Oocyte Donation Cycles Research Articles

Day-5 fresh embryo transfer is associated with superior clinical outcomes in oocyte donation cycles compared with day-3 embryo transfer

Objective Τo compare clinical outcomes between day-5 (D5ET) and day-3 (D3ET) fresh embryo transfer in oocyte donation cycles. Study design A retrospective analysis of prospectively collected cohort data was performed enrolling all participants in an oocyte donation program performed either D5ET or D3ET regarding the period from June 2006 to June 2018. Cycles were compared by the day of embryo transfer. Primary outcomes were the clinical pregnancy rate and live birth rate. Secondary outcomes were implantation rate, biochemical pregnancy rate, early miscarriage rate, and twin pregnancy rate. Outcomes were adjusted for covariates within study groups. Results A total of 8023 cycles meeting our inclusion criteria were analyzed. D5ET consisted of 4865 cycles and D3ET of 3158 cycles. The D5ET group had a significantly higher clinical pregnancy rate (p < .001), live birth rate (p = .004), implantation rate (p < .001), and twin pregnancy rate (p = .02) than the D3ET group. Accordingly, biochemical pregnancy rate (7.4% vs. 5.1%, p < .001) and early miscarriage rate (4.1% vs. 3.2%, p = .04) were significantly higher in D3ET compared to the D5ET group. Conclusion Οocyte donation cycles with fresh D5ET resulted in fewer embryos transferred, higher clinical pregnancy rates, and higher live birth rates compared to D3ET. Our findings are strongly favoring day-5 embryo transfer in oocyte donation cycles.

PGT-A is associated with reduced cumulative live birth rate in first reported IVF stimulation cycles age ≤ 40: an analysis of 133,494 autologous cycles reported to SART CORS.

To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on cumulative live birth rate (CLBR) in IVF cycles. Retrospective cohort study of the SART CORS database, comparing CLBR for patients using autologous oocytes, with or without PGT-A. The first reported autologous ovarian stimulation cycle per patient between January 1, 2014, and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014, and December 31, 2016, were included in the study. Exclusion criteria were donor oocyte cycles, donor embryo cycles, gestational carrier cycles, cycles which included both a fresh embryo transfer (ET) combined with a thawed embryo previously frozen (ET plus FET), or cycles with a fresh ET after PGT-A. A total of 133,494 autologous IVF cycles were analyzed. Amongst patients who had blastocysts available for either ET or PGT-A, including those without transferrable embryos, decreased CLBR was noted in the PGT-A group at all ages, except ages > 40 (p < 0.01). A subgroup analysis of only those patients who had PGT-A and a subsequent FET, excluding those without transferrable embryos, demonstrated a very high CLBR, ranging from 71.2% at age < 35 to 50.2% at age > 42. Rates of multiple gestations, preterm birth, early pregnancy loss, and low birth weight were all greater in the non-PGT-A group. PGT-A was associated with decreased CLBR amongst all patients who had blastocysts available for ET or PGT-A, except those aged > 40. The negative association of PGT-A use and CLBR per cycle start was especially pronounced at age < 35.

The Future Is Coming: Artificial Intelligence in the Treatment of Infertility Could Improve Assisted Reproduction Outcomes-The Value of Regulatory Frameworks.

Infertility is a global health issue affecting women and men of reproductive age with increasing incidence worldwide, in part due to greater awareness and better diagnosis. Assisted reproduction technologies (ART) are considered the ultimate step in the treatment of infertility. Recently, artificial intelligence (AI) has been progressively used in the many fields of medicine, integrating knowledge and computer science through machine learning algorithms. AI has the potential to improve infertility diagnosis and ART outcomes estimated as pregnancy and/or live birth rate, especially with recurrent ART failure. A broad-ranging review has been conducted, focusing on clinical AI applications up until September 2022, which could be estimated in terms of possible applications, such as ultrasound monitoring of folliculogenesis, endometrial receptivity, embryo selection based on quality and viability, and prediction of post implantation embryo development, in order to eliminate potential contributing risk factors. Oocyte morphology assessment is highly relevant in terms of successful fertilization rate, as well as during oocyte freezing for fertility preservation, and substantially valuable in oocyte donation cycles. AI has great implications in the assessment of male infertility, with computerised semen analysis systems already in use and a broad spectrum of possible AI-based applications in environmental and lifestyle evaluation to predict semen quality. In addition, considerable progress has been made in terms of harnessing AI in cases of idiopathic infertility, to improve the stratification of infertile/fertile couples based on their biological and clinical signatures. With AI as a very powerful tool of the future, our review is meant to summarise current AI applications and investigations in contemporary reproduction medicine, mainly focusing on the nonsurgical aspects of it; in addition, the authors have briefly explored the frames of reference and guiding principles for the definition and implementation of legal, regulatory, and ethical standards for AI in healthcare.

IS THERE AN INFLUENCE OF RECIPIENT AGE IN OOCYTE DONATION CYCLES OUTCOMES AFTER CONSTANT OR INCREASING ESTROGEN DOSE FOR ENDOMETRIAL PREPARATION?

Endometrial preparation is a key factor for successful ART outcomes, particularly in oocyte donation (OD) cycles. Estrogen (E2) administration may follow different protocols, including E2 constant dose (CD) or increasing dose (ID), implying in differences on endometrial preparation and receptivity. Until now, no study has considered the recipient age effect on OD cycles success following CD or ID E2 administration. The objective of the present study is to investigate possible differences OD cycles outcomes after CD or ID endometrial preparation taking into consideration the recipients’ age.

THE ASSOCIATION BETWEEN OOCYTE AGE AND REPRODUCTIVE POTENTIAL IN DONOR OOCYTES BETWEEN 21 TO 32 YEARS

Evidence supports that chromosome errors in oocytes occur in a U-shape with the highest incidence at the youngest and oldest ages.1 Our objective was to compare the pregnancy rate per donor oocyte cycle by year of donor age to determine whether younger oocytes have decreased reproductive potential.

ASSESSMENT OF PREGNANCY OUTCOMES IN DONOR OOCYTE THAW CYCLES COMPARING FRESH EMBRYO TRANSFER TO CRYOPRESERVED-THAWED EMBRYO TRANSFER: A SIBLING OOCYTE STUDY

Studies evaluating donor oocyte cycles report that embryo transfers using freshly retrieved oocytes result in a higher live birth rate compared to cryopreserved-thawed oocytes.1 However, due to logistical and financial barriers, many donor oocyte recipients continue to utilize cryopreserved oocytes. Following oocyte thaw and fertilization, resulting embryos can either be transferred at that time (fresh) or the embryo cohort can be cryopreserved followed later by a thaw and embryo transfer (cryopreserved-thawed). The objective of this study was to assess the ongoing pregnancy rates among donor oocyte thaw cycles with a fresh embryo transfer compared to a cryopreserved-thawed embryo transfer.

Comparison of pregnancy outcomes of 7515 same donor oocyte cycle fresh and cryopreserved-thawed oocytes in 609 donor oocyte recipient cycles: A single institution analysis

ObjectiveOocyte donation (OD) cycles have been used extensively over the last decades due to high success regarding live birth rate (LBR). We evaluated the reproductive outcomes of fresh and vitrified sibling oocytes in terms of fertilization rates, blast ratio, clinical pregnancy rates, and LBR. Materials and methodsThis retrospective cohort study was conducted at a tertiary in vitro fertilization (IVF) center. A total of 7515 metaphase II (MII) donor oocytes from 304 donor cycles for 609 oocyte recipients undergoing embryo transfers with either fresh or cryopreserved-thawed donor oocytes. Donor cycles that provided both 12 fresh MII oocytes to be used for one recipient and at least 12 MII oocytes which were suitable for vitrification to be used for another recipient at another time were analyzed. Fertilization rates, blastocyst ratios, clinical pregnancy rates (CPR), LBR were evaluated as main outcome measures. ResultsWhen the fresh and cryopreserved-thawed OD cycles were compared, there was no significant differences between two groups in terms of age of the recipient (41.9 ± 5.7 and 40.3 ± 6.8, p = NS), number of MII oocytes (12.1 ± 0.3 and 12.6 ± 0.8, p = NS), number of 2 pronuclear (PN) (9.1 ± 1.6 and 9.7 ± 2.0, p = NS), blastocyst ratio (58.9 ± 21.7 and 51.3 ± 21.2, p = NS) and number of transferred embryos (1.9 ± 0.3 and 1.9 ± 0.3, p = NS). There was no significant difference between fresh and cryopreserved-thawed sibling donor oocyte cycles in terms of CPR (66.8 % and 60.7 % respectively, p = NS) or LBR (59.5 % and 55.1 %, respectively; p = NS). Miscarriage and multiple gestation rates were similar between groups (p = NS). Log-binomial regression analysis revealed that the use of fresh sibling oocytes was not associated with CPR or LBR, when compared to cryopreserved-thawed oocytes. ConclusionsThere was no significant difference in terms of reproductive outcomes between sibling fresh OD and cryopreserved-thawed OD cycles.

The pivotal role of the number of transferred embryos in oocyte donation cycles: A retrospective cohort study

This research aimed to show the role of the number of transferred embryos on pregnancy outcomes of the oocyte donation cycles (ODC). This retrospective cohort study included 122 ODCs performed at a private in vitro fertilization (IVF) center between 2020 June - 2021 January. Cases with severe male infertility, tuboperitoneal, and endometrial factors were not included in the study. The median (interquartile range) recipient age was 43 (30–54) years. ODC results revealed that 10.7% of the cases were negative, 4.9% were biochemical pregnancies, and 84.4% were clinical pregnancies. Pregnancy outcomes were checked; miscarriage, preterm, and term delivery rates were 5.7%, 3.9%, and 90.4%, respectively. The rate of recipients for the younger than 40 years was 32%, between the 40–44 years was 27%, and between 45–54 years was 41% respectively. Statistically significant difference was not observed between age groups in terms of endometrial thickness (p = 0.059), number of transferred embryos (p = 0.857), number of ODC attempt (p = 0.666), live birth rate (p = 0.1), and other pregnancy outcomes (p &gt; 0.05, for all). A total of 96 (78.7%) embryo transfers (ET) resulted in a live birth. In 8.2% (n=10) of cases, single embryo transfer (SET) and in 91.8% (n=112) of cases, double embryo transfer (DET) was performed. The number of embryos transferred was statistically significantly higher among cases that resulted in live births compared to cases without live births (p = 0.002). Significant difference was not found in terms of the recipient age (p = 0.392), male age (p = 0.108), endometrial thickness (p = 0.478), and the number of attempt (p = 0.777) between cases resulted in live birth or not. The only parameter that affects the live birth rates in ODC is the number of transferred embryos.

Kager’s sign; an underestimated radiographic feature in detecting acute Achilles tendon rupture: A report on two cases

This research aimed to show the role of the number of transferred embryos on pregnancy outcomes of the oocyte donation cycles (ODC). This retrospective cohort study included 122 ODCs performed at a private in vitro fertilization (IVF) center between 2020 June - 2021 January. Cases with severe male infertility, tuboperitoneal, and endometrial factors were not included in the study. The median (interquartile range) recipient age was 43 (30–54) years. ODC results revealed that 10.7% of the cases were negative, 4.9% were biochemical pregnancies, and 84.4% were clinical pregnancies. Pregnancy outcomes were checked; miscarriage, preterm, and term delivery rates were 5.7%, 3.9%, and 90.4%, respectively. The rate of recipients for the younger than 40 years was 32%, between the 40–44 years was 27%, and between 45–54 years was 41% respectively. Statistically significant difference was not observed between age groups in terms of endometrial thickness (p = 0.059), number of transferred embryos (p = 0.857), number of ODC attempt (p = 0.666), live birth rate (p = 0.1), and other pregnancy outcomes (p &gt; 0.05, for all). A total of 96 (78.7%) embryo transfers (ET) resulted in a live birth. In 8.2% (n=10) of cases, single embryo transfer (SET) and in 91.8% (n=112) of cases, double embryo transfer (DET) was performed. The number of embryos transferred was statistically significantly higher among cases that resulted in live births compared to cases without live births (p = 0.002). Significant difference was not found in terms of the recipient age (p = 0.392), male age (p = 0.108), endometrial thickness (p = 0.478), and the number of attempt (p = 0.777) between cases resulted in live birth or not. The only parameter that affects the live birth rates in ODC is the number of transferred embryos.

Agonist triggering in oocyte donation programs-Mini review.

Oocyte donation programs involve young and healthy women undergoing heavy ovarian stimulation protocols in order to yield good-quality oocytes for their respective recipient couples. These stimulation cycles were for many years beset by a serious and potentially lethal complication known as ovarian hyperstimulation syndrome (OHSS). The use of the short antagonist protocol not only is patient-friendly but also has halved the need for hospitalization due to OHSS sequelae. Moreover, the replacement of beta-human chorionic gonadotropin (b-hCG) with gonadotropin-releasing hormone agonist (GnRH-a) triggering has reduced OHSS occurrence significantly, almost eliminating its moderate to severe presentations. Despite differences in the dosage and type of GnRH-a used across different studies, a comparable number of mature oocytes retrieved, fertilization, blastulation, and pregnancy rates in egg recipients are seen when compared to hCG-triggered cycles. Nowadays, GnRH-a tend to be the triggering agents of choice in oocyte donation cycles, as they are effective and safe and reduce OHSS incidence. However, as GnRH-a triggering does not eliminate OHSS altogether, caution should be practiced in order to avoid unnecessary lengthy and heavy ovarian stimulation that could potentially compromise both the donor’s wellbeing and the treatment’s efficacy.

Sperm aminopeptidase N identifies the potential for high-quality blastocysts and viable embryos in oocyte-donation cycles.

Is there a relationship between human sperm aminopeptidase N (APN) and embryo development in humans? Human sperm APN could possibly become a new molecular biomarker for identifying the potential for high-quality and usable embryos. The diagnosis of male fertility is one of the major concerns of reproductive medicine. Approximately 30-40% of men with otherwise normal fertility parameters are still unable to achieve pregnancy. The predictive clinical value of semen analysis to identify fertile or infertile males is limited; therefore, new diagnostic methodologies for sperm are urgently required. Sperm APN may be a relevant molecular marker due to its high concentration in sperm cells and its important roles in sperm physiology, such as its functions in motility, acrosome reaction and embryo development. This study included 81 couples who underwent oocyte-donation cycles at Clínica IVI Bilbao (Spain), yielding 611 embryos, between September 2014 and July 2015. This study was conducted in an assisted reproduction unit and an academic research laboratory. All the semen samples were examined and classified following World Health Organization guidelines. Spermatozoa were isolated from semen using the discontinuous colloidal silica gradient (45-90%) technique. Embryo quality and development were determined according to the Spanish Association of Reproduction Biology Studies (ASEBIR) criteria. Human sperm APN levels were analyzed by quantitative and semiquantitative flow cytometry. The most well-developed and usable blastocysts were associated with low sperm APN levels. Semen samples that had lower APN levels generated more expanded, hatched and usable blastocysts and fewer early, arrested and non-usable blastocysts. The cumulative probability of having well-developed blastocysts increased by 1.38-fold at Day 5 and 1.90-fold at Day 6 of embryo development, and the likelihood of having usable embryos increased by 1.48-fold, when semen samples with low APN levels were used during the ICSI technique. The data were obtained from a single fertility clinic. A multicentre study will be required to confirm the results. Human sperm APN has the potential to become a new molecular biomarker to help identify the potential for high-quality embryos and diagnose male infertility, especially when seminal parameters are close to the threshold values. It could be a crucial tool for couples for whom the number of usable blastocysts is critical for ART success. This study was supported by grants from the Basque Government (GIC15/165) and the University of the Basque Country (UPV/EHU) (EHUA14/17). The authors declare that they have no conflicts of interest. N/A.

Impact of endometrial thickness change in response to progesterone on live birth rates embryo transfers with fresh oocyte donation cycles

Endometrial thickness (ENT) measurements are important to evaluate endometrial receptivity. The effect of endometrial thickness on pregnancy outcomes has been discussed for many years with conflicting results. The aim of our study was to find out the effect of endometrial thickness (ENT) change in response to progesterone on pregnancy outcomes in embryo transfer (ET) of fresh oocyte donation (OD) recipients. The study was designed retrospectively including 134 embryo transfers with fresh OD recipients. ENT was measured by ultrasonography (USG) on the day of initial progesterone administration (ENT1) and on ET day (ENT2). The primary outcome was to determine any correlation between the ENT change and pregnancy outcomes. ENT increased in 56.7% of cases and decreased in 43.4%. Clinical pregnancy rate (CPR) in recipients with increased ENT was 76.3%, and live birth rate (LBR) was 72.4%. CPR in recipients with decreased ENT was 69.0% and LBR was 65.5%. There was no significant difference between recipients with either increased or decreased ENT regarding CPR and LBR (p = .225 and p = .253, respectively). Our study revealed that ENT change after 6 days of progesterone administration, whether increased or decreased, does not have any significant effect on LBR and CPR in fresh OD recipients. IMPACT STATEMENT What is already known on this subject? Measurement of endometrial thickness is beneficial to determine the endometrial receptivity. However, there is controversy in the literature regarding the usefulness of measuring endometrial thickness. What do the results of this study add? To the best of our knowledge, this is the first study performed with fresh oocyte donation cycles with large number of recipients for live birth rate outcomes in the literature so far. In this study, we sought to assess the impact of endometrial thickness change, in response to 6 days of progesterone administration, on live birth rate and clinical pregnancy rate in embryo transfer of fresh oocyte donation recipients. We did not find no significant effect of endometrial thickness change on live birth rate when fresh young donor oocytes are fertilised with sperms having normal parameters, and implanted in oestrogen and progesterone primed endometrium. What are the implications of these findings for clinical practice and/or further research? Measurement of endometrial thickness in patients under infertility treatment provides little benefit to clinical outcomes.

The impact of insurance mandates on donor oocyte utilization: an analysis of 39,338 donor oocyte cycles from the Society for Assisted Reproductive Technology registry

A total of 19 states passed legislation mandating insurance coverage of assisted reproductive technology, and out-of-pocket costs associated with invitro fertilization vary significantly depending on the region. Consequently, it has been observed that assisted reproductive technology utilization differs regionally and is associated with the presence of an insurance mandate. However, it is unknown whether regional differences exist among patients using donor oocytes. This study aimed to determine the patient and cycle-specific parameters associated with the use of donor oocytes according to the insurance mandate status of the Society for Assisted Reproductive Technology clinic in which the assisted reproductive technology cycle was performed. This study was a retrospective cohort study using national data collected from the Society for Assisted Reproductive Technology registry for 39,338 donor oocyte cycles and 242,555 autologous oocyte cycles performed in the United States from January 1, 2014, to December 31, 2016. Cycles were stratified by insurance mandate of the state in which the assisted reproductive technology cycle was performed: comprehensive (coverage for at least 4 cycles of assisted reproductive technology), limited (coverage limited to 1-3 assisted reproductive technology cycles), offer (insurance mandates exist but exclude assisted reproductive technology treatment), and no mandate. The primary outcome was the number of previous autologous assisted reproductive technology cycles of the recipient. The secondary outcomes included age, serum follicle stimulating hormone level, frozen donor oocyte utilization, day of embryo transfer, number of embryos transferred, clinical pregnancy rate, and live birth rate. Analyses were adjusted for day of transfer, number of embryos transferred, and age of the recipient. Patients in no mandate states underwent fewer autologous assisted reproductive technology cycles (mean, 1.1; standard deviation, 1.6) before using donor oocytes than patients in offer (mean, 1.7; standard deviation, 2.5; P<.01), limited (mean, 1.5; standard deviation, 2.5; P<.01), and comprehensive (mean, 1.7; standard deviation, 2.0; P<.01) states. Patients in no mandate states were more likely to use frozen oocytes than patients in offer (relative risk, 0.54; 95% confidence interval, 0.52-0.57), limited (relative risk, 0.50; 95% confidence interval, 0.46-0.54), and comprehensive (relative risk, 0.94; 95% confidence interval, 0.89-0.99) states. Clinical pregnancy and live birth rates were similar among recipients of donor oocytes, regardless of insurance mandate. Despite similar ages and ovarian reserve parameters, patients without state-mandated insurance coverage of assisted reproductive technology were more likely to use frozen donor oocytes and undergo fewer autologous invitro fertilization cycles than their counterparts in partial or comprehensive insurance coverage states. These differences in donor oocyte utilization highlight the financial barriers associated with pursuing assisted reproductive technology in uninsured states.

O-144 Adverse pregnancy and neonatal outcomes in an oocyte donation program. Expanded Carrier Screening can substantially decrease the risk of recessive conditions

Abstract Study question How frequent are adverse outcomes in oocyte donation (OD) programs and how many recessive conditions can be prevented with the implementation of expanded carrier screening(ECS)? Summary answer Adverse outcomes were reported only in 1.55% of cases. ECS prevented 2.66% autosomal recessive and X-linked-conditions, interpreted in a 63% decrease in adverse outcomes. What is known already Nowadays, oocyte donors undergo a rigorous selection process, including the evaluation of genetic risks. ECS has been widely implemented in the screening of gamete donors. Nevertheless, pregnancies conceived after OD cycles are still at risk for genetic adverse outcomes. There are very few reports in the literature regarding children born with an inherited genetic condition from a gamete donor, and they are reported in sperm donation-conceived offspring. To our knowledge, there is no published review of genetic adverse outcomes in oocyte donation offspring so far. Study design, size, duration This is a retrospective observational study that analyses the adverse events reported in 4573 OD cycles carried out between January 2014 and December 2021 in the Reproductive Medicine Unit of Dexeus University Hospital. The study also reviews the number of high-risk assignations that has been identified in the OD program where ECS was applied to the oocyte donors and the recipient’s male partner to avoid high-risk assignations. Participants/materials, setting, methods The study includes patients who underwent OD cycles and reported an adverse outcome with a potential genetic aetiology from 2014 to 2021. Moreover, genetic matchings were revised in the OD program and high-risk assignations were defined as matchings where oocyte donors and recipients’ male partners were carriers of the same autosomal recessive condition or as matchings where oocyte donor candidates were found to be carriers of X-linked conditions. Main results and the role of chance A total of 4.573 OD cycles were performed, including 1696 oocyte donors. Seventy-one recipients (1.55%) reported an adverse outcome of the pregnancy or children born from the OD. A confirmed genetic aetiology was reported in 23 (32.4%) cases including chromosomal abnormalities, microduplications and monogenic disorders. The reported remaining cases were due to congenital malformations, stillbirth, neurodevelopmental disorders, and other conditions for which a genetic aetiology has not been established to our knowledge. Moreover, we identified 211 (4.6%) high-risk assignations due to oocyte donors and recipient’s male partners being carriers of the same autosomal recessive condition when initially assigned, which would have led to an additional 1,15% of children born with an autosomal recessive conditions (25% of 4.6% high-risk assignations). Additionally, we rejected 52 (3.07%) oocyte donor candidates that were carriers of X-linked conditions, which would have led to an additional 1.5% of children born with an X-linked disorder. Based on our results, implementation of ECS, resulted in 63% risk reduction in adverse outcomes observed in our oocyte donation program from a potential adverse event rate of 4.2% to an actual 1.55% incidence of adverse outcomes. Limitations, reasons for caution The actual number of adverse outcomes and high-risk assignations in an OD program could be underestimated given that not all patients report the adverse outcome or in some cases adverse events have not yet developed. Additionally, the number of rejected/avoided high-risk assignations in ECS is not always collected. Wider implications of the findings This study provides evidence that ECS reduces the probability that children born from OD could inherit some autosomal recessive or X-linked conditions. However, there are still several genetic adverse events that cannot be avoided by implementing ECS, mostly caused by de novo monogenic changes, chromosomal abnormalities, or congenital malformations. Trial registration number Not applicable

P-140 A retrospective study on combination of vitrification/warming protocols from different manufacturers

Abstract Study question What is the embryo survival rate when combining freezing and warming media from different manufacturers. Summary answer Vitrification protocol with DMSO in freezing medium and 4-step warming at room temperature resulted in highest implantation and high embryo survival rates. What is known already Cryopreservation media containing 7,5% and 15% DMSO in a two-steps protocol are widely used for vitrification of human embryos. Studies with the data on safety, survival rates, cellular structures integrity and the warmed embryo's implantation potential confirm efficiency of DMSO as cryoprotectant. However, questions remain on whether DMSO have any negative impact, thus interest to DC. Likewise with the choice of cryoprotectant, more data is needed to determine which temperature corresponds to better survival rates. Study design, size, duration This retrospective cohort study covered the period from January 2019 till November 2021. A total of 834 consecutive cycles of frozen/warmed embryo transfers were included in the study. Inclusion criteria were: women's age below 40 years, cryopreservation on the day 5 of embryo culture. Exclusion criteria were: donor oocyte cycles, cycles with pre-implantation genetic testing for aneuploidies and cycles with severe male factor after surgical sperm retrieval. Participants/materials, setting, methods Following groups were compared using Rapid-i carrier device: 1 - Kitazato vitrification/warming protocol, 2 - Kitazato vitrification and Vitrolife's Omni warming, 3 - Vitrolife's Omni vitrification/warming, 4 - Vitrolife's Omni vitrification and Kitazato warming, 5 - Kitazato vitrification/Vitrolife's Omni warming media used in accordance with Kitazato protocol (ambient temperature, Reproplate dish). Efficiency was evaluated comparing embryo survival, implantation, clinical pregnancy and early pregnancy termination rates. Mann-Whitney and Pearson's Chi-square tests were used for statistical analysis. Main results and the role of chance The average patient age in assigned groups was: group 1: 32,5±3,6 years (n = 569); 2:32,2±3,5 years (n = 47); 3:30,4±3,5 years (n = 15); 4:32,3±3,5 years (n = 74); 5:32,7±3,4 years (n = 129). Average number of transferred embryos: 1,3±0,5; 1,2±0,4; 1,1±0,3; 1,3±0,4 and 1,2±0,4 per group, respectively. Embryo survival rates were: 97%, 96%, 100%, 97% and 100% in each group, respectively. Group 5 was significantly different from other groups (p &amp;lt; 0,05; group 3 had too small sample size for an adequate comparison). Implantation rates per group: 43%, 57%, 44%, 40% and 49%, respectively (p &amp;gt; 0,05). Clinical pregnancy rates were not different between groups. The early pregnancy termination rates were: 18,1%, 20,7%, 33,3%, 14,7% and 8,9% per group, respectively (p &amp;gt; 0,05). Therefore, group 2 resulted in a best clinical outcomes. Limitations, reasons for caution The present study is a retrospective cohort study and it has a limited number of patients in compared groups. Additionally, live births and health of newborn children was not taken into account. Wider implications of the findings Freezing medium from one manufacturer can be combined with warming medium from another manufacturer and result in a good clinical outcome. Furthermore, this study sheds the light that there is still a room for the improvement of existing cryopreservation media and protocols. Trial registration number not applicable

P-594 mRNA COVID-19 vaccine does not influence performance during oocyte donation cycles

Study questionWhat is the effect of mRNA SARS-CoV-2 vaccines on oocyte donors regarding oocyte quality, embryo development and clinical outcomes?Summary answerOocyte quality, fertilization, blastocyst formation, embryo quality and pregnancy rates were similar following donors' mRNA SARS-CoV-2 vaccination compared to previous oocyte donation cycles.What is known alreadyThe severe acute respiratory syndrome Coronavirus 2 (SARS–CoV-2) infection, urged scientists to develop safe and effective vaccines. During the ongoing pandemic, the scientific community has promoted vaccination programs to reduce morbidity and mortality.While it has been suggested that SARS–CoV-2 infection might impact fertility, limited evidence shows that vaccination has no influence on sperm parameters, follicular steroidogenesis, or oocyte quality and only one study reported no effects on fertilization or top-quality embryos rate in vaccinated patients undergoing IVF. There is a paucity of evidence with regards to younger population undergoing ovarian stimulation.Study design, size, durationThis prospective, multicentre cohort study evaluated 32 oocyte donors with two controlled and similar ovarian stimulation, before and after complete SARS-CoV-2 vaccination, between November 2020 and January 2022. A total of 64 oocyte recipient cycles were analysed equally separately into these two groups. Severe male factor was excluded.Participants/materials, setting, methodsComplete SARS-CoV-2 vaccination of the oocyte donor made the difference between the two groups of recipients analysed. The time frame between the previous ovarian stimulation and the vaccination was lower than 8 months. We evaluated and compared the rates of matured eggs (metaphase II, MII), the fertilization and blastocyst formation rates, blastocyst quality (A/B ASEBIR categories), positive pregnancy test and clinical pregnancy rates in both groups of recipients. The statistical analysis was performed using SPSS.Main results and the role of chanceThe average number of MII collected were similar before and following vaccination (12.23 vs 12.91, p = 0.198, respectively). In recipients, the outcomes with regards to fertilization rate (81.4% vs 77.3% p = 0.210), blastocyst formation rate (60.2% vs 61.5%, p = 0.771) and high-quality blastocysts (quality A: 31.1% vs 36.4% and quality B: 29.0% vs 25.1%, p = 0.430) did not differ statistically between the control group (n = 32, pre-vaccination) and the study group (n = 32, post-vaccination), respectively.Furthermore, regarding clinical outcomes, there were not statistically differences in pregnancy rates (64.0% vs 77.4%, p = 0.269) or clinical pregnancy rates (60.0% vs 64.5%, p = 0.729) before and after vaccination respectively.Limitations, reasons for cautionOur encouraging results should be interpreted with caution due to the small sample size and the short period of follow-up. Larger controlled trials are needed to corroborate our findings as the countries continue making forward with the vaccination campaign.Wider implications of the findingsThe present study suggests no influence of mRNA SARS-CoV2 vaccines on donor oocyte cycles, reflecting no detrimental effects on the assisted reproduction outcomes. The safety of SARS-CoV-2 vaccination concerning IVF cycles is encouraging for the medical community and the health of our patients.Trial registration numberNot Applicable

O-297 Does advanced paternal age influence live birth rate independent of woman’s age: analysis of 18, 825 fresh IVF/ICSI cycles from a national (HFEA) database

Abstract Study question Does advanced paternal age (APA) impact live birth rates (LBRs) in IVF/ICSI treatment independent of female partner’s age? Summary answer LBRs decline with paternal age ≥40 years, but not when female partner is &amp;lt; 35 or ≥ 40 years. What is known already APA, particularly over 40 years, has been shown to be associated with declining sperm parameters, impaired embryo development, aneuploidy, compromised pregnancy outcomes and mental health abnormalities in the offspring in IVF/ICSI cycles. However, no significant effect of APA on pregnancy outcomes has been noted in donor oocyte cycles, indicating possible positive effect of female age counteracting negative male age-related IVF/ICSI outcomes. Data on whether female and male age influence each other, or are independently related to LBR, are limited and inconclusive. Study design, size, duration Retrospective analysis of 18, 825 autologous IVF or ICSI with fresh single embryo transfer (SET) cycles from the UK’s national anonymised registry, published online by the Human Fertilisation and Embryology Authority (HFEA). Study period: 2 years starting from 1st January 2017 to 31st December 2018. Participants/materials, setting, methods Couples underwent IVF/ ICSI with fresh SET due to unexplained or tubal infertility. Cycles with male factor, donor sperm and preimplantation genetic testing were excluded. Female age was grouped to &amp;lt; 35 years, 35-39 years and 40-44 years; male age to &amp;lt; 35 years (control group), 35-39 years, 40-44 years, 45-50 years, 51-55 years and &amp;gt;55 years. Chi-square to compare binominal data; multiple logistic regression to find correlation of male and female age on LBR adjusting confounders. Main results and the role of chance Overall, LBR per SET declined from 39.1% in men &amp;lt;35 years (control group) to 25.9% (p &amp;lt; 0.0001), 23.0% (p &amp;lt; 0.0001), 22.9% (p &amp;lt; 0.0001) and 25.4% (p = 0.002) in 40-44, 45-50, 51-55 and &amp;gt;55 years, respectively. However, in the subgroups of women &amp;lt;35 years, the LBRs were no different whether men were of &amp;lt; 35 (41.3%), 40-45 (40.8%) or &amp;gt; 55 (41.7%) years. Similar trend was observed in women aged 40-44 years: LBRs were 12.3%, 11.9%, and 17.4% in men aged &amp;lt;35, 40-44, and &amp;gt;55 year, respectively. Only in women aged 35-40 years, LBRs dropped from 32.8% in men aged &amp;lt;35 years down to 27.9% (p = 0.004), 28.1% (p = 0.04), 28.7% (p = 0.33) and 25% (p = 0.22) in 40-44, 45-50, 51-55 and &amp;gt;55 years, respectively. The findings remained the same with ICSI only cycles. Individually, male age, female age, treatment-type (IVF or ICSI) and day of transfer were significantly correlated with LBR. Overall, after adjusting for confounders, both male (p = 0.01) and female’s age (p &amp;lt; 0.0001) remained independently related to LBRs.; male age did not correlate with LBRs in women aged &amp;lt;35 years or 40-44 years. Limitations, reasons for caution Information on ovarian reserve and treatment protocols were not available. However, this may have little impact, given large population studied. Exclusion of male infertility might have reduced the ‘effect-size’ but was important to eliminate non-age-related male factors, in order to assess only men’s age on the pregnancy outcome. Wider implications of the findings Oocytes in women &amp;lt;35 appear to reduce the negative impact of older sperm on LBR, but not in women 35-39 years of age. This is useful information when counselling couples and in fertility education setting. Further research is needed to clarity the mechanism underlying our findings. Trial registration number Does advanced paternal age influence live birth rate independent of woman’s age: analysis of 18, 825 fresh IVF/ICSI cycles from a national (HFEA) database

P-025 Freezing of the semen sample by the patient at home is clinically effective

Abstract Study question To evaluate the efficacy of the method of freezing the seminal sample at home by the patient himself. Summary answer The freezing of the seminal sample at home is an effective method that brings the clinic closer to the patient, eliminating travel and stress. What is known already Seminal sample freezing for reproductive purpose is indicated in different situations: preservation of fertility, before a vasectomy, in patients with dysfunctions and problems obtaining a sample, and for those patients who cannot be present at the time of the oocyte retrieval. In many of these cases, the patient is under pressure to obtain the sample, in a clinical environment and at an exact time. Many experience this as a stressful situation, which in some cases forces them to travel if they live far from the clinic. Study design, size, duration In 2017, the home freezing protocol was validated with volunteers who obtained a semen sample at the clinic. After verifying that the quality of the sample was the same as if it were frozen by an expert biologist, we began offering this technique to our patients in 2019. We compared the results of the DO cycles with a control group to determine the efficacy of the protocol. Participants/materials, setting, methods Until December 2021, a total of 18 patients have used the Freezing Kit at home, 14 were residents in other EU countries, and 4 residents in Spain, but far from the clinic. As a control group, we used 608 oocyte donation cycles with a frozen sample. Patients who decided to freeze their sample at home receive a kit consisting of a travel tank with nitrogen vapors, a box with all the necessary material, and instructions. Main results and the role of chance Regarding the results of the 18 patients who have used the kit to freeze samples for their oocyte donation cycles, they have a mean of 44±7.1 years, and the samples had a post-thaw concentration of 48±30.5 M /ml with a mean mobility of 21.18±14.6%. No statistically significant differences were found in the fertilization rate compared to the control group (76.4±15.1% vs 77.8±18.3%; p = 0.485), blastocyst rate (61%±10 .5% vs 56.1±16.4%; p = 0.387) nor clinical pregnancy rate (62.8% vs 47.6%; p = 0.251). The fact of having a live birth from a sample frozen by the patient himself has just demonstrated the safety and usefulness of this novel freezing protocol. Limitations, reasons for caution The number of patients who have undergone this process is limited due to the nature of the treatment. Wider implications of the findings These results demonstrate the clinical utility of this freezing method for certain patients, where travel to the clinic may be inconvenient. Demonstrating that it is an effective method of cryopreservation of the seminal sample that brings the clinic closer to the patient, eliminating trips and stress. Trial registration number not applicable

P-389 Elevated BMI in oocyte donors or recipients is associated with a higher risk of miscarriage after blastocyst transfer: a multicenter analysis of 1544 procedures

Abstract Study question Is an elevated BMI in either oocyte donors or recipients associated with a higher risk of miscarriage after blastocyst transfer? Summary answer Overweight in oocyte donors and/or obesity in recipients are associated with a 2X-higher risk of miscarriage in egg donation cycles. What is known already Several basic-science, clinical and epidemiological studies revealed an association between BMI and infertility, suggesting a J-shaped relationship: both underweight and especially overweight/obese women can suffer from reproductive impairments. In particular, overweight-obese women are more prone to suffer from a miscarriage even when euploid blastocysts are transferred. Yet, it is still unclear whether this is the consequence of an altered oocyte (and then embryonic) competence and/or an impaired endometrial receptivity. In this context, oocyte donation cycles represent the ideal clinical setting to shed some light on an issue with numerous social, clinical, and logistic implications. Study design, size, duration Retrospective study including 1544 blastocyst single embryo transfers (SETs) conducted in oocyte donation cycles (Jan2019-May2021). All oocytes were vitrified at 2 egg banks in Spain and warmed at 8 clinics part of the same network. The primary outcome was the miscarriage rate (&amp;lt;22nd gestational weeks) per clinical pregnancy according to donors’ and/or recipients’ BMI. Four BMI clusters were defined (underweight: &amp;lt;18.5; normal-weight: 18.5-24.9; over-weight: 25-30; obese: &amp;gt;30). Participants/materials, setting, methods 66.1%,4.9%,20.3% and 8.7% of SETs were conducted in normal-weight, underweight, overweight, and obese recipients. 81.4%,4.5% and 14.1% of SETs with oocytes derived from normal-weight, underweight, and overweight donors. The putative confounders investigated were egg bank, IVF center, fresh/vitrified-warmed SET, blastocyst quality/day, recipient/donor age, endometrial preparation protocol, number of consecutive SET. Before SET, we requested blood test for infections and TORCH, thyroid function, coagulation and immunological assessment, cardiological, gynecologic and breast evaluation. Main results and the role of chance Overweight-obese recipients were slightly older (43.0±4.0yr) than normal-weight ones (42.2±3.8yr; p &amp;lt; 0.01). Similarly, overweight donors were slightly older (27.5±4.5yr) than normal-weight ones (26.4±4.3yr; p &amp;lt; 0.01). Therefore, all outcomes were adjusted for recipients’/donors’ age. The overall positive pregnancy rate per blastocyst SET and biochemical pregnancy loss rate were 51.8% and 12.6%. No association was reported between either recipients’ or donors’ BMI and both these secondary outcomes. Conversely, higher recipients’ and donors’ BMI were significantly associated with a higher risk of miscarriage after blastocyst SET (multivariate-OR 1.05, 95%CI 1.01-1.1, adjusted-p=0.05; multivariate-OR 1.1, 95%CI 1.04-1.2, adjusted-p&amp;lt;0.01). The most significant differences were reported for obese versus normal-weight recipients (N = 18/64,28.1% versus N = 73/448,16.3%; p = 0.03, power=60%; multivariate-OR 1.8, 95%CI 1.01-3.4, adjusted-p=0.05) and for overweight versus normo-weight donors (N = 31/111,27.9% versus N = 94/561,16.8%; p &amp;lt; 0.01, power=73%; multivariate-OR 1.9, 95%CI 1.16-3.0, adjusted-p=0.01). In the 14 clinical pregnancies where the oocytes derived from overweight donors and the blastocysts were transferred to obese women the miscarriage rate was 50%; the same outcome in normal-weight recipients using oocytes from normal-weight donors was 15% (N = 55/366; p &amp;lt; 0.01, power=85%; OR 5.6, 95%CI 1.8-16.8, p &amp;lt; 0.01). The data were similar across both egg banks and all IVF centers. All other parameters assessed were not associated with the primary outcome under investigation. Limitations, reasons for caution The study is retrospective, and the sample size in each sub-group shall be increased. Moreover, BMI is a gross marker of an individual’s metabolic status. Future studies on more accurate markers like percentage and localization of adipose tissue assessed through techniques like bioelectrical impedance analyses are desirable. Wider implications of the findings Both oocyte competence and endometrial receptivity might be impaired from unbalanced nutritional intakes. More studies on this topic are certainly required. Whenever possible, nutritional/lifestyle adjustments should be encouraged in obese patients because of their higher risk of miscarriage, and a BMI limit should be considered also when recruiting egg donors. Trial registration number Not applicable

P-150 clinical pregnancy rates of oocyte donor cycles are similar when universal media and/or oocyte-specific media are used for oocyte vitrification and warming

Abstract Study question Did the use of universal vitrification/warming media have an impact on the clinical pregnancy rates in oocyte donation cycles compared with oocyte-specific vitrification/warming media? Summary answer Using universal media for oocyte vitrification and warming yields similar clinical pregnancy rates but higher oocyte survival rates than oocyte-specific media. What is known already Vitrification is now the gold standard for oocyte and embryo cryopreservation. Several commercial kits are available, some are designed for specific cell types (e.g., oocytes, zygotes, cleavage-stage embryos or blastocysts) and others are suitable for several stages, therefore termed “universal”. While the composition and the exposition protocol of stage specific media are optimized for specific cell types, “universal” media display a single composition, therefore exposition protocols need to be adapted to each specific developmental stage to ensure optimal cell survival rates. The potential use of the universal media allows to optimize the management of media in ART laboratories. Study design, size, duration This is a retrospective monocentric study. We compared the results obtained in our center for oocyte vitrification in donor cycles with the successive use of oocyte-specific vitrification/warming media (RapidVit/Warm™ Oocyte, Vitrolife) and afterwards universal vitrification/warming media (RapidVit/Warm™ Omni, Vitrolife). We analyzed 111 oocyte recipient ICSI cycles performed between March 2016 and July 2020 (86 recipient couples) and their 81 corresponding oocyte donation cycles (79 donors) with these media. Participants/materials, setting, methods Oocyte recipient ICSI cycles were divided in three groups depending on the combination of vitrification and warming media used for the oocyte vitrification and warming procedures: “specific/specific” (S/S), “specific/universal” (S/U) and “universal/universal” (U/U). The primary outcome was the clinical pregnancy rate per embryo transfer. Secondary outcomes were the oocyte survival rates, fertilization rates, cleavage and blastocyst rates, live birth and miscarriage rates. Main results and the role of chance The age of the donors (31.7+/-3.6 yo) and the recipients (35.1+/-4.5) was similar for the three groups (p &amp;gt; 0.05). Total FSH dose was similar for the 3 groups (1814.2+/-505UI) (p &amp;gt; 0.05) Clinical pregnancy rates were similar when universal vitrification/warming media were used (25.6% for S/U; 25.8% for U/U) compared with oocyte-specific vitrification/warming media (12.2% for S/S, p = 0.25). We observed higher oocyte survival rates when universal media were used (93.7% for U/U, 85.5% for S/U) compared with the use of the oocyte-specific media (75.6% for S/S, p &amp;lt; 0.0001). Fertilization (74.9% for U/U; 68% for S/U; 68.1% for S/S), cleavage (97.9% for U/U; 94.6% for S/U; 89.3% for S/S), and blastulation rates (46.6% for U/U; 50.3% for S/U; 41.7% for S/S) were not different between the three groups (p &amp;gt; 0.05). There was no difference in miscarriage (6.5% for U/U; 10.2% for S/U; 4.9% for S/S) and live birth rates (19.4% for U/U; 15.4% for S/U; 7.3% for S/S) between the 3 groups (p &amp;gt; 0.05). Limitations, reasons for caution The preliminary results of this retrospective study need to be confirmed by a larger prospective study. Wider implications of the findings The use of vitrification/warming universal media, which improves the management of media used for vitrification of oocytes and embryos in ART laboratory, allows to obtain similar clinical pregnancy rates for oocyte recipient donors. Trial registration number not applicable