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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2017

Open Access 01-12-2017 | Research

Androstenedione response to recombinant human FSH is the most valid predictor of the number of selected follicles in polycystic ovarian syndrome: (a case-control study)

Authors: Eser Sefik Ozyurek, Tevfik Yoldemir, Gokhan Artar

Published in: Journal of Ovarian Research | Issue 1/2017

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Abstract

Background

We aimed to test the hypothesis that the correlation of the changes in the blood Androstenedione (A4) levels to the number of selected follicles during ovulation induction with low-dose recombinant human follicle stimulating hormone (rhFSH) is as strong as the correlation to changes in the blood Estradiol (E2) levels in polycystic ovary syndrome (PCOS).

Methods

Prospective Case-control study conducted from October 2014 to January 2016. 61 non-PCOS control (Group I) and 46 PCOS (Group II) patients treated with the chronic low-dose step up protocosl with rhFSH. A4, E2, progesterone blood levels and follicular growth were monitored.. Univariate and hierarchical multivariable analysis were performed for age, BMI, HOMA-IR, A4 and E2 (with the number of selected follicles as the dependent variable in both groups). ROC analysis was performed to define threshold values for the significant determinants of the number of selected follicles to predict cyle cancellations due to excessive ovarian response.

Results

The control group (Group I) was comprised of 61 cycles from a group of primary infertile non-PCOS patients, and the study group (Group II) of 46 cycles of PCOS patients. The analysis revealed that the strongest independent predictor of the total number of selected follicles in Group I was the E2(AUC) (B = 0.0006[0.0003-0.001]; P < 0.001); whereas for Group II, it was the A4 (AUC) (B = 0.114[0.04-0.25]; P = 0.01). Optimum thresholds for the A4 related parameters were defined to predict excessive response within Group II were 88.7%, 3.1 ng/mL and 5.4 ng*days for the percentage increase in A4, the maximum A4 value and area under the curve values for A4, respectively.

Conclusion

A4 response to low-dose rhFSH in PCOS has a stronger association with the number of follicles selected than the E2 reponse. A4 response preceding the E2 response is essential for progressive follicle development. Monitoring A4 rather than E2 may be more preemptive to define the initial ovarian response and accurate titration of the rhFSH doses.

Trial registration

The study was registered as a prospective case-control study in the ClinicalTrials.​gov registry with the identifier NCT02329483.
Literature
1.
Homburg R, Howles CM. Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: rationale, results, reflections and refinements. Hum Reprod Update. 1999;5:493–9.CrossRefPubMed
2.
Nastri CO, Teixeira DM, Moroni RM, Leitão VM, Martins WP. Ovarian hyperstimulation syndrome: pathophysiology, staging, prediction and prevention. Ultrasound Obstet Gynecol. 2015;45(4):377–93.CrossRefPubMed
3.
White DM, Polson DW, Kiddy D, Sagle P, Watson H, Gilling-Smith C, et al. Induction of ovulation with low-dose gonadotropins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women. J Clin Endocrinol Metab. 1996;81:3821–4.PubMed
4.
Tsang BK, Taheri A, Ainsworth L, Downey BR. Secretion of 17 alpha-hydroxyprogesterone, androstenedione, and estrogens by porcine granulosa and theca interna cells in culture. Can J Physiol Pharmacol. 1987;65:1951–6.CrossRefPubMed
5.
Arai S, Ito K. Androstenedione. Nihon Rinsho. 2010;68(Suppl 7):374–6.PubMed
6.
Dewailly D, Lujan ME, Carmina E, Cedars MI, Laven J, Norman RJ, et al. Definition and significance of polycystic ovarian morphology: a task force report from the androgen excess and polycystic ovary syndrome society. Hum Reprod Update. 2014;20:334–52.CrossRefPubMed
7.
Catteau-Jonard S, Dewailly D. Anti-Mullerian hormone and polycystic ovary syndrome. Gynecol Obstet Fertil. 2011;39:514–7.CrossRefPubMed
8.
Dewailly D, Pigny P, Soudan B, Catteau-Jonard S, Decanter C, Poncelet E, Duhamel A. Reconciling the definitions of polycystic ovary syndrome: the ovarian follicle number and serum anti-Müllerian hormone concentrations aggregate with the markers of hyperandrogenism. J Clin Endocrinol Metab. 2010;95:4399–405.CrossRefPubMed
9.
Hassa H, Tanir HM, Yildirim A, Senses T, Eskalen M, Mutlu FS. The hirsutism scoring system should be population specific. Fertil Steril. 2005;84:778–80.CrossRefPubMed
10.
Yildiz BO, Bolour S, Woods K, Moore A, Azziz R. Visually scoring hirsutism. Hum Reprod Update. 2010;16:51–64.CrossRefPubMed
11.
Pasquali R, Zanotti L, Fanelli F, Mezzullo M, Fazzini A, et al. Defining Hyperandrogenism in women with polycystic ovary syndrome: a challenging perspective. J Clin Endocrinol Metab. 2016;101:2013–22.CrossRefPubMed
12.
Romualdi D, Di Florio C, Tagliaferri V, De Cicco S, Gagliano D, Immediata V, et al. The role of anti-Müllerian hormone in the characterization of the different polycystic ovary syndrome phenotypes. Reprod Sci. 2016;23:655–1.CrossRefPubMed
13.
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, EscobarMorreale HF, Futterweit W, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab. 2006;91:4237–45.CrossRefPubMed
14.
Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012;27(10):3067–73.CrossRefPubMed
15.
Jonard S, Dewailly D. The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update. 2004;10:107–17.CrossRefPubMed
16.
Brown JB. Pituitary control of ovarian function--concepts derived from gonadotrophin therapy. Aust N Z J Obstet Gynaecol. 1978;18:46–54.CrossRefPubMed
17.
Almahbobi G, Anderiesz C, Hutchinson P, McFarlane JR, Wood C, Trounson AO. Functional integrity of granulosa cells from polycystic ovaries. Clin Endocrinol. 1996;44:571–80.CrossRef
18.
Lenie S, Smitz J. Functional AR signaling is evident in an in vitro mouse follicle culture bioassay that encompasses most stages of folliculogenesis. Biol Reprod. 2009;80:685–95.CrossRefPubMed
19.
Li M, Schatten H, Sun QY. Androgen receptor's destiny in mammalian oocytes: a new hypothesis. Mol Hum Reprod. 2009;15:149–54.CrossRefPubMed
20.
Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J, et al. Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J Clin Endocrinol Metab. 1998;83:2479–85.CrossRefPubMed
21.
Pache TD, Fauser BC. Polycystic ovaries in female-to-male transsexuals. Clin Endocrinol. 1993;39:702–3.
22.
Murray AA, Gosden RG, Allison V, Spears N. Effect of androgens on the development of mouse follicles growing in vitro. J Reprod Fertil. 1998;113:27–33.CrossRefPubMed
23.
Magarelli PC, Zachow RJ, Magoffin DA. Developmental and hormonal regulation of rat theca-cell differentiation factor secretion in ovarian follicles. Biol Reprod. 1996;55:416–20.CrossRefPubMed
24.
Ferrario M, Secomandi R, Cappato M, Galbignani E, Frigerio L, Arnoldi M, et al. Ovarian and adrenal androgens may be useful markers to predict oocyte competence and embryo development in older women. Gynecol Endocrinol. 2015;31:125–30.CrossRefPubMed
25.
Sun B, Wang F, Sun J, Yu W, Sun Y. Basal serum testosterone levels correlate with ovarian response but do not predict pregnancy outcome in non-PCOS women undergoing IVF. J Assist Reprod Genet. 2014;31(7):829–35.CrossRefPubMedPubMedCentral
26.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;1:19–25.
Metadata
Title
Androstenedione response to recombinant human FSH is the most valid predictor of the number of selected follicles in polycystic ovarian syndrome: (a case-control study)
Authors
Eser Sefik Ozyurek
Tevfik Yoldemir
Gokhan Artar
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2017
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-017-0330-7

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