title: Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome.
abstract: Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?
  
  
  
  OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.
  
  
  
  Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.
  
  
  
  This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014.
  
  
  
  At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.
  
  
  
  With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth.
  
  
  
  The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study.
  
  
  
  Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings.
  
  
  
  This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures.
  
  
  
  Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528.
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 157 Jingliu Road, Jinan 250001, China.|Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, 157 Jingliu Road, Jinan 250001, China.
authors.forename: Daimin
authors.initials: D
authors.lastname: Wei
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 157 Jingliu Road, Jinan 250001, China.|Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, 157 Jingliu Road, Jinan 250001, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 157 Jingliu Road, Jinan 250001, China.|Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, 157 Jingliu Road, Jinan 250001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 157 Jingliu Road, Jinan 250001, China.|Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, 157 Jingliu Road, Jinan 250001, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 157 Jingliu Road, Jinan 250001, China.|Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, 157 Jingliu Road, Jinan 250001, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai 200000, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Center for Reproductive Medicine, Maternal and Child Health Hospital in Guangxi, 225 Xinyang Road, Nanning 530003, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Center for Reproductive Medicine, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei 100142, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, 60 Yongqing Road, Nanjing 210029, China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Wu
authors.affiliation: Reproductive Medicine Center of Jinghua Hospital, 156 Nanjing South Road, Shenyang 110005, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Center for Reproductive Medicine, Jiangxi Provincial Maternal and Child Health Hospital, 318 Bayi Avenue, Nanchang 330006, China.
authors.forename: Qiongfang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Center for Reproductive Medicine of Yantai Yuhuangding Hospital, 20 Yuhuangding East Road, Yantai 264000, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai 200000, China.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Du
authors.affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai 200000, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Biostatistics, Yale University School of Public Health, New Haven, 60 College Street, CT 06520, USA.
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 157 Jingliu Road, Jinan 250001, China chenzijiang@hotmail.com.|Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, 157 Jingliu Road, Jinan 250001, China.|Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai 200000, China.
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D001723:Birth Rate; D003278:Contraceptives, Oral, Hormonal / Q000627:therapeutic use*; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D010062:Ovulation Induction / Q000379:methods*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D011372:Progestins / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D003278:Contraceptives, Oral, Hormonal; D011372:Progestins
keywords: embryo transfer; live birth; oral contraceptives; polycystic ovary syndrome; progestin