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The addition of anti-Müllerian hormone in an algorithm for individualized hormone dosage did not improve the prediction of ovarian response-a randomized, controlled trial.
Hum Reprod. 2017 04 01; 32(4):811-819.HR

Abstract

Study question

Does the addition of anti-Müllerian hormone (AMH) to a conventional dosage regimen, including age, antral follicle count (AFC) and BMI, improve the rate of targeted ovarian response, defined as 5-12 oocytes after IVF?

Summary answer

The addition of AMH did not alter the rate of targeted ovarian response, 5-12 oocytes, or decreased the rate of ovarian hyperstimulation syndrome (OHSS) or cancelled cycles due to poor ovarian response.

What is known already

Controlled ovarian hyperstimulation (COH) in connection with IVF is sometimes associated with poor ovarian response resulting in low pregnancy and live birth rates or leading to cycle cancellations, but also associated with excessive ovarian response, causing an increased risk of OHSS. Even though it is well-established that both AMH and AFC are strong predictors of ovarian response in IVF, few randomized trials have investigated their impact on achieving an optimal number of oocytes.

Study design, size and duration

Between January 2013 and May 2016, 308 patients starting their first IVF treatment were randomly assigned, using a computerized randomization program with concealed allocation of patients and in the proportions of 1:1, to one of two dosage algorithms for decisions on hormone starting dose, an algorithm, including AMH, AFC, age and BMI (intervention group), or an algorithm, including only AFC, age and BMI (control group). The study was blinded to patients and treating physicians.

Participants/materials, setting, methods

Women aged >18 and <40 years, with a BMI above 18.0 and below 35.0 kg/m2 starting their first IVF cycle where standard IVF was planned, were eligible. All patients were treated with a GnRH agonist protocol and recombinant FSH was used for stimulation. The study was performed as a single-centre study at a large IVF unit at a university hospital.

Main results and the role of chance

The rate of patients having the targeted number of oocytes retrieved was 81/152 (53.3%) in the intervention group versus 96/155 (61.9%) in the control group (P = 0.16, difference: -8.6, 95% CI: -20.3; 3.0). Cycles with poor response (<5 oocytes) were more frequent in the AMH group, 39/152 (25.7%) versus the non-AMH group, 17/155 (11.0%) (P < 0.01), while the number of cancelled cycles due to poor ovarian response did not differ 7/152 (4.6%) and 4/155 (2.6%) (P = 0.52). An excessive response (>12 oocytes) was seen in 32/152 (21.1%) and 42/155 (27.1%) patients, respectively (P = 0.27). Moderate or severe OHSS was observed among 5/152 (3.3%) and 6/155 (3.9%) patients, respectively (P = 1.0). Live birth rates were 48/152 (31.6%) and 42/155 (27.1%) per started cycle.

Limitations, reasons for caution

The categorization of AMH values in predicted low, normal and high responders was originally established using the Diagnostic Systems Laboratories assay and was translated to more recently released assays, lacking international standards and well-established reference intervals. The interpretation of AMH values between different assays should therefore be made with some caution.

Wider implications of the findings

An individualised dosage regimen including AMH compared with a non-AMH dosage regimen in an unselected patient population did not alter the number of women achieving the targeted number of oocytes, or the cancellation rate due to poor response or the occurrence of moderate/severe OHSS. However, this study cannot answer the question if using an algorithm for dose decision of FSH is superior to a standard dose and neither which ovarian reserve test is the most effective.

Study funding/competing interest

Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940) and unrestricted grants from Ferring Pharmaceuticals and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.

Trial registration

The study was registered at www.clinicaltrials.gov NCT02013973.

Trial registration date

6 December 2013.

DATE OF FIRST PATIENT RANDOMIZED

14 January 2013.

Authors+Show Affiliations

Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Reproductive Medicine, Sahlgrenska University Hospital, SE Gothenburg, Sweden.Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Reproductive Medicine, Sahlgrenska University Hospital, SE Gothenburg, Sweden.Department of Clinical Chemistry, Sahlgrenska University Hospital, SE Gothenburg, Sweden.Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Reproductive Medicine, Sahlgrenska University Hospital, SE Gothenburg, Sweden.Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Reproductive Medicine, Sahlgrenska University Hospital, SE Gothenburg, Sweden.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28175316

Citation

Magnusson, Å, et al. "The Addition of anti-Müllerian Hormone in an Algorithm for Individualized Hormone Dosage Did Not Improve the Prediction of Ovarian Response-a Randomized, Controlled Trial." Human Reproduction (Oxford, England), vol. 32, no. 4, 2017, pp. 811-819.
Magnusson Å, Nilsson L, Oleröd G, et al. The addition of anti-Müllerian hormone in an algorithm for individualized hormone dosage did not improve the prediction of ovarian response-a randomized, controlled trial. Hum Reprod. 2017;32(4):811-819.
Magnusson, Å., Nilsson, L., Oleröd, G., Thurin-Kjellberg, A., & Bergh, C. (2017). The addition of anti-Müllerian hormone in an algorithm for individualized hormone dosage did not improve the prediction of ovarian response-a randomized, controlled trial. Human Reproduction (Oxford, England), 32(4), 811-819. https://doi.org/10.1093/humrep/dex012
Magnusson Å, et al. The Addition of anti-Müllerian Hormone in an Algorithm for Individualized Hormone Dosage Did Not Improve the Prediction of Ovarian Response-a Randomized, Controlled Trial. Hum Reprod. 2017 04 1;32(4):811-819. PubMed PMID: 28175316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The addition of anti-Müllerian hormone in an algorithm for individualized hormone dosage did not improve the prediction of ovarian response-a randomized, controlled trial. AU - Magnusson,Å, AU - Nilsson,L, AU - Oleröd,G, AU - Thurin-Kjellberg,A, AU - Bergh,C, PY - 2016/09/28/received PY - 2017/01/11/accepted PY - 2017/2/9/pubmed PY - 2017/10/19/medline PY - 2017/2/9/entrez KW - algorithm KW - anti-Müllerian hormone KW - dose of FSH KW - individual KW - ovarian KW - prediction KW - response SP - 811 EP - 819 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 32 IS - 4 N2 - Study question: Does the addition of anti-Müllerian hormone (AMH) to a conventional dosage regimen, including age, antral follicle count (AFC) and BMI, improve the rate of targeted ovarian response, defined as 5-12 oocytes after IVF? Summary answer: The addition of AMH did not alter the rate of targeted ovarian response, 5-12 oocytes, or decreased the rate of ovarian hyperstimulation syndrome (OHSS) or cancelled cycles due to poor ovarian response. What is known already: Controlled ovarian hyperstimulation (COH) in connection with IVF is sometimes associated with poor ovarian response resulting in low pregnancy and live birth rates or leading to cycle cancellations, but also associated with excessive ovarian response, causing an increased risk of OHSS. Even though it is well-established that both AMH and AFC are strong predictors of ovarian response in IVF, few randomized trials have investigated their impact on achieving an optimal number of oocytes. Study design, size and duration: Between January 2013 and May 2016, 308 patients starting their first IVF treatment were randomly assigned, using a computerized randomization program with concealed allocation of patients and in the proportions of 1:1, to one of two dosage algorithms for decisions on hormone starting dose, an algorithm, including AMH, AFC, age and BMI (intervention group), or an algorithm, including only AFC, age and BMI (control group). The study was blinded to patients and treating physicians. Participants/materials, setting, methods: Women aged >18 and <40 years, with a BMI above 18.0 and below 35.0 kg/m2 starting their first IVF cycle where standard IVF was planned, were eligible. All patients were treated with a GnRH agonist protocol and recombinant FSH was used for stimulation. The study was performed as a single-centre study at a large IVF unit at a university hospital. Main results and the role of chance: The rate of patients having the targeted number of oocytes retrieved was 81/152 (53.3%) in the intervention group versus 96/155 (61.9%) in the control group (P = 0.16, difference: -8.6, 95% CI: -20.3; 3.0). Cycles with poor response (<5 oocytes) were more frequent in the AMH group, 39/152 (25.7%) versus the non-AMH group, 17/155 (11.0%) (P < 0.01), while the number of cancelled cycles due to poor ovarian response did not differ 7/152 (4.6%) and 4/155 (2.6%) (P = 0.52). An excessive response (>12 oocytes) was seen in 32/152 (21.1%) and 42/155 (27.1%) patients, respectively (P = 0.27). Moderate or severe OHSS was observed among 5/152 (3.3%) and 6/155 (3.9%) patients, respectively (P = 1.0). Live birth rates were 48/152 (31.6%) and 42/155 (27.1%) per started cycle. Limitations, reasons for caution: The categorization of AMH values in predicted low, normal and high responders was originally established using the Diagnostic Systems Laboratories assay and was translated to more recently released assays, lacking international standards and well-established reference intervals. The interpretation of AMH values between different assays should therefore be made with some caution. Wider implications of the findings: An individualised dosage regimen including AMH compared with a non-AMH dosage regimen in an unselected patient population did not alter the number of women achieving the targeted number of oocytes, or the cancellation rate due to poor response or the occurrence of moderate/severe OHSS. However, this study cannot answer the question if using an algorithm for dose decision of FSH is superior to a standard dose and neither which ovarian reserve test is the most effective. Study funding/competing interest: Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940) and unrestricted grants from Ferring Pharmaceuticals and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest. Trial registration: The study was registered at www.clinicaltrials.gov NCT02013973. Trial registration date: 6 December 2013. DATE OF FIRST PATIENT RANDOMIZED: 14 January 2013. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/28175316/The_addition_of_anti_Müllerian_hormone_in_an_algorithm_for_individualized_hormone_dosage_did_not_improve_the_prediction_of_ovarian_response_a_randomized_controlled_trial_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dex012 DB - PRIME DP - Unbound Medicine ER -