Advertisement

Ongoing Developments in ART and Pregnancy Outcome

  • Joo P. TeohEmail author
  • Abha Maheshwari
Chapter

Abstract

IVF is now almost synonymous with all ART. Over the years the practice of IVF has become increasingly common as the treatment option for subfertility. In this field there is no lack of innovative ideas and techniques in exploring new frontiers, largely with the aim to improve pregnancy outcome. New technologies and skills researched by academic and commercial organisations have also significantly widened the scope of ART application; the discovery of ovarian tissue preservation, and the improvement in egg freezing technique have enabled many women to consider fertility preservation in certain circumstances. While these may seem promising in short term, data on long term outcomes of these techniques are limited and take time to accumulate. As more and more data are emerging, their safety for long term health of offspring born have also been questioned. In this chapter we review the evidence of laboratorial, surgical and clinical developments in ART and their impact on pregnancy outcomes as is available now and future directions.

Keywords

ART Safety ICSI IVF MESA TESA TESE IVM PGS PGD Fertility preservation Artificial hatching Immunotherapy 

References

  1. 1.
    Sunderam S, Kissin DM, Crawford SB, Folger SG, Jamieson DJ, Barfield WD. Assisted reproductive technology surveillance – United States, 2011. MMWR Surveil Summ (Washington, DC : 2002). 2014;63(10):1–28.Google Scholar
  2. 2.
    Brison DR, Roberts SA, Kimber SJ. How should we assess the safety of IVF technologies? Reprod Biomed Online. 2013;27(6):710–21.CrossRefPubMedGoogle Scholar
  3. 3.
    Kimura H, Yamagata K. Visualization of epigenetic modifications in preimplantation embryos. Meth Mol Biol (Clifton, NJ). 2015;1222:127–47.CrossRefGoogle Scholar
  4. 4.
    Lanzendorf SE, Maloney MK, Veeck LL, Slusser J, Hodgen GD, Rosenwaks Z. A preclinical evaluation of pronuclear formation by microinjection of human spermatozoa into human oocytes. Fertil Steril. 1988;49(5):835–42.CrossRefPubMedGoogle Scholar
  5. 5.
    Ishihara O, Adamson GD, Dyer S, et al. International committee for monitoring assisted reproductive technologies: world report on assisted reproductive technologies, 2007. Fertil Steril. 2015;103(2):402–413.e411.CrossRefPubMedGoogle Scholar
  6. 6.
    Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015;313(3):255–63.CrossRefPubMedGoogle Scholar
  7. 7.
    Palermo GD, Neri QV, Monahan D, Kocent J, Rosenwaks Z. Development and current applications of assisted fertilization. Fertil Steril. 2012;97(2):248–59.CrossRefPubMedGoogle Scholar
  8. 8.
    Woldringh GH, Janssen IM, Hehir-Kwa JY, et al. Constitutional DNA copy number changes in ICSI children. Hum Reprod. 2009;24(1):233–40.CrossRefPubMedGoogle Scholar
  9. 9.
    Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med. 2002;346(10):725–30.CrossRefPubMedGoogle Scholar
  10. 10.
    Hindryckx A, Peeraer K, Debrock S, et al. Has the prevalence of congenital abnormalities after intracytoplasmic sperm injection increased? The Leuven data 1994–2000 and a review of the literature. Gynecol Obstet Invest. 2010;70(1):11–22.CrossRefPubMedGoogle Scholar
  11. 11.
    Palermo GD, Neri QV, Rosenwaks Z. Safety of intracytoplasmic sperm injection. Meth Mol Biol (Clifton, NJ). 2014;1154:549–62.CrossRefGoogle Scholar
  12. 12.
    Palermo GD, Neri QV, Takeuchi T, Squires J, Moy F, Rosenwaks Z. Genetic and epigenetic characteristics of ICSI children. Reprod Biomed Online. 2008;17(6):820–33.CrossRefPubMedGoogle Scholar
  13. 13.
    Goldbeck L, Gagsteiger F, Mindermann I, Strobele S, Izat Y. Cognitive development of singletons conceived by intracytoplasmic sperm injection or in vitro fertilization at age 5 and 10 years. J Pediatr Psychol. 2009;34(7):774–81.CrossRefPubMedGoogle Scholar
  14. 14.
    Leunens L, Celestin-Westreich S, Bonduelle M, Liebaers I, Ponjaert-Kristoffersen I. Follow-up of cognitive and motor development of 10-year-old singleton children born after ICSI compared with spontaneously conceived children. Hum Reprod. 2008;23(1):105–11.CrossRefPubMedGoogle Scholar
  15. 15.
    Ponjaert-Kristoffersen I, Tjus T, Nekkebroeck J, et al. Psychological follow-up study of 5-year-old ICSI children. Hum Reprod. 2004;19(12):2791–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Basatemur E, Shevlin M, Sutcliffe A. Growth of children conceived by IVF and ICSI up to 12 years of age. Reprod Biomed Online. 2010;20(1):144–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Belva F, Painter R, Bonduelle M, Roelants M, Devroey P, De Schepper J. Are ICSI adolescents at risk for increased adiposity? Hum Reprod. 2012;27(1):257–64.CrossRefPubMedGoogle Scholar
  18. 18.
    Belva F, Roelants M, De Schepper J, et al. Blood pressure in ICSI-conceived adolescents. Hum Reprod. 2012;27(10):3100–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Belva F, Painter RC, Schiettecatte J, et al. Gender-specific alterations in salivary cortisol levels in pubertal intracytoplasmic sperm injection offspring. Horm Res Paediatr. 2013;80(5):350–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Halliday J. Outcomes for offspring of men having ICSI for male factor infertility. Asian J Androl. 2012;14(1):116–20.CrossRefPubMedGoogle Scholar
  21. 21.
    Kallen B, Finnstrom O, Lindam A, Nilsson E, Nygren KG, Otterblad PO. Congenital malformations in infants born after in vitro fertilization in Sweden. Birth defects research. Part A. Clin Mol Teratol. 2010;88(3):137–43.Google Scholar
  22. 22.
    Silber SJ. The Y chromosome in the era of intracytoplasmic sperm injection: a personal review. Fertil Steril. 2011;95(8):2439–2448.e2431–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Ceelen M, van Weissenbruch MM, Roos JC, Vermeiden JP, van Leeuwen FE, Delemarre-van de Waal HA. Body composition in children and adolescents born after in vitro fertilization or spontaneous conception. J Clin Endocrinol Metab. 2007;92(9):3417–23.CrossRefPubMedGoogle Scholar
  24. 24.
    Said TM, Land JA. Effects of advanced selection methods on sperm quality and ART outcome: a systematic review. Hum Reprod Update. 2011;17(6):719–33.CrossRefPubMedGoogle Scholar
  25. 25.
    Shalom-Paz E, Anabusi S, Michaeli M, et al. Can intra cytoplasmatic morphologically selected sperm injection (IMSI) technique improve outcome in patients with repeated IVF-ICSI failure? a comparative study. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2015;31(3):247–51.Google Scholar
  26. 26.
    Teixeira DM, Barbosa MA, Ferriani RA, et al. Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction. Cochrane Database Syst Rev. 2013;(7):CD010167.Google Scholar
  27. 27.
    Yarali H, Polat M, Bozdag G, et al. TESE-ICSI in patients with non-mosaic Klinefelter syndrome: a comparative study. Reprod Biomed Online. 2009;18(6):756–60.CrossRefPubMedGoogle Scholar
  28. 28.
    Greco E, Scarselli F, Minasi MG, et al. Birth of 16 healthy children after ICSI in cases of nonmosaic Klinefelter syndrome. Hum Reprod. 2013;28(5):1155–60.CrossRefPubMedGoogle Scholar
  29. 29.
    Hsiao W, Stahl PJ, Osterberg EC, et al. Successful treatment of postchemotherapy azoospermia with microsurgical testicular sperm extraction: the Weill Cornell experience. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(12):1607–11.CrossRefGoogle Scholar
  30. 30.
    Yuanyuan Z, Qiang D, Xiaoliang L, Wanting C, Rong H, Yanyan Z. [Screening of azoospermia factor microdeletions on Y chromosome in infertile men by QF-PCR]. Yi chuan=Hereditas/Zhongguo yi chuan xue hui bian ji. 2014;36(6):552–7.Google Scholar
  31. 31.
    Oron G, Fisch B, Sapir O, et al. Pregnancy outcome after ICSI with thawed testicular sperm from men with non-obstructive azoospermia compared to ICSI with ejaculated sperm from men with severe oligoasthenoteratozoospermia and IVF with normal ejaculated sperm. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2014;30(2):103–6.CrossRefGoogle Scholar
  32. 32.
    Guo YH, Dong RN, Su YC, Li J, Zhang YJ, Sun YP. Follow-up of children born after intracytoplasmic sperm injection with epididymal and testicular spermatozoa. Chin Med J (Engl). 2013;126(11):2129–33.Google Scholar
  33. 33.
    Fedder J, Loft A, Parner ET, Rasmussen S, Pinborg A. Neonatal outcome and congenital malformations in children born after ICSI with testicular or epididymal sperm: a controlled national cohort study. Hum Reprod. 2013;28(1):230–40.CrossRefPubMedGoogle Scholar
  34. 34.
    Woldringh GH, Horvers M, Janssen AJ, et al. Follow-up of children born after ICSI with epididymal spermatozoa. Hum Reprod. 2011;26(7):1759–67.CrossRefPubMedGoogle Scholar
  35. 35.
    Belva F, De Schrijver F, Tournaye H, et al. Neonatal outcome of 724 children born after ICSI using non-ejaculated sperm. Hum Reprod. 2011;26(7):1752–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Esteves SC, Agarwal A. Reproductive outcomes, including neonatal data, following sperm injection in men with obstructive and nonobstructive azoospermia: case series and systematic review. Clinics (Sao Paulo). 2013;68 Suppl 1:141–50.CrossRefGoogle Scholar
  37. 37.
    He X, Cao Y, Zhang Z, et al. Spermatogenesis affects the outcome of ICSI for azoospermic patients rather than sperm retrieval method. Syst Biol Reprod Med. 2010;56(6):457–64.CrossRefPubMedGoogle Scholar
  38. 38.
    Fedder J, Gabrielsen A, Humaidan P, Erb K, Ernst E, Loft A. Malformation rate and sex ratio in 412 children conceived with epididymal or testicular sperm. Hum Reprod. 2007;22(4):1080–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Wennerholm UB, Bonduelle M, Sutcliffe A, et al. Paternal sperm concentration and growth and cognitive development in children born with a gestational age more than 32 weeks after assisted reproductive therapy. Hum Reprod. 2006;21(6):1514–20.CrossRefPubMedGoogle Scholar
  40. 40.
    Tsai YR, Lan KC, Tsai CC, et al. Pregnancy outcome and neonatal data of children born after intracytoplasmic sperm injection with a different duration of cryopreservation of spermatozoa obtained through testicular sperm extraction. Taiwan J Obstet Gynecol. 2013;52(3):329–34.CrossRefPubMedGoogle Scholar
  41. 41.
    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.CrossRefPubMedGoogle Scholar
  42. 42.
    Carrasco B, Boada M, Rodriguez I, Coroleu B, Barri PN, Veiga A. Does culture medium influence offspring birth weight? Fertil Steril. 2013;100(5):1283–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Strowitzki T. In vitro maturation (IVM) of human oocytes. Arch Gynecol Obstet. 2013;288(5):971–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Fadini R, Mignini Renzini M, Guarnieri T, et al. Comparison of the obstetric and perinatal outcomes of children conceived from in vitro or in vivo matured oocytes in in vitro maturation treatments with births from conventional ICSI cycles. Hum Reprod. 2012;27(12):3601–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Yoshida H, Abe H, Arima T. Quality evaluation of IVM embryo and imprinting genes of IVM babies. J Assist Reprod Genet. 2013;30(2):221–5.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Virant-Klun I, Knez K, Tomazevic T, Skutella T. Gene expression profiling of human oocytes developed and matured in vivo or in vitro. BioMed Res Int. 2013;2013:879489.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Wang YA, Costello M, Chapman M, Black D, Sullivan EA. Transfers of fresh blastocysts and blastocysts cultured from thawed cleavage embryos are associated with fewer miscarriages. Reprod Biomed Online. 2011;23(6):777–88.CrossRefPubMedGoogle Scholar
  48. 48.
    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.CrossRefPubMedGoogle Scholar
  49. 49.
    Dar S, Librach CL, Gunby J, Bissonnette F, Cowan L. Increased risk of preterm birth in singleton pregnancies after blastocyst versus Day 3 embryo transfer: Canadian ART Register (CARTR) analysis. Hum Reprod. 2013;28(4):924–8.CrossRefPubMedGoogle Scholar
  50. 50.
    Luke B, Brown MB, Wantman E, Stern JE. Factors associated with monozygosity in assisted reproductive technology pregnancies and the risk of recurrence using linked cycles. Fertil Steril. 2014;101(3):683–9.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Knopman JM, Krey LC, Oh C, Lee J, McCaffrey C, Noyes N. What makes them split? Identifying risk factors that lead to monozygotic twins after in vitro fertilization. Fertil Steril. 2014;102(1):82–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Kanter JR, Boulet S, Kawwass JF, Jamieson DJ, Kissin D. Trends and correlates of monozygotic twinning after assisted reproductive technology. Obstet Gynecol. 2014;123 Suppl 1:6s.CrossRefGoogle Scholar
  53. 53.
    Campbell A, Fishel S, Laegdsmand M. Aneuploidy is a key causal factor of delays in blastulation: author response to ‘A cautionary note against aneuploidy risk assessment using time-lapse imaging’. Reprod Biomed Online. 2014;28(3):279–83.CrossRefPubMedGoogle Scholar
  54. 54.
    Basile N, Nogales Mdel C, Bronet F, et al. Increasing the probability of selecting chromosomally normal embryos by time-lapse morphokinetics analysis. Fertil Steril. 2014;101(3):699–704.CrossRefPubMedGoogle Scholar
  55. 55.
    Rubio I, Galan A, Larreategui Z, et al. Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope. Fertil Steril. 2014;102(5):1287–94.e1285.CrossRefPubMedGoogle Scholar
  56. 56.
    Kaser DJ, Racowsky C. Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review. Hum Reprod Update. 2014;20(5):617–31.CrossRefPubMedGoogle Scholar
  57. 57.
    Kissin DM, Kawwass JF, Monsour M, Boulet SL, Session DR, Jamieson DJ. Assisted hatching: trends and pregnancy outcomes, United States, 2000–2010. Fertil Steril. 2014;102(3):795–801.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Pfeifer S, Lobo R, Sokol R, et al. Role of assisted hatching in in vitro fertilization: a guideline. Fertil Steril. 2014;102(2):348–51.Google Scholar
  59. 59.
    Carney SK, Das S, Blake D, Farquhar C, Seif MM, Nelson L. Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). Cochrane Database Syst Rev. 2012;(12):CD001894.Google Scholar
  60. 60.
    Martins WP, Rocha IA, Ferriani RA, Nastri CO. Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update. 2011;17(4):438–53.CrossRefPubMedGoogle Scholar
  61. 61.
    Zhou H, Zao W, Zhang W, Shi J, Shi W. No adverse effects were identified on the perinatal outcomes after laser-assisted hatching treatment. Reprod Biomed Online. 2014;29(6):692–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Simpson JL. Preimplantation genetic diagnosis at 20 years. Prenat Diagn. 2010;30(7):682–95.CrossRefPubMedGoogle Scholar
  63. 63.
    Eldar-Geva T, Srebnik N, Altarescu G, et al. Neonatal outcome after preimplantation genetic diagnosis. Fertil Steril. 2014;102(4):1016–21.CrossRefPubMedGoogle Scholar
  64. 64.
    Desmyttere S, De Rycke M, Staessen C, et al. Neonatal follow-up of 995 consecutively born children after embryo biopsy for PGD. Hum Reprod. 2012;27(1):288–93.CrossRefPubMedGoogle Scholar
  65. 65.
    Middelburg KJ, Heineman MJ, Haadsma ML, Bos AF, Kok JH, Hadders-Algra M. Neurological condition of infants born after in vitro fertilization with preimplantation genetic screening. Pediatr Res. 2010;67(4):430–4.CrossRefPubMedGoogle Scholar
  66. 66.
    Liebaers I, Desmyttere S, Verpoest W, et al. Report on a consecutive series of 581 children born after blastomere biopsy for preimplantation genetic diagnosis. Hum Reprod. 2010;25(1):275–82.CrossRefPubMedGoogle Scholar
  67. 67.
    Keltz MD, Vega M, Sirota I, et al. Preimplantation genetic screening (PGS) with Comparative genomic hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages. J Assist Reprod Genet. 2013;30(10):1333–9.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Hodes-Wertz B, Grifo J, Ghadir S, et al. Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos. Fertil Steril. 2012;98(3):675–80.CrossRefPubMedGoogle Scholar
  69. 69.
    Fischer J, Colls P, Escudero T, Munne S. Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for translocation carriers with a history of recurrent losses. Fertil Steril. 2010;94(1):283–9.CrossRefPubMedGoogle Scholar
  70. 70.
    Garrisi JG, Colls P, Ferry KM, Zheng X, Garrisi MG, Munne S. Effect of infertility, maternal age, and number of previous miscarriages on the outcome of preimplantation genetic diagnosis for idiopathic recurrent pregnancy loss. Fertil Steril. 2009;92(1):288–95.CrossRefPubMedGoogle Scholar
  71. 71.
    Schendelaar P, Middelburg KJ, Bos AF, et al. The effect of preimplantation genetic screening on neurological, cognitive and behavioural development in 4-year-old children: follow-up of a RCT. Hum Reprod. 2013;28(6):1508–18.CrossRefPubMedGoogle Scholar
  72. 72.
    Middelburg KJ, van der Heide M, Houtzager B, et al. Mental, psychomotor, neurologic, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial. Fertil Steril. 2011;96(1):165–9.CrossRefPubMedGoogle Scholar
  73. 73.
    Cutting R, Barlow S, Anderson R. Human oocyte cryopreservation: evidence for practice. Hum Fertil (Camb). 2009;12(3):125–36.CrossRefGoogle Scholar
  74. 74.
    Paramanantham J, Talmor AJ, Osianlis T, Weston GC. Cryopreserved oocytes: update on clinical applications and success rates. Obstet Gynecol Surv. 2015;70(2):97–114.CrossRefPubMedGoogle Scholar
  75. 75.
    Levi Setti PE, Albani E, Morenghi E, et al. Comparative analysis of fetal and neonatal outcomes of pregnancies from fresh and cryopreserved/thawed oocytes in the same group of patients. Fertil Steril. 2013;100(2):396–401.CrossRefPubMedGoogle Scholar
  76. 76.
    Oktay K, Cil AP, Bang H. Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril. 2006;86(1):70–80.CrossRefPubMedGoogle Scholar
  77. 77.
    Chian RC, Huang JY, Tan SL, et al. Obstetric and perinatal outcome in 200 infants conceived from vitrified oocytes. Reprod Biomed Online. 2008;16(5):608–10.CrossRefPubMedGoogle Scholar
  78. 78.
    Noyes N, Porcu E, Borini A. Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies. Reprod Biomed Online. 2009;18(6):769–76.CrossRefPubMedGoogle Scholar
  79. 79.
    Wennerholm UB, Soderstrom-Anttila V, Bergh C, et al. Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. Hum Reprod. 2009;24(9):2158–72.CrossRefPubMedGoogle Scholar
  80. 80.
    Levine JM, Kelvin JF, Quinn GP, Gracia CR. Infertility in reproductive-age female cancer survivors. Cancer. 2015;121(10):1532–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Oktay K, Oktem O. Ovarian cryopreservation and transplantation for fertility preservation for medical indications: report of an ongoing experience. Fertil Steril. 2010;93(3):762–8.CrossRefPubMedGoogle Scholar
  82. 82.
    Fabbri R, Vicenti R, Magnani V, et al. Cryopreservation of ovarian tissue in breast cancer patients: 10 years of experience. Fut Oncol (London, Engl). 2012;8(12):1613–9.CrossRefGoogle Scholar
  83. 83.
    Akhanoba F, MacDougall J, Mathur R, Hassan W. Severe systemic candidiasis following immunomodulation therapy in in vitro fertilisation-embryo transfer (IVF-ET). BMJ Case Rep. 2014;2014. pii: bcr2013203202.Google Scholar
  84. 84.
    Clark DA. Anti-TNFalpha therapy in immune-mediated subfertility: state of the art. J Reprod Immunol. 2010;85(1):15–24.CrossRefPubMedGoogle Scholar
  85. 85.
    Lambers MJ, Groeneveld E, Hoozemans DA, et al. Lower incidence of hypertensive complications during pregnancy in patients treated with low-dose aspirin during in vitro fertilization and early pregnancy. Hum Reprod. 2009;24(10):2447–50.CrossRefPubMedGoogle Scholar
  86. 86.
    Groeneveld E, Lambers MJ, Lambalk CB, et al. Preconceptional low-dose aspirin for the prevention of hypertensive pregnancy complications and preterm delivery after IVF: a meta-analysis with individual patient data. Hum Reprod. 2013;28(6):1480–8.CrossRefPubMedGoogle Scholar
  87. 87.
    Siristatidis CS, Dodd SR, Drakeley AJ. Aspirin is not recommended for women undergoing IVF. Hum Reprod Update. 2012;18(3):233.CrossRefPubMedGoogle Scholar
  88. 88.
    Potdar N, Gelbaya TA, Konje JC, Nardo LG. Adjunct low-molecular-weight heparin to improve live birth rate after recurrent implantation failure: a systematic review and meta-analysis. Hum Reprod Update. 2013;19(6):674–84.CrossRefPubMedGoogle Scholar
  89. 89.
    Seshadri S, Sunkara SK, Khalaf Y, El-Toukhy T, Hamoda H. Effect of heparin on the outcome of IVF treatment: a systematic review and meta-analysis. Reprod Biomed Online. 2012;25(6):572–84.CrossRefPubMedGoogle Scholar
  90. 90.
    Li J, Chen Y, Liu C, Hu Y, Li L. Intravenous immunoglobulin treatment for repeated IVF/ICSI failure and unexplained infertility: a systematic review and a meta-analysis. Am J Reprod Immunol. 2013;70(6):434–47.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Concept Fertility CentreSubiaco, PerthAustralia
  2. 2.Aberdeen Royal Infirmary, Department of GynaecologyAberdeen Fertility CentreAberdeenUK

Personalised recommendations