GnRH agonists to sustain the luteal phase in antagonist IVF cycles: a randomized prospective trial

Abstract

BackgroundThe addition of a GnRH analogue to the luteal phase in in vitro fertilization programs has been seldom proposed due to the presence of GnRH receptors in the endometrium. The aim of the study was to evaluate the effect of triptorelin addition in short antagonist cycles, compared to cycles where the only supplementation was progesterone.MethodsThe primary objective of this study was the study of the effect of Triptorelin addiction during the luteal phase on the live birth rate. Secondary objectives of efficacy were pregnancy rates and implantation rates, as well as safety in terms of OHSS risks. The study was a prospective, randomized, open study, performed in two independent Centers from July 2013 to October 2015. Patients were divided into three groups: a) Regular antagonist protocol, with only luteal progesterone; b) Antagonist protocol with luteal triptorelin as multiple injections, c) Antagonist protocol with luteal triptorelin as single bolus. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. Differences between percentages were studied using Chi-square test generalized to the comparison of several proportions.ResultsA total number of 1344 patients completed the study, 786 under the age of 35 years, and 558 over 35 years. It was observed an increase of positive HCG results, Clinical pregnancy rates and Delivery rates when triptorelin was added in the luteal phase, irrespective whether as a single bolus or five injections. This increase was statistically significant both for pregnancy rates and delivery rates. The statistic difference between pregnancies and deliveries obtained with or without luteal triptorelin reached p < 0,01. No increase of OHSS risk was observed.ConclusionsFrom this large study it appears that the concept of luteal phase supplementation should be revisited. From our study it appears that triptorelin addition to the luteal phase of antagonist cycles, either as a single bolus or using multiple injections, is a good tool to optimize ART results.Trial registrationThe study was approved by the Ethics Committee of Provincia di Bergamo (n 1203/2013).

Single-Dose Versus Multiple-Dose GnRH Agonist for Luteal-Phase Support in Women Undergoing IVF/ICSI Cycles: A Network Meta-Analysis of Randomized Controlled Trials

“…However, in addition to single-dose administration, multiple-dose protocol of GnRH agonist as a LPS protocol has become more and more common ( 16 ). Up to now, the paucity of studies directly compared single-dose versus multiple-dose GnRH agonist protocol ( 18 – 20 ) although there were relatively numerous studies directly comparing single-dose ( 16 ) or multiple-dose ( 21 – 23 ) protocol with control protocols, respectively. As a result, optimal administration strategy of GnRH agonist remains debated.…”

“All-In-One” Genetic Tool Assessing Endometrial Receptivity for Personalized Screening of Female Sex Steroid Hormones

“…Thereby, today, a lot of studies are held to select the suitable dosage, duration, and administration routes for progesterone that is typically applied for luteal phase support (Palomba et al, 2015 ; Watters et al, 2020 ). Moreover, much attention is paid to choose more effective alternatives to natural progesterone by testing various progestins and/or other hormonal combinations for endometrial receptivity maintenance during luteal phase (Abate et al, 1999 ; Yu et al, 2018 ; Brum Scheffer et al, 2019 ; Fusi et al, 2019 ; Griesinger et al, 2019 ). Importantly, most of the conclusions relative to this problem are obtained via randomized clinical trials (RCTs) and corresponding systematic reviews, retrospective observational studies, and meta-analysis.…”

“…A plenty of meta-analysis performed either for fresh, frozen, or donor embryo transfers confirms that luteal phase support exerts a significant positive effect on clinical pregnancy (Van der Linden et al, 2011 ; Palomba et al, 2015 ). Although scientific society agreed to recommend exogenous progesterone for luteal phase support, a lot of clinical trials aimed to test its synthetic analogs and various hormonal combinations to find a “golden standard” for increasing IVF effectiveness (Abate et al, 1999 ; Yu et al, 2018 ; Brum Scheffer et al, 2019 ; Fusi et al, 2019 ; Griesinger et al, 2019 ). However, search for the universal approach might not be entirely a rational strategy, as endometrium of different patients can vary significantly in the degree of maturation, expression of progesterone and estrogen receptors, and other marker molecules (Díaz-Gimeno et al, 2011 ).…”

Luteal phase support for in vitro fertilization/intracytoplasmic sperm injection fresh cycles: a systematic review and network meta-analysis

“…A Cochrane review in 2015 evaluated the relative effectiveness and safety of the available methods of LPS for women undergoing ART, and the authors found no conclusive evidence regarding progesterone, HCG or the addition of oestrogen [ 3 ]. Due to the fact that some studies were not included [ 4 – 15 ], as well as the fact that many new randomized controlled trials (RCTs) have recently been published [ 16 – 31 ], the performance of a current, updated systematic review and meta-analysis at this time is warranted. Recently, several meta-analyses have examined the efficacies of oral progesterone, subcutaneous progesterone and GnRH agonists that are used during the luteal phase [ 32 – 35 ].…”