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High ovarian response to ovarian stimulation: effect on morphokinetic milestones and cycle outcomes

  • Assisted Reproduction Technologies
  • Published:
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Abstract

Purpose

To assess the effect of high ovarian response on oocyte quality and ovarian stimulation cycle outcomes.

Methods

A retrospective cohort study conducted at three IVF units. The high ovarian response (HOR) and polycystic ovary syndrome (PCOS) with HOR (PCOS HOR) groups included 151 and 13 women who underwent controlled ovarian stimulation (COS) resulting in more than 15 retrieved oocytes, for a total of 1863 and 116 cultured embryos, respectively. The normal ovarian response (NOR) group comprised 741 women with 6–15 retrieved oocytes, resulting in 4907 cultured embryos. Data collected included fresh cycle data and pregnancy rates, in addition to annotation of morphokinetic events from time of pronuclei fading to time of initiation of blastocyst formation of embryos cultured in a time lapse incubator, including occurrence of direct unequal cleavage at first cleavage (DUC-1) (less than 5 h from two to three blastomeres). Comparison was made between morphokinetic parameters between the 3 groups. Cycle outcomes were compared in the high vs. normal ovarian response groups.

Results

Oocyte maturation rate was significantly lower in the HOR vs. NOR groups (56.5% vs. 90.0%, p < 0.001), while the fertilization rates were similar (60.2% vs. 58.1%, p = 0.397). The prevalence of DUC-1 embryos was higher in the PCOS HOR and the HOR groups as compared to the NOR group (22.7% vs. 16.2% and 12.0%, respectively, p < 0.001). After exclusion of DUC-1 embryos, remaining embryos from the NOR and HOR groups reached the morphokinetic milestones at similar rates, with comparable implantation and clinical pregnancy rates, while the PCOS HOR showed shorter time to 5 blastomeres compared to the NOR and HOR groups.

Conclusions

High ovarian response might be associated with decreased oocyte quality, manifested as a higher proportion of immature oocytes and higher rate of direct uneven cleavage embryos, while embryos exhibiting normal first cleavage have similar temporal milestones and implantation potential.

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Data availability

Available upon request.

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Funding

Israel Innovation Authority – Kamin grant 55326.

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Author notes

    Authors and Affiliations

    1. Infertility and IVF Unit, Department of Obstetrics and Gynecology, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

      Natali Schachter-Safrai, Gilad Karavani & Assaf Ben-Meir

    2. Infertility and IVF unit, department of Obstetrics and Gynecology, Hadassah Mount Scopus Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

      Efrat Esh-Broder

    3. Fertility and IVF Unit, Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel

      Eliahu Levitas & Iris Har-Vardi

    4. Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

      Eliahu Levitas & Iris Har-Vardi

    5. Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

      Tamar Wainstock

    Authors
    1. Natali Schachter-Safrai
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    2. Gilad Karavani
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    Contributions

    Natali Schachter-Safrai and Gilad Karavani have contributed substantially to the conception and design of the study, analysis and interpretation of data, and drafting the article. Efrat Esh-Broder and Eliahu Levitas have contributed substantially to the acquisition, analysis and interpretation of data, and revision of the article. Tamar Wainstock has contributed substantially to the conception and design of the study, analysis and interpretation of data, and revision of the article. Iris Har-Vardi and Assaf Ben-Meir have contributed substantially to the conception and design of the study, acquisition, analysis and interpretation of data, and drafting and revision of the article. All authors have approved the final version of the study.

    Corresponding author

    Correspondence to Gilad Karavani.

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    The authors declare that they have no conflict of interest.

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    Natali Schachter-Safrai and Gilad Karavani should be considered as equal contribution first authors.

    Iris Har-Vardi and Assaf Ben-Meir should be considered as equal contribution last authors.

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    Schachter-Safrai, N., Karavani, G., Esh-Broder, E. et al. High ovarian response to ovarian stimulation: effect on morphokinetic milestones and cycle outcomes. J Assist Reprod Genet 38, 3083–3090 (2021). https://doi.org/10.1007/s10815-021-02323-w

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    • DOI: https://doi.org/10.1007/s10815-021-02323-w

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