O-072 Can preimplantation genetic testing for monogenic conditions represent an indication for DuoStim? A multicenter case series
Authors: Trabucco E , Vaiarelli A , Cimadomo D , Innocenti F , Alfano S , Malagisi F , Della Ragione A , Benini F , Livi C , Colamaria S , Argento C , Bruno G , Conforti A , Rienzi L , Ubaldi F M 
Published: June 2022

Abstract

Study question
Is double stimulation in the same ovarian cycle (DuoStim) a valuable strategy to improve the chance of success in couples carrier of monogenic conditions?

Summary answer
DuoStim is advantageous in patients indicated for preimplantation genetic testing for monogenic diseases and aneuploidy testing (PGT-M/-A) and obtaining ≤5 blastocysts after the I-stimulation.

What is known already
PGT-M is a well-established strategy to identify unaffected blastocysts in a cohort of embryos produced from couples carrier of single gene disorders. When PGT-M is conducted in poor prognosis and/or advanced maternal age (POR/AMA) patients, also aneuploidy-testing among unaffected blastocysts is suggested on a single biopsy. The Poseidon group stated that retrieving an adequate number of oocytes to produce ≥1 euploid blastocyst should be considered the main goal of controlled-ovarian-stimulation (COS). This task is even more complex when PGT-M is required in POR/AMA patients. Therefore, lately we started suggesting DuoStim to these couples to maximize their chance of success.

Study design, size, duration
Multicenter case series (2016-2021). Comprehensive description of IVF outcomes derived from DuoStim application in POR/AMA patients undergoing PGT-M. Aneuploidy-testing was also conducted on unaffected blastocysts. All results were compared between the two stimulations in the same ovarian cycle, and we reported the contribution of II-stimulations to higher chances of success.

Participants/materials, setting, methods
GnRH-antagonist COS was performed with recombinant-gonadotrophins and agonist-trigger. Based on the expected risk each embryo would be affected-aneuploid, DuoStim was suggested to all patients obtaining ≤5 blastocysts (day5-7 from I-retrieval). 61 patients accepted and underwent II-stimulations with the same protocol. Only ICSI, trophectoderm-biopsy, qPCR, and vitrified-warmed unaffected-euploid single-blastocyst-transfer(s) were conducted.

Main results and the role of chance
90 patients (36.7±3.7yr) indicated to PGT-M/-A and obtaining ≤5 blastocysts after I-stimulations were suggested starting a II-stimulation in the same ovarian cycle. Among them, 61 accepted (67%). 7.2±4.4 and 7.4±4.2 cumulus-oocyte-complexes were retrieved after I- and II-stimulations, respectively (p = 0.7). 5.1±3.0 and 5.8±3.4 were metaphase-II oocytes (p = 0.2), resulting in 75±21% and 77±25% maturation-rates (p = 0.6). 3.6±2.1 and 4.6±2.9 2PN-zygotes were obtained (p = 0.04), resulting in 75±27% and 81±20% fertilization-rates (p = 0.19). 1.6±1.3 and 2.2±1.8 blastocysts were obtained (p = 0.04), resulting in 43±32% and 46±32% blastulation-rates (p = 0.6). Lastly, 0.5±0.7 and 0.7±1.0 blastocysts were diagnosed unaffected-euploid (p = 0.3), resulting in 35±40% and 30±36% transferable blastocyst rates per biopsied embryo, respectively (p = 0.53), and identical 10±16% transferable blastocyst rates per metaphase-II oocyte in both groups (p = 0.9). 23 (38%) and 24 (39%) patients obtained ≥1 transferable blastocyst after the I- and II-simulation, respectively. Overall, 36 (59%) patients obtained ≥1 transferable blastocyst thanks to DuoStim. To date, 57 (93%) cycles were concluded, and the cumulative live birth rate (CLBR) was 37% (N = 21/57). The patients with a LB have 1.7 surplus transferable blastocysts, and 3 patients already delivered 2 singleton healthy-LBs. The CLBR among patients undergoing the conventional strategy was 21%, no surplus transferable blastocyst is available, and no patient delivered &gt;1 LB.

Limitations, reasons for caution
Observational case series based on real-life data. Of note, the adoption of DuoStim (or any other oocyte/embryo accumulation strategy) in PGT-M/-A is valuable also to amortize the costs of PGT-M set-up and genetic testing through a larger number of blastocysts. In this context, cost-effectiveness analyses in different settings are desirable.

Wider implications of the findings
DuoStim is a fully-personalized strategy advisable any time lower chance of success and higher treatment costs could be balanced by a larger number of blastocysts produced in a short time-frame. Adopting GnRH-antagonist protocols in these patients allows to suggest DuoStim even in progress, based on the embryological outcomes after I-stimulations.

Trial registration number
Not applicable