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Testosterone therapy for women with poor ovarian response undergoing IVF: a meta-analysis of randomized controlled trials

  • Marco NoventaEmail author
  • Amerigo Vitagliano
  • Alessandra Andrisani
  • Mija Blaganje
  • Paola Viganò
  • Enrico Papaelo
  • Marco Scioscia
  • Francesco Cavallin
  • Guido Ambrosini
  • Mauro Cozzolino
Assisted Reproduction Technologies

Abstract

Purpose

The aim of the present systematic review and meta-analysis was to summarize evidence on the effectiveness of testosterone supplementation for poor ovarian responders (POR) on IVF outcomes. The primary outcome was live birth rate (LBR); secondary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR), total and MII oocytes, and total embryos.

Methods

This meta-analysis of randomized controlled trials (RCTs) evaluates the effects of testosterone administration before/during COS compared with a control group in patients defined as POR. The primary outcome was live birth rate (LBR); secondary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR), total and MII oocytes, and total embryos. Pooled results were expressed as risk ratio (RR) or mean differences (MD) with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroup analysis. All analyses were performed by using the random-effects model.

Results

Women receiving testosterone showed higher LBR (RR 2.29, 95% CI 1.31–4.01, p = 0.004), CPR (RR 2.32, 95% CI 1.47–3.64, p = 0.0003), total oocytes (MD = 1.28 [95% CI 0.83, 1.73], p < 0.00001), MII oocytes (MD = 0.96 [95% CI 0.28, 1.65], p = 0.006), and total embryos (MD = 1.17 [95% CI 0.67, 1.67], p < 0.00001) in comparison to controls, with no difference in MR (p = ns). Sensitivity and subgroup analysis did not provide statistical changes to the pooled results.

Conclusions

Testosterone therapy seems promising to improve the success at IVF in POR patients. Further RCTs with rigorous methodology and inclusion criteria are still mandatory.

Keywords

Poor ovarian responders Testosterone Supplementation IVF outcome Clinical pregnancy rate Live birth rate 

Notes

Author contribution

M.N., A.V., G.A., and M.C. conceptualized the study; M.N., M.C., and A.V. extracted the data; A.V. and F.C. performed the statistical analysis; M.N., A.V., A.A., and G.A. performed the data interpretation; M.N., A.A., M.C., and G.A. wrote the manuscript; M.B., P.V., E.P., and M.S. performed the manuscript revision for fundamental intellectual content, language revision, and manuscript re-editing.

Funding

No financial support was received for this study.

Compliance with ethical standards

Disclosure

All the authors report that they have no conflict of interest.

Ethics approval

None.

Supplementary material

10815_2018_1383_MOESM1_ESM.docx (19 kb)
Table S1 General features and basal hormonal status of patients (treatments and controls) included in this systematic review and meta-analysis divided for each manuscript. (DOCX 19 kb)
10815_2018_1383_MOESM2_ESM.docx (15 kb)
Table S2 Data about COS outcomes (treatments vs controls) of patients included in this systematic review and meta-analysis divided for each manuscript. (DOCX 14 kb)
10815_2018_1383_MOESM3_ESM.docx (18 kb)
Table S3 Data about IVF outcomes (treatments vs controls) of patients included in this systematic review and meta-analysis divided for each manuscript. (DOCX 17 kb)
10815_2018_1383_MOESM4_ESM.docx (66 kb)
Figure S1 Flow diagram of included studies (DOCX 65 kb)
10815_2018_1383_Fig2_ESM.png (961 kb)
Figure S2

Risk of bias in individual studies evaluated through criteria described in the Cochrane’s Handbook for Systematic Reviews of Interventions (PNG 961 kb)

10815_2018_1383_MOESM5_ESM.tif (223 kb)
High-resolution image (TIF 222 kb)
10815_2018_1383_Fig3_ESM.png (2 mb)
Figure S3a

Forest plot of comparison: live birth rate (LBR) according to administration route of testosterone: transdermal versus oral. Fig. S3b: Forest plot of comparison: clinical pregnancy rate (CPR) according to administration route of testosterone: transdermal versus oral (PNG 2071 kb)

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High-resolution image (TIF 1049 kb)
10815_2018_1383_Fig4_ESM.png (2 mb)
Figure S4a

Forest plot of comparison: live birth rate according to the days of testosterone administration; ≥ 21 days versus < 21 days. Fig. S4b: Forest plot of comparison: clinical pregnancy rate according to the days of testosterone administration; ≥ 21 days versus < 21 days (PNG 2014 kb) (PNG 2014 kb)

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High-resolution image (TIF 1022 kb)
10815_2018_1383_Fig5_ESM.png (1.1 mb)
Figure S5

Clinical pregnancy rate according to the timing of testosterone administration: before the starting of ovarian stimulation versus during ovarian stimulation (PNG 1076 kb)

10815_2018_1383_MOESM8_ESM.tif (541 kb)
High-resolution image (TIF 541 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Marco Noventa
    • 1
    Email author
  • Amerigo Vitagliano
    • 1
  • Alessandra Andrisani
    • 1
  • Mija Blaganje
    • 2
  • Paola Viganò
    • 3
  • Enrico Papaelo
    • 3
  • Marco Scioscia
    • 4
  • Francesco Cavallin
    • 5
  • Guido Ambrosini
    • 1
  • Mauro Cozzolino
    • 6
    • 7
  1. 1.Department of Women and Children’s Health, Clinic of Gynecology and ObstetricsUniversity of PaduaPadovaItaly
  2. 2.Division of Gynaecology and ObstetricsUniversity Medical Centre LjubljanaLjubljanaSlovenia
  3. 3.Obstetrics and Gynaecology DepartmentIRCCS San Raffaele Scientific InstituteMilanoItaly
  4. 4.Department of Obstetrics and GynecologyPoliclinico Hospital of Abano TermePadovaItaly
  5. 5.SolagnaItaly
  6. 6.Instituto Valenciano de InfertilidadIVI-RMA GlobalMadridSpain
  7. 7.Department of Gynecology and ObstetricsRey Juan Carlos UniversityAlcorcónSpain

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