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Journal of Assisted Reproduction and Genetics

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01-10-2017 | Assisted Reproduction Technologies

Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort

Authors: Elie Hobeika, Sonali Singh, Shaveta Malik, Eric S. Knochenhauer, Michael L. Traub

Published in: Journal of Assisted Reproduction and Genetics | Issue 10/2017

Abstract

Purpose

Few published articles have compared initial hCG values across all different types of ART cycles, including cycles with fresh or frozen embryo transfer. No articles have compared initial hCG values in cycles utilizing preimplantation genetic screening (PGS). The purpose of this study is to compare initial hCG values after fresh embryo transfer, frozen embryo transfer, and after PGS.

Methods

This was a single-center retrospective cohort study at an academically affiliated private IVF center. All fresh and frozen embryo transfers between January 2013 and December 31, 2015 were included. We compared mean initial serum hCG values 14 days after oocyte retrieval for fresh cycles and 9 days after frozen embryo transfer. We examined cycles of single embryo transfer (SET) and double embryo transfer (DET).

Results

Two hundred elven IVF (fresh embryo transfer), 128 FET (frozen embryo transfer cycles, no PGS), and 111 PGS cycles (ovarian stimulation with embryo cryopreservation, PGS, and frozen transfer in a subsequent estrogen-primed cycle) with initial positive hCG values were analyzed. In patients achieving a positive hCG after SET, initial hCG values were higher after PGS compared to FET (182.4 versus 124.0 mIU/mL, p = 0.02) and IVF (182.4 versus 87.1 mIU/mL, p < 0.001) as well as FET compared to IVF (124.0 versus 87.1 mIU/mL, p < 0.01). After DET, initial hCG values were higher after PGS (222.8 mIU/mL) compared to FET (182.1 mIU/mL, p = 0.02) and IVF (131.1 mIU/mL, p = 0.001).

Conclusions

Our study suggests that initial serum hCG values are higher after using PGS and higher after the transfer of a frozen embryo compared to a fresh embryo. This suggests that initial hCG values relate to the chromosomal status of embryos. Initial hCG values may help determine intervention and monitoring later in pregnancy.

Helmerhorst FM, Perquin DA, Donker D, Keirse MJ. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ. 2004;328(7434):261. doi:10.1136/bmj.37957.560278.EE.CrossRefPubMedPubMedCentral

Jackson RA, Gibson KA, Wu YW, Croughan MS. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol. 2004;103(3):551–63. doi:10.1097/01.AOG.0000114989.84822.51.CrossRefPubMed

Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(5):485–503. doi:10.1093/humupd/dms018.CrossRefPubMed

van Heesch MM, Evers JL, Dumoulin JC, van der Hoeven MA, van Beijsterveldt CE, Bonsel GJ, et al. A comparison of perinatal outcomes in singletons and multiples born after in vitro fertilization or intracytoplasmic sperm injection stratified for neonatal risk criteria. Acta Obstet Gynecol Scand. 2014;93(3):277–86. doi:10.1111/aogs.12328.CrossRefPubMed

Hayashi M, Nakai A, Satoh S, Matsuda Y. Adverse obstetric and perinatal outcomes of singleton pregnancies may be related to maternal factors associated with infertility rather than the type of assisted reproductive technology procedure used. Fertil Steril. 2012;98(4):922–8. doi:10.1016/j.fertnstert.2012.05.049.CrossRefPubMed

Joffe M, Li Z. Association of time to pregnancy and the outcome of pregnancy. Fertil Steril. 1994;62(1):71–5.CrossRefPubMed

Thomson F, Shanbhag S, Templeton A, Bhattacharya S. Obstetric outcome in women with subfertility. BJOG: an international journal of obstetrics and gynaecology. 2005;112(5):632–7. doi:10.1111/j.1471-0528.2004.00489.x.CrossRef

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006;333(7570):679. doi:10.1136/bmj.38919.495718.AE.CrossRefPubMedPubMedCentral

Raatikainen K, Kuivasaari-Pirinen P, Hippelainen M, Heinonen S. Comparison of the pregnancy outcomes of subfertile women after infertility treatment and in naturally conceived pregnancies. Hum Reprod. 2012;27(4):1162–9. doi:10.1093/humrep/des015.CrossRefPubMed

10.

Apantaku O, Chandrasekaran I, Bentick B. Obstetric outcome of singleton pregnancies achieved with in vitro fertilisation and intracytoplasmic sperm injection: experience from a district general hospital. Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology. 2008;28(4):398–402. doi:10.1080/01443610802091792.CrossRef

11.

De Neubourg D, Gerris J, Mangelschots K, Van Royen E, Vercruyssen M, Steylemans A, et al. The obstetrical and neonatal outcome of babies born after single-embryo transfer in IVF/ICSI compares favourably to spontaneously conceived babies. Hum Reprod. 2006;21(4):1041–6. doi:10.1093/humrep/dei424.CrossRefPubMed

12.

Fujii M, Matsuoka R, Bergel E, van der Poel S, Okai T. Perinatal risk in singleton pregnancies after in vitro fertilization. Fertil Steril. 2010;94(6):2113–7. doi:10.1016/j.fertnstert.2009.12.031.CrossRefPubMed

13.

Stehlik E, Stehlik J, Katayama KP, Kuwayama M, Jambor V, Brohammer R, et al. Vitrification demonstrates significant improvement versus slow freezing of human blastocysts. Reprod BioMed Online. 2005;11(1):53–7.CrossRefPubMed

14.

Rezazadeh Valojerdi M, Eftekhari-Yazdi P, Karimian L, Hassani F, Movaghar B. Vitrification versus slow freezing gives excellent survival, post warming embryo morphology and pregnancy outcomes for human cleaved embryos. J Assist Reprod Genet. 2009;26(6):347–54. doi:10.1007/s10815-009-9318-6.CrossRefPubMedPubMedCentral

15.

Kuwayama M, Vajta G, Ieda S, Kato O. Comparison of open and closed methods for vitrification of human embryos and the elimination of potential contamination. Reprod BioMed Online. 2005;11(5):608–14.CrossRefPubMed

16.

Evans J, Hannan NJ, Edgell TA, Vollenhoven BJ, Lutjen PJ, Osianlis T, et al. Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence. Hum Reprod Update. 2014; doi:10.1093/humupd/dmu027.

17.

Song T, Liu L, Zhou F, Lin XN, Zhang SY. Frozen-thawed embryo transfer (FET) versus fresh embryo transfer in clinical pregnancy rate during in vitro fertilization-embryo transfer. Zhonghua Yi Xue Za Zhi. 2009;89(41):2928–30.PubMed

18.

Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril. 2014;102(1):10–8. doi:10.1016/j.fertnstert.2014.05.019.CrossRefPubMedPubMedCentral

19.

Wennerholm UB, Henningsen AK, Romundstad LB, Bergh C, Pinborg A, Skjaerven R, et al. Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group. Hum Reprod. 2013;28(9):2545–53. doi:10.1093/humrep/det272.CrossRefPubMed

20.

Pelkonen S, Koivunen R, Gissler M, Nuojua-Huttunen S, Suikkari AM, Hyden-Granskog C, et al. Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995-2006. Hum Reprod. 2010;25(4):914–23. doi:10.1093/humrep/dep477.CrossRefPubMed

21.

Kato O, Kawasaki N, Bodri D, Kuroda T, Kawachiya S, Kato K, et al. Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified versus fresh single embryo transfer. Eur J Obstet Gynecol Reprod Biol. 2012;161(1):46–50. doi:10.1016/j.ejogrb.2011.12.005.CrossRefPubMed

22.

Maheshwari A, Kalampokas T, Davidson J, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of blastocyst-stage versus cleavage-stage embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2013;100(6):1615–21 e1-10. doi:10.1016/j.fertnstert.2013.08.044.CrossRefPubMed

23.

Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, et al. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod. 2014;29(6):1173–81. doi:10.1093/humrep/deu033.CrossRefPubMed

24.

Taylor TH, Patrick JL, Gitlin SA, Wilson JM, Crain JL, Griffin DK. Comparison of aneuploidy, pregnancy and live birth rates between day 5 and day 6 blastocysts. Reprod BioMed Online. 2014; doi:10.1016/j.rbmo.2014.06.001.

25.

Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril. 2014;101(3):656–63 e1. doi:10.1016/j.fertnstert.2013.11.004.CrossRefPubMed

26.

Munne S, Chen S, Colls P, Garrisi J, Zheng X, Cekleniak N, et al. Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos. Reprod BioMed Online. 2007;14(5):628–34.CrossRefPubMed

27.

Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Clinical rationale for cryopreservation of entire embryo cohorts in lieu of fresh transfer. Fertil Steril. 2014;102(1):3–9. doi:10.1016/j.fertnstert.2014.04.018.CrossRefPubMed

28.

Yang Z, Salem SA, Liu X, Kuang Y, Salem RD, Liu J. Selection of euploid blastocysts for cryopreservation with array comparative genomic hybridization (aCGH) results in increased implantation rates in subsequent frozen and thawed embryo transfer cycles. Mol Cytogenet. 2013;6(1):32. doi:10.1186/1755-8166-6-32.CrossRefPubMedPubMedCentral

29.

al-Sebai MA, Diver M, Hipkin LJ. The role of a single free beta-human chorionic gonadotrophin measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability. Hum Reprod. 1996;11(4):881–8.CrossRefPubMed

30.

Qasim SM, Callan C, Choe JK. The predictive value of an initial serum beta human chorionic gonadotropin level for pregnancy outcome following in vitro fertilization. J Assist Reprod Genet. 1996;13(9):705–8.CrossRefPubMed

31.

Asvold BO, Vatten LJ, Tanbo TG, Eskild A. Concentrations of human chorionic gonadotrophin in very early pregnancy and subsequent pre-eclampsia: a cohort study. Hum Reprod. 2014;29(6):1153–60. doi:10.1093/humrep/deu068.CrossRefPubMed

32.

Eskandar MA, Al-Shahrani M, Shaamash A, El-Emain M, Al-Ahmad M, Payodon B. Early maternal serum beta-human chorionic gonadotropin measurements after ICSI in the prediction of long-term pregnancy outcomes: a retrospective cohort analysis. Journal of clinical medicine research. 2011;3(1):30–5. doi:10.4021/jocmr477e.PubMedPubMedCentral

33.

Singh N, Goyal M, Malhotra N, Tiwari A, Badiger S. Predictive value of early serum beta-human chorionic gonadotrophin for the successful outcome in women undergoing in vitro fertilization. Journal of human reproductive sciences. 2013;6(4):245–7. doi:10.4103/0974-1208.126291.CrossRefPubMedPubMedCentral

34.

McCoy TW, Nakajima ST, Bohler HC Jr. Age and a single day-14 beta-HCG can predict ongoing pregnancy following IVF. Reprod BioMed Online. 2009;19(1):114–20.CrossRefPubMed

35.

Shamonki MI, Frattarelli JL, Bergh PA, Scott RT. Logarithmic curves depicting initial level and rise of serum beta human chorionic gonadotropin and live delivery outcomes with in vitro fertilization: an analysis of 6021 pregnancies. Fertil Steril. 2009;91(5):1760–4. doi:10.1016/j.fertnstert.2008.02.171.CrossRefPubMed

36.

Oron G, Esh-Broder E, Son WY, Holzer H, Tulandi T. Predictive value of maternal serum human chorionic gonadotropin levels in pregnancies achieved by in vitro fertilization with single cleavage and single blastocyst embryo transfers. Fertil Steril. 2015;103(6):1526–31 e2. doi:10.1016/j.fertnstert.2015.02.028.CrossRefPubMed

37.

Kathiresan AS, Cruz-Almeida Y, Barrionuevo MJ, Maxson WS, Hoffman DI, Weitzman VN, et al. Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization. Fertil Steril. 2011;96(6):1362–6. doi:10.1016/j.fertnstert.2011.09.042.CrossRefPubMed

38.

Kumbak B, Oral E, Karlikaya G, Lacin S, Kahraman S. Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome. Reprod BioMed Online. 2006;13(4):459–64.CrossRefPubMed

39.

Gardner DK, Vella P, Lane M, Wagley L, Schlenker T, Schoolcraft WB. Culture and transfer of human blastocysts increases implantation rates and reduces the need for multiple embryo transfers. Fertil Steril. 1998;69(1):84–8.CrossRefPubMed

40.

Reljic M, Knez J, Vlaisavljevic V. Human chorionic gonadotropin levels are equally predictive for pregnancy outcome after fresh and vitrified-warmed blastocyst transfer. J Assist Reprod Genet. 2013;30(11):1459–63. doi:10.1007/s10815-013-0099-6.CrossRefPubMedPubMedCentral

41.

Sung N, Kwak-Kim J, Koo HS, Yang KM. Serum hCG-beta levels of postovulatory day 12 and 14 with the sequential application of hCG-beta fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle. J Assist Reprod Genet. 2016;33(9):1185–94. doi:10.1007/s10815-016-0744-y.CrossRefPubMedPubMedCentral

42.

Pereira N, Elias RT, Christos PJ, Petrini AC, Hancock K, Lekovich JP, et al. Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer. Hum Reprod. 2017:1–8. doi:10.1093/humrep/dex095.

43.

Pereira N, Reichman DE, Goldschlag DE, Lekovich JP, Rosenwaks Z. Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles. J Assist Reprod Genet. 2015;32(4):527–32. doi:10.1007/s10815-015-0434-1.CrossRefPubMedPubMedCentral

44.

Wang H, Zhou C, Chen W, Li T, Huang J, Zhuang G. Supraphysiological estrogen levels adversely impact proliferation and histone modification in human embryonic stem cells: possible implications for controlled ovarian hyperstimulation assisted pregnancy. Eur J Obstet Gynecol Reprod Biol. 2011;155(1):58–64. doi:10.1016/j.ejogrb.2010.11.014.CrossRefPubMed

45.

Schuchter K, Hafner E, Stangl G, Metzenbauer M, Hofinger D, Philipp K. The first trimester ‘combined test’ for the detection of down syndrome pregnancies in 4939 unselected pregnancies. Prenat Diagn. 2002;22(3):211–5.CrossRefPubMed

46.

Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-trimester screening for Down’s syndrome. Prenat Diagn. 1997;17(9):821–9.CrossRefPubMed

47.

Spencer K, Spencer CE, Power M, Moakes A, Nicolaides KH. One stop clinic for assessment of risk for fetal anomalies: a report of the first year of prospective screening for chromosomal anomalies in the first trimester. BJOG: an international journal of obstetrics and gynaecology. 2000;107(10):1271–5.CrossRef

48.

Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience. BJOG: an international journal of obstetrics and gynaecology. 2003;110(3):281–6.CrossRef

49.

Sirikunalai P, Wanapirak C, Sirichotiyakul S, Tongprasert F, Srisupundit K, Luewan S, et al. Associations between maternal serum free beta human chorionic gonadotropin (beta-hCG) levels and adverse pregnancy outcomes. Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology. 2016;36(2):178–82. doi:10.3109/01443615.2015.1036400.CrossRef

50.

Urbancsek J, Hauzman E, Fedorcsak P, Halmos A, Devenyi N, Papp Z. Serum human chorionic gonadotropin measurements may predict pregnancy outcome and multiple gestation after in vitro fertilization. Fertil Steril. 2002;78(3):540–2.CrossRefPubMed

Title: Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort
Authors: Elie Hobeika
Sonali Singh
Shaveta Malik
Eric S. Knochenhauer
Michael L. Traub
Publication date: 01-10-2017
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 10/2017
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-017-0987-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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