A strict infertility diagnosis has poor agreement with the clinical diagnosis entered into the Society for Assisted Reproductive Technology registry
2009; Elsevier BV; Volume: 92; Issue: 6 Linguagem: Inglês
10.1016/j.fertnstert.2009.05.082
ISSN1556-5653
AutoresT.A. Molinaro, Alka Shaunik, Kathleen Lin, Mary D. Sammel, Kurt T. Barnhart,
Tópico(s)Assisted Reproductive Technology and Twin Pregnancy
ResumoBased on a recent review of the medical literature, a clinical diagnosis of infertility may not agree with strict criteria. Standardized definitions of diagnostic categories are essential for accurate patient prognosis and future research. Based on a recent review of the medical literature, a clinical diagnosis of infertility may not agree with strict criteria. Standardized definitions of diagnostic categories are essential for accurate patient prognosis and future research. Before attempting in vitro fertilization (IVF), patients almost always express a desire to know their chance of success. The Society for Assisted Reproductive Technology (SART) makes publicly available the self-reported data of participating IVF clinics throughout the United States. Patients are able to access these data via the SART Web site (http://www.sart.org) and find specific success rates for their age group and diagnostic category. Clinicians often refer to these rates when counseling patients on their prognosis for pregnancy. Previous investigators have demonstrated that age and infertility diagnosis are strong predictors of ultimate success (1Stolwijk A.M. Wetzels A.M. Braat D.D. Cumulative probability of achieving an ongoing pregnancy after in-vitro fertilization and intracytoplasmic sperm injection according to a woman's age, subfertility diagnosis and primary or secondary subfertility.Hum Reprod. 2000; 15: 203-209Crossref PubMed Scopus (112) Google Scholar, 2Lintsen A.M.E. Eijkemans M.J.C. Hunault C.C. Bouwmans C.A.M. Hakkaart L. Habbema J.D.F. et al.Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study.Hum Reprod. 2007; 22: 2455-2462Crossref PubMed Scopus (58) Google Scholar). In one population-based study, older patients were found to be more likely to have “unexplained” and tubal factor infertility, while younger women are more likely to have ovulatory dysfunction or endometriosis (3Maheshwari A. Hamilton M. Bhattacharya S. Effect of female age on the diagnostic categories of infertility.Hum Reprod. 2008; 23: 538-542Crossref PubMed Scopus (105) Google Scholar). Secondary infertility has also been associated with an increased chance of becoming pregnant with IVF (4Kupka M. Dorn C. Richter O. Felberbaum R. van der Ven H. Impact of reproductive history on in vitro fertilization and intracytoplasmic sperm injection outcome: evidence from the German IVF Registry.Fertil Steril. 2003; 80: 508-516Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar).Each participating SART clinic defines the specific criteria for infertility diagnoses given to their patients. In clinical practice, patients may be given one diagnosis when in fact they do not meet the strict criteria for a specific condition. Correct characterization of the cause of a patient's infertility is essential to provide them with their true prognosis for achieving pregnancy. Furthermore, some investigators have questioned whether different clinics can be appropriately compared with each other because of differences in populations, number of cycles, and methods of determining diagnoses (5Garcia J.E. Panel two: reporting and advertising success rates—the Gordian knot of assisted reproductive technology. The role of professional societies.Womens Health Issues. 1997; 7 (94–6): 188-192Abstract Full Text PDF PubMed Scopus (1) Google Scholar). We hypothesize that the clinical criteria by which many of these diagnoses are made affects the prognostic value of the success rate quoted to patients.Materials and methodsWe reviewed in the recent medical literature the current criteria for specific infertility diagnoses that form SART diagnostic categories. Special emphasis was given to position statements from American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) as well as systematic reviews that analyze the breadth of studies available. We determined the objective criteria for each diagnostic category. The IVF patients enrolled for other studies at the University of Pennsylvania between December 2003 and June 2006 had their clinical records reviewed and abstracted, and their infertility diagnosis adjudicated according to these strict criteria by trained personnel. Couples were permitted to have multiple diagnoses as long as they met the minimum criteria in each category. Institutional review board approval was obtained before chart abstraction.Adjudicated “strict” diagnoses were then compared with clinical diagnoses as entered into SART. The degree of agreement between the clinical and strict diagnoses was calculated using kappa statistics for specific diagnostic categories and evaluated according to the method of Landis and Koch (6Landis J.R. Koch G.G. The measurement of observer agreement for categorical data.Biometrics. 1977; 33: 159-174Crossref PubMed Scopus (49726) Google Scholar). Clinical pregnancy rates per transfer were calculated for each stratum and compared using generalized estimating equations models, an extension of logistic regression that adjusts for repeated measures per subject. All calculations were performed by the use of Stata version 10 (StataCorp LP, College Station, TX). This study was designed to assess agreement between diagnostic criteria and was not powered to assess for differences between pregnancy rates of the two groups.ResultsCharts for 590 patients were adjudicated according to strict criteria. Live birth rates for each diagnostic criterion are presented in Table 1. The degree of agreement, represented by kappa coefficients, between clinical and strict diagnoses was poorest among patients with the diagnoses of uterine factor and diminished ovarian reserve. Strict criteria for unexplained infertility and polycystic ovary syndrome (PCOS) showed slightly improved agreement with clinical criteria. Although there was moderate agreement for diagnoses of endometriosis, and tubal factor and male factor infertility, there remained 20% or greater discordance between clinical and strict diagnoses.Table 1Strict diagnostic criteria.DiagnosisCriteriaEndometriosisScores based on revised ASRM classification of endometriosis 14American Society for Reproductive MedicineRevised American Society for Reproductive Medicine classification of endometriosis: 1996.Fertil Steril. 1997; 67: 817-821Abstract Full Text PDF PubMed Scopus (2232) Google Scholar, 15Marcoux S. Maheux R. Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis.N Engl J Med. 1997; 337: 217-222Crossref PubMed Scopus (835) Google ScholarTubal factorBilateral tubal occlusion on HSG or chromotubationHistory of BTL or bilateral salpingectomyUnilateral or bilateral hydrosalpinxHistory of ectopic pregnancy (excluding IVF) 16Pouly J.L. Chapron C. Manhes H. Canis M. Wattiez A. Bruhat M.A. Multifactorial analysis of fertility after conservative laparoscopic treatment of ectopic pregnancy in a series of 223 patients.Fertil Steril. 1991; 56: 453-460Abstract Full Text PDF PubMed Scopus (96) Google Scholar, 17Mol B.W.J. Collins J.A. Burrows E.A. van der Veen F. Bossuyt P.M.M. Comparison of hysterosalpingography and laparoscopy in predicting fertility outcome.Hum Reprod. 1999; 14: 1237-1242Crossref PubMed Scopus (131) Google Scholar, 18Hulka J.F. Adnexal adhesions: a prognostic staging and classification system based on a five-year survey of fertility surgery results at Chapel Hill, North Carolina.Am J Obstet Gynecol. 1982; 144: 141-148Abstract Full Text PDF PubMed Scopus (61) Google Scholar, 19Strandell A. Lindhard A. Waldenstrom U. Thorburn J. Janson P.O. Hamberger L. Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF.Hum Reprod. 1999; 14: 2762-2769Crossref PubMed Scopus (273) Google ScholarPCOS (2 out of 3 criteria)Oligo- or anovulation: intermenstrual periods ≥ 45 days OR ≤ 8 menses/yearClinical or biochemical hyperandrogenismPolycystic ovaries (≥12 follicles per ovary, 2–9 mm)Exclusion of other etiologies 13Rotterdam EA-SPCWGRevised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.Fertil Steril. 2004; 81: 19-25Google Scholar, 20Jonard S. Robert Y. Cortet-Rudelli C. Pigny P. Decanter C. Dewailly D. Ultrasound examination of polycystic ovaries: is it worth counting the follicles?.Hum Reprod. 2003; 18: 598-603Crossref PubMed Scopus (270) Google Scholar, 21Vermeulen A. Verdonck L. Kaufman J.M. A critical evaluation of simple methods for the estimation of free testosterone in serum.J Clin Endocrinol Metab. 1999; 84: 3666-3672Crossref PubMed Google ScholarDiminished ovarian reserveDay-3 FSH ≥11.4 mIU/mLDay-3 E2 ≥ 80 pg/mLAge ≤37Total antral follicle count ≤4 22Practice Committee of the American Society for Reproductive MedicineAging and infertility in women.Fertil Steril. 2006; 86: S248-S252PubMed Google Scholar, 23Smotrich D.B. Widra E.A. Gindoff P.R. Levy M.J. Hall J.L. Stillman R.J. Prognostic value of day 3 estradiol on in vitro fertilization outcome.Fertil Steril. 1995; 64: 1136-1140Abstract Full Text PDF PubMed Google Scholar, 24Barnhart K. Osheroff J. Follicle stimulating hormone as a predictor of fertility.Curr Opin Obstet Gynecol. 1998; 10: 227-232Crossref PubMed Scopus (60) Google Scholar, 25Esposito M.A. Coutifaris C. Barnhart K.T. A moderately elevated day 3 FSH concentration has limited predictive value, especially in younger women.Hum Reprod. 2002; 17: 118-123Crossref PubMed Scopus (86) Google Scholar, 26Scott R.T. Opsahl M.S. Leonardi M.R. Neall G.S. Illions E.H. Navot D. Life table analysis of pregnancy rates in a general infertility population relative to ovarian reserve and patient age.Hum Reprod. 1995; 10: 1706-1710PubMed Google Scholar, 27Frattarelli J.L. Levi A.J. Miller B.T. Segars J.H. A prospective assessment of the predictive value of basal antral follicles in in vitro fertilization cycles.Fertil Steril. 2003; 80: 350-355Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 28Bukulmez O. Arici A. Assessment of ovarian reserve.Curr Opin Obstet Gynecol. 2004; 16: 231-237Crossref PubMed Scopus (58) Google ScholarMale factorCount <13.5 mil/mLMotility <32%Morphology <9% 29World Health OrganizationLaboratory manual for the examination of human semen and sperm-cervical mucus interaction.4th ed. Cambridge University Press, New York1999Google Scholar, 30Guzick D.S. Overstreet J.W. Factor-Litvak P. Brazil C.K. Nakajima S.T. Coutifaris C. et al.Sperm morphology, motility, and concentration in fertile and infertile men.N Engl J Med. 2001; 345: 1388-1393Crossref PubMed Scopus (913) Google ScholarUnexplainedAt least one tube patent with no tubal abnormalitiesAge ≤37Normal ovarian reserveNormal semen analysis 31Guzick D.S. Sullivan M.W. Adamson G.D. Cedars M.I. Falk R.J. Peterson E.P. et al.Efficacy of treatment for unexplained infertility.Fertil Steril. 1998; 70: 207-213Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar, 32Guzick D.S. Carson S.A. Coutifaris C. Overstreet J.W. Factor-Litvak P. Steinkampf M.P. et al.Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network.N Engl J Med. 1999; 340: 177-183Crossref PubMed Scopus (467) Google Scholar, 33Practice Committee of the American Society for Reproductive MedicineEffectiveness and treatment for unexplained infertility.Fertil Steril. 2006; 86: S111-S114PubMed Google Scholar, 34Athaullah N. Proctor M. Johnson N.P. Oral versus injectable ovulation induction agents for unexplained subfertility.Cochrane Database Syst Rev. 2002; 3 (CD003052)PubMed Google Scholar, 35Pandian Z. Bhattacharya S. Nikolaou D. Vale L. Templeton A. The effectiveness of IVF in unexplained infertility: a systematic Cochrane review. 2002.Hum Reprod. 2003; 18: 2001-2007Crossref PubMed Scopus (23) Google ScholarUterinePresence of uterine fibroids/adenomyosisAbbreviations: ASRM, American Society for Reproductive Medicine; BTL, bilateral tubal ligation; E2, estradiol; FSH, follicle-stimulating hormone; HSG, hysterosalpingogram; PCOS, polycystic ovary syndrome. Open table in a new tab There was at least a 3% absolute change in pregnancy rate for every diagnostic criterion when strict and clinical criteria were compared. When pregnancy rates were calculated for each diagnostic category, success rates changed by more than 15% for patients with uterine factor, unexplained infertility, and diminished ovarian reserve. Pregnancy rates decreased when strict criteria were applied for most diagnostic categories with the exception of diminished ovarian reserve. Patients with multiple factors were less likely to achieve a pregnancy regardless of which criteria were applied; however, their likelihood of pregnancy was even lower with adjudicated diagnoses. By strict criteria, these patients were statistically significantly less likely to have a live birth than those with a single diagnosis (odds ratio [OR] 0.61, P=.019). This finding was similar with clinical criteria (OR 0.68, P=.06).ConclusionThese data provide evidence that there is poor agreement between clinical infertility diagnoses and evidence-based, strict infertility diagnoses. Diagnoses with objective criteria showed higher agreement than those with subjective criteria, indicating variability in a clinician's diagnosis. Furthermore, success rates in some diagnostic categories changed markedly when strict criteria were applied. With the exception of diminished ovarian reserve, success rates dropped in all other categories. This discrepancy with patients with diminished ovarian reserve might reflect that isolated diminished ovarian reserve is actually rare and that it may not carry the same implications as diminished ovarian reserve associated with increased age or endometriosis. Furthermore, it is important to note that patients with multiple diagnoses may have lower success than those with a single diagnosis. Given such wide variation in pregnancy rates between clinical and adjudicated diagnoses, we feel it is therefore imperative that clinicians make the most accurate diagnosis when providing their patients with an estimate of their probability of achieving pregnancy.Previous studies have examined the prognosis for pregnancy associated with specific infertility diagnoses such as tubal factor infertility, endometriosis, and PCOS (7Lintsen A.M. Eijkemans M.J. Hunault C.C. Bouwmans C.A. Hakkaart L. Habbema J.D. et al.Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study.Hum Reprod. 2007; 22: 2455-2462Crossref PubMed Scopus (135) Google Scholar, 8Grochowski D. Kulikowski M. Wolczynski S. Kuczynski W. Szamatowicz M. The outcome of an in vitro fertilization program in women with polycystic ovary syndrome.Gynecol Endocrinol. 1997; 11: 259-262Crossref PubMed Scopus (3) Google Scholar, 9Barnhart K. Dunsmoor-Su R. Coutifaris C. Effect of endometriosis on in vitro fertilization.Fertil Steril. 2002; 77: 1148-1155Abstract Full Text Full Text PDF PubMed Scopus (610) Google Scholar, 10Witsenburg C. Dieben S. Van der Westerlaken L. Verburg H. Naaktgeboren N. Cumulative live birth rates in cohorts of patients treated with in vitro fertilization or intracytoplasmic sperm injection.Fertil Steril. 2005; 84: 99-107Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar). Our results may help explain the apparent inconsistencies of studies in the literature. According to SART and previous studies, endometriosis patients have no difference in IVF success compared with other groups (12Calhaz-Jorge C. Chaveiro E. Nunes J. Costa A.P. Implications of the diagnosis of endometriosis on the success of infertility treatment.Clin Exp Obstet Gynecol. 2004; 31: 25-30PubMed Google Scholar). However, there are conflicting studies that suggest that endometriosis may be associated with a lower chance of success. A meta-analysis published by our group confirmed that these patients have a lower chance of pregnancy in IVF and that more severe forms of endometriosis result in lower rates of success (9Barnhart K. Dunsmoor-Su R. Coutifaris C. Effect of endometriosis on in vitro fertilization.Fertil Steril. 2002; 77: 1148-1155Abstract Full Text Full Text PDF PubMed Scopus (610) Google Scholar). The discrepancy between previous studies may be due to differences in how endometriosis was diagnosed or coded in the SART database. Our own small sample did not allow for subdivision of endometriosis into minimal, mild, moderate, and severe subcategories, but instituting these criteria into SART may prove useful in determining patient-specific prognoses. Furthermore, lack of precision in underlying diagnosis may affect the validity of past and future research. It is essential that investigators work toward a standardization of diagnostic criteria for all infertility diagnoses in the same manner that the Rotterdam Conferences standardized the diagnosis of PCOS (13Rotterdam EA-SPCWGRevised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.Fertil Steril. 2004; 81: 19-25Google Scholar).When examining SART clinic-specific success rates, it is important to examine diagnosis-specific rates (11Technology SfAR. National Summary of IVF Success Rates. In, 2006. Last accessed June 1, 2008.Google Scholar). The current SART database does not establish specific criteria for each of these diagnoses; instead, it merely offers diagnostic guidelines to participating clinics. To accurately compare success rates among clinics, standardization of these criteria is necessary. Careful and critical inspection of published studies in a systematic review of the literature is called for to determine which criteria have the most evidence for affecting outcome. Consensus statements such as the Rotterdam criteria for PCOS are particularly helpful in bringing together experts in the field to establish definitive criteria for specific diagnoses. We have demonstrated how merely standardizing these criteria in our own practice affected diagnosis-specific prognoses. As patients also look at these success rates when choosing a clinic, standardized and accurate reporting becomes more important. Accurate infertility diagnoses are important to provide patients with an accurate prognosis and help them in deciding how and where to best pursue fertility. Before attempting in vitro fertilization (IVF), patients almost always express a desire to know their chance of success. The Society for Assisted Reproductive Technology (SART) makes publicly available the self-reported data of participating IVF clinics throughout the United States. Patients are able to access these data via the SART Web site (http://www.sart.org) and find specific success rates for their age group and diagnostic category. Clinicians often refer to these rates when counseling patients on their prognosis for pregnancy. Previous investigators have demonstrated that age and infertility diagnosis are strong predictors of ultimate success (1Stolwijk A.M. Wetzels A.M. Braat D.D. Cumulative probability of achieving an ongoing pregnancy after in-vitro fertilization and intracytoplasmic sperm injection according to a woman's age, subfertility diagnosis and primary or secondary subfertility.Hum Reprod. 2000; 15: 203-209Crossref PubMed Scopus (112) Google Scholar, 2Lintsen A.M.E. Eijkemans M.J.C. Hunault C.C. Bouwmans C.A.M. Hakkaart L. Habbema J.D.F. et al.Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study.Hum Reprod. 2007; 22: 2455-2462Crossref PubMed Scopus (58) Google Scholar). In one population-based study, older patients were found to be more likely to have “unexplained” and tubal factor infertility, while younger women are more likely to have ovulatory dysfunction or endometriosis (3Maheshwari A. Hamilton M. Bhattacharya S. Effect of female age on the diagnostic categories of infertility.Hum Reprod. 2008; 23: 538-542Crossref PubMed Scopus (105) Google Scholar). Secondary infertility has also been associated with an increased chance of becoming pregnant with IVF (4Kupka M. Dorn C. Richter O. Felberbaum R. van der Ven H. Impact of reproductive history on in vitro fertilization and intracytoplasmic sperm injection outcome: evidence from the German IVF Registry.Fertil Steril. 2003; 80: 508-516Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar). Each participating SART clinic defines the specific criteria for infertility diagnoses given to their patients. In clinical practice, patients may be given one diagnosis when in fact they do not meet the strict criteria for a specific condition. Correct characterization of the cause of a patient's infertility is essential to provide them with their true prognosis for achieving pregnancy. Furthermore, some investigators have questioned whether different clinics can be appropriately compared with each other because of differences in populations, number of cycles, and methods of determining diagnoses (5Garcia J.E. Panel two: reporting and advertising success rates—the Gordian knot of assisted reproductive technology. The role of professional societies.Womens Health Issues. 1997; 7 (94–6): 188-192Abstract Full Text PDF PubMed Scopus (1) Google Scholar). We hypothesize that the clinical criteria by which many of these diagnoses are made affects the prognostic value of the success rate quoted to patients. Materials and methodsWe reviewed in the recent medical literature the current criteria for specific infertility diagnoses that form SART diagnostic categories. Special emphasis was given to position statements from American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) as well as systematic reviews that analyze the breadth of studies available. We determined the objective criteria for each diagnostic category. The IVF patients enrolled for other studies at the University of Pennsylvania between December 2003 and June 2006 had their clinical records reviewed and abstracted, and their infertility diagnosis adjudicated according to these strict criteria by trained personnel. Couples were permitted to have multiple diagnoses as long as they met the minimum criteria in each category. Institutional review board approval was obtained before chart abstraction.Adjudicated “strict” diagnoses were then compared with clinical diagnoses as entered into SART. The degree of agreement between the clinical and strict diagnoses was calculated using kappa statistics for specific diagnostic categories and evaluated according to the method of Landis and Koch (6Landis J.R. Koch G.G. The measurement of observer agreement for categorical data.Biometrics. 1977; 33: 159-174Crossref PubMed Scopus (49726) Google Scholar). Clinical pregnancy rates per transfer were calculated for each stratum and compared using generalized estimating equations models, an extension of logistic regression that adjusts for repeated measures per subject. All calculations were performed by the use of Stata version 10 (StataCorp LP, College Station, TX). This study was designed to assess agreement between diagnostic criteria and was not powered to assess for differences between pregnancy rates of the two groups. We reviewed in the recent medical literature the current criteria for specific infertility diagnoses that form SART diagnostic categories. Special emphasis was given to position statements from American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) as well as systematic reviews that analyze the breadth of studies available. We determined the objective criteria for each diagnostic category. The IVF patients enrolled for other studies at the University of Pennsylvania between December 2003 and June 2006 had their clinical records reviewed and abstracted, and their infertility diagnosis adjudicated according to these strict criteria by trained personnel. Couples were permitted to have multiple diagnoses as long as they met the minimum criteria in each category. Institutional review board approval was obtained before chart abstraction. Adjudicated “strict” diagnoses were then compared with clinical diagnoses as entered into SART. The degree of agreement between the clinical and strict diagnoses was calculated using kappa statistics for specific diagnostic categories and evaluated according to the method of Landis and Koch (6Landis J.R. Koch G.G. The measurement of observer agreement for categorical data.Biometrics. 1977; 33: 159-174Crossref PubMed Scopus (49726) Google Scholar). Clinical pregnancy rates per transfer were calculated for each stratum and compared using generalized estimating equations models, an extension of logistic regression that adjusts for repeated measures per subject. All calculations were performed by the use of Stata version 10 (StataCorp LP, College Station, TX). This study was designed to assess agreement between diagnostic criteria and was not powered to assess for differences between pregnancy rates of the two groups. ResultsCharts for 590 patients were adjudicated according to strict criteria. Live birth rates for each diagnostic criterion are presented in Table 1. The degree of agreement, represented by kappa coefficients, between clinical and strict diagnoses was poorest among patients with the diagnoses of uterine factor and diminished ovarian reserve. Strict criteria for unexplained infertility and polycystic ovary syndrome (PCOS) showed slightly improved agreement with clinical criteria. Although there was moderate agreement for diagnoses of endometriosis, and tubal factor and male factor infertility, there remained 20% or greater discordance between clinical and strict diagnoses.Table 1Strict diagnostic criteria.DiagnosisCriteriaEndometriosisScores based on revised ASRM classification of endometriosis 14American Society for Reproductive MedicineRevised American Society for Reproductive Medicine classification of endometriosis: 1996.Fertil Steril. 1997; 67: 817-821Abstract Full Text PDF PubMed Scopus (2232) Google Scholar, 15Marcoux S. Maheux R. Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis.N Engl J Med. 1997; 337: 217-222Crossref PubMed Scopus (835) Google ScholarTubal factorBilateral tubal occlusion on HSG or chromotubationHistory of BTL or bilateral salpingectomyUnilateral or bilateral hydrosalpinxHistory of ectopic pregnancy (excluding IVF) 16Pouly J.L. Chapron C. Manhes H. Canis M. Wattiez A. Bruhat M.A. Multifactorial analysis of fertility after conservative laparoscopic treatment of ectopic pregnancy in a series of 223 patients.Fertil Steril. 1991; 56: 453-460Abstract Full Text PDF PubMed Scopus (96) Google Scholar, 17Mol B.W.J. Collins J.A. Burrows E.A. van der Veen F. Bossuyt P.M.M. Comparison of hysterosalpingography and laparoscopy in predicting fertility outcome.Hum Reprod. 1999; 14: 1237-1242Crossref PubMed Scopus (131) Google Scholar, 18Hulka J.F. Adnexal adhesions: a prognostic staging and classification system based on a five-year survey of fertility surgery results at Chapel Hill, North Carolina.Am J Obstet Gynecol. 1982; 144: 141-148Abstract Full Text PDF PubMed Scopus (61) Google Scholar, 19Strandell A. Lindhard A. Waldenstrom U. Thorburn J. Janson P.O. Hamberger L. Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF.Hum Reprod. 1999; 14: 2762-2769Crossref PubMed Scopus (273) Google ScholarPCOS (2 out of 3 criteria)Oligo- or anovulation: intermenstrual periods ≥ 45 days OR ≤ 8 menses/yearClinical or biochemical hyperandrogenismPolycystic ovaries (≥12 follicles per ovary, 2–9 mm)Exclusion of other etiologies 13Rotterdam EA-SPCWGRevised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.Fertil Steril. 2004; 81: 19-25Google Scholar, 20Jonard S. Robert Y. Cortet-Rudelli C. Pigny P. Decanter C. Dewailly D. Ultrasound examination of polycystic ovaries: is it worth counting the follicles?.Hum Reprod. 2003; 18: 598-603Crossref PubMed Scopus (270) Google Scholar, 21Vermeulen A. Verdonck L. Kaufman J.M. A critical evaluation of simple methods for the estimation of free testosterone in serum.J Clin Endocrinol Metab. 1999; 84: 3666-3672Crossref PubMed Google ScholarDiminished ovarian reserveDay-3 FSH ≥11.4 mIU/mLDay-3 E2 ≥ 80 pg/mLAge ≤37Total antral follicle count ≤4 22Practice Committee of the American Society for Reproductive MedicineAging and infertility in women.Fertil Steril. 2006; 86: S248-S252PubMed Google Scholar, 23Smotrich D.B. Widra E.A. Gindoff P.R. Levy M.J. Hall J.L. Stillman R.J. Prognostic value of day 3 estradiol on in vitro fertilization outcome.Fertil Steril. 1995; 64: 1136-1140Abstract Full Text PDF PubMed Google Scholar, 24Barnhart K. Osheroff J. Follicle stimulating hormone as a predictor of fertility.Curr Opin Obstet Gynecol. 1998; 10: 227-232Crossref PubMed Scopus (60) Google Scholar, 25Esposito M.A. Coutifaris C. Barnhart K.T. A moderately elevated day 3 FSH concentration has limited predictive value, especially in younger women.Hum Reprod. 2002; 17: 118-123Crossref PubMed Scopus (86) Google Scholar, 26Scott R.T. Opsahl M.S. Leonardi M.R. Neall G.S. Illions E.H. Navot D. Life table analysis of pregnancy rates in a general infertility population relative to ovarian reserve and patient age.Hum Reprod. 1995; 10: 1706-1710PubMed Google Scholar, 27Frattarelli J.L. Levi A.J. Miller B.T. Segars J.H. A prospective assessment of the predictive value of basal antral follicles in in vitro fertilization cycles.Fertil Steril. 2003; 80: 350-355Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 28Bukulmez O. Arici A. Assessment of ovarian reserve.Curr Opin Obstet Gynecol. 2004; 16: 231-237Crossref PubMed Scopus (58) Google ScholarMale factorCount <13.5 mil/mLMotility <32%Morphology <9% 29World Health OrganizationLaboratory manual for the examination of human semen and sperm-cervical mucus interaction.4th ed. Cambridge University Press, New York1999Google Scholar, 30Guzick D.S. Overstreet J.W. Factor-Litvak P. Brazil C.K. Nakajima S.T. Coutifaris C. et al.Sperm morphology, motility, and concentration in fertile and infertile men.N Engl J Med. 2001; 345: 1388-1393Crossref PubMed Scopus (913) Google ScholarUnexplainedAt least one tube patent with no tubal abnormalitiesAge ≤37Normal ovarian reserveNormal semen analysis 31Guzick D.S. Sullivan M.W. Adamson G.D. Cedars M.I. Falk R.J. Peterson E.P. et al.Efficacy of treatment for unexplained infertility.Fertil Steril. 1998; 70: 207-213Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar, 32Guzick D.S. Carson S.A. Coutifaris C. Overstreet J.W. Factor-Litvak P. Steinkampf M.P. et al.Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network.N Engl J Med. 1999; 340: 177-183Crossref PubMed Scopus (467) Google Scholar, 33Practice Committee of the American Society for Reproductive MedicineEffectiveness and treatment for unexplained infertility.Fertil Steril. 2006; 86: S111-S114PubMed Google Scholar, 34Athaullah N. Proctor M. Johnson N.P. Oral versus injectable ovulation induction agents for unexplained subfertility.Cochrane Database Syst Rev. 2002; 3 (CD003052)PubMed Google Scholar, 35Pandian Z. Bhattacharya S. Nikolaou D. Vale L. Templeton A. The effectiveness of IVF in unexplained infertility: a systematic Cochrane review. 2002.Hum Reprod. 2003; 18: 2001-2007Crossref PubMed Scopus (23) Google ScholarUterinePresence of uterine fibroids/adenomyosisAbbreviations: ASRM, American Society for Reproductive Medicine; BTL, bilateral tubal ligation; E2, estradiol; FSH, follicle-stimulating hormone; HSG, hysterosalpingogram; PCOS, polycystic ovary syndrome. Open table in a new tab There was at least a 3% absolute change in pregnancy rate for every diagnostic criterion when strict and clinical criteria were compared. When pregnancy rates were calculated for each diagnostic category, success rates changed by more than 15% for patients with uterine factor, unexplained infertility, and diminished ovarian reserve. Pregnancy rates decreased when strict criteria were applied for most diagnostic categories with the exception of diminished ovarian reserve. Patients with multiple factors were less likely to achieve a pregnancy regardless of which criteria were applied; however, their likelihood of pregnancy was even lower with adjudicated diagnoses. By strict criteria, these patients were statistically significantly less likely to have a live birth than those with a single diagnosis (odds ratio [OR] 0.61, P=.019). This finding was similar with clinical criteria (OR 0.68, P=.06). Charts for 590 patients were adjudicated according to strict criteria. Live birth rates for each diagnostic criterion are presented in Table 1. The degree of agreement, represented by kappa coefficients, between clinical and strict diagnoses was poorest among patients with the diagnoses of uterine factor and diminished ovarian reserve. Strict criteria for unexplained infertility and polycystic ovary syndrome (PCOS) showed slightly improved agreement with clinical criteria. Although there was moderate agreement for diagnoses of endometriosis, and tubal factor and male factor infertility, there remained 20% or greater discordance between clinical and strict diagnoses. Abbreviations: ASRM, American Society for Reproductive Medicine; BTL, bilateral tubal ligation; E2, estradiol; FSH, follicle-stimulating hormone; HSG, hysterosalpingogram; PCOS, polycystic ovary syndrome. There was at least a 3% absolute change in pregnancy rate for every diagnostic criterion when strict and clinical criteria were compared. When pregnancy rates were calculated for each diagnostic category, success rates changed by more than 15% for patients with uterine factor, unexplained infertility, and diminished ovarian reserve. Pregnancy rates decreased when strict criteria were applied for most diagnostic categories with the exception of diminished ovarian reserve. Patients with multiple factors were less likely to achieve a pregnancy regardless of which criteria were applied; however, their likelihood of pregnancy was even lower with adjudicated diagnoses. By strict criteria, these patients were statistically significantly less likely to have a live birth than those with a single diagnosis (odds ratio [OR] 0.61, P=.019). This finding was similar with clinical criteria (OR 0.68, P=.06). ConclusionThese data provide evidence that there is poor agreement between clinical infertility diagnoses and evidence-based, strict infertility diagnoses. Diagnoses with objective criteria showed higher agreement than those with subjective criteria, indicating variability in a clinician's diagnosis. Furthermore, success rates in some diagnostic categories changed markedly when strict criteria were applied. With the exception of diminished ovarian reserve, success rates dropped in all other categories. This discrepancy with patients with diminished ovarian reserve might reflect that isolated diminished ovarian reserve is actually rare and that it may not carry the same implications as diminished ovarian reserve associated with increased age or endometriosis. Furthermore, it is important to note that patients with multiple diagnoses may have lower success than those with a single diagnosis. Given such wide variation in pregnancy rates between clinical and adjudicated diagnoses, we feel it is therefore imperative that clinicians make the most accurate diagnosis when providing their patients with an estimate of their probability of achieving pregnancy.Previous studies have examined the prognosis for pregnancy associated with specific infertility diagnoses such as tubal factor infertility, endometriosis, and PCOS (7Lintsen A.M. Eijkemans M.J. Hunault C.C. Bouwmans C.A. Hakkaart L. Habbema J.D. et al.Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study.Hum Reprod. 2007; 22: 2455-2462Crossref PubMed Scopus (135) Google Scholar, 8Grochowski D. Kulikowski M. Wolczynski S. Kuczynski W. Szamatowicz M. The outcome of an in vitro fertilization program in women with polycystic ovary syndrome.Gynecol Endocrinol. 1997; 11: 259-262Crossref PubMed Scopus (3) Google Scholar, 9Barnhart K. Dunsmoor-Su R. Coutifaris C. Effect of endometriosis on in vitro fertilization.Fertil Steril. 2002; 77: 1148-1155Abstract Full Text Full Text PDF PubMed Scopus (610) Google Scholar, 10Witsenburg C. Dieben S. Van der Westerlaken L. Verburg H. Naaktgeboren N. Cumulative live birth rates in cohorts of patients treated with in vitro fertilization or intracytoplasmic sperm injection.Fertil Steril. 2005; 84: 99-107Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar). Our results may help explain the apparent inconsistencies of studies in the literature. According to SART and previous studies, endometriosis patients have no difference in IVF success compared with other groups (12Calhaz-Jorge C. Chaveiro E. Nunes J. Costa A.P. Implications of the diagnosis of endometriosis on the success of infertility treatment.Clin Exp Obstet Gynecol. 2004; 31: 25-30PubMed Google Scholar). However, there are conflicting studies that suggest that endometriosis may be associated with a lower chance of success. A meta-analysis published by our group confirmed that these patients have a lower chance of pregnancy in IVF and that more severe forms of endometriosis result in lower rates of success (9Barnhart K. Dunsmoor-Su R. Coutifaris C. Effect of endometriosis on in vitro fertilization.Fertil Steril. 2002; 77: 1148-1155Abstract Full Text Full Text PDF PubMed Scopus (610) Google Scholar). The discrepancy between previous studies may be due to differences in how endometriosis was diagnosed or coded in the SART database. Our own small sample did not allow for subdivision of endometriosis into minimal, mild, moderate, and severe subcategories, but instituting these criteria into SART may prove useful in determining patient-specific prognoses. Furthermore, lack of precision in underlying diagnosis may affect the validity of past and future research. It is essential that investigators work toward a standardization of diagnostic criteria for all infertility diagnoses in the same manner that the Rotterdam Conferences standardized the diagnosis of PCOS (13Rotterdam EA-SPCWGRevised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.Fertil Steril. 2004; 81: 19-25Google Scholar).When examining SART clinic-specific success rates, it is important to examine diagnosis-specific rates (11Technology SfAR. National Summary of IVF Success Rates. In, 2006. Last accessed June 1, 2008.Google Scholar). The current SART database does not establish specific criteria for each of these diagnoses; instead, it merely offers diagnostic guidelines to participating clinics. To accurately compare success rates among clinics, standardization of these criteria is necessary. Careful and critical inspection of published studies in a systematic review of the literature is called for to determine which criteria have the most evidence for affecting outcome. Consensus statements such as the Rotterdam criteria for PCOS are particularly helpful in bringing together experts in the field to establish definitive criteria for specific diagnoses. We have demonstrated how merely standardizing these criteria in our own practice affected diagnosis-specific prognoses. As patients also look at these success rates when choosing a clinic, standardized and accurate reporting becomes more important. Accurate infertility diagnoses are important to provide patients with an accurate prognosis and help them in deciding how and where to best pursue fertility. These data provide evidence that there is poor agreement between clinical infertility diagnoses and evidence-based, strict infertility diagnoses. Diagnoses with objective criteria showed higher agreement than those with subjective criteria, indicating variability in a clinician's diagnosis. Furthermore, success rates in some diagnostic categories changed markedly when strict criteria were applied. With the exception of diminished ovarian reserve, success rates dropped in all other categories. This discrepancy with patients with diminished ovarian reserve might reflect that isolated diminished ovarian reserve is actually rare and that it may not carry the same implications as diminished ovarian reserve associated with increased age or endometriosis. Furthermore, it is important to note that patients with multiple diagnoses may have lower success than those with a single diagnosis. Given such wide variation in pregnancy rates between clinical and adjudicated diagnoses, we feel it is therefore imperative that clinicians make the most accurate diagnosis when providing their patients with an estimate of their probability of achieving pregnancy.
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