia; known diabetes were excluded. All women underwent ovulation induction with clomiphene citrate followed by single intrauterine insemination. Homeostasis model assessment insulin resistance index (HOMA IR) was calculated HOMA-IR = Fasting S. Glucose (mg/dl) x Fasting insulin (µlU) / 405. Value ≥ 2 denoted insulin resistance Main results and the role of chance : IR was identified in 21/102 (20.5%) cases. Fasting insulin levels were in the range of 5 – 9.9 mIU/ml in 53/102 women; <5mIU/ml in 29 and >10mIU/ml in 20. Fasting insulin > 9.45mIU/ml was found to have 90.5% sensitivity and 96.3% specificity in predicting insulin resistance. None of the cases had abnormal fasting and post prandial plasma glucose levels. IR was seen to be significantly correlated with BMI > 25kg/m2 (p = 0.0018) and waist hip ratio of > 0.85 (p = 0.0024).All women had follicular development and follicle rupture irrespective of presence of IR. Women with IR were more likely to have monofollicular development (17/21 IR cases). Correlation of endometrial thickness with IR was not seen. Mean endometrial thickness was 8.9mm. There were 6 pregnancies among the 102 women studied. None of the women with IR conceived. So IR was found to be affecting one fifth of women with unexplained infertility. Failure of any woman with IR to conceive was significant but the finding needs to be further studied. Limitations, reasons for caution : It was a small study with only 102 cases and the women were followed for only one cycle of ovulation induction and intrauterine insemination so results need to be validated in a larger study with a longer follow up. Wider implications of the findings: If further larger studies corroborate the role of IR in women with unexplained infertility it could elucidate the possibility of using insulin sensitisers in management of such cases. IR may emerge as an important gamechanger in management of unexplained infertility. Trial registration number Not applicable
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