P-626 Eight weeks of androgen priming by low dose hCG before IVF/ICSI in women with low ovarian reserve
Authors: Wang N.F , Bogstad J.W , Pors S.E , Pinborg A , Andersen C.Y , Løssl K 
Published: June 2022

Abstract

Study question
Does eight weeks of low dose hCG priming improve the outcome of ovarian stimulation for IVF/ICSI in women with low ovarian reserve.

Summary answer
Significantly more oocytes were retrieved following eight weeks of low dose hCG priming, when compared to an identical IVF/ICSI treatment immediately before the priming period.

What is known already
Administration of androgens prior to ovarian stimulation for IVF might upregulate the FSH receptor level on granulosa cells making the follicles more responsive to exogenous FSH. LH and hCG stimulate the follicular androgen synthesis, acting through LH receptors on the theca cells, enabling their use as an intra-ovarian androgen priming method. Exogenous testosterone and DHEA priming have been shown to increase the number of retrieved oocytes and the live birth rate, but systemic androgen administration is associated with side effects. Long term ‘intra-ovarian’ priming with hCG without systemic effects in women with low ovarian reserve has not previously been investigated.

Study design, size, duration
A prospective, paired, non-blinded study including 20 women serving as their own controls conducted between January 2021 and July 2021 at The University Hospital Copenhagen Rigshospitalet, Denmark. Participants underwent two identical consecutive IVF/ICSI treatments, a Control cycle including elective freezing of all blastocysts and a Study cycle with fresh blastocyst transfer. The Control and Study cycle were separated by approximately eight weeks (two menstrual cycles) of androgen priming by daily injections of 260 IE hCG.

Participants/materials, setting, methods
Inclusion criteria were age 18-40 years, regular menstrual cycle 23-35 days and AMH &lt;6.29 pmol/L. Control and Study IVF/ICSI cycles were performed in a fixed GnRH-antagonist protocol using a daily dose of 300 IU rFSH and GnRH antagonist 0.25 mg from stimulation day 5-6. Primary endpoint was the follicular output rate defined as the pre-ovulatory follicle count (&gt;16 mm) on hCG trigger day divided by the antral follicle count (2-10 mm) on cycle day 2-3.

Main results and the role of chance
20 women with a mean (SD) age of 36.8 (3.2) years and an AMH level of 3.7 (1.5) pmol/L were included and completed the study. The number of oocytes retrieved was significantly higher in the Study compared to Control Cycle: 4.7 (2.8) vs. 3.2 (1.7), (P = 0.007), and the number of blastocysts was 1.2 (1.6) vs. 0.6 (0.7) in the Study compared to Control cycle, (P = 0.11). The follicular output rate was 0.4 (0.4) in the Study cycle initiated immediately after eight weeks of hCG priming, which was similar to the follicular output rate of 0.38 (0.2) in the Control cycle performed just before initiating the priming period (P = 0.81). The number of follicles above 10 mm on trigger day was 7.3 (5.0) in the Study and 5.3 (2.9) in the Control cycle (P = 0.018). Although the duration of stimulation seemed longer in the Study compared to Control cycle, 10.1 (1.5) and 8.9 (2.7) days respectively (P = 0.05), the same trigger criterion was defined and used in the two cycles confirmed by a similar mean diameter of the two biggest follicles on trigger day: 18.5 (1.1) vs. 18.3 (1.1) mm in the Study and Control cycle, respectively (P = 0.91).

Limitations, reasons for caution
The sample size calculation was based on the follicular output rate, and the study was not powered to look at oocyte retrieval rates. Bigger studies are needed to confirm this finding.

Wider implications of the findings
Although no increase in the follicular output rate was demonstrated, significantly more oocytes were retrieved after eight weeks of hCG priming, which is an important finding in a population of women with low ovarian reserve. Benefits of long term low dose hCG priming must be confirmed in a larger study.

Trial registration number
NCT04643925