Advertisement

Cumulative live birth rate after ovarian stimulation with freeze-all in women with polycystic ovaries: does the polycystic ovary syndrome phenotype have an impact?

  • Shari Mackens
    Affiliations
    Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Jette Brussels 1090, Belgium
    Search for articles by this author
  • Panagiotis Drakopoulos
    Affiliations
    Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Jette Brussels 1090, Belgium

    IVF Athens Centre, Kolonaki Athens, Greece

    Department of Obstetrics and Gynecology, University of Alexandria, Egypt
    Search for articles by this author
  • Margot Fauve Moeykens
    Affiliations
    Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Jette Brussels 1090, Belgium
    Search for articles by this author
  • Linde Mostinckx
    Affiliations
    Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Jette Brussels 1090, Belgium
    Search for articles by this author
  • Liese Boudry
    Affiliations
    Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Jette Brussels 1090, Belgium
    Search for articles by this author
  • Ingrid Segers
    Affiliations
    Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Jette Brussels 1090, Belgium
    Search for articles by this author
  • Herman Tournaye
    Affiliations
    Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Jette Brussels 1090, Belgium

    Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education, Sechenov University, Moscow, Russia
    Search for articles by this author
  • Christophe Blockeel
    Affiliations
    Department of Obstetrics and Gynaecology, School of Medicine, University of Zagreb, Croatia
    Search for articles by this author
  • Michel De Vos
    Correspondence
    Corresponding author.
    Affiliations
    Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Jette Brussels 1090, Belgium

    Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education, Sechenov University, Moscow, Russia

    Follicle Biology Laboratory (FOBI), UZ Brussel, Vrije Universiteit Brussel (VUB), Brussels 1090, Belgium
    Search for articles by this author
Published:November 16, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.11.009

      Abstract

      Research question

      Do cumulative live birth rates (CLBR) differ between polycystic ovary syndrome (PCOS) phenotypes when a freeze-all strategy is used to prevent OHSS after ovarian stimulation?

      Design

      A single-centre, retrospective cohort study of 422 women with PCOS or polycystic ovarian morphology (PCOM), in whom a freeze-all strategy was applied after GnRH agonist triggering because of hyper-response in their first or second IVF/ICSI. Primary outcome was CLBR; multivariate logistic regression analysis was used.

      Results

      Phenotype A (hyperandrogenism + ovulation disorder + PCOM [HOP]) (n = 91/422 [21.6%]); phenotype C (hyperandrogenism + PCOM [HP]) (33/422 [7.8%]; phenotype D (ovulation disorder + PCOM [OP]) (n = 161/422 [38.2%]); and PCOM (n = 137/422 [32.5%]. Unadjusted CLBR was similar among the groups (69.2%, 69.7%, 79.5% and 67.9%, respectively; P = 0.11). According to multivariate logistic regression analysis, the phenotype did not affect CLBR (OR 0.72, CI 0.24 to 2.14 [phenotype C]; OR 1.55, CI 0.71 to 3.36 [phenotype D]; OR 0.84, CI 0.39 to 1.83 [PCOM]; P = 0.2, with phenotype A as reference).

      Conclusions

      In women with PCOS, hyper-response after ovarian stimulation confers CLBR of around 70%, irrespective of phenotype, when a freeze-all strategy is used. This contrasts with unfavourable clinical outcomes in women with hyperandrogenism and women with PCOS who underwent mild ovarian stimulation targeting normal ovarian response and fresh embryo transfer. The results should be interpreted with caution because the study is retrospective and cannot be generalized to all cycles as they pertain to those in which hyper-response is observed.

      KEYWORDS

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

      Subscribe:

      Subscribe to Reproductive BioMedicine Online
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Alvarez M.
        • Gaggiotti-Marre S.
        • Martinez F.
        • Coll L.
        • Garcia S.
        • Gonzalez-Foruria I.
        • Rodriguez I.
        • Parriego M.
        • Polyzos N.P.
        • Coroleu B.
        Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study.
        Hum. Reprod. 2021; 36: 1552-1560
        • Blockeel C.
        • Drakopoulos P.
        • Santos-Ribeiro S.
        • Polyzos N.P.
        • Tournaye H.
        A fresh look at the freeze-all protocol: a SWOT analysis.
        Human reproduction. 2016; 31: 491-497
        • Bosch E.
        • Alviggi C.
        • Lispi M.
        • Conforti A.
        • Hanyaloglu A.C.
        • Chuderland D.
        • Simoni M.
        • Raine-Fenning N.
        • Crépieux P.
        • Kol S.
        • Rochira V.
        • D'Hooghe T.
        • Humaidan P.
        Reduced FSH and LH action: implications for medically assisted reproduction.
        Hum. Rep. 2021; 36: 1469-1480
        • Braam S.C.
        • de Bruin J.P.
        • Mol B.W.J.
        • van Wely M.
        The perspective of women with an increased risk of OHSS regarding the safety and burden of IVF: a discrete choice experiment.
        Hum. Reprod. Open. 2020; 2020 (hoz034)https://doi.org/10.1093/hropen/hoz034
        • Conrad K.P.
        • Petersen J.W.
        • Chi Y.Y.
        • Zhai X.
        • Li M.
        • Chiu K.H.
        • Liu J.
        • Lingis M.D.
        • Williams R.S.
        • Rhoton-Vlasak A.
        • Larocca J.J.
        • Nichols W.W.
        • Segal M.S.
        Maternal Cardiovascular Dysregulation During Early Pregnancy After In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.
        Hypertension. 2019; 74: 705-715
        • Devroey P.
        • Polyzos N.P.
        • Blockeel C.
        An OHSS-Free Clinic by segmentation of IVF treatment.
        Human reproduction. 2011; 26: 2593-2597
        • Dewailly D.
        • Gronier H.
        • Poncelet E.
        • Robin G.
        • Leroy M.
        • Pigny P.
        • Duhamel A.
        • Catteau-Jonard S.
        Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries.
        Hum. Reprod. 2011; 26: 3123-3129
        • De Vos M.
        • Pareyn S.
        • Drakopoulos P.
        • Raimundo J.M.
        • Anckaert E.
        • Santos-Ribeiro S.
        • Polyzos N.P.
        • Tournaye H.
        • Blockeel C.
        Cumulative live birth rates after IVF in patients with polycystic ovaries: phenotype matters.
        Reprod. BioMed. Online. 2018; 37: 163-171
        • Drakopoulos P.
        • Blockeel C.
        • Stoop D.
        • Camus M.
        • De Vos M.
        • Tournaye H.
        • Polyzos N.
        Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos?.
        Hum. Reprod. 2016; 31: 370-376
        • Gonzalez D.
        • Thackeray H.
        • Lewis P.D.
        • Mantani A.
        • Brook N.
        • Ahuja K.
        • Margara R.
        • Joels L.
        • White J.O.
        • Conlan R.S.
        Loss of WT1 expression in the endometrium of infertile PCOS patients: a hyperandrogenic effect?.
        J. Clin. Endocrinol. Metab. 2012; 97: 957-966
        • Griesinger G.
        • Verweij P.
        • Gates D.
        • Devroey P.
        • Gordon K.
        • Stegmann B.
        • Tarlatzis B.
        Prediction of ovarian hyperstimulation syndrome in patients treated with corifollitropin alfa or rFSH in a GnRH antagonist protocol.
        PLoS One. 2016; 11e0149615
        • Ioannidou P.G.
        • et al.
        How frequent is severe OHSS after GnRH-agonist triggering in high risk women: a systematic review and meta-analysis.
        Reprod. Biomed. Online. 2020; 42: 635-650
        • Labarta E.
        • Mariani G.
        • Paolelli S.
        • Rodriguez-Varela C.
        • Vidal C.
        • Giles J.
        • Bellver J.
        • Cruz F.
        • Marzal A.
        • Celada P.
        • Olmo I.
        • Alama P.
        • Remohi J.
        • Bosch E.
        Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone.
        Hum. Reprod. 2021; 36: 683-692
        • Lauritsen M.P.
        • Bentzen J.G.
        • Pinborg A.
        • Loft A.
        • Forman J.L.
        • Thuesen L.L.
        • Cohen A.
        • Hougaard D.M.
        • Nyboe Andersen A.
        The prevalence of polycystic ovary syndrome in a normal population according to the Rotterdam criteria versus revised criteria including anti-Mullerian hormone.
        Hum. Reprod. 2014; 29: 791-801
        • Lebbe M.
        • Woodruff T.K.
        Involvement of androgens in ovarian health and disease.
        Mol. Hum. Reprod. 2013; 19: 828-837
        • Liu X.
        • Shi W.
        • Shi J.
        Natural cycle frozen-thawed embryo transfer in young women with regular menstrual cycles increases the live-birth rates compared with hormone replacement treatment: a retrospective cohort study.
        Fertil. Steril. 2020; 113: 811-817
        • Lizneva D.
        • Suturina L.
        • Walker W.
        • Brakta S.
        • Gavrilova-Jordan L.
        • Azziz R.
        Criteria, prevalence and phenotypes of polycystic ovary syndrome.
        Fertil. Steril. 2016; 106: 6-15
        • Mackens S.
        • Santos-Ribeiro S.
        • van de Vijver A.
        • Racca A.
        • Van Landuyt L.
        • Tournaye H.
        • Blockeel C.
        Frozen Embryo transfer: a review on the optimal endometrial preparation and timing.
        Hum. Reprod. 2017; 32: 2234-2242
        • Moen G.
        • Brumpton B.
        • Willer C.
        • Asvold B.O.
        • Birkeland K.I.
        • Wang G.
        • Neale M.C.
        • Freathy R.M.
        • Smith G.D.
        • Lawlor D.A.
        • Kirkpatrick R.M.
        • Warrington N.M.
        • Evans D.M.
        Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort.
        Nat. Commun. 2020; 11: 5404
        • Oudshoorn S.C.
        • et al.
        Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.
        Hum. Reprod. 2017; 32: 2506-2514
        • 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.
        Fertil. Steril. 2010; 94: 1805-1811
        • Papanikolaou E.G.
        • Pozzobon C.
        • Kolibianakis E.M.
        • Camus M.
        • Tournaye H.
        • Fatemi H.M.
        • Van Steirteghem A.
        • Devroey P.
        Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles.
        Fertility and sterility. 2006; 85: 112-120
        • Polyzos N.
        • Drakopoulos P.
        • Parra J.
        • Pellicer A.
        • Santos-Ribeiro S.
        • Tournaye H.
        • Bosch E.
        • Garcia-Velasco J.
        Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for IVF/ICSI: a multicenter multinational analysis including 15,000 women.
        Fertil. Steril. 2018; 110: 661-670
        • Qiao J.
        • Feng H.L.
        Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence.
        Hum. Reprod. Update. 2011; 17: 17-33
        • Ramezanali F.
        • Ashrafi M.
        • Hemat M.
        • Arabipoor A.
        • Jalali S.
        • Moini A.
        Assisted reproductive outcomes in women with different polycystic ovary syndrome phenotypes: the predictive value of anti-Müllerian hormone.
        Reprod. BioMed. Online. 2016; 32: 503-512
        • Rosas C.
        • Orostica L.
        • Poblete C.
        • Carvajal R.
        • Gabler F.
        • Romero C.
        • Lavandero S.
        • Vega M.
        Hyperandrogenism decreases GRP78 protein level and glucose uptake in human endometrial stromal cells.
        Reprod. Sci. 2016; 23: 761-770
        • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
        Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
        Fertility and Sterility. 2004; 81: 19-25
        • Santos-Ribeiro S.
        • Mackens S.
        • Popovic-Todorovic B.
        • Racca A.
        • Polyzos N.P.
        • Van Landuyt L.
        • Drakopoulos P.
        • De Vos M.
        • Tournaye H.
        • Blockeel C.
        The freeze-all strategy versus agonist triggering with low-dose hCG for luteal phase support in IVF/ICSI for high responders: a randomized controlled trial.
        Hum. Reprod. 2020; 35: 2808-2818
        • Schulte M.M.
        • Tsai J.H.
        • Moley K.H.
        Obesity and PCOS: the effect of metabolic derangements on endometrial receptivity at the time of implantation.
        Reprod. Sci. 2015; 22: 6-14
        • Tal R.
        • Seifer C.M.
        • Khanimov M.
        • Seifer D.B.
        • Tal O.
        High Serum Antimullerian Hormone Levels are Associated With Lower Live Birth Rates in Women With Polycystic Ovarian Syndrome Undergoing Assisted Reproductive Technology.
        Reprod. Biol. Endocrinol. 2020; 18: 20
        • Teede H.
        • Misso M.
        • 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.
        Fertil. Steril. 2018; 110 (Hum Reprod 2018;33(9):1602-1618): 364-379
        • Teede H.
        • Misso M.
        • Tassone E.C.
        • Dewailly D.
        • Ng E.H.
        • Azziz R.
        • et al.
        AntiMüllerian Hormone in PCOS: A Review Informing International Guidelines.
        Trends Endocrinol. Metabol. 2019; 30: 467-478
        • Tomás C.
        • Alsbjerg B.
        • Martikainen H.
        • Humaidan P.
        Pregnancy loss after frozen-embryo transfer–a comparison of three protocols.
        Fertil. Steril. 2012; 98: 1165-1169
        • Van Landuyt L.
        • Stoop D.
        • Verheyen G.
        • Verpoest W.
        • Camus M.
        • Van de Velde H.
        • Devroey P.
        Van den Abbeel E. Outcome of closed blastocyst vitrification in relation to blastocyst quality: evaluation of 759 warming cycles in a single-embryo transfer policy.
        Hum. Reprod. 2011; 26: 527-534
        • Van Landuyt L.
        • Van de Velde H.
        • De Vos A.
        • Haentjens P.
        • Blockeel C.
        • Tournaye H.
        • Verheyen G.
        Influence of cell loss after vitrification or slow-freezing on further in vitro development and implantation of human Day 3 embryos.
        Hum. Reprod. 2013; 28: 2943-2949
        • Vaughan D.A.
        • Leung A.
        • Resetkova N.
        • Ruthazer R.
        • Penzias A.S.
        • Sakkas D.
        • Alper M.M.
        How many oocytes are optimal to achieve multiple live births with one stimulation cycle? The one-and-done approach.
        Fertil. Steril. 2017; 107: 397-404
        • Veleva Z.
        • Tiitinen A.
        • Vilska S.
        • Hydén-Granskog C.
        • Tomás C.
        • Martikainen H.
        • Tapanainen J.S.
        High and low BMI increase the risk of miscarriage after IVF/ICSI and FET.
        Hum. Reprod. 2008; 23: 878-884
        • Vesztergom D.
        • Segers I.
        • Mostinckx L.
        • Blockeel C.
        • De Vos M.
        Live births after in vitro maturation of oocytes in women who had suffered adnexal torsion and unilateral oophorectomy following conventional ovarian stimulation.
        JARG. 2021; https://doi.org/10.1007/s10815-021-02171-8
        • von Versen-Höynck F.
        • Schaub A.M.
        • Chi Y.Y.
        • Chiu K.H.
        • Liu J.
        • Lingis M.
        • Stan Williams R.
        • Rhoton-Vlasak A.
        • Nichols W.W.
        • Fleischmann R.R.
        • Zhang W.
        • Winn V.D.
        • Segal M.S.
        • Conrad K.P.
        • Baker V.L.
        Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.
        Hypertension. 2019; 73: 640-649
        • Xi W.
        • Gong F.
        • Lu G.
        Correlation of Serum Anti-Mullerian Hormone Concentrations on Day 3 of the In Vitro Fertilization Stimulation Cycle With Assisted Reproduction Outcome in Polycystic Ovary Syndrome Patients.
        J. Assist. Reprod. Genet. 2012; 29: 397-402
        • Zegers-Hochschild F.
        • Adamson G.D.
        • Dyer S.
        • Racowsky C.
        • de Mouzon J.
        • Sokol R.
        • Rienzi L.
        • Sunde A.
        • Schmikdt L.
        • Cooke I.D.
        • Simpson J.L.
        • van der Poel S.
        The international glossary on infertility and fertility care, 2017.
        Hum. Reprod. 2017; 32: 1786-1801
        • Zhang J.
        • Liu H.
        • Wang Y.
        • Mao X.
        • Chen Q.
        • Fan Y.
        • Xiao Y.
        • Kuang Y.
        Letrozole use during frozen embryo transfer cycles in women with polycystic ovary syndrome.
        Fertil. Steril. 2019; 112: 371-377
        • Zhang J.
        • Li Z.
        • Sun L.
        • Guan Y.
        • Du M.
        Comparison of pregnancy and neonatal outcomes of single frozen blastocyst transfer between letrozole-induction and HRT cycles in patients with abnormal ovulation.
        Front Endocrinol. 2021; 12664072

      Biography

      Shari Mackens, MD, PhD, is a gynaecologist at the Centre for Reproductive Medicine at the University Hospital Brussels and an associate professor at the Vrije Universiteit Brussel, with a specific interest in reproductive endocrinology and translational research focusing on the role of the endometrium in assisted reproductive technology.
      Key message
      When patients with polycystic ovary syndrome achieve hyper-response after ovarian stimulation, they have excellent success rates following the freeze-all approach, irrespective of their phenotype. It is still, however, unclear how to stimulate these women to obtain optimal reproductive outcomes without compromising safety.