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Clomiphene combined with gonadotropins and GnRH antagonist versus conventional controlled ovarian hyperstimulation without clomiphene in women undergoing assisted reproductive techniques: systematic review and meta-analysis

  • Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To compare the effectiveness and safety of controlled ovarian hyperstimulation (COH) using clomiphene citrate associated with gonadotropin and GnRH antagonist (CC + Ant) versus conventional COH without clomiphene citrate (Non-CC) for women undergoing assisted reproductive techniques (ART).

Methods

Systematic review and meta-analysis of randomized controlled-trials comparing CC + Ant versus non-CC. The last search was performed in Apr 13 2012. The following outcomes were retrieved from included trials and compared between CC + Ant versus non-CC: live birth, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), miscarriage, multiple pregnancy, endometrial thickness, total oocytes retrieved, MII oocytes retrieved, total gonadotropin used, and duration of COH.

Results

Seven trials (702 participants) were included. There was no significant difference in live birth (55/182 = 30.2 % vs. 47/181 = 26.0 %, p = 0.26, CC + Ant vs. non-CC, respectively), clinical pregnancy (98/346 = 28.3 % vs. 84/356 = 23.6 %, p = 0.12), miscarriage (6/35 = 17.1 % vs. 7/32 = 21.9 %, p = 0.42), endometrial thickness, and on the number of oocytes retrieved. There was a significant reduction in OHSS (1/216 = 0.5 % vs. 9/217 = 4.1 %, p = 0.01), consumption of gonadotropins, and duration of COH.

Conclusions

Compared to non-CC, CC + Ant is likely to reduce the risk of OHSS, medication costs, and the duration of COH without evidence of effect on live birth and clinical pregnancy. More trials are still needed to improve the quality of the evidence. Future studies should evaluate women with PCOS or at increased risk of OHSS, quality of life, satisfaction with the treatment, total cost per live birth, and frequency of congenital anomalies.

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Acknowledgments

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil: Conselho Nacional de Desenvolvimento científico e Tecnológico (CNPq), Brazil: Hospital das Clínicas de Ribeirão Preto, Brazil. This review did not receive any outside funding.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Medical School of Ribeirao Preto, University of Sao Paulo (DGO-FMRP-USP), Av. Bandeirantes, 3900, 8 andar, HCRP, Campus Universitário, Ribeirao Preto, SP, 14048-900, Brazil

    J. B. P. Figueiredo, C. O. Nastri, A. D. D. Vieira & W. P. Martins

  2. Ultrasonography and Retraining Medical School of Ribeirao Preto (EURP), Ribeirao Preto, Brazil

    J. B. P. Figueiredo, C. O. Nastri & W. P. Martins

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  1. J. B. P. Figueiredo
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  2. C. O. Nastri
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  3. A. D. D. Vieira
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  4. W. P. Martins
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Correspondence to W. P. Martins.

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Study registration number: PROSPERO number: CRD42012002271.

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Figueiredo, J.B.P., Nastri, C.O., Vieira, A.D.D. et al. Clomiphene combined with gonadotropins and GnRH antagonist versus conventional controlled ovarian hyperstimulation without clomiphene in women undergoing assisted reproductive techniques: systematic review and meta-analysis. Arch Gynecol Obstet 287, 779–790 (2013). https://doi.org/10.1007/s00404-012-2672-0

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