Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)
- PMID: 33844275
- PMCID: PMC8094870
- DOI: 10.1002/14651858.CD005289.pub4
Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)
Abstract
Background: Monitoring of in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) is necessary to detect as well as reduce the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the optimal ovarian response needed for assisted reproduction treatment. Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation IVF and ICSI treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. OBJECTIVES: To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS.
Search methods: In this update conducted in March 2020, two review authors searched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the National Research Register, and web-based trial registers. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data.
Selection criteria: Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included.
Data collection and analysis: Two review authors (IK, AW) independently selected the studies, extracted data and assessed risk of bias. We resolved disagreements by discussion. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods.
Main results: We did not identify any new eligible studies in this update in 2020. The evidence based on the six trials identified in 2014 remained unchanged. They included 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment. None of the six studies reported our primary outcome of live birth rate. Two studies presented pregnancy rate per initiated cycle and per embryo transfer, respectively. Four studies reported pregnancy rate per woman with pooled data; we are uncertain of the effect of monitoring with TVUS only versus combined monitoring on clinical pregnancy rate per woman (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests in women with a 36% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate using TVUS only would be between 31% and 46%. We are uncertain of any effect in the mean number of oocytes retrieved per woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence). We are uncertain whether monitoring with TVUS only versus combined monitoring affected the incidence of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that in women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate monitored by TVUS only would be between 2% and 8%. The cycle cancellation rate was similar in both arms of two studies (0/34 versus 1/31, 1/25 versus 1/25; OR 0.57; 95% CI 0.07 to 4.39; N = 115; I² = 0%; low quality evidence). The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies.
Authors' conclusions: This review update found no new randomised trials. Evidence from the six studies previously identified did not suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. The choice of one or the other method may depend upon the convenience of its use, and the associated costs. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.
Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Conflict of interest statement
IK, SB and AW have no interests to declare.
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Update of
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Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).Cochrane Database Syst Rev. 2014 Aug 24;2014(8):CD005289. doi: 10.1002/14651858.CD005289.pub3. Cochrane Database Syst Rev. 2014. Update in: Cochrane Database Syst Rev. 2021 Apr 12;4:CD005289. doi: 10.1002/14651858.CD005289.pub4. PMID: 25150465 Free PMC article. Updated.
References
References to studies included in this review
Aguirre 2010 {published data only}
-
- Aguirre SG, Hevia IG, García-Carpintero G, DelRosal Ma J. Measuring plasma estradiol levels in in vitro fertilization. Is it useful? Revista Iberoamericana De Fertilidad y Reproduccion Humana 2010;27(1):43-9.
Golan 1994 {published data only}
-
- Golan A, Herman A, Soffer Y, Bukovsky I, Ron-El R. Ultrasonic control without hormone determination for ovulation induction in in-vitro fertilization/embryo transfer with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin. Human Reproduction 1994;9(9):1631-3. - PubMed
Lass 2003 {published data only}
-
- Lass A, UK Timing of hCG Group. Monitoring of in vitro fertilization-embryo transfer cycles by ultrasound versus by ultrasound and hormonal levels: a prospective, multicenter, randomized study. Fertility and Sterility 2003;80(1):80-5. - PubMed
Rongieres 2006 {published data only}
-
- Rongieres C. Monitoring ovarian stimulation: are hormonal assessments necessary? Journal de Gynécologie, Obstétrique et Biologie de la Reproduction 2006;35:2S39-41. - PubMed
Strawn 2007 {published data only}
-
- Strawn EY, Roesler M, Granlund A, Bohling S. In vitro fertilization can be successfully accomplished without routine estradiol monitoring: a randomized pilot study. Fertility and Sterility 2007;88 Suppl 1(P-114):S147.
Wiser 2012 {published data only}
-
- Wiser A, Gonen O, Ghetler Y, Shavit T, Berkovitz A, Shulman A. Monitoring stimulated cycles during in vitro fertilization treatment with ultrasound only – preliminary results. Gynecological Endocrinology 2012;28(6):429–31. - PubMed
References to studies excluded from this review
Gerris 2014 {published data only}
-
- Gerris J, Delvigne A, Vandekerckhove F, Madoc B, Buyle M, Neyskens J, et al. Self-operated endovaginal telemonitoring versus traditional monitoring of ovarian stimulation in assisted reproduction: an RCT. Human Reproduction 2014;29(9):1941-8. [DOI: ] - PubMed
Kably Ambe 1994 {published data only}
-
- Kably Ambe A, Carranza Lira S, Serviere Zaragoza C, Espinoza de los Monteros A, Coria Soto I, Alvarado Duran A. The evaluation of the usefulness of ultrasound independent of estradiol as a prognostic criterion for ovular capture and maturity A comparative double-blind study. Ginecologia y Obstetricia de Mexico 1994;62:288-91. - PubMed
Raine‐Fenning 2010 {published data only}
-
- Raine-Fenning N, Deb S, Jayaprakasan K, Clewes J, Hopkisson J, Campbell B. Timing of oocyte maturation and egg collection during controlled ovarian stimulation: a randomized controlled trial evaluating manual and automated measurements of follicle diameter. Fertility and Sterility 2010;94(1):184-8. - PubMed
Schindler 2001 {published data only}
-
- Schindler L, Janny L, Canis M, Schubert B, Durakovic N. Oestradiol is useless in IVF monitoring: a prospective study. Human Reproduction 2001;16 Suppl 1(P-269):204.
Vandekerckhove 2014 {published data only}
-
- Vandekerckhove F, Gerris J, Vansteelandt S, De Sutter P. Adding serum estradiol measurements to ultrasound monitoring does not change the yield of mature oocytes in IVF/ICSI. Gynecological Endocrinology 2014;30(9):649-52. [DOI: ] - PubMed
Additional references
Abdalla 1989
-
- Abdalla HI, Baber RJ, Leonard T, Kirkland A, Mitchell A, Power M et al. Timed oocyte collection in an assisted conception programme using GnRH analogue. Human Reproduction 1989;4(8):927-30. - PubMed
Asch 1991
-
- Asch RH, Li HP, Balmaceda JP, Weckstein LN, Stone SC. Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups. Human Reproduction 1991;6(10):1395-9. - PubMed
Borase 2012
-
- Borase H, Mathur R. Ovarian hyperstimulation syndrome: clinical features, prevention and management. Obstetrics, Gynaecology and Reproductive Medicine 2012;22(7):186-90.
Bosch 2020
Confino 1996
-
- Confino E, Binor Z, Molo MW, Rawlins R, Balos R, Mullaney K et al. Sonographically monitored ovarian stimulation for assisted reproduction: a prospective, blind study. Journal of Reproductive Medicine 1996;41(1):7-10. - PubMed
Delvigne 2002
-
- Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Human Reproduction Update 2002;8(6):559-77. - PubMed
Ferraretti 2012
-
- Ferraretti AP, Goossens V, Mouzon J, Bhattacharya S, Castilla JA, Korsak V et al. The European IVF-monitoring (EIM), and Consortium, for the European Society of Human Reproduction and Embryology (ESHRE). Human Reproduction 2012;27(9):2571-84. - PubMed
Fiers 2017
Golan 1989
-
- Golan A, Ron-El R, Herman A, Soffer Y, Wainraub Z, Caspi E. Ovarian Hyperstimulation syndrome: an update review [Ovarian Hyperstimulation syndrome: an update review]. Obstetrical and Gynecological Survey 1989;44(6):430-440. - PubMed
GRADE [Computer program]
-
- GRADE Working Group GRADE. Hamilton (ON): GRADE Working Group, accessed 15 December 2013.
Haning 1982
-
- Haning RV Jr, Austin CW, Kuzma DL, Shapiro SS, Zweibel WJ. Ultrasound evaluation of estrogen monitoring for induction of ovulation with menotropins. Fertility and Sterility 1982;37(5):627-32. - PubMed
Hardiman 1990
-
- Hardiman P, Thomas M, Osgood V, Vlassopoulou V, Ginsburg J. Are estrogen assays essential for monitoring gonadotropin stimulant therapy? Gynecological Endocrinology 1990;4(4):261-9. - PubMed
Higgins 2011
-
- Higgins J PT, Green S, editors. Cochrane Handbook of Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Howard 1988
-
- Howard WF, Chihal HJ, Strain CA, Smith M. Programmed follicular stimulation reduces cycle cost and stress with no compromise in cycle quality: use of a modified programmed protocol. Journal of In Vitro Fertilisation and Embryo Transfer 1988;5(6):343-6. - PubMed
Jenkins 2006
-
- Jenkins JM, Drakeley AJ, Mathur RS. The management of ovarian hyperstimulation syndrome (RCOG Green-top Guideline No. 5). London: Royal College of Obstetricians and Gynaecologists, 2006.
Kemeter 1989
-
- Kemeter P, Feichtinger W. Experience with a new fixed-stimulation protocol without hormone determinations for programmed oocyte retrieval for in-vitro fertilization. Human Reproduction 1989;4(8 Suppl):53-8. - PubMed
MacDougall 1992
-
- MacDougall MJ, Tan SL, Jacobs HS. In-vitro fertilization and the ovarian hyperstimulation syndrome. Human Reproduction 1992;7(5):597-600. - PubMed
Martins 2013
-
- Martins WP, Vieira CV, Teixeira DM, Barbosa MA, Dassunção LA, Nastri CO. Ultrasound for monitoring controlled ovarian stimulation: a systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstetrics and Gynecology 2014;43(1):25-33. - PubMed
Mourad 2017
Murad 1998
-
- Murad NM. Ultrasound or ultrasound and hormonal determinations for in vitro fertilization monitoring. International Journal of Gynaecology and Obstetrics 1998;63(3):271-6. - PubMed
Nygren 2002
-
- Nygren KG, Andersen AN. Assisted reproductive technology in Europe, 1999. Results generated from European registers by ESHRE. Human Reproduction 2002;17(12):3260-74. - PubMed
Rainhorn 1987
-
- Rainhorn JD, Forman RG, Belaisch-Allart J, Hazout A, Fries N, Testart J et al. One year's experience with programmed oocyte retrieval for IVF. Human Reproduction 1987;2(6):491-4. - PubMed
Rizk 1992
-
- Rizk B, Smitz J. Ovarian hyperstimulation syndrome after superovulation using GnRH agonists for IVF and related procedures. Human Reproduction 1992;7(3):320-7. - PubMed
Roest 1995
-
- Roest J, Verhoeff A, Heusden AM, Zeilmaker GH. Minimal monitoring of ovarian hyperstimulation: a useful simplification of the clinical phase of in vitro fertilization treatment. Fertility and Sterility 1995;64(3):552-6. - PubMed
Roest 1996
-
- Roest J, Mous HV, Zeilmaker GH, Verhoeff A. The incidence of major clinical complications in a Dutch transport IVF programme. Human Reproduction Update 1996;2(4):345-53. - PubMed
Schenker 1978
-
- Schenker JG, Weinstein D. Ovarian hyperstimulation syndrome: a current survey. Fertility and Sterility 1978;30(3):255-68. - PubMed
Shoham 1991
-
- Shoham Z, Di Carlo C, Patel A, Conway GS, Jacobs HS. Is it possible to run a successful ovulation induction program based solely on ultrasound monitoring? The importance of endometrial measurements. Fertility and Sterility 1991;56(5):836-41. - PubMed
Smitz 1990
-
- Smitz J, Camus M, Devroey P, Erard P, Wisanto A, Van Steirteghem AC. Incidence of severe ovarian hyperstimulation syndrome after GnRH agonist/HMG superovulation for in-vitro fertilization. Human Reproduction 1990;5(8):933-7. - PubMed
Tan 1992
-
- Tan SL, Balen A, el Hussein E, Mills C, Campbell S, Yovich J et al. A prospective randomized study of the optimum timing of human chorionic gonadotropin administration after pituitary desensitization in in vitro fertilization. Fertility and Sterility 1992;57(6):1259-64. - PubMed
Tan 1994
-
- Tan SL. Simplifying in-vitro fertilization therapy. Current Opinion in Obstetrics and Gynecology 1994;6(2):111-4. - PubMed
Thomas 2002
-
- Thomas K, Searle T, Quinn A, Wood S, Lewis-Jones I, Kingsland C. The value of routine estradiol monitoring in assisted conception cycle. Acta Obstetricia et Gynecologica Scandinavica 2002;81(6):551-4. - PubMed
Vlaisavljevic 1992
-
- Vlaisavljevic V, Kovacic B, Gavric V. In vitro fertilization program based on programmed cycles monitored by ultrasound only. Journal of the International Federation of Gynaecology and Obstetrics 1992;39(3):227-31. - PubMed
Zegers‐Hochschild 2017
Zimon 2013
-
- Zimon A, Lannon B, Sheller S, Sakkas D, Ulrich M, Alper M. Venopuncture-free IVF: Measurement of estrogen in controlled ovarian stimulation IVF cycles using a "patient-friendly" saliva-based estradiol assay. Fertility and Sterility 2013;100(3 Suppl 1):S110.
References to other published versions of this review
Kwan 2005
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