Progesterone administration route in gonadotropin-releasing hormone antagonist cycles

Abstract

To the Editor:We read with interest the article of Kahraman et al. (1Kahraman S, Karagozoglu SH, Karlikaya G. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial. Fertil Steril 2009. DOI:10.1016/j.fertnstert.2009.10.004.Google Scholar) comparing the effectiveness of vaginal and intramuscular P as luteal phase support among women undergoing in vitro fertilization with intracytoplasmic sperm injection with GnRH antagonist (1Kahraman S, Karagozoglu SH, Karlikaya G. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial. Fertil Steril 2009. DOI:10.1016/j.fertnstert.2009.10.004.Google Scholar).The authors conducted a prospective study and evaluated 426 women younger than 37 years old undergoing intracytoplasmic sperm injection–embryo transfer cycle with GnRH antagonist cetrorelix. Their results revealed similar clinical pregnancy, implantation, and miscarriage rates among those women after usage of either vaginal or intramuscular P as luteal phase support. In their article they admitted that route of P administration was an important issue in patient compliance and discussed current data about luteal phase support in which only GnRH agonist analogues were used. In this regard, the luteal phase support in GnRH antagonist cycles has not been elucidated clearly yet.This article is so far the first prospective but not randomized controlled trial conducted in GnRH antagonist protocols for the assessment of the type of luteal phase support. However, the results of this study should be interpreted cautiously because the design of the study has several drawbacks. The first one is that the type of allocation of patients was quasi-randomization. There is a greater risk of selection bias in quasi-random trials where allocation is not concealed adequately compared with randomized controlled trials with adequate allocation concealment. Second, the study does not have enough statistical power to detect a clinical significant difference (such as pregnancy or miscarriage rates). Third, it is very interesting that the authors did not have any embryo transfer cancellation after oocyte retrievals in a 10-month period; therefore not even one dropout was mentioned.Last but not least, the authors failed to recognize and discuss the results of the first report on luteal phase support conducted in >1,400 patients in GnRH antagonist protocols (2Bahceci M. Ulug U. Route of progesterone administration for luteal phase support may affect outcome of controlled ovarian hyperstimulation for IVF with ICSI using GnRH antagonist.J Assist Reprod Genet. 2008; 25: 499-502Crossref PubMed Scopus (5) Google Scholar). In this retrospective study, contradictory to the article by Kahraman et al. (1Kahraman S, Karagozoglu SH, Karlikaya G. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial. Fertil Steril 2009. DOI:10.1016/j.fertnstert.2009.10.004.Google Scholar), significant differences were detected in terms of implantation and clinical pregnancy rates in favor of intramuscular injection compared with vaginal P. Conceivably, we believe that comparison of the report mentioned previously with their results merits inclusion in the discussion.Administration of P for luteal phase has been the subject of numerous studies, but all of them reported the results from GnRH agonist protocols. Both the articles by Kahraman et al. (1Kahraman S, Karagozoglu SH, Karlikaya G. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial. Fertil Steril 2009. DOI:10.1016/j.fertnstert.2009.10.004.Google Scholar) (quasi-randomization) and Bahceci and Ulug (2Bahceci M. Ulug U. Route of progesterone administration for luteal phase support may affect outcome of controlled ovarian hyperstimulation for IVF with ICSI using GnRH antagonist.J Assist Reprod Genet. 2008; 25: 499-502Crossref PubMed Scopus (5) Google Scholar) (retrospective) have limitations for clear interpretation of the results. Therefore, the impact of the P route in GnRH antagonist cycles still warrants well-powered prospective randomized clinical trials. To the Editor: We read with interest the article of Kahraman et al. (1Kahraman S, Karagozoglu SH, Karlikaya G. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial. Fertil Steril 2009. DOI:10.1016/j.fertnstert.2009.10.004.Google Scholar) comparing the effectiveness of vaginal and intramuscular P as luteal phase support among women undergoing in vitro fertilization with intracytoplasmic sperm injection with GnRH antagonist (1Kahraman S, Karagozoglu SH, Karlikaya G. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial. Fertil Steril 2009. DOI:10.1016/j.fertnstert.2009.10.004.Google Scholar). The authors conducted a prospective study and evaluated 426 women younger than 37 years old undergoing intracytoplasmic sperm injection–embryo transfer cycle with GnRH antagonist cetrorelix. Their results revealed similar clinical pregnancy, implantation, and miscarriage rates among those women after usage of either vaginal or intramuscular P as luteal phase support. In their article they admitted that route of P administration was an important issue in patient compliance and discussed current data about luteal phase support in which only GnRH agonist analogues were used. In this regard, the luteal phase support in GnRH antagonist cycles has not been elucidated clearly yet. This article is so far the first prospective but not randomized controlled trial conducted in GnRH antagonist protocols for the assessment of the type of luteal phase support. However, the results of this study should be interpreted cautiously because the design of the study has several drawbacks. The first one is that the type of allocation of patients was quasi-randomization. There is a greater risk of selection bias in quasi-random trials where allocation is not concealed adequately compared with randomized controlled trials with adequate allocation concealment. Second, the study does not have enough statistical power to detect a clinical significant difference (such as pregnancy or miscarriage rates). Third, it is very interesting that the authors did not have any embryo transfer cancellation after oocyte retrievals in a 10-month period; therefore not even one dropout was mentioned. Last but not least, the authors failed to recognize and discuss the results of the first report on luteal phase support conducted in >1,400 patients in GnRH antagonist protocols (2Bahceci M. Ulug U. Route of progesterone administration for luteal phase support may affect outcome of controlled ovarian hyperstimulation for IVF with ICSI using GnRH antagonist.J Assist Reprod Genet. 2008; 25: 499-502Crossref PubMed Scopus (5) Google Scholar). In this retrospective study, contradictory to the article by Kahraman et al. (1Kahraman S, Karagozoglu SH, Karlikaya G. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial. Fertil Steril 2009. DOI:10.1016/j.fertnstert.2009.10.004.Google Scholar), significant differences were detected in terms of implantation and clinical pregnancy rates in favor of intramuscular injection compared with vaginal P. Conceivably, we believe that comparison of the report mentioned previously with their results merits inclusion in the discussion. Administration of P for luteal phase has been the subject of numerous studies, but all of them reported the results from GnRH agonist protocols. Both the articles by Kahraman et al. (1Kahraman S, Karagozoglu SH, Karlikaya G. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial. Fertil Steril 2009. DOI:10.1016/j.fertnstert.2009.10.004.Google Scholar) (quasi-randomization) and Bahceci and Ulug (2Bahceci M. Ulug U. Route of progesterone administration for luteal phase support may affect outcome of controlled ovarian hyperstimulation for IVF with ICSI using GnRH antagonist.J Assist Reprod Genet. 2008; 25: 499-502Crossref PubMed Scopus (5) Google Scholar) (retrospective) have limitations for clear interpretation of the results. Therefore, the impact of the P route in GnRH antagonist cycles still warrants well-powered prospective randomized clinical trials. The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trialFertility and SterilityVol. 94Issue 2PreviewWe compared the efficiency of progesterone vaginal gel (PVG) with intramuscular progesterone (IMP) supplementation for luteal phase support after in vitro fertilization and embryo transfer in gonadotropin-releasing hormone (GnRH) antagonist cycles. The treatment outcomes were similar for PVG and IMP for luteal support in GnRH-antagonist protocols. With its ease of use, high tolerability by patients, and fewer side effects, PVG can be a successful alternative to IMP. Full-Text PDF Reply of the Authors: Progesterone administration route in gonadotropin-releasing hormone antagonist cyclesFertility and SterilityVol. 94Issue 3PreviewWe thank the authors for their comments. The result of our study demonstrated that the difference between the treatment outcomes of P vaginal gel and IM P are statistically insignificant for luteal phase support after in vitro fertilization–embryo transfer in gonadotropin-releasing hormone antagonist cycles (1). Full-Text PDF