O-127 Higher probability of live birth after testosterone pretreatment in women with poor ovarian response undergoing IVF: a systematic review and meta-analysis
Authors: Katsika E , Bosdou J , Goulis D , Grimbizis G , Kolibianakis E 
Published: June 2022

Abstract

Study question
Does testosterone pretreatment increase the probability of pregnancy in poor responders undergoing ovarian stimulation with gonadotrophin-releasing hormone (GnRH) analogues and gonadotrophins for in-vitro fertilization (IVF)?

Summary answer
Testosterone pretreatment increases clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF.

What is known already
Androgens have been shown to stimulate early stages of follicular growth, increase the number of primary, pre-antral and antral follicles as well as increase ovarian sensitivity to follicle stimulating hormone (FSH). Although androgen supplementation has been evaluated in several randomized controlled trials (RCTs) and meta-analyzed in six systematic reviews until today currently no solid conclusions can be drawn regarding its effectiveness.

Study design, size, duration
A literature search was performed until September 2021 aiming to identify RCTs evaluating testosterone pretreatment in poor responders. Outcome measures included achievement of pregnancy, total dose of gonadotrophins required, duration of stimulation, estradiol levels, endometrial thickness and number of follicles ≥17 mm on the day of triggering final oocyte maturation, number of cumulus–oocyte complexes (COCs) retrieved, embryos transferred, metaphase II (MII) and 2-pronuclei oocytes (2pn) and the proportion of patients having an embryo transfer (ET).

Participants/materials, setting, methods
Eight RCTs published between 2006 and 2021 were analyzed, including 760 women. Pretreatment with transdermal testosterone gel was performed in all studies with a dose ranging from 10 to 12.5 mg/day for 10 to 56 days. In dichotomous data, estimates were expressed as risk ratio (RR) with 95% confidence intervals (CIs), using the fixed or random effects method. In continuous data, differences were pooled across resulting in a weighted mean difference (WMD) with 95% CI.

Main results and the role of chance
Testosterone pretreatment was associated with a significantly higher live birth (RR: 2.07, 95%CI: 1.09 to 3.92) and clinical pregnancy rate (RR: 2.25, 95%CI: 1.54) in women with POR undergoing IVF, while there was also a significant increase in the number of COCs retrieved (WMD: +0.88, 95% CI: +0.22 to + 1.54). Significantly less days to complete ovarian stimulation (WMD: -0.81 days, 95% CI: -1.46 to −0.16), a lower total dose of gonadotrophins (WMD: -368.8 IUs, 95% CI: −612.4 to -125.2), a thicker endometrium on the day of triggering final oocyte maturation (WMD: +0.83 mm, 95% CI: +0.13 to + 1.53) and a lower cancellation rate due to poor ovarian response (RR: 0.37, 95%CI: 0.20 to 0.71) were observed. No significant differences were observed in estradiol levels (WMD: -8.12 pg/mL, 95% CI: -118.2 to + 101.96), in the numbers of follicles ≥17 mm on the day of triggering final oocyte maturation (WMD: +0.82, 95%CI: -0.11 to + 1.74), of MII oocytes (WMD: +0.50, 95% CI: -0.17 to + 1.17), of 2pn oocytes (WMD: +0.49, 95% CI: -0.11 to + 1.10), of embryos transferred (WMD: +0.21, 95%CI: -0.07 to + 0.49) and in the proportion of patients with ET (RR: 1.00, 95% CI: 0.96 to 1.04).

Limitations, reasons for caution
The definition of poor ovarian response varied among studies and a considerable heterogeneity regarding the type, dose and duration of testosterone pretreatment was present. Although the present study is currently the largest meta-analysis evaluating testosterone pretreatment, the total number of patients is still not large enough to draw solid conclusions.

Wider implications of the findings
The current study suggests that the probability of pregnancy is increased in poor responders pretreated with transdermal testosterone. This increase, in the absence of other proven beneficial interventions in these patients, justifies the conduction of further relevant RCTs.

Trial registration number
CRD42021262098