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IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study.

ABSTRACT: OBJECTIVE: To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol. DESIGN: A prospective, randomized and controlled study. SETTING: ART center of a state public hospital PATIENT(S): Two hundred twenty infertile women underwent IVF/ICSI treatments. INTERVENTION(S): Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E(2) pre-treatment group n=109) or received standard long GnRH agonist protocol as control group (n=111). MAIN OUTCOME MEASURE(S): Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles. RESULT(S): E(2) pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E(2) pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E(2) pre-treatment group had elevated LH at all time (>or= 10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E(2) pre-treatment and control groups. CONCLUSION(S): Luteal E(2) pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E(2) pre-treatment during COH has no negative effect on the IVF/ICSI outcomes.

SUBMITTER: Ye H

PROVIDER: S-EPMC2654939 | biostudies-other | 2009 Mar

REPOSITORIES: biostudies-other

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Project description:Cycles with progesterone elevation during controlled ovarian stimulation (COS) for IVF/ICSI are commonly managed with a "freeze-all" strategy, due to a well-recognized detrimental effect of high progesterone levels on endometrial receptivity. However, also a detrimental effect of elevated progesterone on day-3 embryo quality has recently been found with regards to top quality embryo formation rate. Because blastocyst culture and cryopreservation are largely adopted, we deemed relevant to determine whether this detrimental effect is also seen on blastocyst quality on day 5-6. This issue was investigated through a large two-center retrospective study including 986 GnRH antagonist IVF/ICSI cycles and using top quality blastocyst formation rate as the main outcome. Results showed that on multivariate analysis sperm motility (p<0.01) and progesterone levels at ovulation triggering (p = 0.01) were the only two variables that significantly predicted top quality blastocyst formation rate after adjusting for relevant factors including female age, BMI, basal AMH and total dose of FSH used for COS. More specifically, progesterone levels at induction showed an inverse relation with top quality blastocyst formation (correlation coefficient B = -1.08, 95% CI -1.9 to -0.02) and ROC curve analysis identified P level >1.49 ng/ml as the best cut-off for identification of patients at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study is the first to investigate the top quality blastocyst formation rate in relation to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone is associated with lower rates of top quality blastocyst. Hence, the advantages of prolonging COS to maximize the number of collected oocytes might eventually be hindered by a decrease in top quality blastocysts available for transfer, if increasing progesterone levels are observed. This observation extends the results of two recent studies focused on day-3 embryos and deserves further research.

Project description:IntroductionThe use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer.Material and methodsWe conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates.ResultsA total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54).ConclusionGnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS improved the luteal phase deficiency reported in the first GnRHa trigger studies. However, LPS optimization is needed to further limit OHSS in the subgroup of normoresponder patients (<14 follicles???11?mm).Prospero registration numberCRD42016051091.

Project description:BackgroundMany factors from the oocyte/sperm or the process of fertilization may affect the zygote formation. The zygote score (Z-score) describes the quality of a human zygote based on its pronuclear morphology, nucleolar precursor bodies, and alignment of polar bodies, and it can be used in the selection process at the zygote stage for embryo transfer or cryopreservation.ObjectiveThe aim of this retrospective cohort study was to investigate the relationship between different controlled ovarian stimulation (COS) protocols and the zygote score (Z-score) and to assess the feasibility of the Z-score for predicting embryo survival in the GnRH-antagonist (GnRH-ant) protocol.MethodsIt is a retrospective, single-center cohort study. A total of 3,826 zygotes with normal fertilization were analyzed from 744 in vitro fertilization /intra-cytoplasmic sperm injection (IVF/ICSI) cycles (long protocol n = 392; GnRH-ant n = 352) between Jan 2010 and April 2014 in the IVF unit of Chang-Gung Memorial Hospital Kaohsiung Medical Center.ResultsThe Z-score distribution differed significantly between these two protocols. The overall Z-score was poorer for zygotes from GnRH-ant cycles (p<0.05). Univariate and multivariate analyses indicated the type of COS protocol is one of the main determinants of Z-score grading. Our study found good-quality day 3 embryo/blastocyst formation and the cumulative embryo survival rate were correlated with the Z-score but not the COS protocol. With the GnRH-ant protocol, the number of Z1 in the transferred cohort embryos was significantly correlated with the clinical pregnancy rate (r = 0.976; p = 0.024) and live birth rate (r = 0.971; p = 0.029). This correlation was not seen with the long protocol.ConclusionsThe Z-score distribution for the GnRH antagonist cycles was poorer than that of the long protocol, but the Z-score system is a valuable parameter for predicting embryo viability in the GnRH-ant protocol, providing a strong correlation with the clinical pregnancy rate and live birth rate.

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IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study.

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