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Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 1/2016

01-01-2016 | Assisted Reproduction Technologies

Independent factors influencing large-for-gestation birth weight in singletons born after in vitro fertilization

Authors: Sara Korosec, Helena Ban Frangez, Lili Steblovnik, Ivan Verdenik, Eda Vrtacnik Bokal

Published in: Journal of Assisted Reproduction and Genetics | Issue 1/2016

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Abstract

Purpose

Higher risk for birth of singletons being large for gestational age (LGA) has been revealed after in vitro fertilization (IVF) frozen–thawed embryo-transfer (FET). This phenomenon is now being investigated, since there is a speculation that these neonates could suffer from underlying epigenetic disturbances. The aim of the study was to expose independent LGA risk factors and to identify those connected to the IVF techniques.

Methods

Altogether, 4508 singleton pregnancies and births were included in the cohort case-matched study. Two hundred eleven singleton pregnancies and births after FET and 916 after fresh embryo transfer (ET) were included into two study groups. The IVF procedures were performed at the University Medical Centre Ljubljana between 2004 and 2011. For each IVF pregnancy, three matched consecutive controls after natural conception were included. Using logistic regression models, we observed LGA connection to maternal parameters (smoking, hypertension, parity, BMI, gestational diabetes, IVF conception, FET, double ET, and ICSI procedure).

Results

Singletons born after FET had a significantly higher risk for being LGA (p = 0.032; OR 1.697; 95 % CI 1.047–2.752). BMI 25–30 was a significant independent risk factor for LGA in the IVF groups (FET p = 0.041, OR 2.460, 95 % CI 1.030–5.857 and fresh ET p = 0.003; OR 2.188, 95 % CI 1.297–3.691). ICSI and double ET had no significant effect on LGA occurrence.

Conclusions

Besides maternal BMI, FET is a significant independent LGA risk factor in IVF patients. Other observed factors (smoking, hypertension, multiparity, GDM, ICSI procedure, or number of embryos transferred) do not influence LGA risk significantly.
Literature
1.
Sullivan EA, Zegers-Hochschild F, Mansour R, Ishihara O, de Mouzon J, Nygren KG, et al. International committee for monitoring assisted reproductive technologies (ICMART) world report: assisted reproductive technology 2004. Hum Reprod. 2013;28(5):1375–90.PubMedCrossRef
2.
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.PubMedCrossRef
3.
Ishihara O, Araki R, Kuwahara A, Itakura A, Saito H, Adamson GD. Impact of frozen thawed single-blastocyst transfer on maternal and neonatal outcome: an analysis of 277,042 single-embryo transfer cycles from 2008 to 2010 in Japan. FertilSteril. 2014;101(1):128–33.
4.
Wennerholm UB, Söderström-Anttila V, Bergh C, Aittomäki K, Hazekamp J, Nygren KG, et al. Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. Hum Reprod. 2009;24(9):2158–72.PubMedCrossRef
5.
Henningsen AK, Pinborg A, Lidegaard Ø, Vestergaard C, Forman JL, Andersen AN. Perinatal outcome of singleton siblings born after assisted reproductive technology and spontaneous conception: Danish national sibling-cohort study. Fertil Steril. 2011;95(3):959–63.PubMedCrossRef
6.
Healy DL, Breheny S, Halliday J, Jaques A, Rushford D, Garrett C, et al. Prevalence and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive technology in Victoria Australia. Hum Reprod. 2010;25(1):265–74.PubMedCrossRef
7.
Korosec S, Ban Frangez H, Verdenik I, Kladnik U, Kotar V, Virant-Klun I, et al. Singleton pregnancy outcomes after in vitro fertilization with fresh or frozen-thawed embryo transfer and incidence of placenta previa. Biomed Res Int. 2014;2014:431797.PubMedPubMedCentralCrossRef
8.
Pinborg A, Henningsen AA, Loft A, Malchau SS, Nyboe FJ, Andersen A. Large baby syndrome in singletons born after frozen embryo transfer (FET): is it due to maternal factors or the cryotechnique? Hum Reprod. 2014;29(3):618–27.PubMedCrossRef
9.
Belva F, Henriet S, Van den Abbeel E, Camus M, Devroey P, Van der Elst J. LiebaersI, Haentjens P, Bonduelle M. Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles. Hum Reprod. 2008;23(10):2227–38.PubMedCrossRef
10.
Pelkonen S, Koivunen R, Gissler M, Nuojua-Huttunen S, Suikkari AM, Hydén-Granskog C, Martikainen H, Tiitinen A, Hartikainen 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.
11.
Li Z, Wang YA, Ledger W, Sullivan EA. Birthweight percentiles by gestational age for births following assisted reproductive technology in Australia and New Zealand, 2002–2010. Hum Reprod. 2014;29(8):1787–800.PubMedCrossRef
12.
Marino JL, Moore VM, Willson KJ, Rumbold A, Whitrow MJ, Giles LC, Davies MJ. Perinatal outcomes by mode of assisted conception and sub-fertility in an Australian data linkage cohort. PLoS One. 2014; 8;9(1):e80398.
13.
Sazonova A, Källen K, Thurin-Kjellberg A, Wennerholm UB, Bergh C. Obstetric outcome in singletons after in vitro fertilization with cryopreserved/thawed embryos. Hum Reprod. 2012;27(5):1343–50.PubMedCrossRef
14.
Hansen M, Bower C. The impact of assisted reproductive technologies on intra-uterine growth and birth defects in singletons. Semin Fetal Neonatal Med. 2014;19(4):228–33.PubMedCrossRef
15.
Weissmann-Brenner A, Simchen MJ, Zilberberg E, Kalter A, Weisz B, Achiron R, et al. Maternal and neonatal outcomes of large for gestational age pregnancies. Acta Obstet Gynecol Scand. 2012;91(7):844–9.PubMedCrossRef
16.
Bukowski R, Hansen NI, Willinger M, Reddy UM, Parker CB, Pinar H, et al. Fetal growth and risk of stillbirth: a population-based case-control study. PLoS Med. 2014;11(4):e1001633.PubMedPubMedCentralCrossRef
17.
Henriksen T. The macrosomicfetus: a challenge in current obstetrics. Acta ObstetGynecol Scand. 2008;87:134–45.CrossRef
18.
Grace SK, Sinclair KD. Assisted reproductive technology, epigenetics, and long-term health: a developmental time bomb still ticking. Semin Reprod Med. 2009;27(5):409–16.PubMedCrossRef
19.
Chen Z, Robbins KM, Wells KD, Rivera RM. Large offspring syndrome: a bovie model for the human loss-of-imprinting overgrowth syndrome Beckwith-Wiedemann. Epigenetics. 2013;8(6):591–601.PubMedPubMedCentralCrossRef
20.
Kappil MA, Green BB, Armstrong DA, Sharp AJ, Lambertini L, Marsit CJ, et al. Placental expression profile of imprinted genes impacts birth weight. Epigenetics. 2015;10(9):842–9.PubMedCrossRef
21.
Zhu J, Lin S, Li M, Chen L, Lian Y, Liu P, et al. Effect of in vitro culture period on birthweight of singleton newborns. Hum Reprod. 2014;29(3):448–54.PubMedCrossRef
22.
Lemmen JG, Pinborg A, Rasmussen S, Ziebe S. Birthweight distribution in ART singletons resulting from embryo culture in two different culture media compared with the national population. Hum Reprod. 2014;27.
23.
Eskild A, Monkerud L, Tanbo T. Birthweight and placental weight; do changes in culture media used for IVF matter? Comparisons with spontaneous pregnancies in the corresponding time periods. Hum Reprod. 2013;28(12):3207–14.PubMedCrossRef
24.
Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. Obstetric andperinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. FertilSteril. 2012;98(2):368–77.
25.
Zhu J, Li M, Chen L, Liu P, Qiao J. The protein source in embryo culture media influences birthweight: a comparative study between G1 v5 and G1-PLUS v5. Hum Reprod. 2014;29(7):1387–92.PubMedCrossRef
26.
Griesinger G, Kolibianakis EM, Diedrich K, Ludwig M. Ovarian stimulation for IVF has no quantitative association with birthweight: a registry study. Hum Reprod. 2008;23(11):2549–54.PubMedCrossRef
27.
Ban Frangez H, Korosec S, Verdenik I, Kladnik V, Kotar U, Vrtacnik BE. Preterm delivery risk factors in singletons born after in vitro fertilization procedures. Eur J Obstet Gynecol Reprod Biol. 2014;176:183–6.PubMedCrossRef
28.
Haavaldsen C, Tanbo T, Eskild A. Placental weight in singleton pregnancies with and without assisted reproductive technology: a population study of 536,567 pregnancies. Hum Reprod. 2012;27(2):576–82.PubMedCrossRef
29.
Al-Khaduri M, Kadoch IJ, Couturier B, Dubé J, Lapensée L, Bissonnette F. Vasapraevia after IVF: should there be guidelines? Report of two cases and literature review. Reprod Biomed Online. 2007;14(3):372–4.PubMedCrossRef
30.
Romundstad LB, Romundstad PR, Sunde A, von Düring V, Skjaerven R, Vatten LJ. Increased risk of placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in the same mother. Hum Reprod. 2006;21(9):2353–8.PubMedCrossRef
31.
Farhi J, Ben-Haroush A, Andrawus N, Pinkas H, Sapir O, Fisch B, et al. High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation. Reprod Biomed Online. 2010;21(3):331–7.PubMedCrossRef
32.
Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155–8.PubMedCrossRef
33.
Virant-Klun I, Tomazevic T, Bacer-Kermavner L, Mivsek J, Valentincic-Gruden B, Meden-Vrtovec H. Successful freezing and thawing of blastocysts cultured in sequential media using a modified method. FertilSteril. 2003;79:1428–33.
34.
Verdenik I. Slovene reference standards for weight, length and head circumference at birth for given gestational age of population born in years 1987–96. Zdravniškivestnik. 2000;69(3):153–6.
35.
Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol. 1982;144:768–73.PubMed
36.
Schimmel MS, Bromiker R, Hammerman C, Chertman L, Ioscovich A, Granovsky-Grisaru S, et al. The effects of maternal age and parity on maternal and neonatal outcome. Arch Gynecol Obstet. 2015;291:793–8.PubMedCrossRef
37.
Mäkinen S, Söderström-Anttila V, Vainio J, Suikkari AM, Tuuri T. Does long in vitro culture promote large for gestational age babies? Hum Reprod. 2013;28(3):828–34.PubMedCrossRef
38.
Toshimitsu M, Nagamatsu T, Nagasaka T, Iwasawa-Kawai Y, Komatsu A, Yamashita T, et al. Increased risk of pregnancy-induced hypertension and operative delivery after conception induced by in vitro fertilization/intracytoplasmic sperm injection in women aged 40 years and older. Fertil Steril. 2014;102(4):1065–70.PubMedCrossRef
39.
Sazonova A, Källen K, Thurin-Kjellberg A, Wennerholm UB, Bergh C. Factors affecting obstetric outcome of singletons born after IVF. Hum Reprod. 2011;26(10):2878–86.PubMedCrossRef
40.
Lintsen AM, Pasker-de Jong PC, de Boer EJ, Burger CW, Jansen CA, Braat DD, et al. Effects of subfertility cause, smoking and body weight on the success rate of IVF. Hum Reprod. 2005;20(7):1867–75.PubMedCrossRef
41.
Koning AM, Mutsaerts MA, Kuchenbecker WK, Broekmans FJ, Land JA, Mol BW, et al. Complications and outcome of assisted reproduction technologies in overweight and obese women. Hum Reprod. 2012;27(2):457–67.PubMedCrossRef
40.
Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, El-Toukhy T. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online. 2011;23(4):421–39.PubMedCrossRef
41.
Legge A, Bouzayen R, Hamilton L, Young D. The impact of maternal body mass index on in vitro fertilization outcomes. J Obstet Gynaecol Can. 2014;36(7):613–9.PubMedCrossRef
42.
Bailey AP, Hawkins LK, Missmer SA, Correia KF, Yanushpolsky EH. Effect of body mass index on in vitro fertilization outcomes in women with polycystic ovary syndrome. Am J Obstet Gynecol. 2014;211(2):163.PubMedCrossRef
43.
Pinborg A, Gaarslev C, Hougaard CO, Nyboe Andersen A, Andersen PK, Boivin J, et al. Influence of female bodyweight on IVF outcome: a longitudinal multicentre cohort study of 487 infertile couples. Reprod Biomed Online. 2011;23(4):490–9.PubMedCrossRef
44.
Chavarro JE, Ehrlich S, Colaci DS, Wright DL, Toth TL, Petrozza JC, et al. Body mass index and short-term weight change in relation to treatment outcomes in women undergoing assisted reproduction. Fertil Steril. 2012;98(1):109–16.PubMedPubMedCentralCrossRef
45.
Palomba S, Falbo A, Valli B, Morini D, Villani MT, Nicoli A, et al. Physical activity before IVF and ICSI cycles in infertile obese women: an observational cohort study. RBM Online. 2014;29(1):72–9.PubMed
46.
Nouri K, Ott J, Stoegbauer L, Pietrowski D, Frantal S, Walch K. Obstetric and perinatal outcomes in IVF versus ICSI-conceived pregnancies at a tertiary care center—a pilot study. Reprod Biol Endocrinol. 2013;11:84.PubMedPubMedCentralCrossRef
47.
Grady R, Alavi N, Vale R, Khandwala M, McDonald SD. Elective single embryo transfer and perinatal outcomes: a systematic review and meta-analysis. FertilSteril. 2012;97(2):324–31.
48.
Acosta O, Ramirez VI, Lager S, Gaccioli F, Dudley DJ, Powell TL, et al. Increased glucose and placental GLUT-1 in large babies of obese non-diabetic mothers. Am J Obstet Gynecol. 2015;212(2):227.e1–7.CrossRef
49.
Van Landuyt L, Van de Velde H, De Vos A, Haentjens P, Blockeel C, Tournaye H, et al. Influence of cell loss after vitrification or slow-freezing on further in vitro development and implantation of human Day 3 embryos. Hum Reprod. 2013;28(11):2943–9.PubMedCrossRef
50.
Veleva Z, Orava M, Nuojua-Huttunen S, Tapanainen JS, Martikainen H. Factors affecting the outcome of frozen-thawed embryo transfer. Hum Reprod. 2013;28(9):2425–31.PubMedCrossRef
51.
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.PubMedCrossRef
Metadata
Title
Independent factors influencing large-for-gestation birth weight in singletons born after in vitro fertilization
Authors
Sara Korosec
Helena Ban Frangez
Lili Steblovnik
Ivan Verdenik
Eda Vrtacnik Bokal
Publication date
01-01-2016
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 1/2016
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-015-0601-4

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