Effect of Hyperinsulinemia and Insulin Resistance on Endocrine, Metabolic, and Reproductive Outcomes in Non-PCOS Women Undergoing Assisted Reproduction: A Retrospective Cohort Study

Abstract

Objective: To evaluate the effect of hyperinsulinemia (HI) and insulin resistance (IR) on endocrine, metabolic, and reproductive outcomes in women without polycystic ovary syndrome (PCOS) undergoing assisted reproduction.Materials and Methods: The study included 1,104 non-PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection-fresh embryo transfer. HI was evaluated by serum fasting insulin (FIN), and IR was evaluated by homeostatic model assessment of insulin resistance index (HOMA-IR). In addition, biometric, sex hormone, and metabolic parameters were measured. Independent t-test, linear, and logistic regression examined associations between HI, IR, and endocrine, metabolic, ovarian stimulation characteristics, and reproductive outcomes.Results: Women with HI and IR had lower levels of progesterone, luteinizing hormone, follicle-stimulating hormone, estradiol, high-density lipoproteins, and increased levels of triglycerides low-density lipoproteins. For ovarian stimulation characteristics, those with HI and IR had a longer duration of stimulation, a higher total gonadotropin dose, and a lower peak estradiol level. Linear regression confirmed these associations. For reproductive outcomes, HI and IR were not associated with clinical pregnancy, live birth, and miscarriage.Conclusions: HI and IR did not impair reproductive outcomes in non-PCOS women undergoing assisted reproduction.

Homeostatic Model Assessment for Insulin Resistance Is Associated With Late Miscarriage in Non-Dyslipidemic Women Undergoing Fresh IVF/ICSI Embryo Transfer

“…To our current knowledge, there is no report regarding the relationship between preconception IR and late miscarriage among non-dyslipidemic populations. Consistent with a previous study (31,32), our data shows an increased trend in serum levels of TG, LDL-C and a decreased trend in serum HDL-C level with the increased HOMA-IR group, even though the serum lipid levels were normal. After controlling for potential confounders, we confirmed that HOMA-IR is an independent risk factor for late miscarriage in either normolipidemic or non-PCOS women.…”

“…Other reports, however, dispute these results (17,30,31). Wang et al failed to find significant differences in pregnancy outcomes, including pregnancy rate, clinical pregnancy loss rate, and cumulative live birth rate, between IR and non-IR group (17).…”

“…Wang et al failed to find significant differences in pregnancy outcomes, including pregnancy rate, clinical pregnancy loss rate, and cumulative live birth rate, between IR and non-IR group (17). Among non-PCOS participants, no associations were found between hyperinsulinemia and IR and clinical pregnancy, live birth, and miscarriage (31). A large randomized controlled trial involving PCOS women undergoing ovulation induction indicated that the rates of conception, clinical pregnancies, and live births were all significantly reduced with the increase in FINS or HOMA-IR level, while miscarriage rates were not related to FINS or HOMA-IR (32).…”

Inflammatory and metabolic markers in relation to outcome of in vitro fertilization in a cohort of predominantly overweight and obese women

“…Thus, although not included as variables in the current study, both HOMA and FFA are adipose tissue-related markers with potential impact on pregnancy and live birth outcome of IVF in overweight and obese women. In a recent retrospective cohort study of women undergoing IVF, HOMA was not associated with clinical pregnancy, live birth, and miscarriage 50 . Others report that insulin resistant women with PCOS have a lower implantation rate than non-insulin resistant women with PCOS, controlled for confounding factors including age, BMI, free androgen index and lipid profiles 51 .…”

Advancements in lead therapeutic phytochemicals polycystic ovary syndrome: A review

“…With the development of clinical research on POCS, according to recommendations from the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome from 2018 ( Teede et al, 2018 ), PCOS has been further distinguished into four phenotypes: phenotype A manifested as the excess of androgens, ovulatory dysfunction, and polycystic ovary on ultrasound; phenotype B manifested as the excess of androgens and ovulatory dysfunction; phenotype C manifested as the excess of androgens and polycystic ovary on ultrasound; and phenotype D manifested as ovulatory dysfunction and polycystic ovary on ultrasound. Although the guidelines mentioned above permit the diagnosis of PCOS, the clinical manifestations of PCOS are complex and reference multiple symptoms, such as ovarian enlargement ( Azziz et al, 2016 ; Escobar-Morreale, 2018 ), hyperandrogenism ( Rosenfield and Ehrmann, 2016 ; Ruth et al, 2020 ), insulin resistance ( Diamanti-Kandarakis and Dunaif, 2012 ; Azziz et al, 2016 ), hyperinsulinemia ( Housman and Reynolds, 2014 ; Muscogiuri et al, 2015 ; Cai et al, 2022 ), menstrual irregularity ( Jayasena and Franks, 2014 ; Pena et al, 2020 ), anovulation ( Dewailly et al, 2016 ; Carson and Kallen, 2021 ) or oligo-anovulation ( Hickey et al, 2012 ; Tay et al, 2020 ), infertility ( Carson and Kallen, 2021 ), and others. At the same time, PCOS significantly increases the risk of cardiovascular disease ( Okoth et al, 2020 ; O'Kelly et al, 2022 ), type 2 diabetes ( Diamanti-Kandarakis and Dunaif, 2012 ; Azziz et al, 2016 ; Zhu et al, 2021 ), obesity ( Lim et al, 2012 ; Lim et al, 2013 ; Sermondade et al, 2019 ), and metabolic disorders ( Rosenfield and Ehrmann, 2016 ; Escobar-Morreale, 2018 ).…”