Correlation of in vitro fertilization (IVF) infertility treatment outcomes and body weight index in women of reproductive age

Backgraund: obesity/overweight in women are often the causes of menstrual dysfunction and infertility.Aims: To identify the association between overweight/obesity and IVF outcomes.Materials and methods: retrospective study — data of 1874 patients undergoing IVF in the Endocrinology Research Centre (2012–2019) was analyzed. Exclusion criteria: BMI <18.5 kg/m2, polycystic ovary syndrome, donation of oocytes, ectopic pregnancy, fertilization with partner’s epididymal/testicular sperm. The study included 1583 women aged 21–45 years (median 33.0 y.o. [30.0; 37.0], median BMI 23 kg/m2 [20.7; 26.2]). Statistical data processing was performed using the STATISTICA application package (StatSoft). The threshold level of statistical significance is <0.05.Results: Patients were divided into 5 groups (gr.): normal body weight (NBW) - 1061 people (ppl.) (gr. 1), overweight — 368 (gr. 2), class I obesity — 117 (gr. 3), class II obesity — 36 (gr. 4), class III obesity — 1 (gr. 5). In each group, the estimated pregnancy rate (PR) and its outcomes, the frequency of lightweight newborns (body weight at birth <2500g), newborns with NBW (2500-3999g), births with a large fetus (≥4000g) were measured. The PR didn’t differ: 34.6%, 34.5%, 30,7%, 41,7%, respectively, the woman in gr.5 got pregnant. Among 407 (74.4%) singleton pregnancies urgent delivery was registered in 71.91%, 67,57%, 70,83%, 60,0%, gr. 5 — no information. Premature birth: 7,66%, 5,41%, 8,33%, 0%. Spontaneous abortion in the 1st trimester: 18,30%, 25,68%, 20,83%, 40,0%. Spontaneous abortion in the 2nd trimester: 2,13%, 1,35% in gr. 2, 3, 4. Lightweight newborns: 8,81%, 11,36%, 6,25%, 0%. Newborns with NBW: 84,91%, 84,09%, 75,0%, 60,0%. Large-childbirth — 6,29%, 4,55%, 18,75%, 40,0%.Conclusions: Correlation analysis of the dependence of PR and its outcomes on the BMI was not revealed (p=0.975 and p=0.469, respectively). Large fetus births were more often detected in obese patients (p=0.0016). A large prospective group is needed to expand the estimated body parameters to the IVF outcomes.

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131 APOPTOSIS AND DEVELOPMENT OF IN VITRO-PRODUCED BOVINE EMBRYOS EXPOSED TO SUPRAPHYSIOLOGICAL CONCENTRATIONS OF INSULIN-LIKE GROWTH FACTOR-1 (IGF-1)

Reproduction Fertility and Development ◽

10.1071/rdv21n1ab131 ◽

2009 ◽

Vol 21 (1) ◽

pp. 165

Author(s):

M. A. Velazquez ◽

H. Niemann

Keyword(s):

Laser Scanning ◽

Apoptotic Cell ◽

Polycystic Ovary ◽

Statistical Significance ◽

Laser Scanning Microscopy ◽

Confocal Laser ◽

Control Group ◽

Fisher Exact Test ◽

Bovine Embryos

It has been hypothesized that high non-physiological IGF-1 levels are partially responsible for the recurrent pregnancy loss observed in women with the polycystic ovary syndrome (Eng GS et al. 2007 Diabetes 56, 2228–2234). The aim of this study was to determine the effect of supraphysiological concentrations of IGF-1 on blastocyst production and the occurrence of apoptosis in bovine embryos, which are a good model for human embryo development (Baumann CG et al. 2007 Mol. Reprod. Dev. 74, 1345–1353). COC obtained by slicing from abattoir ovaries were matured (TCM-199, Sigma) for 24 h and fertilized (Fert-TALP) for 18 h (Day 0) in vitro. Two different IGF-1 (Recombinant human IGF-1, R&D Systems GmbH, Wiesbaden, Germany) concentrations (supraphysiological = 1000 ng mL–1 and physiological = 100 ng mL–1) were added to the culture media (Synthetic oviduct fluid/BSA) and compared with a control group (no IGF-1 supplementation). On Day 8, blastocyst rates (22 replicates) were recorded and DNA degradation was detected in blastocyst nuclei using a cell death detection kit (Roche Diagnostics GmbH, Mannheim, Germany) based on the terminal deoxinucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) principle. Embryos (n = 27 [control], n = 29 [both IGF-1 groups]) from 4 replicates were examined by confocal laser scanning microscopy. Data were analyzed by ANOVA and the Fisher exact test using the SigmaStat 2.0 software package (Jandel Scientific, San Rafael, CA). Cleavage was numerically improved by both, 1000 (59.1 ± 1.8) and 100 (58.2 ± 2.8) ng IGF-1 over controls (53.5 ± 2.2), but the differences did not reach statistical significance (P = 0.22). The proportion of hatched blastocysts was enhanced by 100 (5.8 ± 1.0, P = 0.03) and 1000 (5.1 ± 0.7, P = 0.03) ng IGF-1 compared to controls (2.8 ± 0.6). Total blastocyst rate was increased by 100 ng IGF-1 (34.4 ± 1.9, P = 0.02) over controls (28.3 ± 1.7), but not by 1000 ng IGF-1 (29.1 ± 1.6 P = 0.75). The 100 ng IGF-1 group (38.5 ± 3.7) had fewer degenerated embryos (P = 0.01) compared to 1000 ng IGF-1 (49.7 ± 3.3). The proportion of embryos displaying at least one apoptotic cell was greater in the 1000 ng IGF-1 group over controls (96% v. 77% P = 0.04). The number of blastomeres with TUNEL-positive nuclei per embryo was higher in the supraphysiological group (5.5 ± 0.6, P < 0.001) compared with the control (2.3 ± 0.4) and the physiological group (2.5 ± 0.3). There were no significant differences between the control and the 100 ng IGF-1 group in this regard (P = 0.49). In conclusion, supraphysiological concentrations of IGF-1 do not increase blastocyst production but increase levels of apoptosis in bovine embryos produced in vitro. M. A. V. is in the PhD program of the University of Veterinary medicine, Hannover, Germany, and is supported by the German Academic Exchange Service (DAAD)

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Predicting the outcome of different protocols of in vitro fertilization with anti-Muüllerian hormone levels in patients with polycystic ovary syndrome

Journal of International Medical Research ◽

10.1177/0300060517704140 ◽

2017 ◽

Vol 45 (3) ◽

pp. 1138-1147 ◽

Cited By ~ 6

Author(s):

Ya Chen ◽

Bilv Ye ◽

Xiaojing Yang ◽

Jiujia Zheng ◽

Jinju Lin ◽

...

Keyword(s):

In Vitro Fertilization ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Antral Follicle ◽

Antral Follicle Count ◽

Ovary Syndrome ◽

Vitro Fertilization ◽

Ivf Outcomes ◽

Basal Serum

Objective This study evaluated associations of basal serum and follicular fluid (FF) anti-Muüllerian hormone (AMH) levels with in vitro fertilization (IVF) outcomes in polycystic ovary syndrome (PCOS) patients. Methods This prospective study included 179 consecutive women undergoing IVF, including 59 with PCOS and non-PCOS controls. Thirty PCOS cases had long gona-dotrophin-releasing hormone agonist (GnRH-a) and 29 had antagonist (GnRH-ant) protocols. Controls underwent conventional GnRH-a. Associations of basal serum and FF AMH levels with IVF outcomes were assessed. Results Median serum and FF AMH levels, antral follicle count (AFC), oestradiol human chorionic gonadotropin injection day (peak E2), and retrieved oocyte numbers were higher in PCOS patients than in controls (all P < 0.01). Oocyte maturation and high-quality embryo rates were lower in PCOS patients than in controls (P < 0.01), but both groups had similar fertilization, implantation, clinical pregnancy, and newborn rates. Peak E2 was higher in GnRH-ant than in GnRH-a protocols (16.5 nmol/L vs. 12.1 nmol/L, P < 0.05). AMH levels were correlated with AFC in PCOS patients ( P < 0.01). Peak E2 and FF AMH levels were independent predictors of oocyte number. Peak E2 predicted the fertilization rate. Conclusion Serum basal AMH levels are predictive of oocyte quantity, but not oocyte quality or IVF outcomes. Serum AMH, FF AMH, and outcomes are similar among protocols.

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Mesenchymal Stem Cell Therapy Ameliorates Metabolic Dysfunction and Restores Fertility in a PCOS Mouse Model Through Interleukin-10

10.21203/rs.3.rs-444566/v1 ◽

2021 ◽

Author(s):

Rishi Man Chugh ◽

Hang-soo Park ◽

Abdeljabar El Andaloussi ◽

Amro Elsharoud ◽

Sahar Esfandyari ◽

...

Keyword(s):

Gene Expression ◽

Polycystic Ovary ◽

Therapeutic Option ◽

Interleukin 10 ◽

Reproductive Age ◽

Metabolic Dysfunction ◽

Mesenchymal Stem Cell Therapy ◽

Anti Inflammatory

Abstract Background: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models.Methods: For in vitro experiment, we treated conditioned media from BM-hMSC to androgen producing H293R cells, and analyzed androgen producing gene expression. For in vivo experiment, BM-hMSC were implanted into Letrozole (LTZ) induced mouse PCOS model. BM-hMSC effect in androgen producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery.Results: BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improve in metabolic and reproductive markers in our PCOS model and able to restore fertility. Conclusion: Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.

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Assessment of Psycho-emotional Distress Due to Age, Body Mass Index, and Marital Status in Polycystic Ovary Syndrome in North Indian Population

International Journal of Women s Health and Reproduction Sciences ◽

10.15296/ijwhr.2020.59 ◽

2020 ◽

Vol 8 (4) ◽

pp. 368-375

Author(s):

Fauzia Tabassum ◽

Hemali Heidi Sinha ◽

Kavita Dhar ◽

Chandra Jyoti ◽

Md Sayeed Akhtar ◽

...

Keyword(s):

Body Mass Index ◽

Body Weight ◽

Polycystic Ovary Syndrome ◽

Marital Status ◽

Body Mass ◽

Polycystic Ovary ◽

Reproductive Age ◽

Ovary Syndrome ◽

Significant Difference ◽

The Impact

Objectives: Polycystic ovary syndrome (PCOS) is a multifaceted endocrine disorder in reproductive age having a greater impact on health-related quality of life (HRQOL). The aim of this study was to find out PCOS demographics and its related HRQOL effects for improving psychological understanding in disease management. Materials and Methods: A prospective questionnaire-based study was conducted for a period of twelve months at All India Institute of Medical Sciences, Patna, India. The data of 100 PCOS cases were collected about socio-demographic status, clinical history, and dietary intake. Then, a validated PCOS questionnaire (PCOSQ) was used to observe the impact of PCOS symptoms on patients’ HRQOL. Results: The overall 57% and 48% of PCOS cases belonged to the age range of 20-30 years and had a body mass index (BMI) of >25-30, respectively. Based on the results, a significant difference was observed in the mean score of PCOSQ vs. marital status in PCOS cases with respect to emotion (P=0.039), body weight (P=0.002), and infertility (P=0.001). Furthermore, the result showed a significant difference in the domain of emotion (P=0.008), body hair (P=0.035), body weight (P<0.001), and infertility (P=0.018) among BMI group, and a high score was observed in the BMI group <18 in comparison to the other groups of BMI. Conclusions: In general, our findings indicated that infertility, emotions, and BMI had extremely higher impacts on the HRQOL of women suffering from PCOS although their educational status failed to affect HRQOL.

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Dehydroepiandrosterone Inhibits Glucose Flux Through the Pentose Phosphate Pathway in Human and Mouse Endometrial Stromal Cells, Preventing Decidualization and Implantation

Molecular Endocrinology ◽

10.1210/me.2011-0026 ◽

2011 ◽

Vol 25 (8) ◽

pp. 1444-1455 ◽

Cited By ~ 44

Author(s):

Antonina I. Frolova ◽

Kathleen O'Neill ◽

Kelle H. Moley

Keyword(s):

Stromal Cells ◽

Pentose Phosphate Pathway ◽

Glucose Transporter ◽

Polycystic Ovary ◽

Pentose Phosphate ◽

Reproductive Age ◽

Endometrial Stromal Cells ◽

Glucose Transporter 1 ◽

Decidual Cells

Endometrial stromal cells (ESC) must undergo a hormone-driven differentiation to form decidual cells as a requirement of proper embryo implantation. Recent studies from our laboratory have demonstrated that decidualizing cells require glucose transporter 1 expression and an increase in glucose use to complete this step. The present study focuses on the glucose-dependent molecular and metabolic pathways, which are required by ESC for decidualization. Inhibition of glycolysis had no effect on decidualization. However, blockade of the pentose phosphate pathway (PPP) with pharmacologic inhibitors 6-aminonicotinamide or dehydroepiandrosterone (DHEA), and short hairpin RNA-mediated knockdown of glucose-6-phosphate dehydrogenase, the rate-limiting step in the PPP, both led to strong decreases in decidual marker expression in vitro and decreased decidualization in vivo. Additionally, the studies demonstrate that inhibition is due, at least in part, to ribose-5-phosphate depletion, because exogenous nucleoside administration restored decidualization in these cells. The finding that PPP inhibition prevents decidualization of ESC is novel and clinically important, because DHEA is an endogenous hormone produced by the adrenal glands and elevated in a high proportion of women who have polycystic ovary syndrome, the most common endocrinopathy in reproductive age women. Together, this data suggest a mechanistic link between increased DHEA levels, use of glucose via the PPP, and pregnancy loss.

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Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00182.2014 ◽

2015 ◽

Vol 308 (12) ◽

pp. E1076-E1084 ◽

Cited By ~ 16

Author(s):

Ilana B. Ressler ◽

Bernadette E. Grayson ◽

Yvonne M. Ulrich-Lai ◽

Randy J. Seeley

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Forced Swim Test ◽

Rodent Model ◽

Reproductive Age ◽

Female Rats ◽

Ovary Syndrome ◽

Stress Responsivity

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (HFD; 40% butter fat calories) or nutrient-matched low-fat diet (LFD). Irrespective of diet, DHT-treated animals gained more body weight, had irregular cycles, and were glucose intolerant compared with controls on both diets. HFD/DHT animals had the highest levels of fat mass and insulin resistance. DHT animals demonstrated increased anxiety-related behavior in the elevated plus maze by decreased distance traveled and time in the open arms. HFD consumption increased immobility during the forced-swim test. DHT treatment suppressed diurnal corticosterone measurements in both diet groups. In parallel, DHT treatment significantly dampened stress responsivity to a mild stressor. Brains of DHT animals showed attenuated c-Fos activation in the ventromedial hypothalamus and arcuate nucleus; irrespective of DHT-treatment, however, all HFD animals had elevated hypothalamic paraventricular nucleus c-Fos activation. Whereas hyperandrogenism drives overall body weight gain, glucose intolerance, anxiety behaviors, and stress responsivity, HFD consumption exacerbates the effect of androgens on adiposity, insulin resistance, and depressive behaviors.

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Inositol Treatment and ART Outcomes in Women with PCOS

International Journal of Endocrinology ◽

10.1155/2016/1979654 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Deepika Garg ◽

Reshef Tal

Keyword(s):

Ovarian Stimulation ◽

Ovarian Function ◽

Current Knowledge ◽

Polycystic Ovary ◽

Mature Oocyte ◽

Reproductive Age ◽

Vitro Fertilization ◽

Ovulatory Dysfunction ◽

Ovarian Morphology

Polycystic ovary syndrome (PCOS) affects 5–10% of women in reproductive age and is characterized by oligo/amenorrhea, androgen excess, insulin resistance, and typical polycystic ovarian morphology. It is the most common cause of infertility secondary to ovulatory dysfunction. The underlying etiology is still unknown but is believed to be multifactorial. Insulin-sensitizing compounds such as inositol, a B-complex vitamin, and its stereoisomers (myo-inositol and D-chiro-inositol) have been studied as an effective treatment of PCOS. Administration of inositol in PCOS has been shown to improve not only the metabolic and hormonal parameters but also ovarian function and the response to assisted-reproductive technology (ART). Accumulating evidence suggests that it is also capable of improving folliculogenesis and embryo quality and increasing the mature oocyte yield following ovarian stimulation for ART in women with PCOS. In the current review, we collate the evidence and summarize our current knowledge on ovarian stimulation and ART outcomes following inositol treatment in women with PCOS undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI).

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LRH-1 High Expression in the Ovarian Granulosa Cells of PCOS Patients

10.21203/rs.3.rs-342893/v1 ◽

2021 ◽

Author(s):

Xiao Yang ◽

Qiumin Wang ◽

Ying Wang ◽

Tian Song ◽

Yanjun Zheng ◽

...

Keyword(s):

Granulosa Cells ◽

Follicular Fluid ◽

Polycystic Ovary ◽

Pearson Correlation ◽

Statistical Significance ◽

Control Group ◽

Vitro Fertilization ◽

Real Time Quantitative Pcr ◽

Ovarian Granulosa Cells

Abstract Purpose: Polycystic ovary syndrome (PCOS) is considered as one of the most common endocrine disorder with heterogeneity. There are also reports that liver receptor homolog 1 [LRH-1 or nuclear receptor subfamily 5 group A member 2 (NR5A2)] plays an important role in the reproductive system. But up to now, there are no reports related to the link with PCOS and LRH-1. In this study, we aimed to detect the LRH-1 expression in the ovarian granulosa cell of PCOS patients and explore the potential relationship between LRH-1 and PCOS. Methods: 146 follicular fluid sample were collected in this study, including 72 from PCOS patients and 74 from control patients who underwent intracytoplasmic sperm injection (ICSI) or in vitro fertilization-embryo transfer (IVF-ET). The ovarian granulosa cells were extracted from the patient's follicular fluid by magnetic-activated cell sorting (MACS) method, and the real-time quantitative PCR (qRT-PCR) was used to measure the expression of LRH-1 in ovarian granulosa cells. Then we analyzed the correlation between the expression level of LRH-1 and the clinical characteristics of patient by using Pearson Correlation analysis. Results: The expression of LRH-1 was significantly higher in PCOS patients ovarian granulosa cells than that in the control patients [vs(1.38±0.47)vs(1.03±0.32), t=5.327, p<0.0001], and it was positively correlated with antral follicles counting (AFC) (r=0.3607, p<0.0001)and the serum AMH(r=0.2662, p=0.0012)\LH(r=0.2518, p=0.0022)\T(r=0.2516, p=0.0022) in all patients. No statistical significance between LRH-1 and BMI, FSH, HOMA-IR, DHE-S, progesterone. Conclusions: Compared with the control group, we found that LRH-1 was highly expressed in the ovarian granulosa cells of PCOS patients. Our study has revealed the relationship between the LRH-1 expression and PCOS, which suggested that LRH-1 may play an important role in ovulation disorders. While this finding provided new ideas for the study of the pathogenesis, it also provided a theoretical basis for the clinical diagnosis and treatment for PCOS.

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Cerebral venous thrombosis related to the use of combined oral contraceptives

10.5327/1516-3180.514 ◽

2021 ◽

Author(s):

Amanda Mendes Clemente Vilella ◽

Letícia Luísa Mattos

Keyword(s):

Venous Thrombosis ◽

Oral Contraceptives ◽

Cerebral Venous Thrombosis ◽

Polycystic Ovary ◽

Sinus Thrombosis ◽

Rare Condition ◽

Signs And Symptoms ◽

Reproductive Age ◽

Combined Oral Contraceptives ◽

Menstrual Dysfunction

Background: Cerebral venous thrombosis (CVT) is a rare condition (less than 1% of stroke). It occurs in the younger population (less than 50 years old), 3 times more common in women, especially those of reproductive age. Objectives and methodology: Narrative review to correlate CVT with the use of combined oral contraceptives (ACO). The following databases were used: Pubmed, Scielo and Medline. Results: A systematic review had 11 studies included showing that the use of OAC increases the chances of developing CVST (central venous sinus thrombosis). Among the 9 studies that reported odds ratios, the combined probability of developing CVST in women of reproductive age who use OAC was 7.59 times the probability of developing CVST compared to those who do not take oral contraceptives (OR = 7.59, 95 CI % 3.82-15.09). A retrospective study of 37 female adolescents was diagnosed with CVT, 22 (59%) of whom used OAC and the remaining 15 had other etiological factors. The data indicate that adolescents using OAC to treat hirsutism, menstrual dysfunction or polycystic ovary syndrome may also have some risk factors for thrombosis, such as hereditary coagulopathy. The coexistence of these diseases mentioned with the use of OCA can increase the risk of CVT. Conclusions: The two main studies analyzed concluded the association between the use of ACO and cases of CVT in women. It’s necessary to be attentive to suggestive signs and symptoms in this population, as they are common to other pathologies, making the diagnosis of CVT difficult.

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Elevated levels of arachidonic acid metabolites in follicular fluid of PCOS patients

Reproduction ◽

10.1530/rep-19-0136 ◽

2020 ◽

Vol 159 (2) ◽

pp. 159-169 ◽

Cited By ~ 1

Author(s):

Shengxian Li ◽

Jia Qi ◽

Yongzhen Tao ◽

Qinling Zhu ◽

Rong Huang ◽

...

Keyword(s):

Arachidonic Acid ◽

Follicular Fluid ◽

Polycystic Ovary ◽

Reproductive Age ◽

Pathophysiological Mechanism ◽

Obese Women ◽

Liquid Chromatography Mass Spectrometry ◽

Acid Metabolites ◽

Cox 2

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women usually accompanied by lipid metabolic disorders. However, it remains unknown whether arachidonic acid (AA) and its metabolites in follicular fluid (FF) were altered in PCOS patients. This study was intended to measure the levels of AA and its metabolites in the FF of non-obese PCOS patients that underwent in vitro fertilization (IVF) and to explore the possible causes of the alterations. Thirty-nine non-obese women with PCOS and 30 non-obese women without PCOS were enrolled. AA and its metabolites were measured by liquid chromatography-mass spectrometry. The levels of AA metabolites generated via cyclooxygenase-2 (COX-2) pathway and cytochrome P450 epoxygenase pathway but not lipoxygenase (LOX) pathway were significantly higher in the FF of PCOS patients. The metabolites generated via COX-2 pathway were significantly correlated with levels of testosterone and fasting insulin in serum. The in vitro study further demonstrated that insulin but not testosterone could promote the IL-1β and hCG-induced COX-2 expression and prostaglandin E2 (PGE2) secretion in primary human granulosa cells. In conclusion, there was an elevation in AA metabolites in FF of PCOS patients. Insulin played a pivotal role in the increased AA metabolites generated via COX-2, which could be interpreted as another novel molecular pathophysiological mechanism of PCOS.

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