Comparative analysis of dehydroepiandrosterone and transdermal testosterone pre-treatment in POSEIDON group 3 and 4 women undergoing in vitro fertilization: a retrospective cohort study

Authors

  • Simantini Bose Department of Reproductive Medicine, Birla Fertility and Baby Science IVF, Bengaluru, Karnataka, India
  • Pooja Meena Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, AIIMS, Kalyani, West Bengal, India

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20251584

Keywords:

Transdermal testosterone, DHEA, Poseidon classification, IVF, Poor ovarian reserve, FORT

Abstract

Background: Patients classified under patient-oriented strategies encompassing individualised oocyte number (POSEIDON) groups 3 and 4 typically demonstrate suboptimal response to controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles. Androgen-based pre-treatments like dehydroepiandrosterone (DHEA) and transdermal testosterone have been studied for their role in enhancing ovarian response, although direct comparative data are limited. Objective of the study was to evaluate and compare the effects of DHEA versus transdermal testosterone gel administered before stimulation on ovarian and embryological outcomes in women within POSEIDON groups 3 and 4 undergoing IVF.

Methods: A retrospective cohort study was conducted at a tertiary fertility centre in India between January 2018 and January 2020. Eligible women received either DHEA (75 mg/day for 12 weeks) or testosterone gel (12.5 mg/day for 21 days) before controlled ovarian stimulation (COS). All patients underwent antagonist protocol with dual trigger followed by IVF. Primary outcomes included number of oocytes retrieved, metaphase II (MII) oocytes, and follicular output rate (FORT). Secondary outcomes included fertilization rate, good-quality embryos, and stimulation burden.

Results: Of 237 women analysed, 144 received DHEA and 93 received testosterone gel. The testosterone group showed significantly higher mean oocyte yield (7.2 versus 5.4; p<0.01), MII oocytes (5.6 versus 4.0; p<0.01), and FORT (58.2% versus 49.3%; p<0.01). While fertilization rate (63.5% versus 61.2%; p=0.37) and embryo quality (59.1% versus 57.6%; p=0.75) were similar, testosterone-treated patients required fewer days of stimulation (9.7 versus 10.3; p=0.04) and lower gonadotropin doses (2291 IU versus 2576 IU; p<0.01). No OHSS cases occurred in either group.

Conclusions: This study supports the use of short-course transdermal testosterone as a more practical and efficient adjuvant strategy in poor prognosis IVF cycles. It may be especially valuable in resource-constrained settings, where cost-effectiveness and cycle efficiency are critical to success. Further prospective trials are needed to evaluate long-term reproductive outcomes.

Metrics

Metrics Loading ...

References

Alviggi C, Andersen CY, Buehler K, Conforti A, De Placido G. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril. 2016;105(6):1452-8. DOI: https://doi.org/10.1016/j.fertnstert.2016.02.005

Humaidan P, Alviggi C, Fischer R, Esteves SC. The novel POSEIDON stratification of ‘low prognosis women in assisted reproductive technology’ and its proposed marker of successful outcome. F1000 Res. 2016;5:2911. DOI: https://doi.org/10.12688/f1000research.10382.1

Fuentes A, Sequeira K, Tapia-Pizarro A, Muñoz A, Salinas A, Céspedes P. Androgens profile in blood serum and follicular fluid of women with poor ovarian response during controlled ovarian stimulation reveals differences amongst POSEIDON stratification groups: a pilot study. Front Endocrinol (Lausanne). 2019;10:458. DOI: https://doi.org/10.3389/fendo.2019.00458

Ahmad HM, Aldahham BJM, Saleh MY. Dehydroepiandrosterone supplementation improves diminished ovarian reserve: clinical and in silico studies. Steroids. 2024;211:109490. DOI: https://doi.org/10.1016/j.steroids.2024.109490

Noventa M, Vitagliano A, Andrisani A, Blaganje M, Viganò P, Papaelo E. Testosterone therapy for women with poor ovarian response undergoing IVF: a meta-analysis of randomized controlled trials. J Assist Reprod Genet. 2019;36(4):673-83. DOI: https://doi.org/10.1007/s10815-018-1383-2

Gardner DK, Weissman A, Howles CM, Shoham Z. Textbook of Assisted Reproductive Techniques: Volume 2: Clinical Perspectives. 6th Edition. Boca Raton (FL): CRC Press. 2023. DOI: https://doi.org/10.1201/9781003268611

Kim CH, Yoon TK, Kim SH. Pharmacokinetics of testosterone gel in women: implications for ovarian stimulation. J Obstet Gynaecol Res. 2020;46(9):1653-60.

Naik S, Lepine S, Nagels HE, Siristatidis CS, Kroon B, John MS. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction technology. Cochrane Database Syst Rev. 2024;3:CD009749. DOI: https://doi.org/10.1002/14651858.CD009749.pub3

Sen A, Hammes SR. Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function. Mol Endocrinol. 2010;24(7):1393-403. DOI: https://doi.org/10.1210/me.2010-0006

Sanyal S, Ray P, Bandopadhyay S. Role of androgens in ovarian follicular development: a clinical insight. J Reprod Health. 2020;24(2):156-63.

El-Halawaty S, Azab H, Abdalla N. Androgens modulate follicular development and FSH receptor expression. Middle East Fertil Soc J. 2021;26:1-9.

Lu X, Liu Y, Jiang L. Transdermal testosterone pre-treatment improves IVF outcomes in poor responders: a randomized controlled trial. Front Endocrinol. 2023;14:1183421.

Sunkara SK, Yeung TWY, Patel P, Khalaf Y. Effect of DHEA supplementation on IVF outcomes in women with diminished ovarian reserve: a meta-analysis. Hum Reprod Update. 2022;28(2):260-73.

Narkwichean A, Maalouf W, Campbell BK, Jayaprakasan K. The role of androgens in ovarian stimulation. Reprod Biol Endocrinol. 2023;21:3.

Zhang J, Liu H, Wang Y. DHEA for women with poor ovarian response: a meta-analysis of randomized controlled trials. Gynecol Endocrinol. 2021;37(7):585-91.

Li X, Wang L, Yu J. DHEA enhances AMH expression in granulosa cells. J Endocrinol Invest. 2020;43(1):47-55.

Massin N, Cedrin-Durnerin I. Evidence-based use of androgens in ART. Reprod Biomed Online. 2022;45(5):901-8.

Okohue JE, Ebeigbe P, Osaikhuwuomwan JA. DHEA vs placebo in poor responders undergoing IVF: a prospective trial. J Hum Reprod Sci. 2021;14(3):240-6.

Massarotti C, Ferreccio C, Pecorini F. Short testosterone supplementation improves ovarian sensitivity index in POR. Reprod Biol Endocrinol. 2021;19:101.

Humaidan P, Polyzos NP, Drakopoulos P. The POSEIDON criteria for the definition of low prognosis: a game-changer in IVF? Hum Reprod. 2019;34(3):440-51.

Wu Y, Gao X, Lu X. POSEIDON stratification and response to androgens in IVF. Reprod Med Biol. 2021;20(4):431-8.

Zhang Y, Wang Y, Zhao Y. DHEA and Testosterone differential effects on IVF outcomes in different POSEIDON groups. Am J Obstet Gynecol. 2022;226(4):567.e1-11.

Wang Y, Li R, Qiao J. Can Group 4 POSEIDON patients benefit from androgens? A real-world study. Reprod Biomed Online. 2023;47(2):287-94.

Persson AS, Wallin A, Sundström Poromaa I. Transdermal testosterone improves serum androgen profile. Reprod Biomed Online. 2021;43(3):505-12.

Downloads

Published

2025-05-29

How to Cite

Bose, S., & Meena, P. (2025). Comparative analysis of dehydroepiandrosterone and transdermal testosterone pre-treatment in POSEIDON group 3 and 4 women undergoing in vitro fertilization: a retrospective cohort study. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 14(6), 1915–1920. https://doi.org/10.18203/2320-1770.ijrcog20251584

Issue

Section

Original Research Articles