Publication:

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

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.