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“Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial

  • Assisted Reproduction Technologies
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Abstract

Background

This large prospective, randomized study was designed to compare the “mild” protocol with clomiphene citrate, low-dose gonadotropins and a GnRH-antagonist (CC/Gn/GnRH-ant protocol) with the “long” protocol with a GnRH-agonist and high-dose Gn for the controlled ovarian hyperstimulation (COH) of patients with expected poor ovarian responsiveness undergoing IVF.

Materials and Methods

A total of 695 women with clinical, endocrine and ultrasound characteristics suggesting a low ovarian reserve and a poor responsiveness to COH were recruited and randomly assigned to receive the CC/Gn/GnRH-ant “mild” protocol (mild group, n = 355) or the “long” protocol with high-dose Gn (long group, n = 340).

Results

The “mild” stimulation led to significantly shorter follicular phase, lower consumption of exogenous Gn and lower peak estradiol level than the “long” regimen. With the “long” protocol, significantly less cycles were cancelled due to the lack of ovarian response; further, it obtained significantly more oocytes, more mature oocytes, more embryos, and a thicker endometrium. As for the final IVF outcome, however, the two stimulation regimens obtained comparable implantation rate, clinical pregnancy rate, and ongoing pregnancy rate at 12 weeks.

Conclusions

In conclusion, the “mild” CC/Gn/GnRH-ant stimulation protocol is a valid alternative to the long protocol with high Gn dose as it obtains a comparable success rate and requires significantly less medications, with an obvious economical advantage.

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Competing interests

The authors declare that they have no competing interests.

Authors’ contribution

AC, VS, FE and GB collected the data. AC provided the first draft of the manuscript. PD performed the statistical analysis. AR conceived the study, participated in its design and coordination, and helped to draft the manuscript. CB provided critical revision of the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, University of Torino, St. Anna Hospital, via Ventimiglia 3, 10126, Torino, Italy

    Alberto Revelli, Alessandra Chiadò, Veronica Stabile, Francesca Evangelista, Gemma Basso & Chiara Benedetto

  2. Department of Public Health and Pediatrics, University of Torino, Torino, Italy

    Paola Dalmasso

Authors
  1. Alberto Revelli
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  2. Alessandra Chiadò
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  3. Paola Dalmasso
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  4. Veronica Stabile
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  5. Francesca Evangelista
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  6. Gemma Basso
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  7. Chiara Benedetto
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Correspondence to Alberto Revelli.

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“Mild” stimulation protocol for expected poor responders.

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Revelli, A., Chiadò, A., Dalmasso, P. et al. “Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial. J Assist Reprod Genet 31, 809–815 (2014). https://doi.org/10.1007/s10815-014-0227-y

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  • DOI: https://doi.org/10.1007/s10815-014-0227-y

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