ESHRE 2016 · Poster presentation

High gonadotropin dosage does not affect euploidy and pregnancy rates in PGT cycles

O. O. Barash, K. A. Ivani, S. P. Willman, C. F. MacKenzie, S. C. Lefko, F. B. Rabara, N. Huen, L. N. Weckstein

Reproductive Science Center of the San Francisco Bay Area, USA

ESHRE 2016 Annual Meeting

406

IVF PGT cycles

Jan 2013 – Nov 2015

16.26 ± 9.05

Avg. oocytes per retrieval

303/406 had ≥ 10 eggs

85.6 → 496 IU/egg

Dose per egg · ≤25 → ≥45 y.o.

~6× increase

NS across groups

Ongoing PR

42.9 – 60.4 % (<35 y.o.) · p = 0.422

Background

Why this study

The proportion of euploid embryos in IVF PGT cycles decreases significantly with advancing maternal age. Recruitment of an adequate number of follicles is crucial in PGT cycles and can be regulated by the administered gonadotropin dose.

Objective. Compare euploidy and pregnancy rates after administration of different dosages of gonadotropins in PGT cycles.

Materials & Methods

Cohort and groups

Cohort. 406 SNP-based PGT cycles, January 2013 – November 2015. Avg. embryos for ET — 1.17.
Dose groups. < 3,000 IU (132 cycles, 109 patients, 35.4 ± 2.2 y.o.); 3,000–5,000 IU (196 cycles, 153 patients, 37.8 ± 3.0 y.o.); > 5,000 IU (78 cycles, 59 patients, 39.7 ± 4.2 y.o.).
Age groups. ≤ 34, 35–37, 38–40, ≥ 41 y.o.

Results · Euploidy by dose

Dose-level differences in euploidy are not statistically significant in any age group

≤ 34 y.o.: 61.03 / 63.09 / 66.67 % (χ² = 0.454, p = 0.5). 35–37 y.o.: 54.54 – 58.63 % (χ² = 1.31, p = 0.253). 38–40 y.o.: 39.10 – 50.00 % (χ² = 1.153, p = 0.283). ≥ 41 y.o.: 25.78 – 32.86 % (χ² = 0.238, p = 0.623).

Fig. 3 — Euploidy rate by age group across three gonadotropin-dose tiers.

Results · Blastulation & stimulation protocol

Blastulation drops with high dose in young patients; protocols agnostic in euploidy

Blastulation rate (embryos for biopsy ÷ 2PN) was higher with < 3,000 IU than > 5,000 IU — 34.7 % vs 24.2 % (p < 0.05, χ² = 48.48). In patients > 38 y.o. the difference was not statistically significant (27.0 % vs 23.5 %).

Euploidy did not differ between stimulation protocols — FSH/HMG (y = −0.051x + 0.727), FSH/LH (y = −0.028x + 0.610), Lupron microdose (y = −0.081x + 0.927).

Results · Pregnancy

Ongoing PR is not different within any age or dose group

Ongoing PR was not statistically different across all study groups (p = 0.422, χ² = 0.645). In patients < 35 y.o. PR ranged from 42.86 % to 60.42 %; in patients > 41 y.o., from 52.0 % to 61.91 %.

No interrelation between maternal age and PR after euploid ET. Using high gonadotropin dosages in patients > 38 y.o. can significantly increase oocyte yield while maintaining proper blastulation, euploidy, and pregnancy rates.

Conclusion

Summary of findings

Euploidy and ongoing pregnancy rates are not affected by high gonadotropin dosage in IVF PGT cycles. To improve efficiency and cost-effectiveness, the maximum number of follicles recruited in each cycle should be limited only by medical safety concerns and patient well-being.

References

Cited works

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3.Macklon NS, Stouffer RL, Giudice LC, Fauser BC. The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev. 2006;27(2):170–207. PubMed
4.Nagaoka SI, Hassold TJ, Hunt PA. Human aneuploidy: mechanisms and new insights into an age-old problem. Nat Rev Genet. 2012;13(7):493–504. PubMed
5.Bisignano A, Wells D, Harton G, Munné S. Reply: PGD and aneuploidy screening for 24 chromosomes by genome-wide SNP analysis: a responsible path towards greater utility. Reprod Biomed Online. 2012;24(1):4–5. PubMed

Reprint requests

Oleksii Barash, Ph.D. · ivfbigdata@gmail.com