Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval.
To evaluate a single treatment center's experience with autologous IVF using vitrified and warmed oocytes, including fertilization, embryonic development, pregnancy, and birth outcomes, and to estimate the likelihood of live birth of at least one, two, or three children according to the number of mature oocytes cryopreserved by elective fertility preservation patients.
Retrospective cohort study.
Private practice clinic.
Women undergoing autologous IVF treatment using vitrified and warmed oocytes. Indications for oocyte vitrification included elective fertility preservation, desire to limit the number of oocytes inseminated and embryos created, and lack of available sperm on the day of oocyte retrieval.
Oocyte vitrification, warming, and subsequent IVF treatment.
Post-warming survival, fertilization, implantation, clinical pregnancy, and live birth rates.
A total of 1,283 vitrified oocytes were warmed for 128 autologous IVF treatment cycles. Postthaw survival, fertilization, implantation, and birth rates were all comparable for the different oocyte cryopreservation indications; fertilization rates were also comparable to fresh autologous intracytoplasmic sperm injection cycles (70% vs. 72%). Implantation rates per embryo transferred (43% vs. 35%) and clinical pregnancy rates per transfer (57% vs. 44%) were significantly higher with vitrified-warmed compared with fresh oocytes. However, there was no statistically significant difference in live birth/ongoing pregnancy (39% vs. 35%). The overall vitrified-warmed oocyte to live born child efficiency was 6.4%.
Treatment outcomes using autologous oocyte vitrification and warming are as good as cycles using fresh oocytes. These results are especially reassuring for infertile patients who must cryopreserve oocytes owing to unavailability of sperm or who wish to limit the number of oocytes inseminated. Age-associated estimates of oocyte to live-born child efficiencies are particularly useful in providing more explicit expectations regarding potential births for elective oocyte cryopreservation.
Doyle JO
，Richter KS
，Lim J
，Stillman RJ
，Graham JR
，Tucker MJ
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Oocyte vitrification as an efficient option for elective fertility preservation.
To provide a detailed description of the current oocyte vitrification status as a means of elective fertility preservation (EFP).
Retrospective observational multicenter study.
Private university-affiliated center.
A total of 1,468 women who underwent EFP because of age or having associated a medical condition other than cancer (January 2007 to April 2015).
None.
Survival and cumulative live birth rate (CLBR) per consumed oocyte.
Mean age was higher with EFP due to age versus having an associated medical reason (37.7 y [95% confidence interval (CI) 36.5-37.9] vs. 35.7 y [95% CI 34.9-36.3]). In total, 137 patients (9.3%) returned to use their oocytes. Overall survival rate was 85.2% (95% CI 83.2-87.2). Live birth rate per patient was higher in women ≤35 years old than ≥36 years old (50% [95% CI 32.7-67.3] vs. 22.9% [95% CI 14.9-30.9]). CLBR was higher and increased faster in younger women. The gain in CLBR was sharp from 5 (15.4%, 95% CI -4.2 to 35.0) to 8 oocytes (40.8%, 95% CI 13.2-68.4), with an 8.4% gain per additional oocyte, in the ≤35-year-old group. The increase was slower with 10-15 oocytes, reaching a plateau CLBR of 85.2%. A milder increase (4.9% gain) was observed in the ≥36-year-old group (from 5.1% [95% CI -0.6 to 10.7] to 19.9% [95% CI 8.7-31.1] when 5-8 oocytes were consumed), reaching the plateau with 11 oocytes (CLBR 35.6%). Forty babies were born.
At least 8-10 metaphase II oocytes are necessary to achieve reasonable success. Numbers should be individualized in women >36 years old. We suggest encouraging women who are motivated exclusively by a desire to postpone childbearing because of age, to come at younger ages to increase success possibilities.
Cobo A
，García-Velasco JA
，Coello A
，Domingo J
，Pellicer A
，Remohí J
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Efficiency and efficacy of vitrification in 35 654 sibling oocytes from donation cycles.
Is oocyte vitrification/warming as efficient and effective as using fresh oocytes in donation cycles?
IVF with vitrified donor oocytes is less efficient than using fresh oocytes, but its efficacy remains comparable to that of fresh cycles.
Oocyte vitrification is used to preserve the reproductive potential of oocytes. A small number of randomized controlled trials carried out by experienced groups have shown that this technique provides fertilization, pregnancy, implantation and ongoing pregnancy rates comparable to those of fresh oocytes. However, large registry-based analyses have consistently reported lower live birth rates (LBRs) in cycles using vitrified oocytes. It is not clear whether this decrease may be due to the effect of vitrification per se on the oocytes or to the lower efficiency of the technique, as some of the oocytes do not survive after warming.
Retrospective cohort analysis of 1844 cycles of oocyte donation (37 520 oocytes), each donor in the study provided enough oocytes for at least one reception cycle with fresh oocytes (2561 cycles) and one reception cycle with vitrified oocytes (2471 cycles) from the same ovarian stimulation (sibling oocytes). Overall, 35 654 oocytes were considered in the analysis. All embryo transfers (n = 5032) were carried out between 2011 and 2017.
Differences in reproductive outcomes after the first embryo transfer were evaluated using Pearson's Chi-squared test and regression analysis adjusted for recipient's age, BMI, sperm origin and state, day of embryo transfer, morphological score and number of transferred embryos. We performed two additional sub-analyses, to test whether the efficiency and/or effectiveness of vitrification/warming impacts reproductive results. One analysis included paired cycles where the same number of fresh and vitrified oocytes were available for ICSI (SAME sub-analysis), while the second analysis included those cycles with a 100% survival rate post-warming (SAME100 sub-analysis).
Baseline and cycle characteristics of participants were comparable between groups. Overall, fertilization rates and embryo morphological scores were significantly lower (P < 0.001) when using vitrified oocytes; moreover, vitrified oocytes also resulted in lower reproductive outcomes than sibling fresh oocytes using both unadjusted and adjusted analyses: ongoing pregnancy (32.1% versus 37.5%; P < 0.001; OR 0.88, 95% CI 0.77, 1.00) and live birth (32.1% versus 31.9%; P = 0.92; OR 1.16, 95% CI 0.90, 1.49). However, when the efficiency of warming was taken into account, reproductive outcomes in recipients became comparable: ongoing pregnancy (33.5% versus 34.1%; P = 0.82; OR 1.11, 95% CI 0.87, 1.43) and LBR (32.1% versus 32%; P = 0.97; OR 1.15, 95% CI 0.89, 1.48). Moreover, after selecting only cycles that, in addition to having the same number of oocytes available for ICSI, also had 100% post-warming survival rate in the vitrified group, reproductive outcomes were also comparable between fresh and vitrified oocytes: ongoing pregnancy (34.8% versus 32.4%; P = 0.42; OR 1.32, 95% CI 0.98, 1.77) and live birth (32.9% versus 31.0%; P = 0.52; OR 1.27, 95% CI 0.95, 1.71), indicating that reproductive outcomes of these cycles are affected by the efficiency of the vitrification/warming technique performed rather than the oocyte damage due to the fast cooling process to which oocytes are subjected.
An open vitrification system was used for all cases, and oocyte vitrification/warming was performed by experienced embryologists with consistently high survival rates; caution must be exerted when extrapolating our results to data obtained using other open vitrification systems, closed vitrification systems or to IVF units with survival rates <90%.
This is the largest cohort study comparing reproductive outcomes of vitrified and fresh sibling donor oocytes to date. We found that, when the number of oocytes available after warming is equal to the number of fresh oocytes, reproductive results including live birth are comparable. Consequently, the efficiency of vitrification must be taken into account to achieve the same reproductive outcomes as with fresh oocytes. We recommend implementing strict indicators of vitrification/warming efficiency in clinics and refining vitrification/warming protocols to maximize survival.
This work was supported by intramural funding of Clínica EUGIN and by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia (GENCAT 2015 DI 048). The authors declare no conflicts of interest.
N/A.
Cornet-Bartolomé D
，Rodriguez A
，García D
，Barragán M
，Vassena R
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The number of oocytes associated with maximum cumulative live birth rates per aspiration depends on female age: a population study of 221 221 treatment cycles.
What is the number of oocytes where the maximum cumulative live birth rate per aspiration (CLBR) is observed during ART in women of different ages?
The maximum CLBR was observed when around 25 oocytes were retrieved in women between 18-35 years of age, around 9 oocytes in women more than 45 years of age and continued to increase beyond 30 oocytes in women between 36-44 years of age.
The live birth rate per fresh or frozen/thaw embryo transfer (FET) procedure has traditionally been the main measure of ART success. However, with the introduction of highly efficient embryo cryopreservation methods, CLBR encompassing live delivery outcomes from the fresh and all subsequent FET following a single ovarian stimulation and oocyte collection is increasingly viewed as a more meaningful measure of treatment success. There is evidence suggesting that larger oocyte yields are associated with increased likelihood of cumulative live birth per aspiration. Whether this association is the same across female ages has not yet been properly investigated.
This is a large retrospective population-based cohort study using data from the Australian and New Zealand Assisted Reproduction Database (ANZARD). ANZARD contains information from all ART treatment cycles carried out in all fertility centres in Australia and New Zealand. Overall, 221 221 autologous oocyte aspiration cycles carried out between January 2009 to December 2015 were included in the analysis.
Cumulative live birth per aspiration was defined as at least one liveborn baby at ≥20 weeks gestation resulting from an ART aspiration cycle, including all fresh and FET resulting from the associated ovarian stimulation, until one live birth occurred or all embryos were used. Cycles where no oocytes were retrieved were excluded from analysis as there is no possibility of live birth. Analyses of data were performed using generalized estimating equations to account for the clustered nature of data (multiple cycles undertaken by a woman). Univariate and multivariable regression analysis was performed to identify and adjust for factors known to independently affect cumulative live birth per aspiration. An interaction term between female age and the number of oocytes retrieved was included to assess whether the age of the women was associated with a different optimal number of oocytes to achieve at least one live birth from an aspiration cycle (i.e. the effect-modifying role of female age). The likelihood of cumulative live birth per aspiration was calculated as odds ratios (ORs) with 95% CI.
The median number of oocytes retrieved was 7 (interquartile range, 4-12) and median age of patients was 36 (interquartile range, 33-40). The overall CLBR was 32.2%. The results from the multivariable regression analysis showedthat the number of oocytes retrieved remained a significant predictor (P < 0.001) of cumulative live birth per aspiration after adjusting for female age, parity and cycle count. Compared to the reference group of 10-14 oocytes retrieved, the adjusted odds for cumulative live birth per aspiration increased with the number of oocytes retrieved: 1-3 oocytes, 0.21 (95% CI, 0.20-0.22); 4-9 oocytes, 0.56 (95% CI, 0.55-0.58); 15-19 oocytes, 1.38 (95% CI, 1.34-1.43); 20-24 oocytes, 1.75 (95% CI, 1.67-1.84); and 2.10 (95% CI, 1.96-2.25) with more than 25 oocytes. After stratifying by female age group, the rate of increase in CLBR per additional oocyte retrieved was lower in the older age groups, indicating that higher oocyte yields were more beneficial in younger women. CLBR of patients in the <30 years and 30-34 years age groups appeared to reach a plateau (with only minimal increase in CLBR per additional oocyte retrieved) after retrieval of 25 oocytes at 73% and 72%, respectively, while CLBR of patients in the 35-39 years and 40-44 years age groups continued to increase with higher oocyte yields, reaching 68% and 40%, respectively, when 30 or more oocytes were retrieved. CLBR of patients aged 45 years and above remained consistently below 5%. Findings suggest that the number of oocytes retrieved where CLBR appears to be maximized is around 25 in women between 18-35 years, more than 30 in women between 36-44 years and around 9 in women 45 years and older. However, results for women aged 45 years and older may not be as robust due to the relatively small sample size available in this age group.
As with all large retrospective database studies, there are potential confounders that cannot be accounted for. Despite the current study being based on complete ascertainment of ART cycles across two countries, ovarian stimulation protocols, oocyte quality parameters and a number of important patient characteristics are not collected by ANZARD. Additionally, a small number of cycles were available for women over 45 years yielding more than 15 oocytes, making these estimates unreliable.
The results from this study demonstrate that the number of oocytes retrieved where the maximum CLBR is observed during ART is dependent on female age. This provides information for clinicians and patients to understand the modifying effect of age on the number of oocytes retrieved and the likelihood of success with ART.
No external funding was used for this study. The Fertility Society of Australia funds the National Perinatal Epidemiology and Statistics Unit to manage ANZARD and conduct national reporting of ART in Australia and New Zealand. Associate Professor Georgina Chambers (G.C.) is employed by the University of New South Wales (UNSW) and is director of the National Perinatal Epidemiology and Statistics Unit at UNSW. G.C. was also a paid member of the Australian governments Medicare Benefits Scheme taskforce on assisted reproductive technologies in 2017.
Law YJ
，Zhang N
，Venetis CA
，Chambers GM
，Harris K
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ResearchGate
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