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Published in: Reproductive Biology and Endocrinology 1/2019

Open Access 01-12-2019 | ICSI | Research

Anti-Müllerian hormone and progesterone levels in human follicular fluid are predictors of embryonic development

Authors: Yvonne O’Brien, Mary Wingfield, Lynne C. O’Shea

Published in: Reproductive Biology and Endocrinology | Issue 1/2019

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Abstract

Background

Human follicular fluid is an intricate biological fluid contributing to the developing oocyte microenvironment. Accumulating evidence suggests that sex hormones present in follicular fluid (FF) may play an important role in regulating oocyte developmental potential. The aim of this study was to determine if anti-Müllerian hormone (AMH) and progesterone (P4) levels in FF are correlated with oocyte quality as defined by subsequent embryonic development.

Methods

This was a prospective cohort study of 88 women undergoing IVF/ICSI at a university associated fertility clinic. Follicular fluid was collected from the first follicle aspirated at the time of oocyte retrieval. The corresponding oocyte was individually cultured in order to track its developmental outcome. FF-AMH and P4 concentrations from follicles where the oocyte fertilised normally and developed into a blastocyst on day 5 (Group 1: BLAST, n = 23) were compared with FF from follicles where the oocyte fertilised normally but failed to reach blastocyst stage by day 5 (Group 2: FERT, n = 19). No significant differences were observed between the two groups in terms of maternal age, body mass index, previous live births, previous pregnancy loss, number of antral follicles, number of oocytes recovered, IVF:ICSI ratio or percentage of recovered oocytes that fertilised.

Results

FF-AMH and P4 levels were significantly increased in Group 1: BLAST compared to Group 2: FERT (P = 0.007 and P = 0.013 respectively). Twenty-one FF samples had an AMH level > 15 pmol/L, of which 17 related to oocytes that progressed to blastocyst stage, providing a positive prediction value (PPV) of 76.96%. Eleven FF samples had a P4 level > 60 mg/ml, of which 10 progressed to blastocyst stage, providing a PPV of 90.99%. Six samples had an AMH level > 15 pmol/L and a P4 level > 60 mg/ml, of which 100% progressed to blastocyst stage, providing a PPV of 96.83%.

Conclusions

FF-AMH and P4 levels from individual follicles can accurately predetermine subsequent embryonic development. Combining follicular fluid analysis with routine morphological assessment, could allow for a more accurate and sensitive method of determining embryonic developmental competence.
Literature
1.
go back to reference Kovalevsky G, Patrizio P. High rates of embryo wastage with use of assisted reproductive technology: a look at the trends between 1995 and 2001 in the United States. Fertil Steril. 2005;84(2):325–30.CrossRef Kovalevsky G, Patrizio P. High rates of embryo wastage with use of assisted reproductive technology: a look at the trends between 1995 and 2001 in the United States. Fertil Steril. 2005;84(2):325–30.CrossRef
2.
go back to reference O'Shea LC, Mehta J, Lonergan P, Hensey C, Fair T. Developmental competence in oocytes and cumulus cells: candidate genes and networks. Syst Biol Reprod Med. 2012;58(2):88–101.CrossRef O'Shea LC, Mehta J, Lonergan P, Hensey C, Fair T. Developmental competence in oocytes and cumulus cells: candidate genes and networks. Syst Biol Reprod Med. 2012;58(2):88–101.CrossRef
3.
go back to reference Black M, Bhattacharya S. Epidemiology of multiple pregnancy and the effect of assisted conception. Semin Fetal Neonatal Med. 2010;15(6):306–12.CrossRef Black M, Bhattacharya S. Epidemiology of multiple pregnancy and the effect of assisted conception. Semin Fetal Neonatal Med. 2010;15(6):306–12.CrossRef
4.
go back to reference Kreiner D, Liu HC, Itskovitz J, Veeck L, Rosenwaks Z. Follicular fluid estradiol and progesterone are markers of preovulatory oocyte quality. Fertil Steril. 1987;48(6):991–4.CrossRef Kreiner D, Liu HC, Itskovitz J, Veeck L, Rosenwaks Z. Follicular fluid estradiol and progesterone are markers of preovulatory oocyte quality. Fertil Steril. 1987;48(6):991–4.CrossRef
5.
go back to reference Barrera D, Avila E, Diaz L. Immunological role of progesterone in the maintenance of pregnancy. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2007;59(2):139–45.PubMed Barrera D, Avila E, Diaz L. Immunological role of progesterone in the maintenance of pregnancy. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2007;59(2):139–45.PubMed
6.
go back to reference Loutradis D, Beretsos P, Arabatzi E, Anagnostou E, Drakakis P. The role of steroid hormones in ART. J Steroid Biochem Mol Biol. 2008;112(1–3):1–4.CrossRef Loutradis D, Beretsos P, Arabatzi E, Anagnostou E, Drakakis P. The role of steroid hormones in ART. J Steroid Biochem Mol Biol. 2008;112(1–3):1–4.CrossRef
7.
go back to reference O'Shea LC, Hensey C, Fair T. Progesterone regulation of AVEN protects bovine oocytes from apoptosis during meiotic maturation. Biol Reprod. 2013;89(6):146.CrossRef O'Shea LC, Hensey C, Fair T. Progesterone regulation of AVEN protects bovine oocytes from apoptosis during meiotic maturation. Biol Reprod. 2013;89(6):146.CrossRef
8.
go back to reference Basuray R, Rawlins RG, Radwanska E, Henig I, Sachdeva S, Tummon I, et al. High progesterone/estradiol ratio in follicular fluid at oocyte aspiration for in vitro fertilization as a predictor of possible pregnancy. Fertil Steril. 1988;49(6):1007–11.CrossRef Basuray R, Rawlins RG, Radwanska E, Henig I, Sachdeva S, Tummon I, et al. High progesterone/estradiol ratio in follicular fluid at oocyte aspiration for in vitro fertilization as a predictor of possible pregnancy. Fertil Steril. 1988;49(6):1007–11.CrossRef
9.
go back to reference Kobayashi T, Oda T, Yoshimura Y, Takehara Y, Natori M, Nozawa S. Androstenedione and progesterone concentrations in preovulatory follicular fluid correlate with successful fertilization and cleavage of human oocytes in vitro. Fertil Steril. 1991;56(2):301–5.CrossRef Kobayashi T, Oda T, Yoshimura Y, Takehara Y, Natori M, Nozawa S. Androstenedione and progesterone concentrations in preovulatory follicular fluid correlate with successful fertilization and cleavage of human oocytes in vitro. Fertil Steril. 1991;56(2):301–5.CrossRef
10.
go back to reference Vanluchene E, Hinting A, Dhont M, De Sutter P, Van Maele G, Vandekerckhove D. Follicular fluid steroid levels in relation to oocyte maturity and in vitro fertilization. J Steroid Biochem Mol Biol. 1991;38(1):83–7.CrossRef Vanluchene E, Hinting A, Dhont M, De Sutter P, Van Maele G, Vandekerckhove D. Follicular fluid steroid levels in relation to oocyte maturity and in vitro fertilization. J Steroid Biochem Mol Biol. 1991;38(1):83–7.CrossRef
11.
go back to reference Enien WM, el Sahwy S, Harris CP, Seif MW, Elstein M. Human chorionic gonadotrophin and steroid concentrations in follicular fluid: the relationship to oocyte maturity and fertilization rates in stimulated and natural in-vitro fertilization cycles. Hum Reprod. 1995;10(11):2840–4.CrossRef Enien WM, el Sahwy S, Harris CP, Seif MW, Elstein M. Human chorionic gonadotrophin and steroid concentrations in follicular fluid: the relationship to oocyte maturity and fertilization rates in stimulated and natural in-vitro fertilization cycles. Hum Reprod. 1995;10(11):2840–4.CrossRef
12.
go back to reference Ben-Rafael Z, Meloni F, Strauss JF 3rd, Blasco L, Mastroianni L Jr, Flickinger GL. Relationships between polypronuclear fertilization and follicular fluid hormones in gonadotropin-treated women. Fertil Steril. 1987;47(2):284–8.CrossRef Ben-Rafael Z, Meloni F, Strauss JF 3rd, Blasco L, Mastroianni L Jr, Flickinger GL. Relationships between polypronuclear fertilization and follicular fluid hormones in gonadotropin-treated women. Fertil Steril. 1987;47(2):284–8.CrossRef
13.
go back to reference Seifer DB, MacLaughlin DT, Christian BP, Feng B, Shelden RM. Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil Steril. 2002;77(3):468–71.CrossRef Seifer DB, MacLaughlin DT, Christian BP, Feng B, Shelden RM. Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil Steril. 2002;77(3):468–71.CrossRef
14.
go back to reference Vigier B, Picard JY, Tran D, Legeai L, Josso N. Production of anti-Mullerian hormone: another homology between Sertoli and granulosa cells. Endocrinology. 1984;114(4):1315–20.CrossRef Vigier B, Picard JY, Tran D, Legeai L, Josso N. Production of anti-Mullerian hormone: another homology between Sertoli and granulosa cells. Endocrinology. 1984;114(4):1315–20.CrossRef
15.
go back to reference Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, Nachtigal MW, et al. Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology. 2002;143(3):1076–84.CrossRef Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, Nachtigal MW, et al. Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology. 2002;143(3):1076–84.CrossRef
16.
go back to reference Silberstein T, MacLaughlin DT, Shai I, Trimarchi JR, Lambert-Messerlian G, Seifer DB, et al. Mullerian inhibiting substance levels at the time of HCG administration in IVF cycles predict both ovarian reserve and embryo morphology. Hum Reprod. 2006;21(1):159–63.CrossRef Silberstein T, MacLaughlin DT, Shai I, Trimarchi JR, Lambert-Messerlian G, Seifer DB, et al. Mullerian inhibiting substance levels at the time of HCG administration in IVF cycles predict both ovarian reserve and embryo morphology. Hum Reprod. 2006;21(1):159–63.CrossRef
17.
go back to reference Kedem-Dickman A, Maman E, Yung Y, Yerushalmi GM, Hemi R, Hanochi M, et al. Anti-Mullerian hormone is highly expressed and secreted from cumulus granulosa cells of stimulated preovulatory immature and atretic oocytes. Reprod BioMed Online. 2012;24(5):540–6.CrossRef Kedem-Dickman A, Maman E, Yung Y, Yerushalmi GM, Hemi R, Hanochi M, et al. Anti-Mullerian hormone is highly expressed and secreted from cumulus granulosa cells of stimulated preovulatory immature and atretic oocytes. Reprod BioMed Online. 2012;24(5):540–6.CrossRef
18.
go back to reference Fanchin R, Mendez Lozano DH, Frydman N, Gougeon A, di Clemente N, Frydman R, et al. Anti-Mullerian hormone concentrations in the follicular fluid of the preovulatory follicle are predictive of the implantation potential of the ensuing embryo obtained by in vitro fertilization. J Clin Endocrinol Metab. 2007;92(5):1796–802.CrossRef Fanchin R, Mendez Lozano DH, Frydman N, Gougeon A, di Clemente N, Frydman R, et al. Anti-Mullerian hormone concentrations in the follicular fluid of the preovulatory follicle are predictive of the implantation potential of the ensuing embryo obtained by in vitro fertilization. J Clin Endocrinol Metab. 2007;92(5):1796–802.CrossRef
19.
go back to reference Takahashi C, Fujito A, Kazuka M, Sugiyama R, Ito H, Isaka K. Anti-Mullerian hormone substance from follicular fluid is positively associated with success in oocyte fertilization during in vitro fertilization. Fertil Steril. 2008;89(3):586–91.CrossRef Takahashi C, Fujito A, Kazuka M, Sugiyama R, Ito H, Isaka K. Anti-Mullerian hormone substance from follicular fluid is positively associated with success in oocyte fertilization during in vitro fertilization. Fertil Steril. 2008;89(3):586–91.CrossRef
20.
go back to reference Kim JH, Lee JR, Chang HJ, Jee BC, Suh CS, Kim SH. Anti-Mullerian hormone levels in the follicular fluid of the preovulatory follicle: a predictor for oocyte fertilization and quality of embryo. J Korean Med Sci. 2014;29(9):1266–70.CrossRef Kim JH, Lee JR, Chang HJ, Jee BC, Suh CS, Kim SH. Anti-Mullerian hormone levels in the follicular fluid of the preovulatory follicle: a predictor for oocyte fertilization and quality of embryo. J Korean Med Sci. 2014;29(9):1266–70.CrossRef
21.
go back to reference Wunder DM, Guibourdenche J, Birkhauser MH, Bersinger NA. Anti-Mullerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2008;90(6):2203–10.CrossRef Wunder DM, Guibourdenche J, Birkhauser MH, Bersinger NA. Anti-Mullerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2008;90(6):2203–10.CrossRef
22.
go back to reference Erenus M, Zouves C, Rajamahendran P, Leung S, Fluker M, Gomel V. The effect of embryo quality on subsequent pregnancy rates after in vitro fertilization. Fertil Steril. 1991;56(4):707–10.CrossRef Erenus M, Zouves C, Rajamahendran P, Leung S, Fluker M, Gomel V. The effect of embryo quality on subsequent pregnancy rates after in vitro fertilization. Fertil Steril. 1991;56(4):707–10.CrossRef
23.
go back to reference Ji J, Liu Y, Tong XH, Luo L, Ma J, Chen Z. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod. 2013;28(10):2728–34.CrossRef Ji J, Liu Y, Tong XH, Luo L, Ma J, Chen Z. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod. 2013;28(10):2728–34.CrossRef
24.
go back to reference Cobo A, Garcia-Velasco JA, Coello A, Domingo J, Pellicer A, Remohi J. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril. 2016;105(3):755–64 e8.CrossRef Cobo A, Garcia-Velasco JA, Coello A, Domingo J, Pellicer A, Remohi J. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril. 2016;105(3):755–64 e8.CrossRef
25.
go back to reference Takahashi M, Hayashi M, Manganaro TF, Donahoe PK. The ontogeny of mullerian inhibiting substance in granulosa cells of the bovine ovarian follicle. Biol Reprod. 1986;35(2):447–53.CrossRef Takahashi M, Hayashi M, Manganaro TF, Donahoe PK. The ontogeny of mullerian inhibiting substance in granulosa cells of the bovine ovarian follicle. Biol Reprod. 1986;35(2):447–53.CrossRef
26.
go back to reference La Marca A, Volpe A. Anti-Mullerian hormone (AMH) in female reproduction: is measurement of circulating AMH a useful tool? Clin Endocrinol. 2006;64(6):603–10.CrossRef La Marca A, Volpe A. Anti-Mullerian hormone (AMH) in female reproduction: is measurement of circulating AMH a useful tool? Clin Endocrinol. 2006;64(6):603–10.CrossRef
27.
go back to reference Bezard J, Vigier B, Tran D, Mauleon P, Josso N. Immunocytochemical study of anti-Mullerian hormone in sheep ovarian follicles during fetal and post-natal development. J Reprod Fertil. 1987;80(2):509–16.CrossRef Bezard J, Vigier B, Tran D, Mauleon P, Josso N. Immunocytochemical study of anti-Mullerian hormone in sheep ovarian follicles during fetal and post-natal development. J Reprod Fertil. 1987;80(2):509–16.CrossRef
28.
go back to reference McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000;21(2):200–14.PubMed McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000;21(2):200–14.PubMed
29.
go back to reference Monniaux D, Clemente N, Touze JL, Belville C, Rico C, Bontoux M, et al. Intrafollicular steroids and anti-mullerian hormone during normal and cystic ovarian follicular development in the cow. Biol Reprod. 2008;79(2):387–96.CrossRef Monniaux D, Clemente N, Touze JL, Belville C, Rico C, Bontoux M, et al. Intrafollicular steroids and anti-mullerian hormone during normal and cystic ovarian follicular development in the cow. Biol Reprod. 2008;79(2):387–96.CrossRef
30.
go back to reference Veiga-Lopez A, Ye W, Padmanabhan V. Developmental programming: prenatal testosterone excess disrupts anti-Mullerian hormone expression in preantral and antral follicles. Fertil Steril. 2012;97(3):748–56.CrossRef Veiga-Lopez A, Ye W, Padmanabhan V. Developmental programming: prenatal testosterone excess disrupts anti-Mullerian hormone expression in preantral and antral follicles. Fertil Steril. 2012;97(3):748–56.CrossRef
31.
go back to reference Mehta BN, Chimote MN, Chimote NN, Nath NM, Chimote NM. Follicular-fluid anti-Mullerian hormone (FF AMH) is a plausible biochemical indicator of functional viability of oocyte in conventional in vitro fertilization (IVF) cycles. J Human Reprod Sci. 2013;6(2):99–105.CrossRef Mehta BN, Chimote MN, Chimote NN, Nath NM, Chimote NM. Follicular-fluid anti-Mullerian hormone (FF AMH) is a plausible biochemical indicator of functional viability of oocyte in conventional in vitro fertilization (IVF) cycles. J Human Reprod Sci. 2013;6(2):99–105.CrossRef
32.
go back to reference Bieszczad RR, McClintock JS, Pepe GJ, Dimino MJ. Progesterone secretion by granulosa cells from different sized follicles of human ovaries after short term incubation. J Clin Endocrinol Metab. 1982;55(1):181–4.CrossRef Bieszczad RR, McClintock JS, Pepe GJ, Dimino MJ. Progesterone secretion by granulosa cells from different sized follicles of human ovaries after short term incubation. J Clin Endocrinol Metab. 1982;55(1):181–4.CrossRef
33.
go back to reference Aparicio IM, Garcia-Herreros M, O'Shea LC, Hensey C, Lonergan P, Fair T. Expression, regulation, and function of progesterone receptors in bovine cumulus oocyte complexes during in vitro maturation. Biol Reprod. 2011;84(5):910–21.CrossRef Aparicio IM, Garcia-Herreros M, O'Shea LC, Hensey C, Lonergan P, Fair T. Expression, regulation, and function of progesterone receptors in bovine cumulus oocyte complexes during in vitro maturation. Biol Reprod. 2011;84(5):910–21.CrossRef
Metadata
Title
Anti-Müllerian hormone and progesterone levels in human follicular fluid are predictors of embryonic development
Authors
Yvonne O’Brien
Mary Wingfield
Lynne C. O’Shea
Publication date
01-12-2019
Publisher
BioMed Central
Keywords
ICSI
Progesterone
Published in
Reproductive Biology and Endocrinology / Issue 1/2019
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-019-0492-9

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