Advertisement

A meta-analysis of pregnancy-related outcomes and complications in women with polycystic ovary syndrome undergoing IVF

Published:March 28, 2019DOI:https://doi.org/10.1016/j.rbmo.2019.03.203

      Highlights

      • • This meta-analysis provided stronger evidence that women with PCOS undergoing IVF are at increased risk of adverse clinical outcomes.
      • • Sufficient studies make it possible to explore the heterogeneity sources using subgroup analyses
      • • Larger number of included studies enhanced the statistical power for rare adverse outcomes

      Abstract

      This meta-analysis aimed to study whether pregnancy-related outcomes and complications differed between patients with polycystic ovary syndrome (PCOS) and those with other causes of infertility who had undergone IVF. A systematic search of PubMed, Embase, the Cochrane Library and Chinese databases was carried out to identify relevant studies published before July 2018. Outcomes were expressed as odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses and sensitivity analyses were also conducted. Twenty-nine studies were identified for inclusion. Women with PCOS had higher risks of miscarriage (OR 1.41, 95% CI 1.04–1.91), ovarian hyperstimulation syndrome (OR 4.96, 95% CI 3.73–6.60), gestational diabetes mellitus (OR 2.67, 95% CI 1.43–4.98), pregnancy-induced hypertension (OR 2.06, 95% CI 1.45–2.91), preterm birth (OR 1.60, 95% CI 1.25–2.04) and large-for-gestational-age babies (OR 2.10, 95% CI 1.01–4.37). Women with PCOS showed similar rates of clinical pregnancy, multiple pregnancy, ectopic pregnancy, small for gestational age and congenital malformations, and a higher live birth rate, compared with women without PCOS. This study provides an update on and comprehensive evidence to support the observation that despite the fact that PCOS patients achieve a better live birth rate, physicians should continue to consider them to be at high risk of adverse pregnancy-related outcomes.

      Keywords

      To read this article in full you will need to make a payment

      REFERENCES

        • Azziz R.
        • Carmina E.
        • Dewailly D.
        • Diamanti-Kandarakis E.
        • Escobar-Morreale H.F.
        • Futterweit W.
        • Janssen O.E.
        • Legro R.S.
        • Norman R.J.
        • Taylor A.E.
        • Witchel S.F.
        • Androgen Excess Society
        Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline.
        Journal of Clinical Endocrinology & Metabolism. 2006; 91: 4237-4245
        • Beydoun H.A.
        • Stadtmauer L.
        • Zhao Y.
        • Russell H.
        • Matson D.O.
        • Oehninger S.
        Impact of polycystic ovary syndrome on selected indicators of in vitro fertilization and intracytoplasmic sperm injection treatment success.
        Journal of women's health (2002). 2009; 18: 717-723
        • Bezirganoglu N.
        • Seckin K.D.
        • Baser E.
        • Karsli M.F.
        • Yeral M.I.
        • Cicek M.N.
        Isolated polycystic morphology: Does it affect the IVF treatment outcomes?.
        Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology. 2015; 35: 272-274
        • Boomsma C.M.
        • Eijkemans M.J.
        • Hughes E.G.
        • Visser G.H.
        • Fauser B.C.
        • Macklon N.S.
        A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.
        Human Reproduction Update. 2006; 12: 673-683
        • Bozdag G.
        • Mumusoglu S.
        • Zengin D.
        • Karabulut E.
        • Yildiz B.O.
        The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis.
        Hum. Reproduction. 2016; 31: 2841-2855
        • Cenk S.N.
        • Gucer F.
        • Balkanli-Kaplan P.
        • Ali Yuce.M.
        • Yardim T.
        Insulin resistance and lipid profile in women with polycystic appearing ovaries: implications with regard to polycystic ovary syndrome.
        Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. 2003; 17: 387-396
        • Chen Y.
        • Ye B.
        • Yang X.
        • Zheng J.
        • Lin J.
        • Zhao J.
        Predicting the outcome of different protocols of in vitro fertilization with anti-Mullerian hormone levels in patients with polycystic ovary syndrome.
        The Journal of international medical research. 2017; 45: 1138-1147
        • Chen ZJ
        • Shi Y
        • Sun Y
        • Zhang B
        • Liang X
        • Cao Y
        • Yang J
        • Liu J
        • Wei D
        • Weng N
        • Tian L
        • Hao C
        • Yang D
        • Zhou F
        • Shi J
        • Xu Y
        • Li J
        • Yan J
        • Qin Y
        • Zhao H
        • Zhang H
        • Legro RS.
        Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome.
        The New England journal of medicine. 2016; 375: 523-533
        • Chian R.C.
        In-vitro maturation of immature oocytes for infertile women with PCOS.
        Reproductive biomedicine online. 2004; 8: 547-552
        • Conde-Agudelo A.
        • Belizan J.M.
        • Lindmark G.
        Maternal morbidity and mortality associated with multiple gestations.
        Obstetrics and Gynecology. 2000; 95: 899-904
        • Delvigne A.
        • Rozenberg S.
        Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review.
        Human reproduction update. 2002; 8: 559-577
        • Devroey P.
        • Polyzos N.P.
        • Blockeel C.
        An OHSS-Free Clinic by segmentation of IVF treatment.
        Human reproduction (Oxford, England). 2011; 26: 2593-2597
        • Diamanti-Kandarakis E.
        • Kandarakis H.
        • Legro R.S.
        The role of genes and environment in the etiology of PCOS. The role of genes and environment in the etiology of PCOS.
        Endocrine. 2006; 30: 19-26
        • Doldi N.
        • Marsiglio E.
        • Destefani A.
        • Gessi A.
        • Merati G.
        • Ferrari A.
        Elevated serum progesterone on the day of HCG administration in IVF is associated with a higher pregnancy rate in polycystic ovary syndrome.
        Human reproduction (Oxford, England). 1999; 14: 601-605
        • Han A.R.
        • Kim H.O.
        • Cha S.W.
        • Park C.W.
        • Kim J.Y.
        • Yang K.M.
        • Song I.O.
        • Koong M.K.
        • Kang I.S.
        Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study.
        Clinical and experimental reproductive medicine. 2011; 38: 103-108
        • Hardy K.
        • Robinson F.M.
        • Paraschos T.
        • Wicks R.
        • Franks S.
        • Winston R.M.
        Normal development and metabolic activity of preimplantation embryos in vitro from patients with polycystic ovaries.
        Human reproduction (Oxford, England). 1995; 10: 2125-2135
        • Heijnen E.M.
        • Eijkemans M.J.
        • Hughes E.G.
        • Laven J.S.
        • Macklon N.S.
        • Fauser B.C.
        A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome.
        Human reproduction update. 2006; 12: 13-21
        • Homburg R.
        • Berkowitz D.
        • Levy T.
        • Feldberg D.
        • Ashkenazi J.
        • Ben-Rafael Z.
        In vitro fertilization and embryo transfer for the treatment of infertility associated with polycystic ovary syndrome.
        Fertility and sterility. 1993; 60: 858-863
        • Homburg R.
        • Crawford G.
        The role of AMH in anovulation associated with PCOS: a hypothesis.
        Human reproduction (Oxford., England). 2014; 29: 1117-1121
        • Kalra S.K.
        • Ratcliffe S.J.
        • Dokras A.
        Is the fertile window extended in women with polycystic ovary syndrome? Utilizing the Society for Assisted Reproductive Technology registry to assess the impact of reproductive aging on live-birth rate.
        Fertility and sterility. 2013; 100: 208-213
        • Kjerulff LE.
        • Sanchez-Ramos L.
        • Duffy D.
        Pregnancy outcomes in women with polycystic ovary syndrome: a meta-analysis.
        American journal of obstetrics and gynecology. 2011; 204 (558 e551-556): 558
        • Kodama H.
        • Fukuda J.
        • Karube H.
        • Matsui T.
        • Shimizu Y.
        • Tanaka T.
        High incidence of embryo transfer cancellations in patients with polycystic ovarian syndrome.
        Human reproduction (Oxford., England). 1995; 10: 1962-1967
        • Kuivasaari-Pirinen P.
        • Hippelainen M.
        • Hakkarainen H.
        • Randel l K.
        • Heinonen S.
        Cumulative baby take-home rate among women with PCOS treated by IVF.
        Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. 2010; 26: 582-589
        • Lainas T.G.
        • Sfontouris I.A.
        • Zorzovilis I.Z.
        • Petsas G.K.
        • Lainas G.T.
        • Alexopoulou E.
        • Kolibianakis E.M.
        Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT).
        Human reproduction (Oxford., England). 2010; 25: 683-689
        • Li H.W.
        • Lee V.C.
        • Lau E.Y.
        • Yeung W.S.
        • Ho P.C.
        • Ng E.H.
        Cumulative live-birth rate in women with polycystic ovary syndrome or isolated polycystic ovaries undergoing in-vitro fertilisation treatment.
        Journal of assisted reproduction and genetics. 2014; 31: 205-211
        • Liu L.
        • Tong X.
        • Jiang L.
        • Li T.C.
        • Zhou F.
        • Zhang S.
        A comparison of the miscarriage rate between women with and without polycystic ovarian syndrome undergoing IVF treatment.
        European journal of obstetrics, gynecology, and reproductive biology. 2014; 176: 178-182
        • Lu X.E.
        • Yang X.F.
        • Li M.G.
        • Zhou F.Z.
        • Zhu Y.M.
        • Huang H.F.
        [Outcome of in vitro fertilization-embryo transfer in treatment of polycystic ovarian syndrome].
        Zhejiang Da Xue Xue bao Yi Xue ban. 2006; 35: 319-322
        • Ludwig M.
        • Finas D.F.
        • al-Hasani S.
        • Diedrich K.
        • Ortmann O.
        Oocyte quality and treatment outcome in intracytoplasmic sperm injection cycles of polycystic ovarian syndrome patients.
        Human reproduction (Oxford., England). 1999; 14: 354-358
        • March W.A.
        • Moore V.M.
        • Willson K.J.
        • Phillips D.I.
        • Norman R.J.
        • Davies M.J.
        The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria.
        Human reproduction (Oxford., England). 2010; 25: 544-551
        • Mulders A.G.
        • Laven J.S.
        • Imani B.
        • Eijkemans M.J.
        • Fauser B.C.
        IVF outcome in anovulatory infertility (WHO group 2)–including polycystic ovary syndrome–following previous unsuccessful ovulation induction.
        Reproductive biomedicine online. 2003; 7: 50-58
        • Nejad E.S.
        • Saedi T.
        • Saedi S.
        • Rashidi B.H.
        • Nekoo Z.A.
        • Jahangiri N.
        Comparison of in vitro fertilisation success in patients with polycystic ovary syndrome and tubal factor.
        Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. 2011; 27: 117-120
        • Okohue J.E.
        • Onuh S.O.
        • Ikimalo J.I.
        • Onuh S.O.
        Challenges in running/establishing an assisted conception centre in the Niger-Delta region of Nigeria.
        West African Journal of Assisted Reproduction. 2011; 1: 1-17
        • Okohue J.E.
        • Onuh S.O.
        • Ikimalo J.I.
        Comparison of IVF/ICSI outcome in patients with polycystic ovarian syndrome or tubal factor infertility.
        Nigerian journal of clinical practice. 2013; 16: 207-210
        • Palomba S.
        • Falbo A.
        • Russo T.
        • Tolino A.
        • Orio F.
        • Zullo F.
        Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes.
        Fertility and sterility. 2010; 94: 1805-1811
        • Pandey S.
        • Shetty A.
        • Hamilton M.
        • Bhattacharya S.
        • Maheshwari A.
        Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis.
        Human reproduction update. 2012; 18: 485-503
        • Qin J.Z.
        • Pang L.H.
        • Li M.J.
        • Fan X.J.
        • Huang R.D.
        • Chen H.Y.
        Obstetric complications in women with polycystic ovary syndrome: a systematic review and meta-analysis.
        Reproductive biology and endocrinology: RB&E. 2013; 11: 56
        • Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group
        Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).
        Human reproduction (Oxford., England). 2004; 19: 41-47
        • Sengoku K.
        • Tamate K.
        • Takuma N.
        • Yoshida T.
        • Goishi K.
        • Ishikawa M.
        The chromosomal normality of unfertilized oocytes from patients with polycystic ovarian syndrome.
        Human reproduction (Oxford., England). 1997; 12: 474-477
        • Sha T.
        • Yin X.
        • Cheng W.
        • Massey I.Y.
        Pregnancy-related complications and perinatal outcomes resulting from transfer of cryopreserved versus fresh embryos in vitro fertilization: a meta-analysis.
        Fertility and sterility. 2018; 109 (e339): 330-342
        • Siristatidis C.S.
        • Vrachnis N.
        • Creatsa M.
        • Maheshwari A.
        • Bhattacharya S.
        In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction.
        The Cochrane database of systematic reviews. 2013; CD006606
        • Sirmans S.M.
        • Pate KA.
        Epidemiology, diagnosis, and management of polycystic ovary syndrome.
        Clinical epidemiology. 2013; 6: 1-13
        • Sterling L.
        • Liu J.
        • Okun N.
        • Sakhuja A.
        • Sierra S.
        • Greenblatt E.
        Pregnancy outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization.
        Fertility and sterility. 2016; 105 (e792): 791-797
        • Swanton A.
        • Storey L.
        • McVeigh E.
        • Child T.
        IVF outcome in women with PCOS, PCO and normal ovarian morphology.
        European journal of obstetrics., gynecology, and reproductive biology. 2010; 149: 68-71
        • Tang T.
        • Glanville J.
        • Orsi N.
        • Barth J.H.
        • Balen A.H.
        The use of metformin for women with PCOS undergoing IVF treatment.
        Human reproduction (Oxford., England). 2006; 21: 1416-1425
        • Teede H.
        • Deeks A.
        • Moran L.
        Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan.
        BMC medicine. 2010; 8: 41
        • Teede H.J.
        • Misso M.L.
        • Costello M.F.
        • Dokras A.
        • Laven J.
        • Moran L.
        • Piltonen T.
        • Norman R.J.
        • International PCOS Network
        Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.
        Human reproduction (Oxford., England). 2018; 33: 1602-1618
        • Tso L.O.
        • Costello M.F.
        • Albuquerque L.E.
        • Andriolo R.B.
        • Macedo C.R.
        Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome.
        The Cochrane database of systematic reviews. 2014; CD006105
        • Urman B.
        • Fluker M.R.
        • Yuen B.H.
        • Fleige-Zahradka B.G.
        • Zouves C.G.
        • Moon Y.S.
        The outcome of in vitro fertilization and embryo transfer in women with polycystic ovary syndrome failing to conceive after ovulation induction with exogenous gonadotropins.
        Fertility and sterility. 1992; 57: 1269-1273
        • Urman B.
        • Tiras B.
        • Yakin K.
        Assisted reproduction in the treatment of polycystic ovarian syndrome.
        Reproductive biomedicine online. 2004; 8: 419-430
        • Veltman-Verhulst S.M.
        • van, Haeften T.W.
        • Eijkemans M.J.
        • de, Valk H.W.
        • Fauser B.C.
        • Goverde A.J.
        Sex hormone-binding globulin concentrations before conception as a predictor for gestational diabetes in women with polycystic ovary syndrome.
        Human reproduction (Oxford., England). 2010; 25: 3123-3128
        • Wan H.L.
        • Hui P.W.
        • Li H.W.
        • Ng E.H.
        Obstetric outcomes in women with polycystic ovary syndrome and isolated polycystic ovaries undergoing in vitro fertilization: a retrospective cohort analysis.
        The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2015; 28: 475-478
        • Wang J.
        • Wei Y.
        • Diao F.
        • Cui Y.
        • Mao Y.
        • Wang W.
        • Liu J.
        The association between polycystic ovary syndrome and ectopic pregnancy after in vitro fertilization and embryo transfer.
        American journal of obstetrics and gynecology. 2013; 209 (139 e131-139): 139
        • Wang Q.L.
        • Song J.
        • Chen S.L.
        • Luo C.
        • Chen X.
        • Li M.
        • Ni Y.P.
        [Analysis of the clinical outcomes of IVF-ET treatment in infertile patients with polycystic ovary syndrome or polycystic ovaries].
        Nan fang yi ke da xue xue bao. 2009; 29: 962-965
        • Wang T.
        • Fu H.
        • Chen L.
        • Xu Y.
        [Pregnancy complications among women with polycystic ovary syndrome in China: a Meta-analysis].
        Zhong nan da xue xue bao Yi xue ban = Journal of Central South University Medical sciences. 2017; 42: 1300-1310
        • Wang X.X.
        • Luan C.X.
        • Zhang W.
        • Hu S.M.
        [Pregnancy outcomes of in vitro fertilization and embryo transfer in infertile women with polycystic ovarian syndrome].
        Zhonghua fu chan ke za zhi. 2012; 47: 730-733
        • Yan X.
        • Shi Y.H.
        • Sheng Y.
        • Tang R.
        • Xu L.H.
        • Li Y.
        • Chen Z.J.
        [Pregnancy outcomes of patients with polycystic ovary syndrome undergoing in vitro fertilization and embryo transfer].
        Zhonghua fu chan ke za zhi. 2011; 46: 923-927
        • Youssef M.A.
        • van, Wely M.
        • Hassan M.A.
        • Al-Inany H.G.
        • Mochtar M.
        • Khattab S.
        • van, Der. Veen F.
        Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles?.
        A systematic review and meta-analysis. Human reproduction update. 2010; 16: 459-466
        • Yu H.F.
        • Chen H.S.
        • Rao D.P.
        • Gong J.
        Association between polycystic ovary syndrome and the risk of pregnancy complications: A PRISMA-compliant systematic review and meta-analysis.
        Medicine. 2016; 95: e4863
        • Zhang dan.
        • Xu Y.W.
        • Wang Z.L.
        • Jia M.X.
        • Wang Z.Y.
        • Yuan Y.
        • Zhou C.Q.
        Pregnancy Outcomes of Patients with Polycystic Ovary Syndrome after in Vitro Fertilization and Embryo Transfer.
        Journal of sun Yat-Sen University (Medical Sciences). 2013; 34: 596-600
        • Zhong Y.P.
        • Ying Y.
        • Wu H.T.
        • Zhou C.Q.
        • Xu Y.W.
        • Wang Q.
        • Li J.
        • Shen X.T.
        Comparison of Endocrine Profile and In Vitro Fertilization Outcome in Patients with PCOS, Ovulatory PCO, or Normal Ovaries.
        International journal of endocrinology. 2012; 2012492803

      Biography

      Tingting Sha is a doctoral candidate at the Department of Epidemiology and Medical Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China. She is currently engaged in epidemiological studies of infertility, sterility and assisted reproductive technology.
      Key message
      This meta-analysis of 29 observational studies investigated clinical outcomes, including rare outcomes, in women with polycystic ovary syndrome (PCOS) who underwent IVF. Compared with an earlier meta-analysis, the current results provided stronger evidence that women with PCOS undergoing IVF are at significantly elevated risk of adverse pregnancy outcomes.