Abstract
Study question
Can the adipokines levels and ratios in the follicular fluid (FF) be used to predict in vitro fertilization (IVF) outcomes?
Summary answer
The leptin level and ratios leptin/ghrelin and leptin/adiponectin in FF are reliable prognostic factors for IVF outcomes in women with normal body mass index (BMI).
What is known already
The adipose tissue serves not a simple fat storage, rather an important endocrine organ, producing adipokines, such as leptin, adiponectin, ghrelin and others. Adipokines have been shown to regulate the cardiovascular system, food intake, metabolism, inflammation, metastatic spread of tumors,and also reproduction, affecting the activity of the hypothalamo-pituitary-gonadal axis. The plasma and FF adipokines have been used as prognostic factors for IVF outcomes, but the obtained results are controversial. The most promising in this case may be the distribution of patients into groups in accordance with their BMI and a separate study of adipokine ratios in them.
Study design, size, duration
Women (n = 53), who undergo IVF, were divided on two groups, according to their BMI: normal BMI (18.5–24.9 kg/m2, n = 25) and increased BMI (>25.0 kg/m2, n = 28). Depending on IVF outcomes after the antagonist protocol, the groups formed were subsequently subdivided into two groups each: non-pregnant with normal BMI (nPN, n = 16), pregnant with normal BMI (PN, n = 9), non-pregnant with increased BMI (nPI, n = 21), pregnant with increased BMI (PI, n = 7). Participants/materials, setting, methods: Inclusion criteria for participants were: age 18–45 years and infertility due to male/tubal factor. Exclusion criteria were: polycystic ovarian syndrome (PCOS), diabetes mellitus, or plasma level of anti-Müllerian hormone <1.0 ng/mL. The FF from the first punctated follicle was collected and tested for leptin, adiponectin and ghrelin levels using ELISA kits. If gestational sac was seen in uterine cavity using ultrasound on day 21–25 after embryo transfer, pregnancy was diagnosed.
Main results and the role of chance
Women with increased BMI had, as a rule, higher FF levels of leptin and the leptin/ghrelin and leptin/adiponectin ratios, compared with women with normal BMI. Furthermore, leptin level was higher in PN as compared to nPN (21.61±2.55 vs 10.54±1.16, p < 0.05), but did not differ in the PI and nPI groups. The same pattern was obtained for the leptin/ghrelin and leptin/adiponectin ratios. The ghrelin level showed an inverse pattern. It was higher in nPN as compared to PN (3.80±0.78 vs 1.39±0.19, p < 0.05), but did not differ in women with increased BMI. The obtained data demonstrate that the association between the adipokine levels in FF and the IVF outcomes is better in women with normal BMI than in women with increased BMI. Adipokines, which differed among the study groups, were evaluated as prognostic factors in women with normal BMI.The values were calculated at which pregnancy became unlikely: leptin level <15 ng/mL, leptin/ghrelin ratio <9, and leptin/adiponectin ratio <5. For each indicators, the sensitivity and specificity were >88%. The predictive power of these indicators in the clinic using the odds ratio (95% confidence interval) was: leptin level 7.11 (1.23–40.99, p < 0.05), leptin/ghrelin 29.53 (1.53–570.83, p < 0.05), and leptin/adiponectin 7.11 (1.23–40.99, p < 0.05).
Limitations, reasons for caution
The main limitation of the study is a relative small number of patients, although the differences between the investigated groups were significant. Furthermore, women with low ovarian reserve, age > 40 years, endometriosis or PCOS were not included in the study.
Wider implications of the findings: The obtained results indicate the good prospects for using such indicators as the adipokines levels and their ratio in FF to predict IVF outcomes in women with low ovarian reserve, endometriosis and PCOS, but with normal BMI.
Trial registration number
Not applicable
Prognostic factors associated with clinical pregnancy in in vitro fertilization using pituitary down-regulation with depot and daily low-dose luteal phase gonadotropin releasing hormone agonists: A single center′s experience
