Donor Oocyte Recipients Research Articles

Assessing the effect of below-benchmark vitrified/warmed donor-oocyte survival rates in subsequent laboratory and clinical outcomes

To assess the impact of below-benchmark (95-100%) donor oocyte survival rates to vitrification/warming in the laboratory and clinical outcomes of recipient cycles. Retrospective cohort study. We analyzed 12690 vitrified-warmed donor oocyte recipient cycles carried out in a network of European private IVF units from 2018-2022. All cycles analyzed used exclusively vitrified/warmed donor oocytes. The cycles were grouped according to the survival rate experienced: benchmark 95-100%; competence 85-95%; below-competence 70-85%; poor 50-70%; very poor <50%. The primary endpoint of the study was the total usable blastocyst rate per 2PN zygote. Secondary endpoints were the fertilization rate, the live birth rate after the first single blastocyst transfer, and the cumulative live birth rate. The mean number of warmed oocytes per ICSI cycle was 11.4±3.2 with a mean survival rate of 89.1%. More oocytes per cycle were consumed in the lower survival groups, yet the total oocytes available for ICSI was smaller in the below-competence, poor and very-poor survival groups. The total usable blastocyst rate was lower in the lower survival groups (benchmark: 48.9%; competence: 47.0%, below-competence: 46.0%; poor: 43.6%; very-poor:43.6%, p<0.001), as well as the fertilization rates (benchmark: 76.8%; competence: 76.6%, below-competence: 75.6%; poor: 74.7%; very-poor:75.5%, p<0.001). The adjusted relative risk of live-birth rate of the first embryo transferred was equal to the benchmark survival group in all the lower survival groups (Benchmark: 40.9%; Competence: RR=0.986, 95%CI:0.931-1.045; below-competence: RR=0.992, 95%CI:0.929-1.059; poor: RR=1.103, 95%CI:1.009-1.207; and very-poor: RR=1.169, 95%CI:0.963-1.419). The cumulative live-birth rate decreased in lower survival groups compared to benchmark survival (Benchmark: 79.2%; Competence: RR=0.988, 95%CI:0.961-1.015; below-competence: RR=0.911, 95%CI:0.880-0.944; poor: RR=0.802, 95%CI: 0.757-0.851; and very-poor: RR=0.793, 95%CI: 0.693-0.907). The lower cumulative rates maintained in a sub-analysis with equal M-II available for ICSI (Benchmark: 69.5%; Competence: RR=0.909, 95%CI:0.827-1.000; below-competence: RR=0.942, 95%CI:0.848-1.046; poor: RR=0.833, 95%CI:0.7386-0.941; and very-poor: RR=0.873, 95%CI:0.695-1.097). Lower donor-oocyte cryo-survival rates have a moderate negative impact on the blastocyst utilization rate per 2PN zygote, fertilization rate and the cumulative live-birth rates of a donation cycle, even after adjusting for equal M-II oocytes available for ICSI. Nonetheless, the surviving oocytes of a cohort seem to maintain a high competence level, with very similar laboratory outcomes, irrespectively of the cohort's survival rates, as well as equal implantation potential of the resulting blastocysts.

O-216 The impact of maternal age on cumulative life birth rates after single euploid embryo transfer: differences between autologous and donor oocyte cycles

Abstract Study question How much of an impact has the maternal age on cumulative life births after euploid Single Embryo Transfer (SET) in autologous and donor oocyte cycles? Summary answer A maternal age ≥ 42 years old affects negatively the cumulative Life Birth Rates (cLBRs) even after euploid SET, but only in the autologous cycles. What is known already Despite the improvements in assisted reproduction technologies (ART) in the last decades, the LBRs remain suboptimal, especially when advanced maternal age is considered. Although several factors could explain these outcomes (i.e. infertility history; uterine pathologies/surgery; advanced paternal age), maternal age-related aneuploidies remain the most limiting factor for a favorable clinical outcome. Thus, the Genetic Testing for Aneuploidies (PGT-A) has been integrated into ART as a strategy to evaluate chromosomal status before transfer. Interestingly, recent studies show that, even after the transfer of euploid blastocyst, the maternal age negatively influences the LBRs. Study design, size, duration This study, carried out in Villa Mafalda Reproductive Medicine Department (Italy), included 568 euploid SET: 542 from autologous cycles (divided in four subgroups according to maternal age: ≤ 34 y.o. (n = 207); 35-38 y.o. (n = 193); 39-41 y.o. (n = 106); ≥ 42 y.o. (n = 36)) and 26 from oocyte donation (OD) cycles (average recipient age is 44.2). All cycles were performed from May 2020 to February 2023. PGT for Monogenic disorders (PGT-M) cycles were excluded. Participants/materials, setting, methods All blastocysts included in this study were analyzed by Next Generation Sequencing (NGS) after a day 5/6 trophectoderm biopsy. For each subgroup was annotated the embryo morphology- divided into good (AA-AB-BA); average (BB-BC-CB) and poor (CC) according to Gardner/Schoolcraft blastocyst grading system- and the day of expanded blastocyst formation (grade 4 of Gardner/Schoolcraft blastocyst grading system). Primary analysis included the cumulative LBRs. Secondarily, blastocyst morphology and blastocyst expansion were examined for all embryo categories considered. Main results and the role of chance The pairwise comparison between groups was performed by Chi-square analysis and p &amp;lt; 0.05 was considered statistically significant. The cLBRs for each subgroup were respectively: ≤ 34 (63.09%); 35-38 (58.47%); 39-41 (56.84%); ≥ 42 (48.57%); OD (69.23%). Data showed that cLBRs decreased with the increase of maternal age, although statistical significance was observed only among women ≤ 34 y.o. and ≥ 42 y.o. (P=0.029). Notably, there was no statistical significance in cLBRs comparing women ≤ 34 y.o. and OD patients (P=0.086). The good-quality blastocyst rate was respectively: ≤ 34 y.o. (54.58%); 35-38 y.o. (47.66%); 39-41 y.o. (60.37%); ≥ 42 y.o. (50%); OD (59.37%). The pairwise comparison showed no significant difference between groups. Furthermore, there was not found significant difference about the day of expanded blastocyst formation: ≤ 34 y.o. (D5: 78.92%; D6 21.07%); 35-38 y.o. (D5: 78.49%; D6: 21.50%); 39-41 y.o. (D5:75.70%;D6: 24.29%); ≥ 42 y.o. (D5:69.44%; D6: 30.55%); OD (D5: 87.5%; D6: 12.5%). Data showed that maternal age ≥ 42 y.o. affects negatively cLBRs even after euploid SET, suggesting that other factors age-related, rather than aneuploidies, influence implantation. Interestingly, these factors do not affect OD recipients, with advanced maternal age, who, instead, reach successful LBRs like patients ≤ 34. Limitations, reasons for caution These results should be evaluated carefully because of the small sample size of the OD patients. A greater number of OD cycles are needed to verify the results obtained. Wider implications of the findings Our findings suggest that embryonic age-related factors - changes in gene expression, metabolism or epigenetics - could influence the embryo capability to, successfully, support implantation other than the ploidy status. This thesis was supported by the OD recipient’s behavior, who had cLBRs comparable to young autologous patients. Trial registration number Not Applicable

P-217 Keep calm and carry on: assessing the effect of below-benchmark vitrified/warmed donor oocyte survival rates in subsequent laboratory and clinical key performance indicators

Abstract Study question When we experience below benchmark donor oocyte survival rates, are the laboratory and clinical outcomes of the recipient cycle affected? Summary answer Donor-oocyte cryo-survival rates below the benchmark (95-100%) result in slightly lower laboratory KPIs, equivalent live birth rates (LBR) and lower cumulative LBR (CLBR) per cycle. What is known already The use of vitrified/warmed donor oocytes allows overcoming many logistic challenges, but it is hindered by the loss of oocytes due to degeneration after warming. The 2012 Vienna Consensus established the benchmark rate of oocyte survival at 95-100%, competency level at &amp;gt; 85%. Results of &amp;lt; 85% cryo-survival are considered below competency, &amp;lt;70% can be considered poor, and &amp;lt;50% very poor. Below-benchmark rates of survival may not only limit the number of donor oocytes for the cycle, but they can also translate into lower per-oocyte cycle KPIs if the lower survival correlates with lower performance of the surviving oocytes. Study design, size, duration We analyzed 12690 vitrified-warmed donor oocyte recipient cycles, encompassing a total 144793 vitrified/warmed donor oocytes, carried out in a network of European private IVF units from 2018-2022. Cycles with PGT-A and spermatozoa from testicular biopsy were excluded. The primary endpoint of the study was the blastocyst utilization rate per 2PN zygote. Secondary endpoints were fertilization rate, live birth rate after the first single blastocyst transfer (SET-LBR) of each cycle, and cumulative LBR (CLBR). Participants/materials, setting, methods In all cases, fertilization was carried out by ICSI, and embryos were cultured to the blastocyst stage at low oxygen tension. Blastocysts with good or fair quality (A, B &amp; C by ASEBIR Criteria) were considered usable (transferred + cryopreserved blastocyts / zygotes). Differences in proportions were analyzed using chi-square and the adjusted odds ratio (OR) was calculated using multivariable logistic regression. Main results and the role of chance Baseline donor and patient characteristics such as age, stimulation duration and dose, total donor oocytes per cycle, male factor, and fresh/frozen/donor spem were compared between groups and adjusted for when necessary. The mean number of warmed oocytes per cycle was 11.4±3.22 with a mean survival rate of 89.2%. More oocytes per cycle were consumed in the lower survival groups, yet the total oocytes available for ICSI was smaller in the below competency, poor and very poor survival groups. There were differences in the proportion of usable blastocysts per zygote amongst the survival rate groups (benchmark: 48.9%; competence: 47.0%, below-competence: 46.0%; poor: 43.6%; very-poor:43.6%, p &amp;lt; 0.001). Fertilization rates also differed between survival groups (benchmark: 76.9%; competence: 76.5%, below-competence: 75.6%; poor: 74.7%; very-poor:75.4%, p &amp;lt; 0.001) The adjusted odds ratio of live birth on the first SET of the cycle was not lower to the benchmark survival group in all the lower survival groups (Benchmark: 40.9%; Competence: OR:0.995; 95%CI:0.971-1.018; below-competence: OR:0.996; 95%CI:0.970-1.023; poor: OR:1.044; 95%CI:1.003-1.086, and very-poor: OR:1.069; 95%CI:0.976-1.170). The CLBR decreased in lower survival groups, with 80.8% for the benchmark survival group, 80.3% (p = 0.539) for competence, 76.2% (p &amp;lt; 0.001) for below-competence, 72.5% (p &amp;lt; 0.001) for poor, and 74.8% (p = 0.056) for very-poor. Limitations, reasons for caution These results are limited to a donor-oocyte population. Wider implications of the findings Lower oocyte-cryo-survival rates resulted in a lower total number of usable blastocysts obtained for the recipient, and consequently, lower CLBR. However, the competence of surviving oocytes is encouraging, with laboratory KPIs in very close range irrespectively of the cohort survival rates, and similar implantation potential of the obtained blastocysts. Trial registration number not applicable

P-311 Impact of adenomyosis on reproductive outcomes applying the revised Morphological Uterus Sonographic Assessment criteria in fresh donor oocyte recipients pretreated with GnRH agonist

Abstract Study question Could the diagnosis of adenomyosis (AD) impact reproductive outcomes when applying the revised Morphological Uterus Sonographic Assessment (MUSA) criteria in fresh donor oocyte cycles? Summary answer Adenomyosis diagnosis following the revised MUSA criteria in recipients did not have adversely affect reproductive outcomes in fresh donor oocyte recipients pretreated with GnRH agonist What is known already Prior metanalysis on IVF outcomes in patients with adenomyosis suggested lower clinical pregnancy and live birth rates, and increased miscarriage rates. Some studies suggest improved pregnancy rates with ultra-long GnRH agonist pretreatment. Most studies focused on autologous embryo transfer without euploidy confirmation, and diagnostic criteria lacked consensus, in 2021 MUSA redefined criteria distinguishing direct and indirect features with different implications. Study design, size, duration A retrospective cohort study included all fresh oocyte donation cycles from January 2014 to September 2023, evaluating adenomyosis impact on implantation rate, clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate. The study analyzed 252 cycles without a formal sample size calculation due to its retrospective nature. Participants/materials, setting, methods The study included 252 first fresh oocyte reception cycle with a fresh embryo transfer. Severe male factor cases were excluded. A transvaginal ultrasound (TUS) screening for adenomyosis criteria was performed, diagnosis required at least two criteria, with one being direct. Endometrial preparation involved one dose of 3,75mg triptorelin acetate intramuscularly injected in mid luteal phase, to facilitate the synchronization with donor and estradiol patches. Main results and the role of chance Adenomyosis was diagnosed in 10,7% (AD), endometriosis (END) was present in 21,8 % and 26,6% of patients presented both diagnoses. Endometriosis patients received more pre-treatment (oral contraceptive or 2-3 long-agonist doses) than those without (40,7% AD, 43,6% END vs 17,3% non-AD/END). Comparing patients with and without adenomyosis, no statistical differences were found in embryo transfer results between groups: clinical pregnancy rate (63% vs 56,9%), miscarriage rate (23,5% vs 14,1%), ectopic pregnancy rate (11,8% vs 4,7%) and live birth rate (40,7% vs 45,8%). No differences in gestational outcomes were observed in terms of the number of adenomyosis criteria present, the number of direct criteria, the type of criteria, or when differentiating between focal and diffuse adenomyosis. Similarly, there were no differences when comparing patients with both diagnoses to those with isolated adenomyosis. The most prevalent adenomyosis features reported were hyperechogenic islands (direct criteria), followed by an irregular junctional zone and asymmetrical wall thickening (indirect criteria). Finally, no differences were found in perinatal outcomes or complications during the pregnancy follow-up between groups. Limitations, reasons for caution Although this is the largest serie evaluating adenomyosisto the low adenomyosis prevalence in our population, these results should be confirmed in larger series. In our center all adenomyosis/endometriosis symptomatic patients are under medical treatment before assisted reproduction techniques, that may modify adenomyosis criteria over time and probably pregnancy outcomes. Wider implications of the findings This is the first study to characterize adenomyosis using the revised MUSA definitions in an oocyte donation programme. Applying these criteria and preparing endometrium with GnRH analog pretreatment and treating medically symptomatic patients before ART, adenomyosis did not adversely affect reproductive outcomes. Trial registration number Not applicable

P-712 A national survey of women’s perspectives and experiences of pursuing donor eggs

Abstract Study question What are the experiences of women who consider a donor egg, and the outcomes of those who receive donor eggs for conception? Summary answer Of 255 respondents, 59 women (23.1%) were formally placed on a donor egg waitlist, despite 80.6% respondents considering donor eggs with an IVF clinic (166/206). What is known already There is a shortage of donor eggs worldwide. Oocyte donation is a treatment option that is increasingly used for infertile women, as seen through the percentage of patients undergoing IVF who are over 40 years. Previous international studies report oocyte donation recipients to be predominantly aged 34-40 years, white, nulliparous, well-educated, married and financially secure. Although there are records in Australia for the number of donor and recipient cycles undertaken, there is no published data on the number of patients considering a donor oocyte, or on oocyte donor waitlists. In Australia egg donation is altruistic, non-commercial and not anonymous. Study design, size, duration A 52-point online survey was distributed via social media to women in Australia who had ever considered or pursued donor eggs, or come to the end of their own IVF treatment. The survey was sent to all clinical members of the Fertility Society of Australia and New Zealand (FSANZ) and available on the Victorian Assisted Reproductive Technology Authority (VARTA) website. The survey was open from 1 February to 30 April 2023. Hospital ethics approved. Participants/materials, setting, methods A cross-sectional, anonymous, online survey of women in Australia who were potential egg donor recipients. Survey questions included demographics, potential donor egg recipient preferences, IVF clinic experiences, barriers, any impact of the COVID-19 pandemic, attitudes around the reimbursement for donor eggs, and fertility costs already incurred. Responses were collected via the Qualtrics XM platform. Statistical analysis for quantitative data was analysed using Microsoft 365 Excel. Qualitative coding performed on the commentary in free text fields. Main results and the role of chance This study identified a large gap between those who considered a donor egg (80.6%), pursue a donor egg on an IVF clinic waitlist (23.1%), and those who actually received a donor egg. Of the 59/255 women who were placed on an oocyte donor waitlist at an IVF clinic in Australia, less than a quarter (23.1%) received a donor egg (13/58), with a pregnancy and live birth rate of 76.9% and 61.5%, respectively. Thus, of those that were on an Australian waitlist, one quarter received donor eggs, with over half of these recipients having a live birth. ‘Women preferred donor eggs from Australia than overseas, preferred an unknown donor from an IVF clinic program, and wished to know source information for themselves and children in the future. Attitudes towards financial reimbursement were generally positive towards compensation. Barriers to pursuing donor eggs included grief of loss of own fertility, cost, availability and time. When on an Australian donor egg list, many respondents still looked at other sources of donor eggs in Australia and overseas. Reasons women came off an Australian donor egg waitlist included receiving donor eggs and donor embryos elsewhere, including from overseas, as well as advancing age and expense. Limitations, reasons for caution Risk of respondent selection bias of those who chose to response to a public survey, with incomplete data for some respondents. Given survey in English, may have underrepresentation of some cultural groups and sampling a limited range of women from diverse social, economic and religious settings. Wider implications of the findings In this first paper of potential egg recipients’ preferences in the Asia-Pacific region, we have identified a gap where demand for donor eggs exceeds local supply. A majority of potential recipients would support financial reimbursement for eggs already cryopreserved by women initially freezing for own elective purposes. Trial registration number not applicable

Addressing Privacy Concerns Surrounding Oocyte Donation in the United States: Gone With Anonymity.

Oocyte donation has greatly expanded in the past several decades since the first procedure was performed in 1983. According to the Centers for Disease Control, the number of cycles using donor oocytes increased from 18,011 cycles in 2010 to 27,131 cycles in 2019. Oocyte donation has become an important reproductive option for women with diminished ovarian reserve, recurrent failed in vitro fertilization, or heritable genetic conditions. It is also particularly important for single men, same-sex male couples, and men with a transgender woman partner. More recently, societal changes accompanying the expansion of social media and broader access to direct-to-consumer DNA testing have raised concerns about privacy and anonymity. In this article, we review two specific aspects of donor privacy: privacy related to personal identifiers provided by clinics or donor egg bank websites and privacy related to direct-to-consumer genetic testing. We also provide clinical recommendations specific to the United States for working with oocyte donors and donor oocyte recipients.

Live Birth After Oocyte Donation In Vitro Fertilization Cycles in Women With Endometriosis

Although multiple mechanisms have been proposed to explain the infertility related to endometriosis, there are no conclusive data on the association of endometriosis with endometrial receptivity. The oocyte donation model in assisted reproduction technology (ART) cycles can clarify this issue. To explore the association of a history of endometriosis with ART outcomes in recipients of oocyte donation. In this systematic review and meta-analysis, electronic databases were searched from inception until August 31, 2023, using combinations of relevant keywords. Moreover, we retrieved data from the databases of the Society for Assisted Reproductive Technology (SART) in the US and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom. Observational studies were included if they investigated the impact of endometriosis on ART outcomes with donor oocytes. Publicly available data related to ART from various sources were gathered, and a retrospective aggregate and nonaggregate analysis using registries of in vitro fertilization cycles with oocyte or embryo donation was conducted. The primary outcome was live birth rate (LBR) following oocyte donor cycles. The effect measures of comparisons between groups are presented as odds ratios (ORs) with a 95% CI. This study analyzed 7212 oocyte donation cycles from 4 studies for the meta-analysis, along with 162 082 cycles from 2 registries (137 182 from SART and 24 900 from HFEA). No significant differences between the groups were observed in the meta-analysis of published data after adjusting for confounding factors (OR, 0.54; 95% CI, 0.19-1.57). A statistically significant lower LBR was identified in women with endometriosis when analyzing the aggregate data from SART and HFEA databases (OR, 0.89; 95% CI, 0.81-0.97). This study found a modest decrease in LBR among women with a history of endometriosis, although only results from the pooled analysis of registry data and not those from the meta-analysis reached statistical significance. These findings suggest that a marginal impairment of uterine receptivity may contribute to infertility mechanisms in women affected by endometriosis.

Optimal antimüllerian hormone levels in oocyte donors: a national database analysis

To study the relationship between high antimüllerian hormone (AMH) levels in oocyte donors and embryo development and pregnancy outcomes among donor oocyte recipients. Retrospective cohort study. Donor Egg Bank Database. Patients undergoing invitro fertilization using vitrified donor oocytes from 35 invitro fertilization centers in the United States between 2013 and 2021. For each recipient, the first oocyte lot that was received with a planned insemination and embryo transfer (ET) was included. Oocyte donor-recipient cycles. Ongoing pregnancy rate (OPR) per ET. A total of 3,871 donor oocyte-recipient thaw cycles were analyzed. On the basis of donor AMH serum concentration, cycles were stratified into the high AMH group (AMH ≥5 ng/mL; n = 1,821) and the referent group (AMH <5 ng/mL; n = 2,050). Generalized estimating equation models were used to account for donors that contributed more than one lot of oocytes. The number of usable embryos per lot (median [interquartile range]) was significantly increased in the high AMH group (2 [2-4]) compared with the referent group (2 [1-3]) (relative risk [RR] 1.06; confidence interval [CI] 1.01-1.12). Among recipients with a planned ET, there was no difference in OPR between the high AMH group (45.4%) and the referent group (43.5%) (RR 1.04; 95% CI 0.94-1.15). Among preimplantation genetic testing for aneuploidy cycles, the embryo euploidy rate per biopsy was similar at 66.7% (50%-100%) in both groups (RR 1.04; CI 0.92-1.17). The OPR per euploid ET among patients who used preimplantation genetic testing for aneuploidy was also comparable, at 52% in the high AMH group and 54.1% in the referent group (RR 0.95; CI 0.74-1.23). This large national database study observed that there was no association between a high level of AMH (≥5 ng/mL) in oocyte donors and an OPR in the recipient after the first ET. On the basis of these findings, recipients and physicians can be reassured that oocyte donors with a high AMH level can be expected to produce outcomes that are at least as good as donors with an AMH level (<5 ng/mL).

P-519 Is oral dydrogesterone a good alternative to vaginal micronized progesterone for luteal phase support in women receiving oocyte donation?

Abstract Study question Does oral dydrogesterone (OD) in luteal phase support (LPS) provide equivalent clinical pregnancy and miscarriage rates as micronized vaginal progesterone (MVP) in oocyte donation recipients? Summary answer No significant difference in clinical pregnancy and miscarriage rates was observed when using OD instead of MVP for LPS in oocyte donation. What is known already Dydrogesterone has a higher bioavailability than MVP due to its high specificity for progesterone receptors allowing the use of lower doses limiting side effects. In addition, because of its route of administration, its tolerance is better. The use of OD for LPS in fresh IVF cycles is now well recognized. However, few data are available on its use in frozen-thawed embryo transfer especially in artificial cycles. In this situation, the lack of corpus luteum leads to a total dependence on exogenous progestogens for implantation and maintenance of the pregnancy. Study design, size, duration A retrospective observational study was performed from prospectively collected data in the ART Department of Lille University Hospital from July 2018 to July 2022. Participants/materials, setting, methods Our study analysed 372 oocyte donation cycles with embryo transfer. Recipients underwent endometrial preparation by hormone replacement treatment (artificial cycles). LPS was provided by weekly intramuscular progesterone (500 mg/2ml) and either OD 40 mg per day or MVP 800 mg per day for 12 weeks if the pregnancy test was positive. The primary endpoint was clinical pregnancy rate. Main results and the role of chance This study compared the outcome of 162 transfers with dydrogesterone + IM progesterone to the outcome of 210 transfers with the MVP + IM progesterone. No significant difference was found between the two groups except for the number of embryos transferred, embryo quality, donor BMI and fresh or frozen status of the embryo. After adjustment for these criteria, our two groups were comparable in clinical pregnancy rates with 36.67% in the MVP group versus 30.25% in the OD group (OR 0.868 [0.529 ; 1.423], p = 0.57), ongoing pregnancy rates (29.05% versus 25.31%, OR 0.993 [0.591; 1.669], p = 0.97), miscarriage rates (7.62% versus 4.94%, OR 0.640 [0.248; 1.650], p = 0.35) and live birth rates (26.67% versus 17.69%, OR 0.727 [0.412; 1.284], p = 0.27). Limitations, reasons for caution The main limitation of this study is the non-randomisation of data between the two treatment groups. Wider implications of the findings Our study suggests that dydrogesterone has a place in our LPS strategies in artificial cycle for frozen embryo transfers or in oocyte donation, especially as this route is often preferred by patients and very well tolerated. Further prospective cohorts or randomized trials could continue to inform clinical practice on LPS. Trial registration number DEC 16-25

P-187 Vitrified-warmed donor oocytes’ cryo-survival rate is not associated with subsequent embryological outcomes and clinical pregnancy rate per first transfer

Abstract Study question Is the survival rate of a cohort of donor oocytes used for each recipient associated with the outcomes of the cycle? Summary answer Oocyte cryo-survival rates (benchmark = 95-100%, competency = 85-95%, below-competency = 70-85%, and poor = 50-70%) are not associated with embryological outcomes and clinical pregnancy in the first transfer of the cycle. What is known already The use of vitrified-warmed donor oocytes allows overcoming many logistic challenges, but it is hindered by the loss of oocytes due to degeneration after warming. The 2012 Vienna Consensus established the benchmark rate of oocyte survival at 95-100%, competency level at &amp;gt; 85%. Results &amp;lt;85% cryo-survival are considered below competency, and &amp;lt;70% can be considered poor. Below-benchmark rates of survival may not only limit the number of oocytes, but also could translate into lower cycle KPIs. Study design, size, duration We analyzed 2190 vitrified-warmed donor oocyte recipient cycles, encompassing a total 20280 vitrified oocytes from 1036 donors. Cycles were carried out in 6 private IVF units from the same group. Cycles from 2018 to 2022 were included in the analysis. Cycles with PGT-A and spermatozoa from testicular biopsy were excluded. The outcome of the first transfer of each cycle was analyzed. Participants/materials, setting, methods Vitrification was performed using open carriers and two different commercial media (Irvine-Scientific and Kitazato). In all cases, fertilization was carried out by ICSI, and embryos were cultured to the blastocyst stage at low oxygen tension. Blastocysts with good or fair quality (A, B &amp; C by ASEBIR Criteria) were considered usable, and the usable blastocyst rate was the sum of all blastocysts transferred and cryopreserved, divided by the number of zygotes on day1. Main results and the role of chance The mean number of warmed oocytes per cycle was 9.3, with a survival rate of 93.7%. A pairwise comparison of fertilization rates with Bonferroni correction revealed that the benchmark survival rate group had similar results to the 85-95%, 70-85% and the 50-70% groups (95-100%: 73.7%; 85-95: 72.1%, 70-85%: 70.9%, 50-70%: 73.1%, p = 1 in all cases). The usable blastocyst rate was similar between the benchmark survival rate and the 85-95% and 50-70% groups, but higher than the 70-85% group (95-100%: 49.0%; 85-95: 48.5%, p = 1.00; 70-85%: 43.5%, p = 0.012, 50-70%: 51.3%, p = 1.00). Of 1368 Day5, SET, first-attempt transfers, 53.5% had a clinical pregnancy. The mean age of recipients undergoing embryo transfer was 42.6 ± 4.5 years and they had undergone 1.1 ± 1.8 previous IVF cycles. Adjusted-OR of clinical pregnancy was only significantly lowered in comparison to the benchmark survival rate in the 70-85% survival group (OR:0.49; 95%CI:0.34−0.71), but not it in the 50-70% group (OR:1.50, 95%CI: 0.92-2.46) nor the 85-95% group (OR:1.00, 95%CI: 0.70-1.42). The use of a sperm donor was positively correlated with clinical pregnancy (OR:1.39; 95%CI:1.04-1.88). Recipient age, male factor, and number of previous IVF cycles were not correlated with clinical pregnancy. Limitations, reasons for caution Retrospective study. Only open carriers were used for vitrification. Cumulative outcomes were not assessed. Wider implications of the findings Sub-benchmark levels of oocyte cryo-survival were not directly associated with worse laboratory outcomes or clinical pregnancy rates. These results are encouraging for cases with lower cryo-survival and useful to counsel patients in this regard. Nevertheless, striving to meet benchmark cryo-survival rates is essential. Trial registration number Not Applicable

A longitudinal study of C1q and anti-C1q autoantibodies in homologous and heterologous pregnancies for predicting pre-eclampsia.

C1q, the recognition molecule of the classical pathway of the complement system, plays a central role in pregnancy. Lack of C1q is characterized by poor trophoblast invasion and pregnancy failure. C1q can be the target of an antibody response: anti-C1q autoantibodies (anti-C1q) are present in several infectious and autoimmune diseases. The presence of these autoantibodies has been detected also in 2-8% of the general population. Recent evidence indicates that women who undergo assisted reproductive technology (ART) have an increased risk of developing pre-eclampsia (PE), particularly oocyte donation (OD) pregnancies. The aim of this study was to characterize the levels of C1q and anti-C1q in PE gestations, in healthy spontaneous, homologous and heterologous ART pregnancies. Serum of the following four groups of women, who were followed throughout two or three trimesters, were collected: PE, patients diagnosed with PE; OD, oocyte donation recipients; HOM, homologous ART women; Sp, spontaneous physiological pregnancy. Our results indicate that PE patients have lower levels of anti-C1q. In ART pregnant women, the trend of C1q and anti-C1q levels were similar to PE patients, even though these women did not develop PE-like symptoms during pregnancy. This finding suggests an immunological dysfunction at the foetal-maternal interface in ART pregnancies, a hypothesis confirmed by the observation of C1q deposition in placentae derived from OD, comparable to PE. Since significantly lower levels of anti-C1q were detected in PE compared to healthy control sera, we hypothesize the possible binding on placental syncytiotrophoblast microvesicles (STBM), which are increased in the circulation of PE mothers. Furthermore, the characterization of the binding-epitope of anti-C1q revealed that "physiological" autoantibodies were mainly directed against C1q globular domain. We concluded that anti-C1q could have a physiological role in pregnancy: during the healthy spontaneous pregnancy the raised levels of these autoantibodies can be important for the clearance of STBM. In PE and in pathological pregnancies (but also in OD pregnancies), the increase in syncytiotrophoblast apoptosis and consequent increase of the circulating STMB levels lead to a consumption of C1q and anti-C1q.

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.

OBESITY IS ASSOCIATED WITH INCREASED MISCARRIAGE RATES IN PAIRED SIBLING DONOR OOCYTE RECIPIENT CYCLES

Obesity rates in the United States have increased over the past several decades. Obesity has many known adverse consequences on fertility and obstetrical outcomes. This study aimed to determine whether body mass index (BMI) adversely affects pregnancy outcomes following donor egg IVF embryo transfer, by analyzing donor oocyte recipient cycles using paired sibling oocytes.

VITRIFIED DONOR OOCYTES ARE ASSOCIATED WITH IMPROVED PREGNANCY OUTCOMES COMPARED WITH FRESH DONOR OOCYTES IN PATIENTS UNDERGOING SINGLE FROZEN EMBRYO TRANSFER

This study compares embryology and pregnancy outcomes resulting from fresh versus vitrified donor oocytes in donor oocyte recipients undergoing frozen 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.

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.

Endometriosis and oocyte quality: an analysis of 13 614 donor oocyte recipient and autologous IVF cycles.

STUDY QUESTIONDoes endometriosis affect live birth following donor oocyte recipient versus autologous IVF?SUMMARY ANSWERThere was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient cycles versus autologous IVF cycles.WHAT IS KNOWN ALREADYFor infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis. It has been debated whether the lower pregnancy rate is due to the effect on oocyte quality or the endometrium, thus affecting implantation. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study, using a donor oocyte recipient model, where the recipients were women diagnosed with endometriosis and compared their outcomes with women who underwent autologous IVF, who had also been diagnosed with endometriosis.STUDY DESIGN, SIZE, DURATIONHuman Fertilization and Embryology Authority (HFEA) anonymized data from 1996 to 2016 were analyzed. This comprised of a total of 758 donor oocyte recipients, where the recipients were women diagnosed with endometriosis, and 12 856 autologous IVF cycles where the women were diagnosed with endometriosis as the sole cause of infertility.PARTICIPANTS/MATERIALS, SETTING, METHODSData on all women with endometriosis undergoing donor oocyte recipient and autologous IVF cycles were analyzed to compare live birth outcomes. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryos transferred and fresh or frozen embryo transfer cycle.MAIN RESULTS AND THE ROLE OF CHANCEThere was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles compared to women undergoing autologous IVF fresh embryo transfer cycles (31.6% vs 31.0%; odds ratio (OR) 1.03, 99.5% CI 0.79–1.35). After adjusting for confounders, there was no significant difference in LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles versus autologous fresh embryo transfer cycles (adjusted OR (aOR) 1.05, 99.5% CI 0.79–1.41).There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient frozen embryo transfer cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs 24.0%; OR 0.77, 99.5% CI 0.47–1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing donor oocyte recipient frozen embryo transfer cycles compared with autologous frozen embryo transfer cycles (aOR 0.85, 99.5% CI 0.51–1.41).LIMITATIONS, REASONS FOR CAUTIONAlthough the analysis was adjusted for potential confounders, there was no information on the extent and classification of endometriosis as well as oocyte number. Furthermore, adenomyosis is thought to co-exist in women with endometriosis and may have independent pathophysiological mechanisms affecting fertility, for which there was no information.WIDER IMPLICATIONS OF THE FINDINGSThe study shows no difference in LBR between donor oocyte recipient cycles in which all recipients had endometriosis compared to autologous IVF cycles in women with endometriosis. Therefore, this study finding suggests that there may be a minimal or no effect of oocyte quality on IVF outcomes in women with endometriosis.STUDY FUNDING/COMPETING INTEREST(S)No funding was obtained. M.S.K. is an associate editor with Human Reproduction Open. He was not involved in the editorial or peer review process for the manuscript.TRIAL REGISTRATION NUMBERN/A.

Elevated Body Mass Index in Donor Oocyte Recipients Does Not Affect Implantation of Euploid Embryos.

Background: Obesity is a worldwide epidemic that has been shown to have serious implications on health outcomes. Regarding reproductive health, increased body mass index (BMI) reduces fertility and increases the time to conceive. It is unclear how excess weight in females affects the development of oocytes and embryos or the impact of implantation. Materials and Methods: This retrospective single-center study aimed to determine if overweight and obese oocyte recipients had similar pregnancy outcomes compared with healthy weight controls after the transfer of a single euploid frozen-thawed embryo transfer (FET). Five hundred twenty-eight patients who underwent a transfer from 2016 to 2021 were included. The primary outcome studied was the clinical pregnancy (CP) rate. Secondary outcomes included live birth (LB) rate, biochemical pregnancy loss (BPL) rate, and clinical pregnancy loss (CPL) rate. Results: The overall CP rate was 54.9% and did not differ significantly among normal weight (n = 318), overweight (n = 129), and obese (n = 81) BMI categories (0.56 vs. 0.56 vs. 0.49, p = 0.56). There were no significant differences in LB rate (0.47 vs. 0.43 vs. 0.38, p = 0.33), BPL rate (0.14 vs. 0.09 vs. 0.11, p = 0.59), and CPL rate (0.15 vs. 0.21 vs. 0.18, p = 0.38) among BMI groups. Conclusions: Our findings provide support that BMI alone does not adversely alter endometrial receptivity and is not the cause of poor in vitro fertilization (IVF) outcomes in patients with increased BMI. These deleterious IVF outcomes might be to the result of diminished oocyte and/or embryo quality or other factors that have not yet been elucidated.

Racial and ethnic disparities among donor oocyte banks in the United States

To determine whether racial and ethnic distributions of oocyte donors contributing to US oocyte banks differ from the demographics of US women and donor oocyte recipients. Cross-sectional study. United States donor oocyte banks, US census, and fertility clinics reporting to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Oocyte donors from 12 banks, women aged 18-44 years based on the 2019 census, and US recipients of cryopreserved donor oocytes from 2012 to2015. None. Proportions of donors identifying as each racial and ethnic group. Of the 1,574 oocyte donors, 678 (43.1%) identified as white compared with 54.8% of US women and 69.1% of donor oocyte recipients. Proportions of donors identifying as Hispanic or two or more races were larger than those of US women and donor oocyte recipients (Hispanic: 24.1% vs. 20.8%, and 24.1% vs. 8.8%, respectively; two or more races: 16.1% vs. 2.3%, and 16.1% vs. 0.5%, respectively). African American donors were underrepresented compared with US women (8.9% vs. 14.0%) and oocyte recipients (8.9% vs. 10.8%). Although the proportion of Asian donors was similar to that of US women (7.7% vs. 7.1%), Asian donors were underrepresented compared with donor oocyte recipients (7.7% vs. 10.6%). Racial and ethnic distribution of oocyte donors differs significantly from the demographics of US women and cryopreserved donor oocyte recipients. These data suggest a need for targeted recruitment of African American and Asian oocyte donors.