A pilot study comparing corifollitropin alfa associated with hp-HMG versus high dose rFSH antagonist protocols for ovarian stimulation in poor responders

Abstract Does corifollitropin alfa associated with hp-HMG protocol from the beginning of ovarian stimulation perform better than high dose rFSH alone for ovarian stimulation with GnRH antagonist in poor responders? This retrospective, monocentric, case-control pilot study was conducted in 65 poor responders (Bologna criteria) undergoing 2 consecutive IVF cycles. All patients underwent a first ovarian stimulation cycle with high dose rFSH (≥300 IU/day) alone in antagonist protocol, unfortunately leading to poor ovarian response and no pregnancy. The following cycle was performed with 150 μg of corifollitropin alfa associated with daily injections of hp-HMG from the beginning of the cycle. The primary outcome was the number of mature oocytes retrieved. The secondary outcomes were ovarian stimulation cancellation and embryo transfer rate per initiated cycle. The number of mature oocytes was not significantly different between the 2 groups. However, cycle cancellation rate was significantly lower and the proportion of cycles with embryo transfer was significantly higher with corifollitropin + hp-HMG protocol, leading to an encouraging clinical pregnancy rate of 24.1% per oocyte retrieval. This pilot study based on corifollitropin alfa associated with hp-HMG from the onset of stimulation appears to be promising for ovarian stimulation in poor responders.

[1]  E. Somigliana,et al.  Prognosis and cost-effectiveness of IVF in poor responders according to the Bologna Criteria. , 2018, Minerva ginecologica.

[2]  H. Tournaye,et al.  Corifollitropin alfa followed by highly purified HMG versus recombinant FSH in young poor ovarian responders: a multicentre randomized controlled clinical trial , 2017, Human reproduction.

[3]  H. Yarali,et al.  Live birth rates in various subgroups of poor ovarian responders fulfilling the Bologna criteria. , 2017, Reproductive biomedicine online.

[4]  B. D. de Carvalho,et al.  Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction , 2017, JBRA assisted reproduction.

[5]  T. T. Nguyen,et al.  The effectiveness of transdermal testosterone gel 1% (androgel) for poor responders undergoing in vitro fertilization , 2017, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[6]  P. Humaidan,et al.  Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders , 2017, Human reproduction.

[7]  M. van Wely,et al.  Recombinant luteinizing hormone (rLH) and recombinant follicle stimulating hormone (rFSH) for ovarian stimulation in IVF/ICSI cycles. , 2017, The Cochrane database of systematic reviews.

[8]  I. Koenig,et al.  Ovarian response to 150 µg corifollitropin alfa in a GnRH-antagonist multiple-dose protocol: a prospective cohort study. , 2017, Reproductive biomedicine online.

[9]  A. Copperman,et al.  The cumulative dose of gonadotropins used for controlled ovarian stimulation does not influence the odds of embryonic aneuploidy in patients with normal ovarian response , 2017, Journal of Assisted Reproduction and Genetics.

[10]  K. Dafopoulos,et al.  Mild Versus Conventional Ovarian Stimulation for Poor Responders Undergoing IVF/ICSI. , 2017, In vivo.

[11]  S. Esteves,et al.  The novel POSEIDON stratification of ‘Low prognosis patients in Assisted Reproductive Technology’ and its proposed marker of successful outcome , 2016, F1000Research.

[12]  C. Haddad,et al.  Evaluation of results obtained with corifollitropin alfa after poor ovarian response in previous cycle using recombinant follicular stimulating hormone in the long-term protocol , 2016, JBRA assisted reproduction.

[13]  R. Boostanfar,et al.  Corifollitropin alfa versus recombinant follicle-stimulating hormone: an individual patient data meta-analysis. , 2016, Reproductive biomedicine online.

[14]  C. Farquhar,et al.  Long-acting follicle-stimulating hormone versus daily follicle-stimulating hormone for women undergoing assisted reproduction. , 2016, Fertility and sterility.

[15]  F. Ubaldi,et al.  A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. , 2016, Fertility and sterility.

[16]  S. Bhattacharya,et al.  Trends in 'poor responder' research: lessons learned from RCTs in assisted conception. , 2016, Human reproduction update.

[17]  B. Tarlatzis,et al.  Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol , 2016, PloS one.

[18]  E. Kolibianakis,et al.  Regimen of ovarian stimulation affects oocyte and therefore embryo quality. , 2016, Fertility and sterility.

[19]  T. Freour,et al.  Stimulation ovarienne à fortes doses de gonadotrophines en FIV : étude rétrospective cas-témoin au CHU de Nantes , 2016 .

[20]  P. Barrière,et al.  [High doses of gonadotropins for controlled ovarian hyperstimulation: A case-control study]. , 2016, Gynecologie, obstetrique & fertilite.

[21]  C. Siristatidis,et al.  Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction. , 2015, The Cochrane database of systematic reviews.

[22]  Morton B. Brown,et al.  Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles. , 2015, Fertility and sterility.

[23]  C. Venetis,et al.  Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders. , 2015, Human reproduction.

[24]  M. Hill,et al.  Diminished ovarian reserve in the United States assisted reproductive technology population: diagnostic trends among 181,536 cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. , 2015, Fertility and sterility.

[25]  H. Tournaye,et al.  Corifollitropin alfa followed by hpHMG in GnRH agonist protocols. Two prospective feasibility studies in poor ovarian responders , 2015, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[26]  H. Phung,et al.  Recombinant follicle-stimulating hormone and recombinant luteinizing hormone versus recombinant follicle-stimulating hormone alone during GnRH antagonist ovarian stimulation in patients aged ≥35 years: a randomized controlled trial. , 2015, Human reproduction.

[27]  S. Dar,et al.  [Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?]. , 2015, Harefuah.

[28]  E. Papaleo,et al.  A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria. , 2015, Human reproduction.

[29]  C. Venetis,et al.  Corifollitropin alfa compared with follitropin beta in poor responders undergoing ICSI: a randomized controlled trial. , 2015, Human reproduction.

[30]  I. Izhaki,et al.  The effect of LH supplementation following GnRH antagonist administration in advanced reproductive ageing women undergoing IVT-ET: a prospective randomized controlled study , 2014 .

[31]  C. Lambalk,et al.  Recombinant LH supplementation to a standard GnRH antagonist protocol in women of 35 years or older undergoing IVF/ICSI: a randomized controlled multicentre study. , 2014, Human reproduction.

[32]  H. Tournaye,et al.  Corifollitropin α followed by menotropin for poor ovarian responders’ trial (COMPORT): a protocol of a multicentre randomised trial , 2013, BMJ Open.

[33]  H. Tournaye,et al.  Addition of highly purified HMG after corifollitropin alfa in antagonist-treated poor ovarian responders: a pilot study. , 2013, Human reproduction.

[34]  H. Tournaye,et al.  Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients: an observational pilot study. , 2013, Fertility and sterility.

[35]  L. Gianaroli,et al.  ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. , 2011, Human reproduction.

[36]  Lisa Cowan,et al.  The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. , 2011, Human reproduction.

[37]  C. Simón,et al.  Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles: an age-adjusted analysis. , 2011, Fertility and sterility.

[38]  P. Devroey,et al.  A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol , 2009, Human reproduction.

[39]  P. Devroey,et al.  Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency. , 2009, Human reproduction update.

[40]  M. Eijkemans,et al.  Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. , 2007, Human reproduction.

[41]  A. Burfoot.  A review of the third annual meeting of the European Society of Human Reproduction and Embryology. , 1988, Reproductive and genetic engineering.

[42]  W. Kesteven.  On Live-Birth , 1861, The British and foreign medico-chirurgical review.