Assessment of follicular fluid leptin levels and insulin resistance as outcome predictors in women undergoing in vitro fertilization intracytoplasmic sperm injection

Capsule:
High follicular fluid leptin levels were associated with a lower probability of live birth in women undergoing in vitro fertilization–intracytoplasmic sperm injection. Serum progesterone, follicle number, and leptin levels seem to predict IVF outcome.

Authors:
David Llaneza-Suarez, Ph.D., Placido Llaneza, M.D., Celestino Gonzalez, Ph.D., M.D., Pedro De-la-Fuente, M.D., Carlos Garcia-Ochoa, M.D., Pablo Garrido, Ph.D., Vanesa Castañon, Ph.D., Faustino Perez-Lopez, Ph.D., M.D.

Volume 102, Issue 6, Pages 1619-1625

Abstract:

Objective:
To analyze follicular fluid leptin (FFL) levels, abdominal obesity, and insulin resistance as predictors of in vitro fertilization (IVF)–intracytoplasmic sperm injection (ICSI) outcome.

Design:
Observational study.

Setting:
Academic medical center.

Patient(s):
A sample of 130 infertile women aged 26–40 years without polycystic ovary syndrome.

Intervention(s):
Measurement of FFL levels in controlled ovarian hyperstimulation cycles with an antagonist and agonist protocol for IVF-ICSI.

Main Outcome Measure(s):
Live birth rate.

Result(s):
Mean FFL values were significantly higher in pregnancies not ending in a live birth, even after adjustment for waist circumference and insulin resistance. A multivariable model obtained with the use of logistic binary regression analysis showed that waist circumference and insulin resistance had no influence over IVF-ICSI outcomes, but a higher number of follicles, lower serum progesterone levels on the day before α-hCG administration, and lower FFL concentrations were significantly associated with a higher probability of having a live birth. The multivariate model reached a sensitivity of 87% and a specificity of 71% for predicting the possibility of pregnancy ending in a live birth.

Conclusion(s):
High FFL levels were associated with abdominal obesity, insulin resistance, and a lower live birth rate after IVF-ICSI. Further investigations are warranted to define the precise roles of leptin, obesity, and insulin resistance on IVF-ICSI outcomes.

  • Shvetha Zarek

    Thank you for an interesting research question given the increasing interest in the role of leptin and fertility! This was an observational study of infertile women without PCOS (n=130) who underwent ICSI cycles with antagonist or agonist controlled ovarian stimulation protocols. Of the 130 women, 11 were obese, 37 were overweight and 82 had a normal BMI. 48 (36.9%) had abdominal obesity and 30 women (23.1%) were diagnosed with insulin resistance. Leptin levels were assessed from follicular fluid (FFL) collected from the first follicle at the time of oocyte retrieval via ELISA. Fasting serum was obtained to measure glucose and insulin levels and anthropometric measurements to assess waist circumference etc. Day 2 or 3 embryos were utilized for embryo transfer. The primary outcome was live birth. The authors performed a sample size calculation stating a sample size of greater than 22 patients would provide 90% power for a two sided alpha level of 0.05 assuming a mean leptin level of 16.4 ng/ml.

    FFL were significantly higher in women with abdominal obesity and insulin resistance (P <.001). Mean FFL were lower in women with a live birth (11.5 ± 4.6 ng/ml) compared with women did not achieve pregnancy or did not have a live birth (16.8 ± 6.2 ng/ml). Multivariable regression modeling demonstrated that a higher rate of live birth was associated with lower FFL but not waist circumference, HOMA IR, and estradiol levels.
    It would be useful if the authors could comment on the following: Were there any criteria for patient selection? Was the analysis restricted to first cycle of ART? Was the measurement of serum leptin levels considered? The overall live birth rate of 17.6% seems lower than average, do the authors have any comments on how this may affect the results? In the multivariable modeling, there is no mention of covariate adjustments (age, male infertility, number of embryos transferred, endometrial thickness, etc)
    This is a very interesting study that demonstrates that higher follicular leptin levels have a negative impact on live birth. Thank you the authors!

    • David Llaneza-Suarez

      Thank you very much for your comments.
      In our study, apart from the PCOS exclusion, other criteria selection was: women between 18 and 40 years old without oncology pathology or any other medical contraindication for fertility treatment or pregnancy. Not all women were in their first cycle and, as we stated at the end of the first paragraph in the Material and Methods section, women were studied during their first (37.1%), second (41.4%) or third cycle (21.4%).

      Unfortunately we have not evaluated serum leptin due to the objective of the study was to analyze follicular fluid leptin (FFL) levels, abdominal obesity, and insulin resistance as predictors of in vitro fertilization (IVF)–intracytoplasmic sperm injection (ICSI) outcome.

      As you comment, the overall live rate of 17.6% was lower than literature usually referenced. However, according to the Spanish Fertility Society data, during 2012 year (https://www.registrosef.com/public/docs/sef2012_IAFIV.pdf)
      a total of 31676 cycles of IVF-ICSI were reported with a total of 5064 deliveries and 6103 live birth (due to multiple pregnancies). This data is very similar to our rate, especially if it is considered the low rate of multiple pregnancy in our sample. Lastly, in the multivariable model analysis adjusting for the age, BMI and transfered embryos were made.

      • Shvetha Zarek

        Thank you very much for your comments and information. They were very helpful in clarifying the analysis. This is a very interesting study. Thank you!

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