P–761 Can modified luteal support in fresh cycle after agonist trigger “rescue” the cumulative live birth rate (CLBR) in high responders

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
D Chowdhury ◽  
Y Kopeika

Abstract Study question Can modified luteal support in fresh cycle “rescue” the cumulative live birth rate (CLBR) in high responders who receive agonist trigger? Summary answer Live birth rate in high responders who had agonist trigger in fresh cycle was significantly reduced despite modified luteal support. What is known already Previous studies, including small randomised controlled trials, claimed that good live birth rate could be achieved at fresh transfer in “high responders” who had GnRHa trigger with modified luteal phase support. However, majority of these studies exclude the true high responders (patients with 20 and above oocytes) and average number of collected eggs reported in many of these studies in the range of 9 to 12. The data on outcome of fresh transfer in true high responders is very limited. Study design, size, duration A prospective observational study was conducted in 407 patients, aged 23–42 years who were expected to be at risk of high response (AFC>18, AMH>20 pmol/l) undergoing controlled ovarian stimulation between 2014–2019 triggered either with HCG or GnRH agonist. Live birth rate (LBR) in a fresh and subsequent 3 frozen transfers were compared in groups with different triggers and freeze all. Participants/materials, setting, methods Patients were stimulated in short antagonist protocol. The trigger was chosen based on the background characteristics, peak oestradiol and clinician discretion. Triggering was achieved either with 0.5 mg buserelin (GnRHa) 0.5mgin 230 patients (A) or with 250 mcg of hCG(H) in 177 patients. Modified luteal support included vaginal progesterone, oral oestrogen and 1500 iu of hCG on the day of egg retrieval. The later was omitted with more than 20 oocytes. Main results and the role of chance The mean age, AFC, number of previous cycles, number of embryos transferred were 33.3, 22.4, 0.26 and 1.2 respectively and did not have significant difference between different triggers. Whereas AMH (53 pmol/l (A) vs 43.1 pmol/l (H), P = 0.003), peak oestradiol (15140.74 (A) vs 9738.59 (H), P = 5.59X10–14), and number of oocytes collected (21 vs.17, P = 5.63X10–7) were significantly higher in GnRHa group. Seventeen patients in buserelin group had elective freeze all. Ovarian Hyperstimulation Syndrome (OHSS) rate was 3.9% in buserelin group (more then half of these cases had a bolus of hCG at egg collection; most were mild/moderate). On the other hand, hCG group had 2.5% of OHSS (all severe). Live birth rate in fresh cycle was 31% in hCG and 21% in GnRHa groups. If freeze all was undertaken in fresh cycle after GnRHa trigger, then LBR in the first frozen cycle of this group was 53% (P = 0.003, fresh vs frozen GnRHa group). CLBR was not different between GnRHa and hCG groups (51%). However, this was significantly lower than CLBR in GnRHa trigger freeze all group 76% (P = 0.03) Limitations, reasons for caution The limitation of this study is its non-randomised nature. However, since it is one of the biggest studies for high responders it has a power to minimise bias by adjusting for multiple variables. Wider implications of the findings: Proceeding with fresh transfer in high responders after GnRHa trigger with modified luteal support not only maintains the risk of OHSS (equivalent to hCG group) but also significantly impairs the LBR not compensated even after 3 subsequent frozen embryo transfers. Therefore, freeze-all approach should be preferred in this group. Trial registration number NA

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M J Chen ◽  
C Ya-Fang ◽  
G Hwa-Fen ◽  
Y Yu-Chiao ◽  
K Hsioa-Fan ◽  
...  

Abstract Study question Is there a suitable range of serum progestereone level at triggering day to optimize the cumulative live birth rate (LBR) in high responders? Summary answer Fom the point of view of cLBR, the optimal P4 range for triggering is between 1.5 to 2.5 ng/ml generally and in the high responders. What is known already It is well established that premature progesterone rise (PPR) affect adversely the pregnancy outcome in fresh embryo transfer cycle. It is inferred that PPR alters synchrony between endometrium and the embryos. However, detailed study of the effect of PPR on efficiency of oocyte retrieval , embryo quality and the subsequent cumulative pregnancy outcome is still lacking. Hence we sort to analyze the effect of PPR on the final cumulative LBR in our program especially focused on high responders. Study design, size, duration ART Database in our center was retrospectively reviewed. Total 1523 cycles between 20160101 and 20191231 were recruited under the condition of GnRH antagonist cycle with duration of ovulation induction for more than 5 days and available serum P4 level data on triggering day for data analysis for the relationship between serum P4 value and final cumulative LBRs. Participants/materials, setting, methods Cycles with serum P4 level < 1.5 ng/ml were defined as without PPR (Group A: n = 1383). Cycles with serum P4 level >1.5 were defined as with PPR: P4 between 1.5 and 2.5 as Group B (n = 113), P4 > 2.5 as Group C (n = 27). Those high responding cycles (n = 404) were analyzed similarly and separately as Group A’ (n = 304), B’ (n = 81) and C’(n = 19). The statistics were carried out by SPSS-PC ver. 22.0 with p < 0.05 as statistical significance. Main results and the role of chance Group A had significantly lower number of oocytes (9.8 + 8.0) retrieved as compared to Group B (19.3 + 11.2) and Group C (18.2 + 9.9). However there were no differences in fertilization rate, good embryo rates and BC formation rates between groups. The cumulative LBR (cLBR) were significantly higher in Group B (65.1%) as compared to Group A (40.9%, p < 0.001) and Group C (37.0%, p = 0.008). For the high responding cycles, Group B’ also had marginally significant higher cLBR (75.3%) as compared to group A’(63.8% ; p=0.051) and Group C’ (52.6%; p = 0.050). Comparisons between Group A’ and C revealed significantly less oocytes retrieved but significantly higher blastocyst formation rates in Group A’ and the resultant cLBR were comparable between these two groups. Comparisons between Groups B’ and C’ revealed comparable oocytes retrieved but significant lower blastocyst formation rates and cLBRs in Group C’. The baseline of the first part analysis revealed higher age and lower AMH in Group A, but comparable age and AMH between groups B and C.The lower cLBR in group A could be due to selection bias.The second part (high responders) showed comparable baselines between three groups. However, the case numbers are too few in group C’ which might also result in uncertainty. Limitations, reasons for caution Although the data revealed interesting, significantly different results between groups, this is only a retrospective analysis from our ART patient series. Selection bias could not be precluded. Analysis restricted to high responders could have a more balanced population for comparisons. However, more cases are needed to affirm the findings. Wider implications of the findings: We still do not know the tolerable ceiling of serum P4 at the triggering day in high responders if future FET already planned. Pushing P4 value too high not only could not increase mature oocyte yields and possibly may decrease the number of available good blastocysts for optimizing final cLBRs. Trial registration number Not applicable


2021 ◽  
Vol 8 ◽  
Author(s):  
Fumei Gao ◽  
Yanbin Wang ◽  
Min Fu ◽  
Qiuxiang Zhang ◽  
Yumeng Ren ◽  
...  

“Dual triggering” for final oocyte maturation using a combination of a gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) can improve clinical outcomes in high responders during in vitro fertilization–intracytoplasmic sperm injection (IVF–ICSI) GnRH-antagonist cycles. However, whether this dual trigger is also beneficial to normal responders is not known. We retrospectively analyzed the data generated from 469 normal responders from 1 January to 31 December 2017. The final oocyte maturation was undertaken with a dual trigger with a GnRHa combined with hCG (n = 270) or hCG alone (n = 199). Patients were followed up for 3 years. The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen–thawed embryos) among both groups. Women in the dual-trigger group achieved a slightly higher number of oocytes retrieved (11.24 vs. 10.24), higher number of two-pronuclear (2PN) embryos (8.37 vs. 7.67) and a higher number of embryos available (4.45 vs. 4.03). However, the cumulative live-birth rate and the all-inclusive success rate for assisted reproductive technology was similar between the two groups (54.07 vs. 59.30%). We showed that a dual trigger was not superior to a hCG-alone trigger for normal responders in GnRH-antagonist cycles in terms of the cumulative live-birth rate.


2021 ◽  
Author(s):  
Fumei Gao ◽  
Yanbin Wang ◽  
Min Fu ◽  
Qiuxiang Zhang ◽  
Yumeng Ren ◽  
...  

Abstract It has been widely acknowledged that the dual triggering for final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) improve clinical outcomes in high responders during IVF-ICSI GnRH-antagonist cycles. However, it remains elusive whether this dual trigger is also benifical to the normal responders. The aim of this study was to investigate this issue. In the present study, we retrospectively analysed the data generated from a total of 469 normal responders from 1st January to 31st December 2017 and final oocyte maturation was performed with dual trigger with GnRH agonist combined hCG (n=270) or hCG alone (n=199). All the patients were followed up for three years. Cumulative live birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (fresh cycles as well as thawing cycles) among both groups. Subjects in the dual trigger group achieved a slightly higher number of oocytes retrieved (11.24 vs. 10.24), higher number of two-pronuclear embryo (2PN) (8.37 vs.7.67) and a higher number of embryos available (4.45 vs.4.03). But the cumulative live birth rate, an all-inclusive success rate for assisted reproductive technology, was similar between the two groups (54.07% vs.59.30%). This study showed that the dual trigger was not superior to only hCG trigger for normal responders in GnRH antagonist cycles in terms of cumulative live birth rate.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e042395
Author(s):  
Simone Cornelisse ◽  
Liliana Ramos ◽  
Brigitte Arends ◽  
Janneke J Brink-van der Vlugt ◽  
Jan Peter de Bruin ◽  
...  

IntroductionIn vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen–thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited.Methods and analysisWe have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients’ treatment burden.Ethics and disseminationThe study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals.Trial registration numberNetherlands Trial Register (NL 6857).


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