Use of Stimulated Serum Estradiol Measurements for the Prediction of Hyperresponse to Ovarian Stimulation in in Vitro Fertilization (IVF)
Tóm tắt
Purpose: In ovarian stimulation an exaggerated ovarian response is often seen and is related to medical complications, such as ovarian hyperstimulation syndrome (OHSS), and increased patient discomfort. If it were possible to identify hyperresponders at an early stage of the stimulation phase, adaptation of the stimulation protocol would become feasible to minimize potential complications. Therefore, we studied the usefulness of measuring stimulated serum estradiol (E
2) levels in predicting ovarian hyperresponse.
Methods: A total of 109 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospectively included. The E
2 level was evaluated on day 3 and 5 of the stimulation phase. Two outcome measures were defined. The first was ovarian hyperresponse (collection of ≥15 oocytes at retrieval and/or peak E
2 >10000 pmol/L, or cancellation due to ≥30 follicles growing and/or peak E
2 >15000 pmol/L, or OHSS developed). The second outcome measure comprised a subgroup representing the more severe hyperresponders, named extreme-response (cancellation or OHSS developed).
Results: The data of 108 patients were analyzed. The predictive accuracy of E
2 measured on stimulation day 3 towards ovarian hyperresponse was clearly lower than that of E
2 measured on stimulation day 5 (area under the receiver operating characteristic curve (ROCAUC) 0.75 and 0.81, respectively). For extreme-response the predictive accuracy of E
2 measured on stimulation day 3 or 5 was comparable (ROCAUC 0.81 and 0.82, respectively). For both outcome measures the stimulated E
2 tests yielded only acceptable specificity with moderate sensitivity at higher cutoff levels. Prediction of extreme-response seemed slightly more effective due to a lower error rate.
Conclusions: There is a significant predictive association between E
2 levels measured on stimulation day 3 and 5 and both ovarian hyperresponse and extreme-response in IVF. However, the clinical value of stimulated E
2 levels for the prediction of hyperresponse is low because of the modest sensitivity and the high false positive rate. For the prediction of extreme-response the clinical value of stimulated E
2 levels is moderate.
Tài liệu tham khảo
Morris RS, Paulson RJ, Sauer MV, Lobo RA: Predictive value of serum estradiol concentrations and oocyte number in severe ovarian hyperstimulation syndrome. Hum Reprod 1995;10:811-814
Delvigne A, Vandromme J, Barlow P, Lejeune B, Leroy F: Are there predictive criteria of complicated ovarian hyperstimulation in IVF? Hum Reprod 1991;6:959-962
Navot D, Bergh PA, Laufer N: Ovarian hyperstimulation syndrome in novel reproductive technologies: Prevention and treatment. Fertil Steril 1992;58:249-261
Brinsden PR, Wada I, Tan SL, Balen A, Jacobs HS: Diagnosis, prevention and management of ovarian hyperstimulation syndrome. Br J Obstet Gynaecol 1995;102:767-772
Kligman I, Rosenwaks Z: Differentiating clinical profiles: Predicting good responders, poor responders, and hyperresponders. Fertil Steril 2001;76:1185-1190
Pena JE, Chang PL, Chan LK, Zeitoun K, Thornton MH, Sauer MV: Supraphysiological estradiol levels do not affect oocyte and embryo quality in oocyte donation cycles. Hum Reprod 2002;17:83-87
Tarin JJ, Sampaio MC, Calatayud C, Castellvi RM, Bonilla-Musoles F, Pellicer A: Relativity of the concept 'high responder to gonadotrophins.' Hum Reprod 1992;7:19-22
Simon C, Garcia Velasco JJ, Valbuena D, Peinado JA, Moreno C, Remohi J, Pellicer A: Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle-stimulating hormone step-down regimen. Fertil Steril 1998;70:234-239
Ertzeid G, Storeng R: The impact of ovarian stimulation on implantation and fetal development in mice. Hum Reprod 2001;16:221-225
Agrawal R, Tan SL, Wild S, Sladkevicius P, Engmann L, Payne N, Bekir J, Campbell S, Conway G, Jacobs H: Serum vascular endothelial growth factor concentrations in in vitro fertilization cycles predict the risk of ovarian hyperstimulation syndrome. Fertil Steril 1999;71:287-293
Eldar-Geva T, Margalioth EJ, Ben Chetrit A, Gal M, Robertson DM, Healy DL, Diamant YZ, Spitz IM: Serum inhibin B levels measured early during FSH administration for IVF may be of value in predicting the number of oocytes to be retrieved in normal and low responders. Hum Reprod 2002;17:2331-2337
Enskog A, Nilsson L, Brannstrom M: Peripheral blood concentrations of inhibin B are elevated during gonadotrophin stimulation in patients who later develop ovarian OHSS and inhibin A concentrations are elevated after OHSS onset. Hum Reprod 2000;15:532-538
Fawzy M, Lambert A, Harrison RF, Knight PG, Groome N, Hennelly B, Robertson WR: Day 5 inhibin B levels in a treatment cycle are predictive of IVF outcome. Hum Reprod 2002;17:1535-1543
Phelps JY, Levine AS, Hickman TN, Zacur HA, Wallach EE, Hinton EL: Day 4 estradiol levels predict pregnancy success in women undergoing controlled ovarian hyperstimulation for IVF. Fertil Steril 1998;69:1015-1019
van Kooij RJ, Looman CW, Habbema JD, Dorland M, te Velde ER: Age-dependent decrease in embryo implantation rate after in vitro fertilization. Fertil Steril 1996;66:769-775
Navot D, Bergh PA: Ovarian hyperstimulation syndrome: A practical approach. In Ovarian Endocrinopathies. The proceedings of the 8th Reinier de Graaf Symposium, Amsterdam 2-4 September 1993, pp. 215-225
Hanley JA, McNeil BJ: The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143:29-36
Fauser BC, Devroey P, Yen SS, Gosden R, Crowley WF Jr, Baird DT, Bouchard P: Minimal ovarian stimulation for IVF: Appraisal of potential benefits and drawbacks. Hum Reprod 1999;14:2681-2686
Hohmann FP, Macklon NS, Fauser BC: A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol. J Clin Endocrinol Metab 2003;88:166-173
Tomas C, Nuojua-Huttunen S, Martikainen H: Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization. Hum Reprod 1997;12:220-223
Van Rooij IA, Broekmans FJ, te Velde ER, Fauser BC, Bancsi LF, Jong FH, Themmen AP: Serum anti-Mullerian hormone levels: A novel measure of ovarian reserve. Hum Reprod 2002;17:3065-3071
Danninger B, Brunner M, Obruca A, Feichtinger W: Prediction of ovarian hyperstimulation syndrome by ultrasound volumetric assessment of baseline ovarian volume prior to stimulation. Hum Reprod 1996;11:1597-1599
Dor J, Shulman A, Levran D, Ben Rafael Z, Rudak E, Mashiach S: The treatment of patients with polycystic ovarian syndrome by in-vitro fertilization and embryo transfer: A comparison of results with those of patients with tubal infertility. Hum Reprod 1990;5:816-818