Archives of Gynecology and Obstetrics

, Volume 300, Issue 3, pp 737–750 | Cite as

Effect of pretreatment with combined oral contraceptives on outcomes of assisted reproductive technology for women with polycystic ovary syndrome: a meta-analysis

  • Soo Youn Song
  • Jung Bo Yang
  • Min Soon Song
  • Hye Young Oh
  • Geon Woo Lee
  • Mina Lee
  • Young Bok Ko
  • Ki Hwan Lee
  • Ha Kyun Chang
  • Sang Mi Kwak
  • Heon Jong YooEmail author
Gynecologic Endocrinology and Reproductive Medicine



To evaluate the effect of pretreatment with combined oral contraceptives (COC) on outcomes in women with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology for subfertility.


Two authors independently searched MEDLINE, EMBASE, and the Cochran Library to identify and review articles published from October 1995 until December 2018 according to selection criteria. Outcomes are expressed as mean difference and odds ratio (OR) in a meta-analysis model.


A total of seven studies were included in this meta-analysis: one randomized controlled study and two prospective and four retrospective cohort studies. Meta-analysis showed that the COC pretreatment did not affect rate of clinical pregnancy (OR = 0.93, 95% confidence interval CI 0.65–1.34, I2 = 76%) or ovarian hyperstimulation syndrome (OR = 0.90, 95% CI 0.57–1.44, I2 = 0%). However, the rate of miscarriage in the COC group was significantly higher (OR = 1.33, 95% CI 1.02–1.72, I2 = 9%) and the rate of cumulative live birth was significantly lower compared with the control group (OR = 0.72, 95% CI 0.54–0.98, I2 = 55%). Subgroup analysis showed higher rates of miscarriage and lower rates of cumulative live birth in studies with a gonadotropin-releasing hormone (GnRH) antagonist protocol (OR = 1.69, 95% CI 1.17–2.44, I2 = 0% and OR = 0.38, 95% CI 0.29–0.50, respectively).


Pretreatment with COC in women with PCOS before assisted reproductive technology may have an adverse effect on clinical outcomes, especially with a GnRH antagonist protocol.


Combined oral contraceptives Assisted reproductive technology Polycystic ovary syndrome 



This work was supported by a research fund of KMI (Korea Medical Institute).

Compliance with ethical standards

Conflicts of interest

The authors have no financial disclosures to declare and no conflicts of interest to report.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Patient anonymity was completely preserved and the unique nature of identifying patients was not included in this manuscript.

Informed consent

This study was based on retrospective review of published studies, it was not necessary to obtain informed consent from individual participants.

Supplementary material

404_2019_5210_MOESM1_ESM.docx (14 kb)
Supplementary file1 (DOCX 14 kb)
404_2019_5210_MOESM2_ESM.docx (16 kb)
Supplementary file2 (DOCX 16 kb)
404_2019_5210_MOESM3_ESM.docx (18 kb)
Supplementary file3 (DOCX 17 kb)


  1. 1.
    Lagowska K, Bajerska J, Jamka M (2018) The role of vitamin D oral supplementation in insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Nutrients 10(11):1637. CrossRefGoogle Scholar
  2. 2.
    ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome (2018). Obstet Gynecol 131(6):e157–e171.
  3. 3.
    Heijnen EM, Eijkemans MJ, Hughes EG, Laven JS, Macklon NS, Fauser BC (2006) A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update 12(1):13–21. CrossRefGoogle Scholar
  4. 4.
    Franks S, Stark J, Hardy K (2008) Follicle dynamics and anovulation in polycystic ovary syndrome. Hum Reprod Update 14(4):367–378. CrossRefGoogle Scholar
  5. 5.
    Dumesic DA, Abbott DH (2008) Implications of polycystic ovary syndrome on oocyte development. Semin Reprod Med 26(1):53–61. CrossRefGoogle Scholar
  6. 6.
    Palomba S, Falbo A, Orio F Jr, Russo T, Tolino A, Zullo F (2008) Pretreatment with oral contraceptives in infertile anovulatory patients with polycystic ovary syndrome who receive gonadotropins for controlled ovarian stimulation. Fertil Steril 89(6):1838–1842. CrossRefGoogle Scholar
  7. 7.
    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 Oxf Engl 12(11):2359–2365CrossRefGoogle Scholar
  8. 8.
    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. CrossRefGoogle Scholar
  9. 9.
    Decanter C, Robin G, Thomas P, Leroy M, Lefebvre C, Soudan B, Lefebvre-Khalil V, Leroy-Martin B, Dewailly D (2013) First intention IVF protocol for polycystic ovaries: Does oral contraceptive pill pre-treatment influence COH outcome? Reprod Biol Endocrinol 11(1):54. CrossRefGoogle Scholar
  10. 10.
    Ozmen B, Cetinkaya SE, Sonmezer M, Atabekoglu CS, Berker B, Seval M (2013) Dual suppression in gnrh antagonist cycles for PCOS patients undergoing ICSI cycles. Fertil Steril 100(3):S354. CrossRefGoogle Scholar
  11. 11.
    Zhao JZ, Lin JJ, Yang HY, Zhang W, Huang XF (2002) Huang YP (2010) Effects of oral contraceptives and metformin on the outcome of in vitro maturation in infertile women with polycystic ovary syndrome. J Women's Health 19(2):261–265. CrossRefGoogle Scholar
  12. 12.
    Kalem MN, Kalem Z, Gurgan T (2017) Effect of metformin and oral contraceptives on polycystic ovary syndrome and IVF cycles. J Endocrinol Invest 40(7):745–752. CrossRefGoogle Scholar
  13. 13.
    Xu Z, Meng L, Pan C, Chen X, Huang X, Yang H (2018) Does oral contraceptives pretreatment affect the pregnancy outcome in polycystic ovary syndrome women undergoing ART with GnRH agonist protocol? Gynecol Endocrinol 35:1–4. Google Scholar
  14. 14.
    Wei D, Shi Y, Li J, Wang Z, Zhang L, Sun Y, Zhou H, Xu Y, Wu C, Liu L, Wu Q, Zhuang L, Du Y, Li W, Zhang H, Legro RS, Chen ZJ (2017) Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome. Hum Reprod Oxf Engl 32(2):354–361. CrossRefGoogle Scholar
  15. 15.
    Zeng X, Zhang Y, Kwong JS, Zhang C, Li S, Sun F, Niu Y, Du L (2015) The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med 8(1):2–10. CrossRefGoogle Scholar
  16. 16.
    Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13. CrossRefGoogle Scholar
  17. 17.
    Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14:135. CrossRefGoogle Scholar
  18. 18.
    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 Natl J Androl 18(7):623–626Google Scholar
  19. 19.
    Farhi J, Sapir O, Maman M, Fisch B, Ben-Haroush A (2011) Novel protocol for scheduling oocyte retrieval in IVM cycles in PCOS patients: a case series. Reprod Biomed Online 23(6):765–768. CrossRefGoogle Scholar
  20. 20.
    Farquhar C, Rombauts L, Kremer JA, Lethaby A, Ayeleke RO (2017) Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques. Cochrane Database Syst Rev 5:CD006109. Google Scholar
  21. 21.
    Creus M, Ordi J, Fabregues F, Casamitjana R, Carmona F, Cardesa A, Vanrell JA, Balasch J (2003) The effect of different hormone therapies on integrin expression and pinopode formation in the human endometrium: a controlled study. Hum Reprod Oxf Engl 18(4):683–693CrossRefGoogle Scholar
  22. 22.
    Aflatoonian A, Karimzadeh Maybodi MA, Aflatoonian N, Tabibnejad N, Amir-Arjmand MH, Soleimani M, Aflatoonian B, Aflatoonian A (2016) Perinatal outcome in fresh versus frozen embryo transfer in ART cycles. Int J Reprod Biomed Yazd, Iran 14(3):167–172CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Soo Youn Song
    • 1
    • 2
  • Jung Bo Yang
    • 1
    • 2
  • Min Soon Song
    • 1
    • 2
  • Hye Young Oh
    • 1
    • 2
  • Geon Woo Lee
    • 1
    • 2
  • Mina Lee
    • 1
    • 2
  • Young Bok Ko
    • 1
    • 2
  • Ki Hwan Lee
    • 1
    • 2
  • Ha Kyun Chang
    • 3
  • Sang Mi Kwak
    • 4
  • Heon Jong Yoo
    • 1
    • 2
    Email author
  1. 1.Department of Obstetrics and GynecologyChungnam National University HospitalDaejeonRepublic of Korea
  2. 2.Chungnam National University School of MedicineDaejeonRepublic of Korea
  3. 3.Center for Uterine CancerResearch Institute and Hospital, National Cancer CenterGoyangRepublic of Korea
  4. 4.Total Healthcare Center, Kangbuk Samsung Hospital, School of MedicineSungkyunkwan UniversitySeoulRepublic of Korea

Personalised recommendations