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Mild stimulation protocol vs conventional controlled ovarian stimulation protocol in poor ovarian response patients: a prospective randomized controlled trial



To compare the efficacy of mild ovarian stimulation protocol and conventional controlled ovarian stimulation (COS) protocol for poor ovarian response (POR) patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).


This single-center prospective randomized controlled trial conducted from September 2013 to September 2015, including 191 patients who met the Bologna criteria of POR. Ninety-seven patients allocated to the mild ovarian stimulation group (MS group) were stimulated according to the letrozole/antagonist protocol, while 94 patients in the controlled ovarian stimulation group (COS group) were stimulated according to a high dose of gonadotropin (Gn) combined with gonadotropin-releasing hormone agonist (GnRH-a) stop protocol. The cumulative live birth rate was the primary outcome. Chinese clinical trial number ChiCTR-TRC-13003454.


Comparing with the COS group, both the stimulation duration and the total gonadotropin dose were significantly shorter and lower in the MS group (P < 0.001). A higher number of retrieved oocytes (P = 0.003) and transferrable embryos (P = 0.029) were obtained in the COS group. The cumulative live birth rates (OR 1.103; 95% CI 0.53 to 2.28; P = 0.791) were comparable between the two groups.


The increase of Gn dose during ovulation stimulation was associated with a higher number of transferrable embryos for POR patients, but this increase did not lead to a concomitant improvement of reproductive outcome, especially in terms of the cumulative live birth rate. Using a mild stimulation protocol was economically preferential while it was as effective as higher doses of Gn stimulation protocol in reproductive outcome for POR patients.

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The authors thank Shen Chen for providing language help and writing assistance, also we want to thank the participating infertile women and all doctors, laboratory staff, nurses and clerks at the Reproductive Medicine Research Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.


There was no funding in this study.

Author information




Liu: data collection and management, data analysis, manuscript writing. Li: data collection, data interpretation. Wang: data collection, data interpretation. Xiao: data collection. Liang: project development. Huang: project development, data interpretation, manuscript revision.

Corresponding author

Correspondence to Rui Huang.

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The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Sixth Affiliated Hospital of Sun Yat-sen University Ethical Committee, and all eligible patients received a detailed informed consent form that they signed to allow recruitment. The study was registered with a Chinese Clinical Trial Number, ChiCTR-TRC-13003454.

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Liu, X., Li, T., Wang, B. et al. Mild stimulation protocol vs conventional controlled ovarian stimulation protocol in poor ovarian response patients: a prospective randomized controlled trial. Arch Gynecol Obstet 301, 1331–1339 (2020).

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  • Cumulative live birth rate
  • Poor ovarian response
  • Mild ovarian stimulation
  • Conventional controlled ovarian stimulation
  • Randomized controlled trial