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      Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles

      Author(s): , , , , ,
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      Journal: Human Reproduction
      Publisher: Oxford University Press (OUP)

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          Abstract

          While live birth is the principal clinical outcome following in vitro fertilization (IVF) treatment, the number of eggs retrieved following ovarian stimulation is often used as a surrogate outcome in clinical practice and research. The aim of this study was to explore the association between egg number and live birth following IVF treatment and identify the number of eggs that would optimize the IVF outcome. Anonymized data on all IVF cycles performed in the UK from April 1991 to June 2008 were obtained from the Human Fertilization and Embryology Authority (HFEA). We analysed data from 400 135 IVF cycles. A logistic model was fitted to predict live birth using fractional polynomials to handle the number of eggs as a continuous independent variable. The prediction model, which was validated on a separate HFEA data set, allowed the estimation of the probability of live birth for a given number of eggs, stratified by age group. We produced a nomogram to predict the live birth rate (LBR) following IVF based on the number of eggs and the age of the female. The median number of eggs retrieved per cycle was 9 [inter-quartile range (IQR) 6-13]. The overall LBR was 21.3% per fresh IVF cycle. There was a strong association between the number of eggs and LBR; LBR rose with an increasing number of eggs up to ∼15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. During 2006-2007, the predicted LBR for women with 15 eggs retrieved in age groups 18-34, 35-37, 38-39 and 40 years and over was 40, 36, 27 and 16%, respectively. There was a steady increase in the LBR per egg retrieved over time since 1991. The relationship between the number of eggs and live birth, across all female age groups, suggests that the number of eggs in IVF is a robust surrogate outcome for clinical success. The results showed a non-linear relationship between the number of eggs and LBR following IVF treatment. The number of eggs to maximize the LBR is ∼15.

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          The role of antimullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count.

          S L Broer, F Broekmans, Ben Mol … (2009)
          To assess the value of antimullerian hormone (AMH) as a test to predict poor ovarian response and pregnancy occurrence after IVF and to compare it with the performance of the antral follicle count (AFC). A systematic review of existing literature and a meta-analysis were carried out. After a comprehensive search, studies were included if 2 x 2 tables for outcomes poor response and pregnancy in IVF patients in relation to AMH or AFC could be constructed. Academic referral center for tertiary care. Cases indicated for IVF. None. Poor response and nonpregnancy after IVF. A total of 13 studies were found reporting on AMH and 17 on AFC. Because of heterogeneity among studies, calculation of a summary point estimate for sensitivity and specificity was not possible. However, for both tests summary receiver operating characteristic curves for the outcome measures poor response and nonpregnancy could be estimated and compared. The curves for the prediction of poor response indicated no significant difference between the performances of AMH and AFC. For the prediction of nonpregnancy, poor performance for both AMH and AFC was found. In this meta-analysis it was shown that AMH has at least the same level of accuracy and clinical value for the prediction of poor response and nonpregnancy as AFC.
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            A systematic review of tests predicting ovarian reserve and IVF outcome.

            F J Broekmans, J Kwee, D J Hendriks … (2006)
            The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (approximately 3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.
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              Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo.

              Diana Valbuena, Julio Martín, Jose Luis De Pablo … (2001)
              To investigate whether the deleterious effect of E(2) on embryonic implantation is due to a direct effect on the endometrium, on the embryo, or both. Prospective, controlled in vitro study. Tertiary infertility center. Fertile patients in the luteal phase with histologically normal endometrium who were attending the infertility clinic as oocyte donors (n = 14). E(2) dose-response (0, 10(-8), 10(-7), 10(-6), 10(-5), and 10(-4) M) and time course (day 2 vs. day 5) experiments were performed in an in vitro embryo adhesion assay composed of human polarized endometrial epithelial cells obtained from fertile patients and mouse embryos. Blastocyst formation rate and embryo adhesion rate. Monolayers of polarized endometrial epithelial cells expressed ERalpha at the mRNA level. The E(2) dose response of blastocysts with polarized endometrial epithelial cells (n = 235) demonstrated a progressive reduction in embryonic adhesion that was statistically significant at 10(-6) M. When polarized endometrial epithelial cells were treated alone with increasing doses of E(2) for 3 days and E(2) was then removed and blastocysts added (n = 410), embryonic adhesion was not significantly reduced, except at 10(-4) M. When 2-day mouse embryos (n = 609) were treated with increasing E(2) concentrations until day 5, the rate of blastocyst formation significantly decreased at a concentration >or= 10(-6) M, and embryonic adhesion decreased when blastocysts (n = 400) were obtained at a concentration >or= 10(-7) M. Time course experiments of embryos cultured for 2 days with polarized endometrial epithelial cells (n = 426) showed that the adhesion rate was higher at E(2) levels of 10(-7), 10(-6) and 10(-5) M compared with embryos cultured for 5 days (n = 495). High E(2) levels are deleterious to embryo adhesion in vitro, mainly because they have a direct toxic effect on the embryo that may occur at the cleavage stage.
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                Author and article information

                Journal
                Title: Human Reproduction
                Publisher: Oxford University Press (OUP)
                ISSN (Electronic): 1460-2350
                ISSN (Print): 0268-1161
                Publication date Created: July 2011
                Publication date Created: July 01 2011
                Publication date Created: May 10 2011
                Publication date (Print): July 2011
                Publication date (Print): July 01 2011
                Publication date (Electronic): May 10 2011
                Volume: 26
                Issue: 7
                Pages: 1768-1774
                Article
                DOI: 10.1093/humrep/der106
                PubMed ID: 21558332
                SO-VID: 4241a018-cef8-43f7-9417-0939ad4fe60d
                Copyright © © 2011
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