P–184 Assisted hatching does not improve live birth rates, a prospective double-blinded randomized study

Abstract Study question Does Assisted hatching (AH) improve success rates when applied to frozen embryo transfers? Summary answer AH does not improve implantation, ongoing pregnancy or live birth rates when applied to thawed embryos. What is known already Vitrification has been proven to be the most efficient technique to preserve human embryos. However, vitrification has some consequences for the embryos, zona pellucida (ZP) hardening being one of them. Multiple studies suggest the need to apply laser Assisted hatching or ZP thinning to thawed embryos in order to improve success rates. Still, there is not enough evidence to ensure the utility of AH, and considering the great variation in design between studies more evidence is needed. Study design, size, duration Study performed from October 2019 and January 2020. Disregarding embryos with natural Hatching and PGT-A. Embryos that, immediately after thawing, were completely expanded (trophectoderm in contact with ZP) were also excluded from the study. We applied a randomization to choose in which embryos we had to perform AH. Neither the gynecologist nor the embryologist performing the embryo transfer knew whether the embryo had AH performed or not. Participants/materials, setting, methods 353 frozen embryo transfers of one blastocist were considered for the study, 71 excluded for expansion after thawing, 65 excluded because of PGT-A, 103 in which we performed AH (AH+) and 114 without AH (AH-). In the AH+ group we performed laser-AH of 1/3 of the ZP, avoiding to damage the trophectoderm and performing the laser shots as far away to the ICM as possible. We used Chi-square testing to assess the effects of AH. Main results and the role of chance We assessed all relevant clinical data parameters. No statistical differences were found in egg age, maternal age, embryo quality, nor endometrial thickness between groups. Implantation and miscarriage rates were equivalent between AH+ group (40.9%; 20.5%) and AH- group (47.4%; 18.5%). The main outcome of this study was live birth rates. No statistical differences were found between groups (AH-= 38.6%; AH + = 30.1%; p = 03221) proving that making it easier to get out of the ZP does not affect success rates. Analyzing the data from the excluded embryos we found no improvement on live birth rates when embryos were expanded just after thawing (38.0%; p = 0.457). As expected, PGT-A embryos yielded higher live birth rates (52.3%; p < 0,05) Limitations, reasons for caution Preliminary study with a small data set. Wider implications of the findings: This study suggest that thawed embryos have the capacity to get out of the ZP regardless if AH was performed or not. Having no positive effects, AH seems to be unnecessary in this scenario. Trial registration number Not applicable

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O-014 How effective is oocyte cryopreservation?

Human Reproduction ◽

10.1093/humrep/deab125.063 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

A Cobo

Keyword(s):

Cancer Patients ◽

Live Birth ◽

Ovarian Reserve ◽

Oocyte Retrieval ◽

Success Rates ◽

Birth Rates ◽

Oocyte Vitrification ◽

Live Birth Rates ◽

Cumulative Live Birth ◽

Different Populations

Abstract text The challenge of cryopreserve, store for prolonged period, and successfully implant the female gamete is nowadays feasible thanks to vitrification. The technology that was initially validated in oocyte recipients is currently applied to a vast population, including women at risk of losing their ovarian function due either to iatrogenic causes as occurs in cancer patients, or due to the natural depletion of the ovarian reserve as a result of age related fertility decline. That is the case of a growing population of women who wish to postpone childbearing and decide on oocyte vitrification as a means of fertility preservation (FP). At present, there is a growing body of evidence regarding the use of vitrified oocytes by many women under different indications, which makes it possible to evaluate the approach from different scenarios. So that vitrification can be evaluated in terms on survival rates, embryo development and the rate at which vitrified oocytes develop into live-born children in IVF cycles using vitrified oocytes which were initially stored due to different reasons. The effects of vitrification at the subcellular level and its impact on oocyte competence is of interest in the evaluation of the efficacy of the technology. Some studies have indicated that vitrification may affect ultrastructure, reactive oxygen species (ROS) generation, gene expression, and epigenetic status. However, it is still controversial whether oocyte vitrification could induce DNA damage in the oocytes and the resulting early embryos. Recent studies show that oocytes survival and clinical outcome after vitrification can be impaired by patients’ age and the clinical indication or the reason for vitrification. These studies show that age at oocyte retrieval strongly affects the survival and reproductive prognosis. In our experience, oocyte survival, pregnancy and cumulative live birth rates are significantly higher when patients are aged 35 years or younger versus patients older than 35 years at oocyte retrieval. Therefore, elective-FP patients should be encouraged to decide at young ages to significantly increase their chances of success. There is also evidence that the reason for vitrification is associated to the success rates. Poorer reproductive outcome was reported in cancer patients, low responders and endometriosis patients when compared to healthy women in age matching groups. Moreover, there are certain individualities linked to specific populations, as occurs when endometriosis patients had cystectomy earlier than the oocyte retrieval for FP. These women achieved lower success rates as compared to non-operated age matching counterparts. In this case, the lower cumulative live birth rates observed in operated women are, most probably, due to the smaller number of oocytes available, as a consequence of the detrimental effect of the surgery on the ovarian reserve. In this regard, several reports show that the number of oocytes available per patient is another variable closely related to the outcome in all populations using vitrified oocytes after FP. Thus, a significant improvement in the cumulative live birth rates can be achieved by adding a few oocytes, especially in healthy young patients. Different populations using vitrified oocytes under several indications achieve differential results in terms of pregnancy rates, when calculated in overall. Nonetheless, when the calculations for the cumulative probability of achieving a baby are made according the number of oocytes used per patient belonging to the same group of age, the results become comparable between different populations, as shown by the comparison between elective freezers versus endometriosis patients. Undoubtedly, vitrification can be recognized as one of the latest brakethrough in the ART field, but certainly the next step forward would be the successfull automatization of the vitrification and warming processes to achieve fully consistency among different laboratories.

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P–183 Air quality oscillations inside the IVF laboratory do not affect clinical outcomes

Human Reproduction ◽

10.1093/humrep/deab130.182 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

J Mass. Hernaez ◽

V Montalvo ◽

A Garcia-Faura ◽

B Marques ◽

M López-Teijón

Keyword(s):

Live Birth ◽

Active Carbon ◽

Clinical Results ◽

Success Rates ◽

Air Contaminants ◽

Birth Rates ◽

Fertilization Rates ◽

Live Birth Rates ◽

Implantation Rates

Abstract Study question Do air contaminant oscillations impair in vitro fertilization clinical results? Summary answer Oscillations of the main air contaminants (SO2, NO, NO2, O3, CO, PM10, C6H6) inside the IVF laboratory do not impair success rates. What is known already Pollution is a challenge that as humans we face around the world. Given the limited number of studies that demonstrate the effect of pollution into IVF treatments, the effect that air contaminants have on in vitro human gametes/embryos is not clear. IVF laboratories are designed to limit the stress that gametes and embryos suffer during culture and manipulation. Controlling temperature, humidity, light, and filtering the air is essential to have a successful IVF program. However, HEPA and active carbon filters are not enough to ensure that gametes/embryos are not exposed to contaminants, exposing them to potentially harmful gases and particles. Study design, size, duration Prospective study comprising treatments throughout 2019, recording levels of the main air contaminants (SO2, NO, NO2, O3, CO, PM10, C6H6) every 10 minutes inside the IVF laboratory in order to assess the effect of these pollutants. We included egg donor cycles without PGT-A. Participants/materials, setting, methods A total of 724 egg donation treatments were included. Using uninterrupted culture (Global, CooperSurgical) in time lapse incubators (Embryoscope, Vitrolife). A mean concentration of every pollutant during the 6 days of every treatment was calculated. We analyzed success rates such as fertilization rates, blastocyst rates, pregnancy rates, implantation rates, miscarriage rates, and live birth rates. Main results and the role of chance Our results show that no contaminant affects neither fertilization rates nor good quality blastocyst rates. The only pollutants that have an association with pregnancy rates are NO and CO (p = 0.014 y p = 0.021) in both the univariate and the multivariate statistical analysis. Still, this association is week and could be explained due to the large data set. When analyzing further data we do not find any association between the dose of contaminants and implantation rates, miscarriage rates nor live birth rates (p > 0.01) demonstrating that oscillations in levels of these contaminants do not affect clinical results. Our results differ with the results from a previous study where they detected an effect of SO2 and O3 when analyzing frozen embryo transfer results. This might be explained because the levels of these gases were lower in our clinic and the pregnancy and live birth rates are higher. Limitations, reasons for caution Although we measured the levels of the contaminants inside the IVF laboratory, we did not measure the levels inside the incubators. Wider implications of the findings: This results show that IVF success rates are not impaired by oscillations in air quality if the laboratory does use the necessary HEPA and active-carbon air filter systems. Trial registration number Not applicable

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Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles

BMC Medicine ◽

10.1186/s12916-019-1429-z ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 3

Author(s):

Andrew D. A. C. Smith ◽

Kate Tilling ◽

Deborah A. Lawlor ◽

Scott M. Nelson

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Lower Risk ◽

Rate Ratio ◽

Perinatal Outcomes ◽

In Vitro Fertilisation ◽

Birth Rates ◽

Live Birth Rates ◽

Frozen Embryo Transfers

Abstract Background It is not known whether segmentation of an in vitro fertilisation (IVF) cycle, with freezing of all embryos prior to transfer, increases the chance of a live birth after all embryos are transferred. Methods In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated the impact of segmentation, compared with initial fresh embryo followed by frozen embryo transfers, on live birth rate and perinatal outcomes. We used generalised linear models to assess the effect of segmentation in the whole cohort, with additional analyses within women who had experienced both segmentation and non-segmentation. We compared rates of live birth, low birthweight (LBW < 2.5 kg), preterm birth (< 37 weeks), macrosomia (> 4 kg), small for gestational age (SGA < 10th centile), and large for gestational age (LGA > 90th centile) for a given ovarian stimulation cycle accounting for all embryo transfers. Results We assessed 202,968 women undergoing 337,148 ovarian stimulation cycles and 399,896 embryo transfer procedures. Live birth rates were similar in unadjusted analyses for segmented and non-segmented cycles (rate ratio 1.05, 95% CI 1.02–1.08) but lower in segmented cycles when adjusted for age, cycle number, cause of infertility, and ovarian response (rate ratio 0.80, 95% CI 0.78–0.83). Segmented cycles were associated with increased risk of macrosomia (adjusted risk ratio 1.72, 95% CI 1.55–1.92) and LGA (1.51, 1.38–1.66) but lower risk of LBW (0.71, 0.65–0.78) and SGA (0.64, 0.56–0.72). With adjustment for blastocyst/cleavage-stage embryo transfer in those with data on this (329,621 cycles), results were not notably changed. Similar results were observed comparing segmented to non-segmented within 3261 women who had both and when analyses were repeated excluding multiple embryo cycles and multiple pregnancies. When analyses were restricted to women with a single embryo transfer, the transfer of a frozen-thawed embryo in a segmented cycles was no longer associated with a lower risk of LBW (0.97, 0.71–1.33) or SGA (0.84, 0.61–1.15), but the risk of macrosomia (1.74, 1.39–2.20) and LGA (1.49, 1.20–1.86) persisted. When the analyses for perinatal outcomes were further restricted to solely frozen embryo transfers, there was no strong statistical evidence for associations. Conclusions Widespread application of segmentation and freezing of all embryos to unselected patient populations may be associated with lower cumulative live birth rates and should be restricted to those with a clinical indication.

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