P-661 dydrogesterone as an alternative to supress LH surge in single stimulus protocols with follitropin delta
Authors: Antunes R , Souza M.C , Souza M , Mancebo A.C , Raupp V , Sequeira F , Silva L , Barbeitas A.L , Arêas P , Vaz B , Souza A.L 
Published: June 2022

Abstract

Study question
Is oral dydrogesterone (DYG) 30 mg daily efficient on prevention of premature luteinizing hormone (LH) surge in ART cycles?

Summary answer
Oral dydrogesterone demonstrated to be as safe and effective as GnRH-ant in IVF/ICSI cycles intended to freeze-all / PGT-A, oocyte preservation and embryo banking programs

What is known already
The use of progesterone (PG) to inhibit pituitary LH surge during ovarian stimulation have been described over the last decades. Due to its harmful effect on the endometrium, PG suppression is mainly reserved for freeze-all cycles. Dydrogesterone (DYG), a known and safe synthetic progesterone, has been tested for this purpose based on the concept of its more selective PG receptors activity, which could reduce the inconveniences of side effects with less relevant androgenic, estrogenic, glyco or mineralocorticoid activity. Accordind to some recent work, DYG would be an effective tool both in cycles intended to freeze-all or in oocyte preservation strategies.

Study design, size, duration
Observational, comparative single center study, comparing the effect of DYG and gonadotropin releasing hormone (GnRH) antagonists on prevention of premature luteinizing hormone (LH) surge as well as to evaluate the number of metaphase II oocytes. From January 2019 to January 2020, 143 no age restrictions patients underwent both IVF/ICSI or oocyte preservation, all of them receiving the same single stimulus protocol with follitropin delta (Rekovelle).

Participants/materials, setting, methods
92 IVF/ICSI plus 51 oocyte cryopreservation cycles underwent deltafollitropin (Rekovelle®, Ferring Pharmaceuticals) in a fixed daily and individualized SC-dose. Clinical decision led to a GnRH-antagonist (CTA-Cetrorelix acetate, Cetrotide®, Merck) 0,25 mg/d initiated in a flexible schedule in presence of one follicle ≥14 mm and continued throughout the stimulation period (48 cycles) or dydrogesterone (DYG), 10mg 8/8 hours (Duphaston®, Abbott) combined to gonadotrophin from the beginning of stimulation until the day after the trigger (95 cycles).

Main results and the role of chance
DYG-group had a mean age significantly higher (37.8 x 35.8-p 0.002) but there were no differences in mean parameters of BMI (24.08 x 24.81), days of stimulation (9.95 x 10.08), AMH (2.30 x 2.52), AFC (14.6 x 16.2). In the same way, no differences were observed between follicles 15 mm to 18 mm (3.06 x 3.68) and ≥ 18 mm (4.56 x 3.9), with a tendency for a greater number of larger follicles in the DYG-group. Metaphase II oocytes (7.48 x 7.33) was similar in both groups. One patient from each group experienced a premature LH surge (3.54 x 3.06) and one case in the DYG-group had no oocyte in a single 20mm aspirated follicle. There happened no cancelling. No patients experienced moderate to severe ovarian hyper stimulation syndrome, even when AMH&gt;3 ng/mL. Cancelling criteria: no follicles with a diameter 17 mm by day 15. Oocyte retrieval took place 36 hours after trigging. Primary outcome was the incidence of premature LH surge. Secondary outcomes included follicles ≥ 15 mm and &lt; 18 mm and ≥ 18 mm on hCG day, metaphase II oocytes, number of cancelled cycles and OHSS symptoms. Statistics were performed by Mann-Whitney test.

Limitations, reasons for caution
The main limitation point is the small number of patients. Despite having relative experience with the use of DYG, in this work we limited the sample to consider only one type of stimulus protocol, making the groups more homogeneous for the analysis.

Wider implications of the findings
Dydrogesterone is as effective as GnRH-ant in reducing premature LH surge. It can be considered for IVF/ICSI cycles intended to freeze-all / PGT-A, oocyte preservation and for embryo banking strategies, representing lower costs in these cases.

Trial registration number
not applicable