Serum anti-Mullerian hormone levels are negatively related to Follicular Output RaTe (FORT) in normo-cycling women undergoing controlled ovarian hyperstimulation

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V.K. Genro1,2,3,4, M. Grynberg1,2,3, J.B. Scheffer1,2,3, I. Roux1,2,3, R. Frydman1,2,3 and R. Fanchin1,2,3,*

1Service de Gynécologie-Obstétrique et Médecine de la Reproduction, AP-HP, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, Clamart F-92141, France

2Univ Paris-Sud, Clamart F-92140, France

3INSERM, U782, Clamart F-92140, France

4Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Porto Alegre, Brazil *Correspondence address. Tel: +33-1-45-37-40-53; Fax: +33-1-45-37-49-80; E-mail: renato.fanchin{at}abc.ap-hop-paris.frReceived August 25, 2010. Revision received November 9, 2010. Accepted November 24, 2010. BACKGROUND Since in rodents anti-Müllerian hormone (AMH) has been shown to inhibit antral follicle responsiveness to FSH, we aimed at verifying whether a relationship exists between serum AMH levels and antral follicle responsiveness to exogenous FSH in normo-cycling women.

METHODS Serum AMH, estradiol (E2) and FSH levels were prospectively measured on cycle day 3 in patients undergoing controlled ovarian hyperstimulation (COH) with a time-release GnRH agonist and standardized FSH doses. In 162 patients, follicles were counted after pituitary suppression and before FSH administration (baseline; small antral follicles; 3–8 mm), and on the day of hCG (dhCG; pre-ovulatory follicles; 16–22 mm). Antral follicle responsiveness to FSH was estimated by the Follicular Output RaTe (FORT), determined by the ratio pre-ovulatory follicle count on dhCG × 100/small antral follicle count at baseline.

RESULTS Serum AMH levels were positively correlated with the number of small antral follicles at baseline (r = 0.59; P < 0.0001) and pre-ovulatory follicles on dhCG (r = 0.17; P < 0.04). Overall, FORT was 47.5 ± 1.4% and failed to be influenced by the woman's age, BMI or basal E2 and FSH level. Conversely, multiple regression analysis showed that FORT was negatively correlated with AMH levels (r = -0.30; P < 0.001), irrespective of duration of COH and total FSH dose.

CONCLUSIONS The percentage of follicles that effectively respond to FSH by reaching pre-ovulatory maturation is negatively and independently related to serum AMH levels. Although the mechanisms underlying this finding remain unclear, it is in keeping with the hypothesis that AMH inhibits follicle sensitivity to FSH.

© The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (3): 671-677. doi: 10.1093/humrep/deq361 First published online: December 21, 2010

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A multi-faceted strategy to improve the use of national fertility guidelines; a cluster-randomized controlled trial

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Selma M. Mourad1,2, Rosella P.M.G. Hermens2, Janine Liefers2, Reinier P. Akkermans2, G.A. Zielhuis3, E. Adang3, Richard P.T.M. Grol2, Willianne L.D.M. Nelen1 and Jan A.M. Kremer1,*

1Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

2Scientific Institute for Quality of Healthcare (IQ Healthcare), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

3Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands *Correspondence address. E-mail: j.kremer{at}obgyn.umcn.nlReceived February 2, 2010. Revision received August 9, 2010. Accepted September 30, 2010. BACKGROUND Proper use of clinical practice guidelines can decrease variation in care between settings. However, actual use of fertility guidelines is suboptimal and in need of improvement. Hence, a cluster-randomized controlled trial was designed to study the effects of two strategies to implement national Dutch guidelines on comprehensive fertility care.

METHODS Sixteen fertility clinics participated in the trial. A minimal, professional-oriented implementation strategy of audit and feedback was tested versus a maximal multi-faceted strategy that was both professional and patient oriented. The extent of adherence to guideline recommendations, reflected in quality indicator scores, was the primary outcome measure. To gain an insight into unwanted side effects, patient anxiety and depression scores were gathered as secondary outcomes. Data collection encompassed medical record search, patient and professional questionnaires.

RESULTS A total of 1499 couples were included at baseline and 1396 at the after-measurement. No overall significant improvement in indicator scores was found for either strategy [odds ratios ranging from 0.23 (95% confidence interval (CI): 0.06–0.95) to 6.66 (95% CI: 0.33–132.8]. Secondary outcomes did not differ significantly for both groups, although selected anxiety scores appeared lower in the maximal intervention group. Process evaluation of the trial revealed positive patient experiences with the intervention material [e.g. an increased understanding of their doctor's treatment policy (61%), an increased ability to ask questions about the treatment (61%)]. Professionals’ appreciation of intervention elements varied, and execution of the multi-faceted strategy appeared incomplete.

DISCUSSION Absence of an intervention effect may be due to the nature of the strategies, incomplete execution or flaws in study design. Process evaluation data raise the question of whether professionals should be the only stakeholder responsible for guideline implementation. This study therefore contributes to an increased understanding of fertility guideline implementation in general, and the role of patients in particular.

Clinical Trials.gov: NCT00119925.

© The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org This ArticleHum. Reprod. (2011) 26 (4): 817-826. doi: 10.1093/humrep/deq299 First published online: December 6, 2010

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

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