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Second stimulation in the same ovarian cycle: an option to fully-personalize the treatment in poor prognosis patients undergoing PGT-A

Abstract

Purpose

Our primary objective was to assess whether immediately undergoing a second stimulation in the same ovarian cycle (DuoStim) for advanced-maternal-age and/or poor-ovarian-reserve (AMA/POR) patients obtaining ≤ 3 blastocysts for preimplantation-genetic-testing-for-aneuploidies (PGT-A) is more efficient than the conventional-approach.

Methods

All AMA/POR patients obtaining ≤ 3 blastocysts after conventional-stimulation between 2017 and 2019 were proposed DuoStim, and 143 couples accepted (DuoStim-group) and were matched for the main confounders to 143 couples who did not accept (conventional-group). GnRH-antagonist protocol with recombinant-gonadotrophins and agonist trigger, intra-cytoplasmatic-sperm-injection (ICSI) with ejaculated sperm, PGT-A and vitrified-warmed euploid single-blastocyst-transfer(s) were performed. The primary outcome was the cumulative-live-birth-delivery-rate per intention-to-treat (CLBdR per ITT) within 1 year. If not delivering, the conventional-group had 1 year to undergo another conventional-stimulation. A cost-effectiveness analysis was also conducted.

Results

The CLBdR was 10.5% in the conventional-group after the first attempt. Only 12 of the 128 non-pregnant patients returned (165 ± 95 days later; drop-out = 116/128,90.6%), and 3 delivered. Thus, the 1-year CLBdR was 12.6% (N = 18/143). In the DuoStim-group, the CLBdR was 24.5% (N = 35/143; p = 0.01), 2 women delivered twice and 13 patients have other euploid blastocysts after a LB (0 and 2 in the conventional-group). DuoStim resulted in an incremental-cost-effectiveness-ratio of 23,303€. DuoStim was costlier and more effective in 98.7% of the 1000 pseudo-replicates generated through bootstrapping, and the cost-effectiveness acceptability curves unveiled that DuoStim would be more cost-effective than the conventional-approach at a willingness-to-pay threshold of 23,100€.

Conclusions

During PGT-A treatments in AMA/POR women, DuoStim can be suggested in progress to rescue poor blastocyst yields after conventional-stimulation. It might indeed prevent drop-out or further aging between attempts.

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Data availability

The data underlying this article are available in the article and in its online supplementary material.

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Authors and Affiliations

Authors

Contributions

AV, DC, LR and FMU designed the study. AV, SC, CA, MG, and FMU recruited the patients. AV and DC analyzed the data and drafted the manuscript. DC, VC and ADA designed and performed the cost-effectiveness analyses. All authors contributed to the discussion of the results.

Corresponding author

Correspondence to Alberto Vaiarelli.

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Institutional Review Board approval for this study was obtained from Clinica Valle Giulia.

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Supplementary Information

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10815_2022_2409_MOESM1_ESM.pdf

Supplementary Figure 1. Results from the couples in the conventional approach (COS 1 + COS 2) group and their matched* couples in the DuoStim (Stim I + Stim II in the same ovarian cycle) group. Each circle represents a cumulus oocyte complex (COC) retrieved. If green, it developed as an euploid blastocyst and resulted in a live birth after transfer; if purple, it developed as an euploid blastocyst but did NOT result in a live birth after transfer; if orange, it developed as an euploid blastocyst which is still available for transfer; if red, it developed as an aneuploid blastocyst; if grey, it did not reach the blastocyst stage. In the conventional approach group, we highlighted the couples who dropped-out from the treatment after a failed first attempt. In the DuoStim group, we highlighted the patients who did not respond to the second stimulation in the same ovarian cycle. *The couples were matched for maternal age, sperm factor, number of cumulus oocytes complexes (COCs) and blastocysts obtained after the first COS.

Supplementary file1 (PDF 264 kb)

10815_2022_2409_MOESM2_ESM.pdf

Supplementary Figure 2. Sub-analysis of the cumulative live birth delivery rates (CLBdR) in the conventional approach and the matched* DuoStim groups according to the number of blastocysts obtained after the first controlled ovarian stimulation (COS). The treatment drop-out rate among couples who failed the first attempt has been reported also for the former group. Below each cluster we reported also the mean maternal age. *Besides maternal age and number of blastocysts obtained after the first COS, the couples were matched also for sperm factor and number of cumulus oocyte complexes retrieved after first COS.

Supplementary file2 (PDF 77 kb)

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Vaiarelli, A., Cimadomo, D., Gennarelli, G. et al. Second stimulation in the same ovarian cycle: an option to fully-personalize the treatment in poor prognosis patients undergoing PGT-A. J Assist Reprod Genet 39, 663–673 (2022). https://doi.org/10.1007/s10815-022-02409-z

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Keywords

  • DuoStim
  • Double stimulation
  • Treatment personalization
  • Poor prognosis
  • Advanced maternal age