Day Of Oocyte Maturation Research Articles

Clinically significant intra-day variability of serum progesterone levels during the final day of oocyte maturation: a prospective study with repeated measurements

Is there significant variability in progesterone levels during the final day of oocyte maturation in women undergoing ovarian stimulation? Progesterone levels drop from the basal level up to 44% during the final day of oocyte maturation in women undergoing ovarian stimulation. It has been suggested that elevated progesterone levels on the final day of ovarian stimulation may be related to poorer outcomes in in vitro fertilization fresh cycles due to a negative impact on the endometrium. However, despite conflicting results regarding the actual effect of progesterone on pregnancy rates and the lack of a well-established cut off, currently many IVF patients have their embryo transfer deferred when progesterone values surpass a threshold of 1.5ng/ml on the day of ovulation triggering. This was a prospective cohort study conducted in 22 oocyte donors of a university-affiliated fertility centre between November 2017 and January 2018. We calculated the sample size to detect a difference of 15% between the first and last progesterone measurements with a 5% false-positive rate in a two-sided test with 80% statistical power and a 95% confidence interval (CI). Progesterone circulating levels were evaluated at four different times during the final day of oocyte maturation (08:00, 12:00, 16:00 and 20:00) before ovulation triggering in healthy oocyte donors. A flexible antagonist protocol was used, and ovarian stimulation was achieved with recombinant follicle-stimulating hormone (FSH) in all cases. The pairwise percentage differences in progesterone levels for each patient were calculated. Univariate linear regression analysis was adopted in order to evaluate variables associated with progesterone levels on the first measurement. The intra-day variability of progesterone was analysed using mixed models. Mean serum progesterone values at 08:00, 12:00, 16:00 and 20:00 were 1.75ng/ml, 1.40ng/ml, 1.06ng/ml and 0.97ng/ml. The progesterone difference between 08:00 and 20:00 was 0.77 (95% CI, 0.56-0.99), which is equivalent to a 44% decline in the mean progesterone values between the first (08:00) and the last determination (20:00; P< 0.001). Among those patients with basal (08:00) progesterone levels >1.5ng/ml (n= 10), 70% (n= 7) showed levels reduced to <1.5ng/ml on the last determination of the day (20:00). A mixed model analysis revealed that the progesterone reduction during the day was significantly associated with time and total recombinant FSH dose administered. Only young healthy oocyte donors stimulated with an antagonist protocol using recombinant FSH were included. Extrapolation to the general IVF population, with different stimulation protocols and gonadotropins, needs to be confirmed. This study suggests that a single progesterone determination on the final day of oocyte maturation is not reliable enough to make clinical decisions due to the enormous variation in progesterone during the day. Further studies are needed to better define the impact of the follicular progesterone rise on the endometrium of IVF cycles. Funding was granted from Fundació Santiago Dexeus Font. N.P.P. received unrestricted grants and/or lectures fees from Roche Diagnostics, MSD, Merck, Ferring Pharmaceuticals, IBSA, Theramex and BESINS International, not associated with the current study. The remaining authors have no competing interests. Clinicaltrials.gov NCT03366025.

Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles.

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.

Does elevated progesterone on day of oocyte maturation play a role in the racial disparities in IVF outcomes?

The aim of this study was to evaluate if premature progesterone elevation on the last day of assisted reproduction technique stimulation contributes to racial disparities in IVF outcome. A total of 3289 assisted reproduction technique cycles were evaluated in Latino, Asian, African American, and white women. Live birth was more likely in white women (42.6%) compared with Asian (34.8%) and African American women (36.3%), but was similar to Latino women (40.7%). In all racial groups, progesterone was negatively associated with live birth and the negative effect of progesterone persisted when adjusting for confounders. Although the effect of elevated progesterone was similar in all racial groups, the prevalence of elevated progesterone differed. Progesterone > 1.5 ng/ml occurred in only 10.6% of cycles in white women compared with 18.0% in Latino and 20.2% in Asian women. Progesterone > 2 ng/ml occurred in only 2.3% of cycles in white women compared with 6.3% in Latino, 5.9% in Asian and 4.4% in African American women. The increased prevalence of premature elevated progesterone persisted when controlling for IVF stimulation parameters. In conclusion, premature progesterone elevation had a negative effect on live birth in all racial groups studied. The prevalence of elevated progesterone was higher in racial minorities.

Does prevalence and effect of elevated progesterone on the day of oocyte maturation differ by ethnicity?

Does prevalence and effect of elevated progesterone on the day of oocyte maturation differ by ethnicity?

Are good patient and embryo characteristics protective against the negative effect of elevated progesterone level on the day of oocyte maturation?

To evaluate if an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration is associated with a decrease in live-birth rate in patients with a good prognosis. Retrospective cohort study. Large, private, assisted reproductive technology (ART) practice. One thousand six hundred twenty fresh autologous ART cycles. None. Live-birth rate. A total of 934 blastocyst and 686 cleavage-stage embryo transfer (ET) cycles were evaluated. Serum P levels were not associated with markers of oocyte or embryo quality, including fertilization, embryo stage at transfer, and embryos available for cryopreservation. Patient age, stage of ET, embryo quality, the number of embryos transferred, and P level on the day of hCG administration were all significantly associated with live birth. Higher P levels were associated with decreased odds of live birth for cleavage- and blastocyst-stage embryos, poor-fair and good-quality embryos, and poor- and high-responder patients. The nonsignificance of interaction tests of P levels with embryo stage, embryo quality, patient age, and ovarian response indicated that the relationship between P level and live birth was similar regardless of these factors. An elevated serum P level on the day of hCG administration was negatively associated with live birth, even in ETs with a good prognosis.

Doppler assessment of uterine artery blood flow for the prediction of pregnancy after assisted reproduction treatment

Doppler assessment of uterine artery blood flow for the prediction of pregnancy after assisted reproduction treatment

Course of proteolytic cleavage in three classes of yolk proteins during oocyte maturation in barfin flounderVerasper moseri, a marine teleost spawning pelagic eggs

Proteolytic degradation of three classes of vitellogenin-derived yolk proteins (lipovitellin, phosvitin, and β′-component) was quantitatively examined during oocyte maturation in barfin flounder, Verasper moseri, a marine teleost which spawns pelagic eggs. Oocyte maturation takes place over 7 days at a water temperature of 6°C. Morphological changes in maturing oocytes, characterized by increasing size and transparency, occurred markedly during the latter half of oocyte maturation. Lipovitellin, which has a native molecular weight of 410,000 in post-vitellogenic oocytes, was cleaved into 170,000 fragments after the fourth day of oocyte maturation. A quantitative immunological assay showed a decline of total intact lipovitellin content in maturing oocytes of about 74%, corresponding to maturation-associated alterations of its molecular structure. An additional class of yolk protein, β′-component, also decreased in abundance during the same period. Indirect quantification of phosvitin in egg yolk, done by measuring serine content in gel chromatography fractions, demonstrated rapid degradation of this protein from the fourth to fifth day of oocyte maturation. Quantitative analysis of free amino acids in maturing oocytes showed a reverse correlation between the amount of intact forms of these three classes of yolk proteins and the water content of oocytes. All three classes of yolk proteins clearly undergo proteolytic cleavage during the latter half of oocyte maturation, possibly to provide osmotic effectors for oocyte hydration, which increases egg buoyancy, and to ensure an available stock of nutrients usable for early development. J. Exp. Zool. 278:189–200, 1997.© 1997 Wiley-Liss, Inc.