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Published in: Journal of Endocrinological Investigation 7/2017

01-07-2017 | Original Article

Effect of metformin and oral contraceptives on polycystic ovary syndrome and IVF cycles

Authors: M. N. Kalem, Z. Kalem, T. Gurgan

Published in: Journal of Endocrinological Investigation | Issue 7/2017

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Abstract

Aim

The aim of this study is to investigate the effect of metformin and/or OC added to the treatment of PCOS patients at our clinic on IVF outcome.

Materials and methods

This study is a retrospective study that assesses the data of PCOS patients who received IVF between 2005 and 2015 at a private IVF center. The study included 496 PCOS cases aged between 24 and 40. Participants diagnosed with PCOS were divided into 4 groups according to the use of metformin and OC prior to the IVF cycle: 11.1% were in the metformin group, 31.3% in the OC group, 14.9% in the Metformin + OC group, and 42.7% in the control group.

Results

No difference was found in the total gonadotropin dose and duration of stimulation between the groups. Clinical pregnancy rates and implantation rates were similar in all groups, although the numbers of oocytes, mature oocytes, fertilized oocytes, and transferred embryos were lower in the treatment groups received metformin compared to the OC group and control group. There was no significant difference in the presence of OHSS and the singleton and multiple pregnancies between the four groups.

Conclusion

The present study established no positive role of metformin and OC use in increasing the treatment success in IVF/ICSI cycles in PCOS patients. It would be appropriate to limit the use of these agents with special indications such as decreasing insulin resistance or synchronizing follicular cohort.
Literature
1.
go back to reference Fauser, BCJM, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Barnhart K (2012) Consensus on women’s health aspects of polycystic ovary syndrome (PCOS). Hum Reprod 27(1):14–24CrossRef Fauser, BCJM, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Barnhart K (2012) Consensus on women’s health aspects of polycystic ovary syndrome (PCOS). Hum Reprod 27(1):14–24CrossRef
2.
go back to reference ESHRE TT, Group ASPCW (2008) Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 89(3):505–522CrossRef ESHRE TT, Group ASPCW (2008) Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 89(3):505–522CrossRef
3.
go back to reference Kalem MN, Kalem Z, Gürgan T (2016) Problems and complications during the treatment of infertility in women with polycystic ovary syndrome. Gynecol Obstet Reprod Med 22(2):113–124CrossRef Kalem MN, Kalem Z, Gürgan T (2016) Problems and complications during the treatment of infertility in women with polycystic ovary syndrome. Gynecol Obstet Reprod Med 22(2):113–124CrossRef
4.
go back to reference Amato MC et al (2015) Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance. J Endocrinol Invest 38:1319–1326CrossRefPubMed Amato MC et al (2015) Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance. J Endocrinol Invest 38:1319–1326CrossRefPubMed
5.
go back to reference Polak K et al (2017) New markers of insulin resistance in polycystic ovary syndrome. J Endocrinol Invest 40:1–8CrossRefPubMed Polak K et al (2017) New markers of insulin resistance in polycystic ovary syndrome. J Endocrinol Invest 40:1–8CrossRefPubMed
6.
go back to reference Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH (2012) Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 16:CD003053 Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH (2012) Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 16:CD003053
7.
go back to reference Palomba S, Falbo A, Zullo F (2009) Management strategies for ovulation induction in women with polycystic ovary syndrome and known clomifene citrate resistance. Curr Opin Obstet Gynecol 21:465–473CrossRefPubMed Palomba S, Falbo A, Zullo F (2009) Management strategies for ovulation induction in women with polycystic ovary syndrome and known clomifene citrate resistance. Curr Opin Obstet Gynecol 21:465–473CrossRefPubMed
8.
go back to reference Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Freitas V (2009) Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2:CD006105 Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Freitas V (2009) Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2:CD006105
9.
go back to reference Karande VC (2014) Use of oral contraceptives in assisted reproductive cycles. IVF Lite 1(1), 6.CrossRef Karande VC (2014) Use of oral contraceptives in assisted reproductive cycles. IVF Lite 1(1), 6.CrossRef
10.
go back to reference Huirne JA, van Loenen AC, Donnez J, Pirard C, Homburg R, Schats R et al (2006) Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study. Reprod Biomed Online 13:235–245CrossRefPubMed Huirne JA, van Loenen AC, Donnez J, Pirard C, Homburg R, Schats R et al (2006) Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study. Reprod Biomed Online 13:235–245CrossRefPubMed
11.
go back to reference Al-Inany H, Aboulghar M (2002) GnRH antagonist in assisted reproduction: a cochrane review. Hum Reprod 17:874-85PubMed Al-Inany H, Aboulghar M (2002) GnRH antagonist in assisted reproduction: a cochrane review. Hum Reprod 17:874-85PubMed
12.
go back to reference ESHRE TR, Group ASPCW (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81(1):19–25CrossRef ESHRE TR, Group ASPCW (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81(1):19–25CrossRef
13.
go back to reference Kjøtrød SB, von Düring V, Carlsen SM (2004) Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study. Hum Reprod 19(6):1315–1322CrossRefPubMed Kjøtrød SB, von Düring V, Carlsen SM (2004) Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study. Hum Reprod 19(6):1315–1322CrossRefPubMed
14.
go back to reference Costello MF, Chapman M, Conway U (2006) A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotrophin ovulation induction or IVF in women with polycystic ovary syndrome. Hum Reprod 21(6):1387–1399CrossRefPubMed Costello MF, Chapman M, Conway U (2006) A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotrophin ovulation induction or IVF in women with polycystic ovary syndrome. Hum Reprod 21(6):1387–1399CrossRefPubMed
15.
go back to reference Tang T, Glanville J, Orsi N, Barth JH, Balen AH (2006) The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod 21(6):1416–1425CrossRefPubMed Tang T, Glanville J, Orsi N, Barth JH, Balen AH (2006) The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod 21(6):1416–1425CrossRefPubMed
16.
go back to reference Wang L, Zhao Y, Dong X, Huang K, Wang R, Ji L, Zhang H (2015) Could pretreatment with oral contraceptives before pituitary down regulation reduce the incidence of ovarian hyperstimulation syndrome in the IVF/ICSI procedure? Int J Clin Exper Med 8(2):2711 Wang L, Zhao Y, Dong X, Huang K, Wang R, Ji L, Zhang H (2015) Could pretreatment with oral contraceptives before pituitary down regulation reduce the incidence of ovarian hyperstimulation syndrome in the IVF/ICSI procedure? Int J Clin Exper Med 8(2):2711
17.
go back to reference Andersen AN, Witjes H, Gordon K, Mannaerts B (2011) Xpect investigators. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment. Hum Reprod 26:3413–3423CrossRefPubMed Andersen AN, Witjes H, Gordon K, Mannaerts B (2011) Xpect investigators. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment. Hum Reprod 26:3413–3423CrossRefPubMed
18.
go back to reference Griesinger G, Venetis CA, Marx T, Diedrich K, Tarlatzis BC, Kolibianakis EM (2008) Oral contraceptive pill pretreatment in ovarian stimulation with GnRH antagonists for IVF: a systematic review and meta-analysis. Fertil Steril 90:1055–1063CrossRefPubMed Griesinger G, Venetis CA, Marx T, Diedrich K, Tarlatzis BC, Kolibianakis EM (2008) Oral contraceptive pill pretreatment in ovarian stimulation with GnRH antagonists for IVF: a systematic review and meta-analysis. Fertil Steril 90:1055–1063CrossRefPubMed
19.
go back to reference Kolibianakis EM, Papanikolaou EG, Camus M, Tournaye H, Van Steirteghem AC, Devroey P (2006) Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial. Hum Reprod 21:352–357CrossRefPubMed Kolibianakis EM, Papanikolaou EG, Camus M, Tournaye H, Van Steirteghem AC, Devroey P (2006) Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial. Hum Reprod 21:352–357CrossRefPubMed
20.
go back to reference Stadtmauer LA, Toma SK, Riehl RM, Talbert LM (2001) Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors. Fertil Steril 75(3):505–509CrossRefPubMed Stadtmauer LA, Toma SK, Riehl RM, Talbert LM (2001) Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors. Fertil Steril 75(3):505–509CrossRefPubMed
21.
go back to reference Decanter C, Robin G, Thomas P, Leroy M, Lefebvre C, Soudan B, Dewailly D (2013) First intention IVF protocol for polycystic ovaries: does oral contraceptive pill pretreatment influence COH outcome? Reprod Biol Endocrinol 11(1):1CrossRef Decanter C, Robin G, Thomas P, Leroy M, Lefebvre C, Soudan B, Dewailly D (2013) First intention IVF protocol for polycystic ovaries: does oral contraceptive pill pretreatment influence COH outcome? Reprod Biol Endocrinol 11(1):1CrossRef
22.
go back to reference Wu CC, Lei P, Ruan YM, Lin XM, Xiong YL, Yang GY (2012) Effects of oral contraceptive pretreatment on controlled ovarian hyperstimulation and outcomes of IVF-ET. Zhonghua Nan Ke Xue 18(7):623–626 (Chinese)PubMed Wu CC, Lei P, Ruan YM, Lin XM, Xiong YL, Yang GY (2012) Effects of oral contraceptive pretreatment on controlled ovarian hyperstimulation and outcomes of IVF-ET. Zhonghua Nan Ke Xue 18(7):623–626 (Chinese)PubMed
23.
go back to reference Damario MA, Barmat L, Liu HC, Davis OK, Rosenwaks Z (1997) Dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves in-vitro fertilization outcome in high responder patients. Hum Reprod 12 (11): 2359–2365. doi:10.1093/humrep/12.11.2359 CrossRef Damario MA, Barmat L, Liu HC, Davis OK, Rosenwaks Z (1997) Dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves in-vitro fertilization outcome in high responder patients. Hum Reprod 12 (11): 2359–2365. doi:10.​1093/​humrep/​12.​11.​2359 CrossRef
24.
go back to reference Tang T, Balen AH (2013) Use of metformin for women with polycystic ovary syndrome. Hum Reprod Update 19(1):1–1CrossRefPubMed Tang T, Balen AH (2013) Use of metformin for women with polycystic ovary syndrome. Hum Reprod Update 19(1):1–1CrossRefPubMed
25.
go back to reference Moll E, van der Veen F, van Wely M (2007) The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update 13(6):527–537CrossRefPubMed Moll E, van der Veen F, van Wely M (2007) The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update 13(6):527–537CrossRefPubMed
26.
go back to reference Morin-Papunen L, Rantala AS, Unkila-Kallio L, Tiitinen A, Hippeläinen M, Perheentupa A, Tapanainen JS (2012) Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial. J Clin Endocrinol Metab 97(5):1492–1500CrossRefPubMed Morin-Papunen L, Rantala AS, Unkila-Kallio L, Tiitinen A, Hippeläinen M, Perheentupa A, Tapanainen JS (2012) Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial. J Clin Endocrinol Metab 97(5):1492–1500CrossRefPubMed
27.
go back to reference Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Marjoribanks J, Macedo CR (2015) Metformin treatment before and during in vitro fertilization or intracytoplasmic sperm injection in women with polycystic ovary syndrome: summary of a Cochrane review. Fertil Steril 104(3):542–544CrossRefPubMed Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Marjoribanks J, Macedo CR (2015) Metformin treatment before and during in vitro fertilization or intracytoplasmic sperm injection in women with polycystic ovary syndrome: summary of a Cochrane review. Fertil Steril 104(3):542–544CrossRefPubMed
28.
go back to reference Pan JX, Liu Y, Ke ZH, Zhou CL, Meng Q, Ding GL, Xu GF, Sheng JZ, Huang HF (2015) Successive and cyclic oral contraceptive pill pretreatment improves IVF/ICSI outcomes of PCOS patients and ameliorates hyperandrogenism and antral follicle excess. Gynecol Endocrinol 31(4):332–336. doi:10.3109/09513590.2014.995621 Epub 2015 Jan 5 CrossRefPubMed Pan JX, Liu Y, Ke ZH, Zhou CL, Meng Q, Ding GL, Xu GF, Sheng JZ, Huang HF (2015) Successive and cyclic oral contraceptive pill pretreatment improves IVF/ICSI outcomes of PCOS patients and ameliorates hyperandrogenism and antral follicle excess. Gynecol Endocrinol 31(4):332–336. doi:10.​3109/​09513590.​2014.​995621 Epub 2015 Jan 5 CrossRefPubMed
29.
go back to reference Wang W, Tang Y, Liu H (2015) Protective effects of DHEA and metformin on the viability of early embryos under oxidative stress are mediated by sustaining mitochondrial biogenesis. Fertil Steril 104(3):e146–e147CrossRef Wang W, Tang Y, Liu H (2015) Protective effects of DHEA and metformin on the viability of early embryos under oxidative stress are mediated by sustaining mitochondrial biogenesis. Fertil Steril 104(3):e146–e147CrossRef
30.
go back to reference Huang X, Wang P, Tal R, Lv F, Li Y, Zhang X (2015) A systematic review and meta-analysis of metformin among patients with polycystic ovary syndrome undergoing assisted reproductive technology procedures. Int J Gynecol Obstet 131(2):111–116CrossRef Huang X, Wang P, Tal R, Lv F, Li Y, Zhang X (2015) A systematic review and meta-analysis of metformin among patients with polycystic ovary syndrome undergoing assisted reproductive technology procedures. Int J Gynecol Obstet 131(2):111–116CrossRef
31.
go back to reference Palomba S, Falbo A, La Sala GB (2013) Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilisation and intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of randomised controlled trials. BJOG 120(3):267–276CrossRefPubMed Palomba S, Falbo A, La Sala GB (2013) Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilisation and intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of randomised controlled trials. BJOG 120(3):267–276CrossRefPubMed
32.
go back to reference Palomba S, Falbo A, Carrillo L, Villani MT, Orio F, Russo T, Colao A (2011) Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril 96(6):1384–1390CrossRefPubMed Palomba S, Falbo A, Carrillo L, Villani MT, Orio F, Russo T, Colao A (2011) Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril 96(6):1384–1390CrossRefPubMed
33.
go back to reference Swanton A, Lighten A, Granne I, McVeigh E, Lavery S, Trew G, Child T (2011) Do women with ovaries of polycystic morphology without any other features of PCOS benefit from short-term metformin co-treatment during IVF? A double-blind, placebo-controlled, randomized trial. Hum Reprod der120 Swanton A, Lighten A, Granne I, McVeigh E, Lavery S, Trew G, Child T (2011) Do women with ovaries of polycystic morphology without any other features of PCOS benefit from short-term metformin co-treatment during IVF? A double-blind, placebo-controlled, randomized trial. Hum Reprod der120
34.
go back to reference Palomba S, Falbo A, Orio F, Manguso F, Russo T, Tolino A, Zullo F (2005) A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination. Hum Reprod 20(10):2879–2886CrossRefPubMed Palomba S, Falbo A, Orio F, Manguso F, Russo T, Tolino A, Zullo F (2005) A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination. Hum Reprod 20(10):2879–2886CrossRefPubMed
35.
go back to reference Kalem MN, Kalem Z, Sarı T, Ateş C, Gürgan T (2016) Effect of body mass index and age on in vitro fertilization in polycystic ovary syndrome. J Turkish Ger Gynecol Assoc 17(2):83CrossRef Kalem MN, Kalem Z, Sarı T, Ateş C, Gürgan T (2016) Effect of body mass index and age on in vitro fertilization in polycystic ovary syndrome. J Turkish Ger Gynecol Assoc 17(2):83CrossRef
36.
go back to reference Çakıroğlu Y, Vural F, Vural B (2016) The inflammatory markers in polycystic ovary syndrome: association with obesity and IVF outcomes. J Endocrinol Invest 39(8):899–907CrossRefPubMed Çakıroğlu Y, Vural F, Vural B (2016) The inflammatory markers in polycystic ovary syndrome: association with obesity and IVF outcomes. J Endocrinol Invest 39(8):899–907CrossRefPubMed
Metadata
Title
Effect of metformin and oral contraceptives on polycystic ovary syndrome and IVF cycles
Authors
M. N. Kalem
Z. Kalem
T. Gurgan
Publication date
01-07-2017
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation / Issue 7/2017
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-017-0634-x

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