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Hum. Reprod. Advance Access first published online on August 25, 2005
This version published online on October 18, 2005
Human Reproduction, doi:10.1093/humrep/dei270
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Received January 5, 2005
Revised May 25, 2005
Accepted July 8, 2005

Article

Müllerian inhibiting substance levels at the time of HCG administration in IVF cycles predict both ovarian reserve and embryo morphology

T. Silberstein 1, D.T. MacLaughlin 2, I. Shai 3, J.R. Trimarchi 1, G. Lambert-Messerlian 4, D.B. Seifer 5, D.L. Keefe 1, and A.S. Blazar 1*

1 Women and Infants’ Hospital of Rhode Island, Brown University Division of Biology and Medicine, Providence, Rhode Island
2 Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
3 Departments of Epidemiology and Nutrition, Harvard School of Public Health, Women and Infants’ Hospital of Rhode Island, Brown University Division of Biology and MedicineProvidence, Rhode Island
4 Department of Pathology and Laboratory Medicine, Division of Prenatal and Special Testing, Providence, Rhode Island
5 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology Maimonides Medical Center, Brooklyn, New York, USA

* To whom correspondence should be addressed.
A.S. Blazar, E-mail: Ablazar{at}wihri.org


  Abstract

BACKGROUND: Pre-antral and early antral follicles secrete Müllerian inhibiting substance (MIS), suggesting that MIS may directly reflect ovarian reserve. Since little is known about how ovarian reserve affects oocyte quality, we attempt here to assess the predictive value of MIS on embryo morphology and IVF outcome. To do so, we measured MIS at the time of HCG administration 36 h prior to oocyte retrieval. METHODS: A total of 257 patients undergoing IVF were prospectively recruited. We measured MIS levels by enzyme-linked immunosorbent assay at the time of HCG, and compared the MIS values to day 3 FSH levels in the prediction of embryo morphology and IVF outcome. RESULTS: The distribution of MIS levels was skewed, with a median of 2.7 ng/ml (range 0 to 28.5 ng/ml). MIS values at the time of HCG administration inversely correlated with basal FSH levels (P = 0.002), and both correlated significantly with patient age, number of mature follicles, number of oocytes retrieved and serum estradiol levels. MIS levels correlated significantly with a greater number of 6-cell embryos and better embryo morphology score, while basal FSH levels did not correlate with these outcome variables. MIS levels ≥2.7 ng/ml portended improved oocyte quality as reflected in a higher implantation rate (P = 0.001) and a trend toward a better clinical pregnancy rate (P = 0.084). CONCLUSIONS: MIS levels seem to predict not only ovarian reserve, but also embryo morphology. Measurement of MIS at the time of HCG administration may, therefore, in the future improve management of patients undergoing treatments with assisted reproductive technology.

Keywords: embryo morphology/IVF/Müllerian inhibiting substance/ovarian reserve/pregnancy rate.
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