Role of transdermal testosterone gel pre-treatment on IVF outcome: a prospective randomized controlled trial with active control


  • Neeta Singh Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
  • Padmashri Parimalam Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
  • Sunesh Kumar Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
  • Perumal Vanamail Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India



Testosterone, IVF, Androgen, Poor ovarian responder, Response


Background: Dealing with poor ovarian responders is the newest challenge for the present-day reproductive physicians. Androgens are said to increase pregnancy outcomes due to enhanced oocyte retrieval in poor responders. The aim of the study was to measure the effect of transdermal testosterone gel in women with unexplained poor ovarian response.

Methods: It was a prospective randomized controlled trial with active control conducted at ART centre, department of obstetrics and gynaecology, AIIMS, New Delhi from August 2017-August 2018. Seventy women with previously failed IVF/ICSI who had ≤5 oocyte retrieval in previous cycle having normal ovarian reserve with normal or low testosterone levels were randomized. Study arm (N=35) received testosterone gel pre-treatment whereas the control arm (N=35) received standard treatment. GnRH antagonist stimulation protocol was followed. The number of oocytes retrieved and pregnancy outcomes were studied.

Results: Of the 70 women in the study, the number of oocytes retrieved was significantly higher (6.5±5.8 vs 3.1±2.1; p=0.002), cycle cancellation rate was lower (8.6% vs 22.9%; p=0.094), implantation rate (8.2% vs 2.6%; p=0.228), clinical pregnancy, ongoing pregnancy, live birth rates (14.7% vs 2.9%; p=0.092) and take home baby rates (17.6% vs 2.9%; p=0.049) were higher in testosterone group compared to controls. One woman in testosterone group developed mild OHSS.

Conclusions: The study shows that transdermal testosterone gel is found to improve oocyte retrieval significantly in unexpected poor responders, although there was not a significant improvement in pregnancy outcomes. Hence further studies are of utmost importance to establish the effectiveness of the gel.


Vollset SE, Goren E, Yuan CW, Cao J, Smith AE, Hsiao T, Bisignano C, et al. Fertility, mortality, migration, and population scenarios for 195 countries and territories from 2017 to 2100: a forecasting analysis for the Global Burden of Disease Study. Lancet. 2020;396(10258):1285-306.

Zhang Y, Zhang C, Shu J, Guo J, Chang HM, Leung PCK, et al. Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis. Hum Reprod Update. 2020;26(2):247-63.

Frattarelli JL, Gerber MD. Basal and cycle androgen levels correlate with in vitro fertilization stimulation parameters but do not predict pregnancy outcome. Fertil Steril. 2006;86(1):51-7.

Gervasio CG, Bernuci MP, Silva MF, Rosa SAC. The role of androgen hormones in early follicular development. ISRN Obstet Gynecol. 2014;2014:818010.

Kim CH, Howles CM, Lee HA. The effect of transdermal testosterone gel pretreatment on controlled ovarian stimulation and IVF outcome in low responders. Fertil Steril. 2011;95(2):679-83.

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270-83.

Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod. 2000;15(10):2129-32.

Massin N, Durnerin I, Coussieu C, Fontaine J, Wolf JP, Hugues JN. Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique--a prospective, randomized, double-blind study. Hum Reprod. 2006;21(5):1204-11.

Fabregues F, Penarrubia J, Creus M, Manau D, Casals G, Carmona F, et al. Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial. Hum Reprod. 2009;24(2):349-59.

Bosdou JK, Venetis CA, Dafopoulos K, Zepiridis L, Chatzimeletiou K, Anifandis G, et al. Transdermal testosterone pretreatment in poor responders undergoing ICSI: a randomized clinical trial. Hum Reprod. 2016;31(5):977-85.

Doan HT, Quan LH, Nguyen TT. The effectiveness of transdermal testosterone gel 1% (androgel) for poor responders undergoing in vitro fertilization. Gynecol Endocrinol. 2017;33(12):977-9.

Gleicher N, Kushnir VA, Darmon SK, Wang Q, Zhang L, Albertini DF, Barad DH. Suspected ontogeny of a recently described hypo-androgenic PCOS-like phenotype with advancing age. Endocrine. 2018;59(3):661-76.






Original Research Articles