Global Transcriptional Profiling of Granulosa Cells from Polycystic Ovary Syndrome Patients: Comparative Analyses of Patients with or without History of Ovarian Hyperstimulation Syndrome Reveals Distinct Biomarkers and Pathways.

Ovarian hyperstimulation syndrome (OHSS) is often a complication of polycystic ovarian syndrome (PCOS), the most frequent disorder of the endocrine system, which affects women in their reproductive years. The etiology of OHSS is multifactorial, though the factors involved are not apparent. In an attempt to unveil the molecular basis of OHSS, we conducted transcriptome analysis of total RNA extracted from granulosa cells from PCOS patients with a history of OHSS (n = 6) and compared them to those with no history of OHSS (n = 18). We identified 59 significantly dysregulated genes (48 down-regulated, 11 up-regulated) in the PCOS with OHSS group compared to the PCOS without OHSS group (p-value < 0.01, fold change >1.5). Functional, pathway and network analyses revealed genes involved in cellular development, inflammatory and immune response, cellular growth and proliferation (including DCN, VIM, LIFR, GRN, IL33, INSR, KLF2, FOXO1, VEGF, RDX, PLCL1, PAPPA, and ZFP36), and significant alterations in the PPAR, IL6, IL10, JAK/STAT and NF-κB signaling pathways. Array findings were validated using quantitative RT-PCR. To the best of our knowledge, this is the largest cohort of Saudi PCOS cases (with or without OHSS) to date that was analyzed using a transcriptomic approach. Our data demonstrate alterations in various gene networks and pathways that may be involved in the pathophysiology of OHSS. Further studies are warranted to confirm the findings.

Infertility treatment outcome in sub groups of obese population.

BACKGROUND: Obesity is a common disorder with a negative impact on IVF treatment outcome. It is not clear whether morbidly obese women (BMI >= 35 kg/m2) respond to treatment differently as compared to obese women (BMI = 30-34.9 kg/m2) in IVF. Our aim was to compare the outcome of IVF or ICSI treatments in obese patients to that in morbidly obese patients. METHODS: This retrospective cohort study was conducted in a tertiary care centre. Patients inclusion criteria were as follows; BMI >or= 30, age 20-40 years old, first cycle IVF/ICSI treatment with primary infertility and long follicular pituitary down regulation protocol. RESULTS: A total of 406 obese patients (group A) and 141 morbidly obese patients (group B) satisfied the inclusion criteria. Average BMI was 32.1 +/- 1.38 kg/m2 for group A versus 37.7 +/- 2.99 kg/m2 for group B. Patient age, cause of infertility, duration of stimulation, fertilization rate, and number of transferred embryos were similar in both groups. Compared to group A, group B had fewer medium size and mature follicles (14 vs. 16), fewer oocytes collected (7 vs. 9) and required higher doses of HMG (46.2 vs. 38.5 amps). There was also a higher cancellation rate in group B (28.3% vs. 19%) and lower clinical pregnancy rate per started cycle (19.9% vs. 28.6%). CONCLUSION: In a homogenous infertile and obese patient population stratified according to their BMI, morbid obesity is associated with unfavorable IVF/ICSI cycle outcome as evidenced by lower pregnancy rates. It is recommended that morbidly obese patients undergo appropriate counseling before the initiation of this expensive and invasive therapy.