Semin Reprod Med 2015; 33(02): 065-076
DOI: 10.1055/s-0035-1545364
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prognostic Factors for IVF Success: Diagnostic Testing and Evidence-Based Interventions

Athanasios Papathanasiou
1   Bourn-Hall Clinic, Wymondham, Norwich, United Kingdom
Siladitya Bhattacharya
2   Aberdeen University, Foresterhill, Aberdeen, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
03 March 2015 (online)


Numerous tests and interventions have been proposed for optimizing performance in preparation for in vitro fertilization (IVF) treatment. We critically appraised the available evidence underpinning some of the popular investigations and treatments, including the role of hysteroscopy, laparoscopy, ovarian reserve tests, sperm function tests, as well as the role of lifestyle modifications or surgery for endometriosis, fibroids, and endometrial polyps. We also reviewed the evidence behind novel techniques, such as the use of endometrial injury before IVF. Only a few of the aforementioned modalities are justified based on the available research evidence. Other factors may affect the uptake of a test or intervention before IVF, namely the complexity of the proposed modality, its potential for harm, and its cost-effectiveness.

  • References

  • 1 Nelson SM, Lawlor DA. Predicting live birth, preterm delivery, and low birth weight in infants born from in vitro fertilisation: a prospective study of 144,018 treatment cycles. PLoS Med 2011; 8 (1) e1000386
  • 2 Maheshwari A, Stofberg L, Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology—a systematic review. Hum Reprod Update 2007; 13 (5) 433-444
  • 3 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) 421-439
  • 4 Jungheim ES, Schon SB, Schulte MB, DeUgarte DA, Fowler SA, Tuuli MG. IVF outcomes in obese donor oocyte recipients: a systematic review and meta-analysis. Hum Reprod 2013; 28 (10) 2720-2727
  • 5 Dechanet C, Anahory T, Mathieu Daude JC , et al. Effects of cigarette smoking on reproduction. Hum Reprod Update 2011; 17 (1) 76-95
  • 6 Freour T, Dessolle L, Jean M, Masson D, Barriere P. Predictive value of ovarian reserve markers in smoking and non-smoking women undergoing IVF. Reprod Biomed Online 2010; 20 (6) 857-860
  • 7 Waylen AL, Metwally M, Jones GL, Wilkinson AJ, Ledger WL. Effects of cigarette smoking upon clinical outcomes of assisted reproduction: a meta-analysis. Hum Reprod Update 2009; 15 (1) 31-44
  • 8 Joesbury KA, Edirisinghe WR, Phillips MR, Yovich JL. Evidence that male smoking affects the likelihood of a pregnancy following IVF treatment: application of the modified cumulative embryo score. Hum Reprod 1998; 13 (6) 1506-1513
  • 9 Nicolau P, Miralpeix E, Solà I, Carreras R, Checa MA. Alcohol consumption and in vitro fertilization: a review of the literature. Gynecol Endocrinol 2014; 30 (11) 759-763
  • 10 Pundir J, El Toukhy T. Uterine cavity assessment prior to IVF. Womens Health (Lond Engl) 2010; 6 (6) 841-847 , quiz 847–848
  • 11 Hendriks DJ, Kwee J, Mol BW, te Velde ER, Broekmans FJ. Ultrasonography as a tool for the prediction of outcome in IVF patients: a comparative meta-analysis of ovarian volume and antral follicle count. Fertil Steril 2007; 87 (4) 764-775
  • 12 Broer SL, Dólleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Update 2011; 17 (1) 46-54
  • 13 Scheffer GJ, Broekmans FJ, Bancsi LF, Habbema JD, Looman CW, Te Velde ER. Quantitative transvaginal two- and three-dimensional sonography of the ovaries: reproducibility of antral follicle counts. Ultrasound Obstet Gynecol 2002; 20 (3) 270-275
  • 14 El-Mazny A, Abou-Salem N, El-Sherbiny W, Saber W. Outpatient hysteroscopy: a routine investigation before assisted reproductive techniques?. Fertil Steril 2011; 95 (1) 272-276
  • 15 Taşkın EA, Berker B, Ozmen B, Sönmezer M, Atabekoğlu C. Comparison of hysterosalpingography and hysteroscopy in the evaluation of the uterine cavity in patients undergoing assisted reproductive techniques. Fertil Steril 2011; 96 (2) 349-352.e2
  • 16 Elsetohy KA, Askalany AH, Hassan M, Dawood Z. Routine office hysteroscopy prior to ICSI vs. ICSI alone in patients with normal transvaginal ultrasound: a randomized controlled trial. Arch Gynecol Obstet 2014;
  • 17 El-Toukhy T, Khalaf Y, Coomarasamy A , et al. A multicentre randomised study of pre-IVF outpatient hysteroscopy in women with recurrent IVF-et failure – the trophy trial. Hum Reprod 2014; 17 (1) xx
  • 18 Potdar N, Gelbaya T, Nardo LG. Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis. Reprod Biomed Online 2012; 25 (6) 561-571
  • 19 Saunders RD, Shwayder JM, Nakajima ST. Current methods of tubal patency assessment. Fertil Steril 2011; 95 (7) 2171-2179
  • 20 Valentini AL, Muzii L, Marana R , et al. Improvement of hysterosalpingographic accuracy in the diagnosis of peritubal adhesions. AJR Am J Roentgenol 2000; 175 (4) 1173-1176
  • 21 Duffy JM, Arambage K, Correa FJ , et al. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev 2014; 4: CD011031
  • 22 Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril 2012; 98 (2) 302-307
  • 23 Verhoeve HR, Moolenaar LM, Hompes P, van der Veen F, Mol BW. Cost-effectiveness of tubal patency tests. BJOG 2013; 120 (5) 583-593
  • 24 Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011; 26 (7) 1768-1774
  • 25 Al-Inany HG, Youssef MA, Aboulghar M , et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2011; (5) CD001750
  • 26 Padilla SL, Dugan K, Maruschak V, Shalika S, Smith RD. Use of the flare-up protocol with high dose human follicle stimulating hormone and human menopausal gonadotropins for in vitro fertilization in poor responders. Fertil Steril 1996; 65 (4) 796-799
  • 27 Peñarrubia J, Fábregues F, Manau D , et al. Previous cycle cancellation due to poor follicular development as a predictor of ovarian response in cycles stimulated with gonadotrophin-releasing hormone agonist-gonadotrophin treatment. Hum Reprod 2005; 20 (3) 622-628
  • 28 Mutlu MF, Erdem M, Erdem A , et al. Antral follicle count determines poor ovarian response better than anti-Müllerian hormone but age is the only predictor for live birth in in vitro fertilization cycles. J Assist Reprod Genet 2013; 30 (5) 657-665
  • 29 Jayaprakasan K, Campbell B, Hopkisson J, Johnson I, Raine-Fenning N. A prospective, comparative analysis of anti-Müllerian hormone, inhibin-B, and three-dimensional ultrasound determinants of ovarian reserve in the prediction of poor response to controlled ovarian stimulation. Fertil Steril 2010; 93 (3) 855-864
  • 30 La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update 2014; 20 (1) 124-140
  • 31 Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L ; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011; 26 (7) 1616-1624
  • 32 Iliodromiti S, Kelsey TW, Wu O, Anderson RA, Nelson SM. The predictive accuracy of anti-Müllerian hormone for live birth after assisted conception: a systematic review and meta-analysis of the literature. Hum Reprod Update 2014; 20 (4) 560-570
  • 33 Li HW, Lee VC, Lau EY, Yeung WS, Ho PC, Ng EH. Role of baseline antral follicle count and anti-Mullerian hormone in prediction of cumulative live birth in the first in vitro fertilisation cycle: a retrospective cohort analysis. PLoS ONE 2013; 8 (4) e61095
  • 34 Xie BG, Huang YH, Zhu WJ, Jin S. Comparison of the outcome of conventional in vitro fertilization and intracytoplasmic sperm injection in moderate male infertility from ejaculate. Urol Int 2013;
  • 35 Shuai HL, Ye Q, Huang YH, Xie BG. Comparison of conventional in vitro fertilisation and intracytoplasmic sperm injection outcomes in patients with moderate oligoasthenozoospermia. Andrologia 2014;
  • 36 Robinson L, Gallos ID, Conner SJ , et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod 2012; 27 (10) 2908-2917
  • 37 Collins JA, Barnhart KT, Schlegel PN. Do sperm DNA integrity tests predict pregnancy with in vitro fertilization?. Fertil Steril 2008; 89 (4) 823-831
  • 38 Jiang H, He RB, Wang CL, Zhu J. The relationship of sperm DNA fragmentation index with the outcomes of in-vitro fertilisation-embryo transfer and intracytoplasmic sperm injection. J Obstet Gynaecol 2011; 31 (7) 636-639
  • 39 Van Assche E, Bonduelle M, Tournaye H , et al. Cytogenetics of infertile men. Hum Reprod 1996; 11 (Suppl. 04) 1-24 , discussion 25–26
  • 40 De Braekeleer M, Dao TN. Cytogenetic studies in male infertility: a review. Hum Reprod 1991; 6 (2) 245-250
  • 41 Anguiano A, Oates RD, Amos JA , et al. Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis. JAMA 1992; 267 (13) 1794-1797
  • 42 Pryor JL, Kent-First M, Muallem A , et al. Microdeletions in the Y chromosome of infertile men. N Engl J Med 1997; 336 (8) 534-539
  • 43 Krausz C, Quintana-Murci L, McElreavey K. Prognostic value of Y deletion analysis: what is the clinical prognostic value of Y chromosome microdeletion analysis?. Hum Reprod 2000; 15 (7) 1431-1434
  • 44 Brandell RA, Mielnik A, Liotta D , et al. AZFb deletions predict the absence of spermatozoa with testicular sperm extraction: preliminary report of a prognostic genetic test. Hum Reprod 1998; 13 (1O): 2812-2815
  • 45 Kent-First MG, Kol S, Muallem A , et al. The incidence and possible relevance of Y-linked microdeletions in babies born after intracytoplasmic sperm injection and their infertile fathers. Mol Hum Reprod 1996; 2 (12) 943-950
  • 46 Jorgez CJ, Weedin JW, Sahin A , et al. Aberrations in pseudoautosomal regions (PARs) found in infertile men with Y-chromosome microdeletions. J Clin Endocrinol Metab 2011; 96 (4) E674-E679
  • 47 Papachatzi E, Dimitriou G, Dimitropoulos K, Vantarakis A. Pre-pregnancy obesity: maternal, neonatal and childhood outcomes. J Neonatal Perinatal Med 2013; 6 (3) 203-216
  • 48 Castles A, Adams EK, Melvin CL, Kelsch C, Boulton ML. Effects of smoking during pregnancy. Five meta-analyses. Am J Prev Med 1999; 16 (3) 208-215
  • 49 Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update 2011; 17 (5) 589-604
  • 50 Gray R. Low-to-moderate alcohol consumption during pregnancy and child development—moving beyond observational studies. BJOG 2013; 120 (9) 1039-1041
  • 51 Anderson K, Norman RJ, Middleton P. Preconception lifestyle advice for people with subfertility. Cochrane Database Syst Rev 2010; (4) CD008189
  • 52 van Oers AM, Mutsaerts MAQ, Burggraaff JM , et al. The effectiveness of a structured lifestyle program in overweight and obese subfertile women. preliminary data from a randomised controlled trial (LIFEstyle study). Hum Reprod 2014; 29 (Suppl. 01) i75
  • 53 Agha M, Agha RA, Sandell J. Interventions to reduce and prevent obesity in pre-conceptual and pregnant women: a systematic review and meta-analysis. PLoS ONE 2014; 9 (5) e95132
  • 54 Murray DL, Sagoskin AW, Widra EA, Levy MJ. The adverse effect of hydrosalpinges on in vitro fertilization pregnancy rates and the benefit of surgical correction. Fertil Steril 1998; 69 (1) 41-45
  • 55 He RH, Gao HJ, Li YQ, Zhu XM. The associated factors to endometrial cavity fluid and the relevant impact on the IVF-ET outcome. Reprod Biol Endocrinol 2010; 8: 46
  • 56 Savaris RF, Giudice LC. The influence of hydrosalpinx on markers of endometrial receptivity. Semin Reprod Med 2007; 25 (6) 476-482
  • 57 Johnson N, van Voorst S, Sowter MC, Strandell A, Mol BW. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. Cochrane Database Syst Rev 2010; (1) CD002125
  • 58 Strandell A, Lindhard A, Waldenström U, Thorburn J. Hydrosalpinx and IVF outcome: cumulative results after salpingectomy in a randomized controlled trial. Hum Reprod 2001; 16 (11) 2403-2410
  • 59 Ni L, Sadiq S, Mao Y, Cui Y, Wang W, Liu J. Influence of various tubal surgeries to serum antimullerian hormone level and outcome of the subsequent IVF-ET treatment. Gynecol Endocrinol 2013; 29 (4) 345-349
  • 60 Ye XP, Yang YZ, Sun XX. A retrospective analysis of the effect of salpingectomy on serum antiMüllerian hormone level and ovarian reserve. Am J Obstet Gynecol 2015; 212 (1) 53.e1-53.e10
  • 61 Arora P, Arora RS, Cahill D. Essure(®) for management of hydrosalpinx prior to in vitro fertilisation—a systematic review and pooled analysis. BJOG 2014; 121 (5) 527-536
  • 62 Bosteels J, Weyers S, Mathieu C, Mol BW, D'Hooghe T. The effectiveness of reproductive surgery in the treatment of -female infertility: facts, views and vision. Facts Views Vis Obgyn 2010; 2 (4) 232-252
  • 63 Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane Database Syst Rev 2008; (2) CD004992
  • 64 Kuivasaari P, Hippeläinen M, Anttila M, Heinonen S. Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates. Hum Reprod 2005; 20 (11) 3130-3135
  • 65 Harb HM, Gallos ID, Chu J, Harb M, Coomarasamy A. The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis. BJOG 2013; 120 (11) 1308-1320
  • 66 Opøien HK, Fedorcsak P, Byholm T, Tanbo T. Complete surgical removal of minimal and mild endometriosis improves outcome of subsequent IVF/ICSI treatment. Reprod Biomed Online 2011; 23 (3) 389-395
  • 67 Gupta S, Agarwal A, Agarwal R, Loret de Mola JR. Impact of ovarian endometrioma on assisted reproduction outcomes. Reprod Biomed Online 2006; 13 (3) 349-360
  • 68 Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG. The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril 2009; 92 (1) 75-87
  • 69 Tang Y, Chen SL, Chen X , et al. Ovarian damage after laparoscopic endometrioma excision might be related to the size of cyst. Fertil Steril 2013; 100 (2) 464-469
  • 70 Dunselman GA, Vermeulen N, Becker C , et al; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod 2014; 29 (3) 400-412
  • 71 Vercellini P, Somigliana E, Viganò P, De Matteis S, Barbara G, Fedele L. The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: a systematic review. Acta Obstet Gynecol Scand 2009; 88 (10) 1074-1082
  • 72 Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst Rev 2007; 3 (3) CD000155
  • 73 Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev 2006; 1 (1) CD004635
  • 74 Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril 2009; 91 (4) 1215-1223
  • 75 Sunkara SK, Khairy M, El-Toukhy T, Khalaf Y, Coomarasamy A. The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta-analysis. Hum Reprod 2010; 25 (2) 418-429
  • 76 Bosteels J, Weyers S, Puttemans P , et al. The effectiveness of hysteroscopy in improving pregnancy rates in subfertile women without other gynaecological symptoms: a systematic review. Hum Reprod Update 2010; 16 (1) 1-11
  • 77 Bosteels J, Kasius J, Weyers S, Broekmans FJ, Mol BW, D'Hooghe TM. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities. Cochrane Database Syst Rev 2013; 1: CD009461
  • 78 Surrey ES, Minjarez DA, Stevens JM, Schoolcraft WB. Effect of myomectomy on the outcome of assisted reproductive technologies. Fertil Steril 2005; 83 (5) 1473-1479
  • 79 Pérez-Medina T, Bajo-Arenas J, Salazar F , et al. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study. Hum Reprod 2005; 20 (6) 1632-1635
  • 80 Chan YY, Jayaprakasan K, Zamora J, Thornton JG, Raine-Fenning N, Coomarasamy A. The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review. Hum Reprod Update 2011; 17 (6) 761-771
  • 81 Tomaževič T, Ban-Frangež H, Virant-Klun I, Verdenik I, Požlep B, Vrtačnik-Bokal E. Septate, subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI. Reprod Biomed Online 2010; 21 (5) 700-705
  • 82 Smit JG, Kasius JC, Eijkemans MJ , et al. The international agreement study on the diagnosis of the septate uterus at office hysteroscopy in infertile patients. Fertil Steril 2013; 99 (7) 2108-13.e2
  • 83 Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Hum Reprod Update 2012; 18 (4) 374-392
  • 84 Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, Somigliana E. Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis. Hum Reprod 2014; 29 (5) 964-977
  • 85 Taran FA, Stewart EA, Brucker S. Adenomyosis: Epidemiology, risk factors, clinical phenotype and surgical and interventional alternatives to hysterectomy. Geburtshilfe Frauenheilkd 2013; 73 (9) 924-931
  • 86 Siristatidis C, Vrachnis N, Vogiatzi P , et al. Potential pathophysiological mechanisms of the beneficial role of endometrial injury in in vitro fertilization outcome. Reprod Sci 2014; 21 (8) 955-965
  • 87 Nastri CO, Gibreel A, Raine-Fenning N , et al. Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev 2012; 7: CD009517
  • 88 El-Toukhy T, Sunkara S, Khalaf Y. Local endometrial injury and IVF outcome: a systematic review and meta-analysis. Reprod Biomed Online 2012; 25 (4) 345-354
  • 89 Nastri CO, Ferriani RA, Raine-Fenning N, Martins WP. Endometrial scratching performed in the non-transfer cycle and outcome of assisted reproduction: a randomized controlled trial. Ultrasound Obstet Gynecol 2013; 42 (4) 375-382
  • 90 Yeung TW, Chai J, Li RH, Lee VC, Ho PC, Ng EH. The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: a randomized controlled trial. Hum Reprod 2014; 29 (11) 2474-2481
  • 91 Dunne C, Taylor B. Does endometrial injury improve implantation of frozen-thawed embryos?. Arch Gynecol Obstet 2014; 290 (3) 575-579
  • 92 Dain L, Ojha K, Bider D , et al. Effect of local endometrial injury on pregnancy outcomes in ovum donation cycles. Fertil Steril 2014; 102 (4) 1048-1054
  • 93 Showell MG, Brown J, Clarke J, Hart RJ. Antioxidants for female subfertility. Cochrane Database Syst Rev 2013; 8: CD007807
  • 94 Manheimer E, van der Windt D, Cheng K , et al. The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update 2013; 19 (6) 696-713
  • 95 Cao H, Han M, Ng EH , et al. Can Chinese herbal medicine improve outcomes of in vitro fertilization? A systematic review and meta-analysis of randomized controlled trials. PLoS ONE 2013; 8 (12) e81650
  • 96 Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev 2011; (1) CD007411