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Metabolic changes in follicular fluids of patients treated with recombinant versus urinary human chorionic gonadotropin for triggering ovulation in assisted reproductive technologies: a metabolomics pilot study

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Introduction

The main goal of this retrospective cohort study is the assessment of the effects of administration of recombinant-hCG (r-hCG) versus urinary-hCG (u-hCG) on follicular fluid (FF) composition of women who underwent in vitro fertilization (IVF) treatments.

Materials and methods

We selected 70 patients with infertility attributable to tubal diseases, unexplained infertility, and male factor. Metabolomics analysis of their FFs was performed by 1H nuclear magnetic resonance (1H NMR) spectroscopy in combination with multivariate analysis to interpret the spectral data. Univariate statistical analysis was applied to investigate the possible correlations between clinical parameters and between clinical parameters and metabolites identified by NMR.

Results

According to the type of hCG used, significant differences were detected in FFs of women with male factor and unexplained infertility, both in qualitative and quantitative terms, for some metabolites as cholesterol, citrate, creatine, β-hydroxybutyrate, glycerol, lipids, amino acids (Glu, Gln, His, Val, Lys) and glucose. No significant difference was observed in women with tubal diseases. Besides, the number of MII oocytes in the u-hCG-treated groups correlates positively with glutamate in tubal disease and with glycerol in unexplained infertility. In the r-hCG-treated groups, the number of MII oocytes correlates positively with lipid in tubal disease, positively with citrate and negatively with glucose in male infertility.

Conclusions

Metabolite composition of FF changes according to different type of hCG treatment and this can be related to oocyte development and subsequent outcome. According to the data of this study, different types of hCG should be used in relation to the diagnosis of infertility to obtain better results in inducing oocyte maturation in women undergoing IVF.

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Abbreviations

ART:

Assisted reproductive technologies

β-HB:

β-Hydroxybutyrate

BMI:

Body mass index

CPMG:

Carr–Purcell–Meiboom–Gill

D2O:

Deuterated water

FF:

Follicular fluid

FSH:

Follicle-stimulating hormone

GnRH:

Gonadotropin-releasing hormone

hCG:

Human chorionic gonadotropin

ICSI:

Intracytoplasmic sperm injection

IVF:

In vitro fertilization

MAP:

Medically assisted procreation

NMR:

Nuclear magnetic resonance

PCA:

Principal component analysis

PLS-DA:

Partial least squares discriminant analysis

r-hCG:

Recombinant human chorionic gonadotropin

TSP:

3-Trimethylsilyl propionic acid-d4 sodium salt

u-hCG:

Urinary human chorionic gonadotropin

VIP:

Variable importance in the projection

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Funding

The authors received no financial support for this study.

Author information

Authors and Affiliations

  1. Department of Sciences, University of Basilicata, viale Ateneo Lucano 10, 85100, Potenza, Italy

    Maria Antonietta Castiglione Morelli, Licia Viggiani & Angela Ostuni

  2. Center for Reproductive Medicine of “San Carlo” Hospital, via Potito Petrone, 85100, Potenza, Italy

    Assunta Iuliano, Sergio Crescenzo Antonio Schettini, Donatina Petruzzi, Angela Ferri & Paola Colucci

Authors
  1. Maria Antonietta Castiglione Morelli
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  2. Assunta Iuliano
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  3. Sergio Crescenzo Antonio Schettini
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  4. Donatina Petruzzi
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  5. Angela Ferri
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  6. Paola Colucci
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  7. Licia Viggiani
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  8. Angela Ostuni
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Contributions

SS, AI, and AO designed the study. AI selected the patients and executed oocyte retrieval. DP executed oocyte retrieval. AF identified oocytes in follicular fluid and executed their fertilization. PC selected the follicular fluids to be used for metabolomic analyses. CM performed the analysis of NMR data and multivariate analysis. LV ran the NMR experiments. AO performed statistical analysis. AO, AI, and CM were responsible for conducting the study and writing the manuscript which was critically discussed, edited and approved by all co-authors.

Corresponding author

Correspondence to Angela Ostuni.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the local ethical committee, Comitato Etico Unico Regionale per la Basilicata (CEUR, approval number: 2015/00585), and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by CEUR on November 27, 2015.

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Written informed consent for publication was obtained from the patients.

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The authors consider that the first two authors should be regarded as joint first authors.

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Castiglione Morelli, M.A., Iuliano, A., Schettini, S.C.A. et al. Metabolic changes in follicular fluids of patients treated with recombinant versus urinary human chorionic gonadotropin for triggering ovulation in assisted reproductive technologies: a metabolomics pilot study. Arch Gynecol Obstet 302, 741–751 (2020). https://doi.org/10.1007/s00404-020-05609-z

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