scholarly journals Comparison of Reproductive Outcomes on addition of GnRH agonist for Luteal phase Support in Antagonist IVF cycle

2021 ◽  
Vol 25 (3) ◽  
pp. 55-64
Author(s):  
LUKMAN OMOKANYE
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Safrai ◽  
S Hertsberg ◽  
A Be Meir ◽  
B Reubinoff ◽  
T Imbar ◽  
...  

Abstract Study question Can luteal oral Dydrogesterone (Duphaston) supplementation in an antagonist cycle after a lone GnRH agonist trigger rescue the luteal phase, allowing the possibility to peruse with fresh embryo transfer? Summary answer Functionality of the luteal phase in an antagonist cycle after a lone GnRH agonist trigger can be restored by adding Duphaston to conventional luteal support. What is known already Ovarian hyperstimulation syndrome (OHSS) is dramatically reduced when using antagonist cycle with lone GnRH agonist trigger before ovum pick up. This trigger induces short luteinizing hormone (LH) and follicle-stimulating hormone (FSH) peaks, associated with reduced progesterone and estrogen levels during the luteal phase. They cause an inadequate luteal phase and a significantly reduced implantation rate leading to a freeze all practice in those cycles. Study design, size, duration A retrospective cohort study. The study group (n = 123) included women that underwent in vitro fertilization cycles from January 2017 to May 2020. Patients received a GnRH-antagonist with a lone GnRH-agonist trigger due to imminent OSHH. The control group (n = 374) included patients under 35 years old that, during the same time period, underwent a standard antagonist protocol with a dual trigger of a GnRH-agonist and hCG. Participants/materials, setting, methods Study patients were given Dydrogesterone (Duphaston) in addition to micronized progesterone vaginal pills (Utrogestan) for luteal support (Duphaston group). Controls were treated conventionally with Utrogestan for luteal phase support (hCG group). The outcomes measured were pregnancy rate and OHSS events. Main results and the role of chance Our study was the first to evaluate the addition of Duphaston to standard luteal phase support in an antagonist cycle triggered by a lone GnRH agonist before a fresh embryo transfer. The mean number of oocytes retrieved and estradiol plasma levels were significantly higher in the Duphaston group than in the hCG group (16.9 ±7.7 vs. 10.8 ± 5.3 and 11658 ± 5280 pmol/L vs. 6048 ± 3059 pmol/L, respectively). The fertilization rate was comparable between the two groups. The mean number of embryos transferred and the clinical pregnancy rate were also comparable between groups (1.5 ± 0.6 vs 1.5 ± 0.5 and 46.3% vs 40.9%, respectively). No OHSS event was reported in either group. Limitations, reasons for caution This retrospective study may carry an inherent selection and information bias, derived from medical record coding. An additional limitation was the choice of physician for the lone GnRH trigger, which may have introduced a selection bias and another potential caveat was the relatively small sample size of our study groups. Wider implications of the findings: The addition of Duphaston to conventional luteal support could effectively salvage the luteal phase without increasing the risk for OHSS. This enables, to peruse in those cycle, with fresh embryo transfer, avoiding the need to freeze all the embryos and postponed embryo transfer. Leading to lower psychological burden and costs. Trial registration number 0632–20-HMO


2015 ◽  
Vol 104 (3) ◽  
pp. e346 ◽  
Author(s):  
P. Casanova ◽  
E. Szlit Feldman ◽  
G.J. Rey Valzacchi ◽  
L.A. Blanco ◽  
C.A. Carrere ◽  
...  

2020 ◽  
Vol 35 (12) ◽  
pp. 2808-2818 ◽  
Author(s):  
Samuel Santos-Ribeiro ◽  
Shari Mackens ◽  
Biljana Popovic-Todorovic ◽  
Annalisa Racca ◽  
Nikolaos P Polyzos ◽  
...  

Abstract STUDY QUESTION Does the freeze-all strategy in high-responders increase pregnancy rates and improve safety outcomes when compared with GnRH agonist triggering followed by low-dose hCG intensified luteal support with a fresh embryo transfer? SUMMARY ANSWER Pregnancy rates after either fresh embryo transfer with intensified luteal phase support using low-dose hCG or the freeze-all strategy did not vary significantly; however, moderate-to-severe ovarian hyperstimulation syndrome (OHSS) occurred more frequently in the women who attempted a fresh embryo transfer. WHAT IS KNOWN ALREADY Two strategies following GnRH agonist triggering (the freeze-all approach and a fresh embryo transfer attempt using a low-dose of hCG for intensified luteal phase support) are safer alternatives when compared with conventional hCG triggering with similar pregnancy outcomes. However, these two strategies have never been compared head-to-head in an unrestricted predicted hyper-responder population. STUDY DESIGN, SIZE, DURATION This study included women with an excessive response to ovarian stimulation (≥18 follicles measuring ≥11 mm) undergoing IVF/ICSI in a GnRH antagonist suppressed cycle between 2014 and 2017. Our primary outcome was clinical pregnancy at 7 weeks after the first embryo transfer. Secondary outcomes included live birth and the development of moderate-to-severe OHSS. PARTICIPANTS/MATERIALS, SETTING, METHODS Following GnRH agonist triggering, women were randomized either to cryopreserve all good-quality embryos followed by a frozen embryo transfer in an subsequent artificial cycle or to perform a fresh embryo transfer with intensified luteal phase support (1500 IU hCG on the day of oocyte retrieval, plus oral estradiol 2 mg two times a day, plus 200 mg of micronized vaginal progesterone three times a day). MAIN RESULTS AND THE ROLE OF CHANCE A total of 212 patients (106 in each arm) were recruited in the study, with three patients (one in the fresh embryo transfer group and two in the freeze-all group) later withdrawing their consent to participate in the study. One patient in the freeze-all group became pregnant naturally (clinical pregnancy diagnosed 38 days after randomization) prior to the first frozen embryo transfer. The study arms did not vary significantly in terms of the number of oocytes retrieved and embryos produced/transferred. The intention to treat clinical pregnancy and live birth rates (with the latter excluding four cases lost to follow-up: one in the fresh transfer and three in the freeze-all arms, respectively) after the first embryo transfer did not vary significantly among the fresh embryo transfer and freeze-all study arms: 51/105 (48.6%) versus 57/104 (54.8%) and 41/104 (39.4%) versus 42/101 (41.6%), respectively (relative risk for clinical pregnancy 1.13, 95% CI 0.87–1.47; P = 0.41). However, moderate-to-severe OHSS occurred solely in the group that received low-dose hCG (9/105, 8.6%, 95% CI 3.2% to 13.9% vs 0/104, 95% CI 0 to 3.7, P < 0.01). LIMITATIONS, REASONS FOR CAUTION The sample size calculation was based on a 19% absolute difference in terms of clinical pregnancy rates, therefore smaller differences, as observed in the trial, cannot be reliably excluded as non-significant. WIDER IMPLICATIONS OF THE FINDINGS This study offers the first comparative analysis of two common strategies applied to women performing IVF/ICSI with a high risk to develop OHSS. While pregnancy rates did not vary significantly, a fresh embryo transfer with intensified luteal phase support may still not avoid the risk of moderate-to-severe OHSS and serious consideration should be made before recommending it as a routine first-line treatment. Future trials may allow us to confirm these findings. STUDY FUNDING/COMPETING INTEREST(S) The authors have no conflicts of interest to disclose. No external funding was obtained for this study. TRIAL REGISTRATION NUMBER ClinicalTrials.gov identifier NCT02148393. TRIAL REGISTRATION DATE 28 May 2014 DATE OF FIRST PATIENT’S ENROLMENT 30 May 2014


2020 ◽  
Vol 35 (1) ◽  
pp. 157-166 ◽  
Author(s):  
Lan N Vuong ◽  
Tuong M Ho ◽  
Toan D Pham ◽  
Vu N A Ho ◽  
Claus Yding Andersen ◽  
...  

Abstract STUDY QUESTION What is the early luteal phase hormonal profile in patients undergoing ovarian stimulation for IVF/ICSI followed by hCG trigger and a freeze-all strategy without luteal phase support? SUMMARY ANSWER The peak concentration of progesterone occurred 4 days after oocyte pick-up (OPU + 4), with an average 35% fall from OPU + 4 to OPU + 6, and progesterone levels before and 12 h after hCG administration predicted levels during the early luteal phase. WHAT IS KNOWN ALREADY The luteal phase during IVF differs from that during normal cycles, particularly with respect to the serum progesterone level profile. This can cause asynchrony between the embryo and the endometrium, potentially resulting in implantation failure and poor reproductive outcomes. STUDY DESIGN, SIZE, DURATION This prospective study included 161 women with normal ovarian reserve receiving GnRH antagonist co-treatment during ovarian stimulation with FSH who were followed up to 6 days after OPU in a single IVF cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged 18–42 years undergoing IVF with ovarian stimulation using FSH were included. Ovulation was triggered with recombinant hCG 250 μg. Hormone levels were determined from blood samples taken on the day of trigger, before hCG, at 12, 24 and 36 h after hCG and at 1, 2, 3, 4, 5 and 6 days after OPU. The primary endpoint was early luteal phase serum concentrations of progesterone, LH, estradiol and hCG. MAIN RESULTS AND THE ROLE OF CHANCE One outlier with a pre-hCG serum progesterone level of 11.42 ng/mL was excluded, so all analyses included 160 subjects. Progesterone levels began to increase 1 day after OPU, peaked 4 days after OPU (114 ng/mL), then declined from OPU + 5 onwards. Peak progesterone levels were at OPU + 4, OPU + 5 or OPU + 6 in 38.8, 29.4 and 13.8% of patients, respectively. Approximately two-thirds of patients had a fall in serum progesterone from OPU + 4 to OPU + 6. Pre-hCG progesterone levels correlated significantly with those at 24 h after hCG (r2 = 0.28; P < 0.001), which in turn correlated significantly with progesterone at OPU + 4 (r2 = 0.32; P < 0.001). LH peaked (4.4 IU/L) 12 h after hCG trigger, persisting for 24 h but was barely elevated compared with physiological levels. Serum estradiol peaked twice: at 24 h post-trigger and at OPU + 4. Highest hCG levels (130 mIU/mL) occurred at 24 h post-injection. The best correlations between the number of follicles ≥11 mm and serum progesterone level were seen at 24 and 36 h after hCG and OPU + 1. LIMITATIONS, REASONS FOR CAUTION The influence of different profiles of serum progesterone on reproductive outcomes could not be determined because a freeze-all strategy was used in all patients. In addition, data were not available to relate serum hormone level findings with endometrial histology or endometrial receptivity analysis to clearly identify the relationship between serum hormones and the window of implantation. WIDER IMPLICATIONS OF THE FINDINGS Detailed information about early luteal phase hormone levels could be used to optimize and individualize luteal phase support to improve reproductive outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by My Duc Hospital, Ho Chi Minh City, Vietnam. All authors state that they have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER NCT02798146; NCT03174691.


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