Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Outcomes of Preimplantation Genetic Testing for Single Gene Defects in a Privately Funded Period and Publicly Funded Period: A North-American Single Center Experience

Authors
Talya Shaulov 1
Li Zhang 1
Jin-Tae Chung 1
Weon-Young Son 1
William Buckett 1
Asangla Ao 2
1 MUHC Reproductive Centre, Department of Obstetrics and Gynecology, Montreal, Quebec, Canada
2 MUHC Reproductive Centre, Department of Obstetrics and Gynecology, Montreal, Quebec, Canada; Department of Human Genetics, McGill University, Montreal, Quebec, Canada; McGill University Health Centre Research Institute, Montreal,
Abstract
Background: The purpose of this study was to assess whether the outcomes from IVF-preimplantation genetic testing (IVF-PGT) cycles for single gene defects (SGD) (PGT-M) differ between a privately funded period (PRP) and publicly funded period (PUP). Methods: A retrospective cohort study was conducted in a North-American single tertiary center. The PRP (March 1998 to July 2010) comprised 56 PGT-M cycles from 58 IVF cycles in 38 couples, and the PUP (August 2010 to May 2015) comprised 59 PGT-M cycles from 87 IVF cycles in 38 couples. One PGT-M cycle is defined as one biopsy procedure from one or serial IVF cycles. A p-value of 0.05 was considered statistically significant. Results: The clinical pregnancy rates (CPR) per PGT-M cycle were 30.4% and 52.5% in each period, respectively (p=0.021). The live birth rates (LBR) per PGT-M cycle were 21.5% versus 40.9% in each period, respectively (p=0.037). A sub-analysis within the PUP comparing 39 PGT-M cycles from 39 IVF cycles with 20 PGT-M cycles from 49 IVF cycles yielded CPRs per PGT-M cycle of 64.1% and 30.0% and LBRs per PGT-M cycle of 53.8% and 15.0%, in each group, respectively (p<0.05 for both). Conclusion: The transition from private to public funding and a single embryo transfer (ET) guideline has little impact on embryological and clinical outcomes of PGT-M cycles, and results in lower rates of multiple pregnancies. However, these two systems may serve different populations.
Keywords
In vitro
Preimplantation genetic testing
Public funding
Single embryo transfer
Bissonnette F, Phillips SJ, Gunby J, Holzer H, Mahutte N, St-Michel P, et al. Working to eliminate multiple pregnancies: a success story in Quebec. Reprod Biomed Online. 2011;23(4):500-4.
Velez MP, Connolly MP, Kadoch IJ, Phillips S, Bissonnette F. Universal coverage of IVF pays off. Hum Reprod. 2014;29(6):1313-9.
El-Toukhy T, Kamal A, Wharf E, Grace J, Bolton V, Khalaf Y, et al. Reduction of the multiple pregnancy rate in a preimplantation genetic diagnosis programme after introduction of single blastocyst transfer and cryopreservation of blastocysts biopsied on day 3. Hum Reprod. 2009;24(10):2642-8.
Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990;344(6268):768-70.
Delhanty JD, Harper JC. Pre-implantation genetic diagnosis. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14(4):691-708.
Treff NR, Su J, Tao X, Levy B, Scott RT Jr. Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertil Steril. 2010;94(6):2017-21.
Harper JC, Sengupta SB. Preimplantation genetic diagnosis: state of the art 2011. Hum Genet. 2012;131(2):175-86.
Harton GL, Munne S, Surrey M, Grifo J, Kaplan B, McCulloh DH, et al. Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization. Fertil Steril. 2013;100(6):1695-703.
Fiorentino F, Bono S, Biricik A, Nuccitelli A, Cotroneo E, Cottone G, et al. Application of next-generation sequencing technology for comprehensive aneuploidy screening of blastocysts in clinical preimplantation genetic screening cycles. Hum Reprod. 2014;29(12):2802-13.
Tobler KJ, Brezina PR, Benner AT, Du L, Xu X, Kearns WG. Two different microarray technologies for preimplantation genetic diagnosis and screening, due to reciprocal translocation imbalances, demonstrate equivalent euploidy and clinical pregnancy rates. J Assist Reprod Genet. 2014;31(7):843-50.
Navarro JL, Castilla JA, Martinez L, Hernandez E, Fontes J. Coverage and current practice patterns regarding assisted reproduction techniques. Eur J Obstet Gynecol Reprod Biol. 2008;138(1):3-9.
Castilla JA, Hernandez E, Cabello Y, Navarro JL, Hernandez J, Gomez JL et al. Assisted reproductive technologies in public and private clinics. Reprod Biomed Online. 2009;19(6):872-8.
Shaulov T, Belisle S, Dahan MH. Public health implications of a North American publicly funded in vitro fertilization program; lessons to learn. J Assist Reprod Genet. 2015;32(9):1385-93.
Zhang L, Yilmaz A, Chian RC, Son WY, Zhang XY, Kong D et al. Reliable preimplantation genetic diagnosis in thawed human embryos vitrified at cleavage stages without biopsy. J Assist Reprod Genet. 2011;28(7):597-602.
McCullagh P, Nelder JA. Generalized linear models. 2nd ed. New York: Chapman & Hall/CRC Press; 1989. 526 p.
Agresti A, Booth JG, Hobert JP, Caffo B. Random-effects modeling of categorical response data. Sociol Methodol. 2000;30(1):27-80.
De Rycke M. Singling out genetic disorders and disease. Genome Med. 2010;2(10):74.
De Rycke M, Belva F, Goossens V, Moutou C, SenGupta SB, Traeger-Synodinos J, et al. ESHRE PGD consortium data collection XIII: cycles from January to december 2010 with pregnancy follow-up to october 2011. Hum Reprod. 2015;30(8):1763-89.
De Sutter P, Van der Elst J, Coetsier T, Dhont M. Single embryo transfer and multiple pregnancy rate reduction in IVF/ICSI: a 5-year appraisal. Reprod Biomed Online. 2003;6(4):464-9.
Debrock S, Spiessens C, Meuleman C, Segal L, De Loecker P, Meeuwis L, et al. New belgian legislation regarding the limitation of transferable embryos in in vitro fertilization cycles does not significantly influence the pregnancy rate but reduces the multiple pregnancy rate in a threefold way in the Leuven University Fertility Center. Fertil Steril. 2005;83(5):1572-4.
Van Landuyt L, Verheyen G, Tournaye H, Camus M, Devroey P, Van Steirteghem A. New belgian embryo transfer policy leads to sharp decrease in multiple pregnancy rate. Reprod Biomed Online. 2006;13(6):765-71.
Ryan GL, Sparks AE, Sipe CS, Syrop CH, Dokras A, Van Voorhis BJ. A mandatory single blastocyst transfer policy with educational campaign in a United States IVF program reduces multiple gestation rates without sacrificing pregnancy rates. Fertil Steril. 2007;88(2):354-60.
Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P. Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study. BJOG. 2008;115(3):385-90.
Kresowik JD, Stegmann BJ, Sparks AE, Ryan GL, van Voorhis BJ. Five-years of a mandatory single-embryo transfer (mSET) policy dramatically reduces twinning rate without lowering pregnancy rates. Fertil Steril. 2011;96(6):1367-9.
Kutlu P, Atvar O, Vanlioglu OF, Kutlu U, Arici A, Yilmaz S, et al. Effect of the new legislation and single-embryo transfer policy in Turkey on assisted reproduction outcomes: preliminary results. Reprod Biomed Online. 2011;22(2):208-14.
Esinler I, Bozdag G, Karakoc Sokmensuer L. Mandatory single embryo transfer policy dramatically decreases multiple pregnancy rates. J Obstet Gynaecol Res. 2014;40(1):75-9.
Henne MB, Bundorf MK. Insurance mandates and trends in infertility treatments. Fertil Steril. 2008;89(1):66-73.
Tur-Kaspa I. Clinical management of in vitro fertilization with preimplantation genetic diagnosis. Semin Reprod Med. 2012;30(4):309-22.
Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011;26(7):1768-74.
Ji J, Liu Y, Tong XH, Luo L, Ma J, Chen Z. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod. 2013;28(10):2728-34.
Steward RG, Lan L, Shah AA, Yeh JS, Price TM, Goldfarb JM, et al. Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril. 2014;101(4):967-73.
Briggs R, Kovacs G, MacLachlan V, Motteram C, Baker HW. Can you ever collect too many oocytes? Hum Reprod. 2015;30(1):81-7.
Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016;31(2):370-6.
Vandervorst M, Liebaers I, Sermon K, Staessen C, De Vos A, Van de Velde H, et al. Successful preimplantation genetic diagnosis is related to the number of available cumulus-oocyte complexes. Hum Reprod. 1998;13(11):3169-76.
Verpoest W, Haentjens P, De Rycke M, Staessen C, Sermon K, Bonduelle M, et al. Cumulative reproductive outcome after preimplantation genetic diagnosis: a report on 1498 couples. Hum Reprod. 2009;24(11):2951-9.
Hu X, Wang J, Li Y, Wang Y, Ding C, Zeng Y, et al. Clinical considerations of preimplantation genetic diagnosis for monogenic diseases. PLoS One. 2015;10(9):e0139613.
Journal of Reproduction & Infertility
Volume 21, Issue 2
Spring 2020
Pages 107-115