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Basal serum level of Δ4-androstenedione reflects the ovaries’ ability to respond to stimulation in IVF cycles: setting up a new reliable index of both ovarian reserve and response

  • Assisted Reproduction Technologies
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Adequate androgen levels are necessary for regular follicular growth, progression beyond the pre-antral stage, and prevention of follicular atresia. The main purpose of this study was to investigate whether baseline androgen levels had a predictive value on stimulation outcomes in IVF cycles. The secondary purpose was to compare the possible predictive value of androgens with that of already known markers.

Methods

The study included 91 infertile patients aged 30–45 years awaiting the first IVF cycle. All women underwent the same stimulation protocol and the same starting dose of recombinant FSH. As stimulation outcomes, the number of follicles recruited, estradiol and progesterone levels on the day of trigger, the total dose of gonadotropins administered, and the number of oocytes collected were recorded. Multiple linear regression and multivariate logistic regression were used to evaluate the significant predictive value of the variables for response to controlled ovarian stimulation (COS). By studying the reliability of different markers, an attempt was made to develop a single index with the highest predictive value.

Results

Pearson’s correlation revealed a statistically significant inverse correlation between oocytes collected and age (r =  − 0.333, p < 0.001) and a positive correlation with AMH (anti-müllerian hormone) (r = 0.360, p < 0.001), antral follicle count (AFC) (r = 0.639, p < 0.001), and androstenedione (Δ4-A) (r = 0.359, p < 0.001). No significant correlation was reported with FSH (r =  − 0.133, p = 0.207) and total testosterone (r = 0.180, p = 0.088). In COS good responders, the G-index (= AMH ng/mL*AFC/Δ4-A ng/dL) revealed a significantly higher level (p < 0.001) than AMH, AFC, and Δ4-A alone.

Conclusion

Baseline serum Δ4-A, presumably crucial for ensuring a regular follicular growth, is a reliable marker of ovarian response to stimulation. Since the ovarian capacity to respond to gonadotropins does not depend exclusively on the presence of follicles, we suggest a new index, the G-index, able to contemplate both the ovarian reserve and the Δ4-A level.

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Authors and Affiliations

  1. Reproductive Medicine Unit, Department of Mother and Child, San Paolo Hospital Medical School, ASST Santi Paolo e Carlo, 20142 via di Rudinì, 8, Milan, Italy

    Emanuele Garzia, Valentina Galiano, Ellade Guermandi, Jennifer Riparini & Patrizia Sulpizio

  2. Istituto Di Medicina Aerospaziale “A. Mosso,” Aeronautica Militare, Milan, Italy

    Emanuele Garzia & Giovanni Marfia

  3. Gynecology and Obstetrics Unit, San Carlo Borromeo Hospital, ASST Santi Paolo e Carlo, Milan, Italy

    Valentina Galiano

  4. Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Laura Guarnaccia & Giovanni Marfia

  5. Aldo Ravelli Research Center, Milan, Italy

    Laura Guarnaccia & Giovanni Marfia

  6. Gynecology and Obstetrics Unit, ASST Rhodense, Ospedale G. Salvini, Garbagnate Milanese, Italy

    Giulia Murru

  7. Gynecology and Obstetrics Unit, Department of Mother and Child, Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, Milan, Italy

    Anna Maria Marconi

Authors
  1. Emanuele Garzia
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Contributions

E.G. conceived the presented idea and managed the project. V.G., G.M., G.Ma, E.Gu, and J.R. contributed to acquisition of data. A.M.M. and P.S. helped supervise the project. L.G. helped analyze the data. V.G., L.G., and E.G. drafted and finalized the manuscript. All authors agreed with the submission of the manuscript and gave approval to the final version to be published.

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Correspondence to Emanuele Garzia.

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Garzia, E., Galiano, V., Guarnaccia, L. et al. Basal serum level of Δ4-androstenedione reflects the ovaries’ ability to respond to stimulation in IVF cycles: setting up a new reliable index of both ovarian reserve and response. J Assist Reprod Genet 39, 1917–1926 (2022). https://doi.org/10.1007/s10815-022-02546-5

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