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      IVF outcomes of women with discrepancies between age and serum anti-Müllerian hormone levels

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          Abstract

          Background

          To determine the effects of age and the serum anti-Müllerian hormone (AMH) level on in vitro fertilization (IVF) outcomes, especially among young women with low serum AMH levels and older women with high AMH levels.

          Methods

          This study was a cohort study in which a total of 9431 women aged 20–51 years who were undergoing their first IVF cycles were recruited. Ovarian response parameters included the number of retrieved oocytes, the number of 2 pronuclear zygotes (2PN), and the frequency of good-quality embryos (GQE). Pregnancy outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), miscarriage rate (MR), and cumulative CPR and LBR (CCPR and CLBR).

          Results

          Among women under 35 years of age, the ovarian response, CPR, CCPR, LBR and CLBR ( p < 0.01) were significantly lower in the low-AMH group than in the average-AMH and high-AMH groups. In women above 35 years of age, the ovarian response, CPR, CCPR and CLBR ( p < 0.01) were significantly higher in the average-AMH and low-AMH groups. The LBR in the older high-AMH group was significantly higher (37.45% vs 20.34%, p < 0.01) than that in the older low-AMH group, but there was no difference (37.45% vs 32.46%, p = 0.11) compared with the older average-AMH group. When there was a discrepancy between age and the AMH level, the young low-AMH group showed a poorer ovarian response but a better CPR (58.01% vs 49.44%, p < 0.01) and LBR (48.52% vs 37.45%, p < 0.01) than the older high-AMH group. However, the CCPR (65.37% vs 66.11%, p = 0.75) and CLBR (56.35% vs 52.89%, p = 0.15) between the two groups were comparable. The conservative CLBR in the two discrepancy groups increased until the third embryo transfer and reached a plateau thereafter.

          Conclusion(s)

          Even with a relatively low AMH level, young women still had better pregnancy outcomes following IVF than older women. However, increasing the AMH level improves the cumulative outcomes of the older group to a comparable level through a notable and superior ovarian response.

          Electronic supplementary material

          The online version of this article (10.1186/s12958-019-0498-3) contains supplementary material, which is available to authorized users.

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          Most cited references25

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          Ovarian aging: mechanisms and clinical consequences.

          F. Broekmans, M Soules, B. C. Fauser (2009)
          Menopause is the final step in the process referred to as ovarian ageing. The age related decrease in follicle numbers dictates the onset of cycle irregularity and the final cessation of menses. The parallel decay in oocyte quality contributes to the gradual decline in fertility and the final occurrence of natural sterility. Endocrine changes mainly relate to the decline in the negative feedback from ovarian factors at the hypothalamo-pituitary unit. The declining cohort of antral follicles with age first results in gradually elevated FSH levels, followed by subsequent stages of overt cycle irregularity. The gradual decline in the size of the antral follicle cohort is best represented by decreasing levels of anti-Mullerian hormone. The variability of ovarian ageing among women is evident from the large variation in age at menopause. The identification of women who have severely decreased ovarian reserve for their age is clinically relevant. Ovarian reserve tests have appeared to be fairly accurate in predicting response to ovarian stimulation in the assisted reproductive technology (ART) setting. The capacity to predict the chances for spontaneous pregnancy or pregnancy after ART appears very limited. As menopause and the preceding decline in oocyte quality seem to have a fixed time interval, tests that predict the age at menopause may be useful to assess individual reproductive lifespan. Especially genetic studies, both addressing candidate gene and genome wide association, have identified several interesting loci of small genetic variation that may determine fetal follicle pool development and subsequent wastage of his pool over time. Improved knowledge of the ovarian ageing mechanisms may ultimately provide tools for prediction of menopause and manipulation of the early steps of folliculogenesis for the purpose of contraception and fertility lifespan extension.
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            Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles.

            Sesh Kamal Sunkara, Vivian Rittenberg, Nick Raine-Fenning … (2011)
            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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              Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment.

              Christien Weenen, Joop Laven, Anne Von Bergh … (2004)
              Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-beta superfamily, which plays an important role in both ovarian primordial follicle recruitment and dominant follicle selection in mice. However, the role of AMH in folliculogenesis in humans has not been investigated in detail. In the present study, AMH expression was assessed using immunohistochemistry in ovarian sections, obtained from healthy regularly cycling women. To this end, a novel monoclonal antibody to human AMH was developed. AMH expression was not observed in primordial follicles, whereas 74% of the primary follicles showed at least a weak signal in the granulosa cells. The highest level of AMH expression was present in the granulosa cells of secondary, preantral and small antral follicles
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                Author and article information

                Contributors
                Linlin Cui: 86-531-85651554 , fdclear3@126.com
                Journal
                Journal ID (nlm-ta): Reprod Biol Endocrinol
                Journal ID (iso-abbrev): Reprod. Biol. Endocrinol
                Title: Reproductive Biology and Endocrinology : RB&E
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-7827
                Publication date (Electronic): 16 July 2019
                Publication date PMC-release: 16 July 2019
                Publication date Collection: 2019
                Volume: 17
                Electronic Location Identifier: 58
                Affiliations
                [1 ]ISNI 0000 0004 1769 9639, GRID grid.460018.b, Center for Reproductive Medicine, , Shandong Provincial Hospital Affiliated to Shandong University, ; Jingliu Road 157, Jinan, 250001 China
                [2 ]National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
                [3 ]ISNI 0000 0004 1761 1174, GRID grid.27255.37, The Key laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, ; Jinan, China
                [4 ]Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan, China
                [5 ]Shandong Provincial Key Laboratory of Reproductive Medicine, No.157 Jingliu Road, Jinan, 250001 China
                [6 ]GRID grid.415946.b, Center of Reproductive Medicine, , Linyi People,s Hospital, ; Linyi, China
                [7 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, , Shanghai Jiao Tong University, ; Shanghai, China
                [8 ]Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
                Article
                Publisher ID: 498
                DOI: 10.1186/s12958-019-0498-3
                PMC ID: 6636016
                PubMed ID: 31311571
                SO-VID: 81c9c5e7-be2a-4a80-870d-6596ddae9b83
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 29 March 2019
                Date accepted : 3 July 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81501223
                Award Recipient :
                Funded by: The national key research and development program
                Award ID: 2017YFC1001000
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Human biology
                Keywords: advanced age,amh,ivf,live birth,ovarian reserve
                Data availability:
                ScienceOpen disciplines: Human biology
                Keywords: advanced age, amh, ivf, live birth, ovarian reserve

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