title: Brief co-incubation of sperm and oocytes for in vitro fertilization techniques.
abstract: BACKGROUND
  The in vitro fertilization (IVF) technique is commonly used and is the only treatment option for a proportion of infertile couples. To obtain better outcomes of IVF, it is important to enhance embryo quality by optimizing IVF techniques. In IVF procedures, oocytes and sperm are routinely co-incubated overnight, which may expose oocytes and zygotes to suboptimal culture conditions with increased reactive oxygen species (ROS) produced by sperm in this long term culture. As an attempt to avoid possible detrimental effects on the oocytes from long exposure to sperm, the brief co-incubation insemination protocol was developed. However, despite a number of studies in this area, it is unclear whether brief co-incubation improves the IVF outcomes compared with the standard overnight insemination protocol.
  
  
  OBJECTIVE
  This Cochrane review aimed to determine whether brief co-incubation of sperm and oocytes improves outcomes compared with the standard overnight insemination protocol for women undergoing IVF.
  
  
  METHODS
  We searched the Cochrane Menstrual Disorders and Subfertility Group Register (14 June 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, 1st quarter), MEDLINE (1948 to 14 June 2012), EMBASE (1989 to 14 June 2012), PsycINFO (1806 to 14 June 2012) and CINAHL (1980 to 26 July 2012). In addition, we searched trials registers, reference lists of articles, conference proceedings (American Society for Reproductive Medicine (ASRM), European Society of Human Reproduction and Embryology (ESHRE)) and contacted experts in the field.
  
  
  METHODS
  We included randomized controlled trials (RCTs) comparing brief co-incubation of gametes with the standard overnight insemination protocol.
  
  
  METHODS
  Two review authors independently assessed studies for inclusion and trial quality, and extracted data. Disagreements were resolved by discussion with a third author. Statistical analysis was performed using RevMan software.
  
  
  RESULTS
  Eight RCTs with 733 women in total that compared brief co-incubation and the standard insemination protocol were included. Live birth was not reported in the included studies. For ongoing pregnancy rate, there were 127 ongoing pregnancies in two trials including 426 women. The low quality evidence showed that brief co-incubation was associated with an increased ongoing pregnancy rate compared to the standard insemination protocol (pooled odds ratio (OR) 2.42, 95% confidence interval (CI) 1.55 to 3.77; P < 0.0001, I(2) = 0%). Measuring clinical pregnancy rate, there were 93 clinical pregnancies in three trials including 372 women. The low quality evidence showed that brief co-incubation was associated with a significantly higher clinical pregnancy rate than the overnight insemination protocol (pooled OR 2.36, 95% CI 1.45 to 3.85; P = 0.0006, I(2) = 0%). For the miscarriage rate, there were six miscarriages in one trial including 167 women. This low quality evidence suggested no significant difference in the odds of miscarriage between brief co-incubation and standard insemination (OR 1.98, 95% CI 0.35 to 11.09; P = 0.44).
  
  
  CONCLUSIONS
  This review has provided evidence that brief co-incubation of sperm and oocytes may improve the ongoing pregnancy and clinical pregnancy rates for infertile women undergoing IVF cycles. More RCTs are required to assess whether brief co-incubation would contribute to a higher live birth rate and a lower miscarriage rate compared to the standard overnight insemination protocol.
authors: Reproductive Medical Centre, Department of Obstetrics and Gynecology, West China 2nd Hospital, Sichuan University, Chengdu,China. huangzyhxyd@scu.edu.cn
authors: Zhongying
authors: Z
authors: Huang
authors: Jun
authors: J
authors: Li
authors: Li
authors: L
authors: Wang
authors: Jing
authors: J
authors: Yan
authors: Yijiang
authors: Y
authors: Shi
authors: Shangwei
authors: S
authors: Li
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology; D018920:Coculture Techniques / Q000379:methods*; D003470:Culture Media; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D008297:Male; D011247:Pregnancy; D018873:Pregnancy Rate; D016032:Randomized Controlled Trials as Topic; D017382:Reactive Oxygen Species / Q000378:metabolism; D013084:Sperm-Ovum Interactions / Q000502:physiology*; D013997:Time Factors
chemical_list: D003470:Culture Media; D017382:Reactive Oxygen Species
references: Fertil Steril. 1993 Nov;60(5):888-92
references: 8224276
references: J Assist Reprod Genet. 2008 Jul;25(7):305-10
references: 18670871
references: Fertil Steril. 2005 Jul;84(1):228-31
references: 16009190
references: Hum Reprod. 1998 Jun;13(6):1429-36
references: 9688366
references: Fertil Steril. 2010 Nov;94(6):2141-6
references: 20117780
references: Fertil Steril. 1998 Mar;69(3):399-402
references: 9531865
references: Int J Epidemiol. 2002 Feb;31(1):88-95
references: 11914301
references: Reprod Biomed Online. 2001;3(1):21-24
references: 12513887
references: Am J Reprod Immunol. 1996 Jun;35(6):541-51
references: 8792938
references: J Assist Reprod Genet. 2000 Jul;17(6):344-8
references: 11042832
references: Cochrane Database Syst Rev. 2007 Apr 18;(2):MR000001
references: 17443625
references: Hum Reprod. 2000 Aug;15(8):1717-22
references: 10920092
references: Gynecol Endocrinol. 2003 Oct;17(5):397-403
references: 14710587
references: Fertil Steril. 1998 Mar;69(3):528-32
references: 9531891
references: Fertil Steril. 2004 May;81(5):1289-95
references: 15136092
references: Development. 1990 Jun;109(2):501-7
references: 2401209
references: Cochrane Database Syst Rev. 2007 Apr 18;(2):MR000010
references: 17443631
references: J Assist Reprod Genet. 2011 Dec;28(12):1205-11
references: 21898104
references: J Assist Reprod Genet. 1994 Feb;11(2):97-103
references: 7819709
references: Microsc Res Tech. 2003 Jul 1;61(4):335-41
references: 12811738
references: Arch Androl. 2000 Jul-Aug;45(1):73-6
references: 10959505
references: Hum Reprod. 1996 Jan;11(1):166-71
references: 8671180
references: Int J Androl. 2003 Oct;26(5):279-85
references: 14511216
references: Hum Reprod. 1992 Aug;7(7):1010-3
references: 1430118
references: Hum Reprod. 2002 Sep;17(9):2402-9
references: 12202431
references: Ann N Y Acad Sci. 1985;442:88-95
references: 3860066
references: Fertil Steril. 2003 Oct;80(4):1017-21
references: 14556826
references: Fertil Steril. 2003 Jun;79 Suppl 3:1597-605
references: 12801566
references: Hum Reprod Update. 2010 Nov-Dec;16(6):577-89
references: 20581128
references: Methods Cell Sci. 2000;22(2-3):169-89
references: 11264952
references: Fertil Steril. 1994 Sep;62(3):599-605
references: 8062957
references: Cochrane Database Syst Rev. 2007 Apr 18;(2):MR000011
references: 17443632
references: Cytogenet Cell Genet. 1986;42(1-2):1-7
references: 3720355
references: J Assist Reprod Genet. 2001 Jan;18(1):18-20
references: 11292990
references: Asian J Androl. 2011 Jan;13(1):43-52
references: 21076433
references: Reprod Biomed Online. 2003 Oct-Nov;7(4):477-84
references: 14656411
references: J Reprod Fertil. 1987 Nov;81(2):459-69
references: 2828610
references: Fertil Steril. 2011 Feb;95(2):652-7
references: 20864101
references: Hum Reprod Update. 2000 May-Jun;6(3):279-89
references: 10874573
references: Arch Gynecol Obstet. 2011 Jan;283(1):121-6
references: 20814688
references: Fertil Steril. 2004 Sep;82(3):593-600
references: 15374701
references: Hum Reprod. 2006 Feb;21(2):518-23
references: 16239314
references: J Assist Reprod Genet. 1998 Nov;15(10):605-8
references: 9866069
references: Vet Med Int. 2010 Sep 07;2010:
references: 20871827
references: Zhonghua Nan Ke Xue. 2009 Jun;15(6):538-41
references: 19593996
references: Hum Reprod. 1996 Nov;11(11):2507-11
references: 8981145
references: Hum Reprod. 1999 Oct;14(10):2562-4
references: 10527987