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GnRH Antagonist Protocol Enhances Coagulation During Controlled Ovarian Stimulation for IVF

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Abstract

Changes in coagulation and fibrinolysis have been reported in women undergoing controlled ovarian hyperstimulation (COH) supporting a potential hypercoagulable condition related to this treatment. This study aimed at evaluating the changes in fibrin clot properties and thrombin generation induced by two different COH protocols: long with gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant). Primary outcomes included determination of plasma fibrin clot properties, including clot permeability (Ks) and efficiency of fibrinolysis using clot lysis time (CLT), along with thrombin generation (prothrombin fragments 1 + 2) and endogenous thrombin potential (ETP) and fibrinolysis inhibitor levels. One hundred twenty-nine infertile women were included in the final analysis. The GnRH-ant protocol resulted in increased ETP (+ 9.8%) and reduced Ks (− 2.4%). Conversely, COH with the GnRH-a protocol reduced thrombin generation by decreasing both ETP (− 6.6%) and F1 + 2 (− 30.8%) together with favorably altered fibrin clot properties represented by increased Ks (+ 21.7%) and reduced CLT (− 13.8%) as well as decreased PAI-1 levels (by 2.5 times). The GnRH-ant compared to the GnRH-a protocol increased PAI-1 levels (+ 77.3%), thrombin generation (9.3% higher ETP), and Ks (+ 13.7%). In the GnRH-a group, post-COH Ks was 14.3% higher (Ks ≥ 7.92 × 10−9 cm2) in women with positive vs. negative pregnancy outcomes. Our results show that the GnRH-ant protocol enhanced thrombin generation and slightly decreased fibrin clot density. COH with the GnRH-a reduced thrombin generation and improved fibrin clot features. This trial was registered (NCT04166825). Clinical Trial Registration Number: NCT04166825.

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Data Availability

All data are stored in Gynecological Endocrinology Department and available at request.

Code Availability

iCentrum software.

Abbreviations

COH:

Controlled ovarian hyperstimulation

PCOS:

Polycystic ovary syndrome

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Acknowledgements

We would like to thank Prof. Anetta Undas for the contribution to this work.

Funding

This work was supported by a grant of the Polish National Science Center (UMO-2016/21/N/NZ4/03269 to MP).

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Authors and Affiliations

  1. Gynecological Endocrinology Department, Jagiellonian University Medical College, ul. Kopernika 23, 31-501, Krakow, Poland

    Magdalena Piróg, Olga Kacalska-Janssen, Robert Jach, Jakub Wyroba & Bartosz Chrostowski

  2. Institute of Cardiology, Jagiellonian University Medical College and John Paul II Hospital, Krakow, Poland

    Michał Ząbczyk & Joanna Natorska

Authors
  1. Magdalena Piróg
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  2. Olga Kacalska-Janssen
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  3. Robert Jach
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  6. Michał Ząbczyk
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  7. Joanna Natorska
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Contributions

M.P.: preparation of samples, experimental design, data collection and analysis, drafting the manuscript; O.K-J.: experimental design and interpretation of data; R.J.: interpretation of data and analysis of the manuscript; J.W. data collection, interpretation of data; B.C. data collection, interpretation of data; M.Z.: laboratory investigations, statistical analysis, interpretation of data; J.N.: laboratory investigations, interpretation of data and drafting the manuscript.

Corresponding author

Correspondence to Magdalena Piróg.

Ethics declarations

Ethics Approval

The Ethics Committee at Jagiellonian University Medical College in Krakow approved the study (date of approval: 18 December 2014 and extension of approval: 30 September 2018; reference number KBET/292/B/2014).

Consent to Participate

All participants provided informed consent in accordance with the Declaration of Helsinki.

Consent for Publication

All patients included in this study had signed the approved informed consent to allow publication of anonymous data.

Competing Interests

The authors declare no competing interests.

Additional information

Headings: A comparison between two controlled ovarian hyperstimulation (COH) protocols: long with gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant), focusing on the impact on thrombin generation, fibrinolysis, and fibrin clot properties. .

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Piróg, M., Kacalska-Janssen, O., Jach, R. et al. GnRH Antagonist Protocol Enhances Coagulation During Controlled Ovarian Stimulation for IVF. Reprod. Sci. 29, 3521–3531 (2022). https://doi.org/10.1007/s43032-022-01026-6

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  • DOI: https://doi.org/10.1007/s43032-022-01026-6

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