Oocyte Donation Research Articles

The effects of intraovarian injection of autologous menstrual blood-derived mesenchymal stromal cells on pregnancy outcomes in women with poor ovarian response

BackgroundAssisted reproduction faces a significant obstacle in the form of poor ovarian response (POR) to controlled ovarian stimulation. To address this challenge, mesenchymal stem cell therapy has been proposed as a potential treatment for female infertility and/or restoration of ovarian function in POR women. Our previous research has demonstrated that menstrual blood-derived-mesenchymal stromal cells (MenSCs) injected into the ovaries of women with POR can increase pregnancy rates. The objective of this study was to examine whether MenSC therapy could enhance ovarian reserve parameters and pregnancy outcomes in a larger population of individuals with POR.MethodThis study consisted of 180 infertile individuals with POR who declined oocyte donation. Participants were divided into two groups: those who received bilateral MenSCs intraovarian injection and those who received no intervention. Our primary aim was to compare the rates of spontaneous pregnancy between the two groups, followed by an investigation of any alterations in the ovarian reserve parameters, such as serum FSH, AMH, and AFC levels, as well as the ICSI/IVF outcomes, in both groups of participants.ResultsThe MenSC therapy exhibited a favourable tolerability profile and did not raise any safety concerns. Following the 2-month follow-up period, women who received MenSC treatment demonstrated a significantly higher rate of spontaneous pregnancy (P < 0.005) and an improvement in anti-Müllerian hormone (AMH) levels (P = 0.0007) and antral follicle count (AFC) (P < 0.001), whereas the control group demonstrated a considerable decline in these parameters (Both P < 0.001). The MenSC therapy led to a greater number of mature oocytes and embryos among women who underwent ICSI/IVF. Our age subgroup analysis demonstrated a significant difference in the number of spontaneous pregnancies and ICSI/IVF outcomes between the treatment and control groups only among individuals below 40 years of age.ConclusionThe results of our study indicate that MenSCs treatment may be a viable option for treating women experiencing POR. However, in order to be widely implemented in clinical practice, the clinical effectiveness of MenSCs therapy will need to be established through rigorous prospective randomized clinical trials.Trial registration: ClinicalTrials.gov Identifier: NCT05703308. Registered 01/26/2023, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05703308. IRCT, IRCT20180619040147N4. Registered 08/01/2020.

Contribution of medico-administrative databases to health vigilance: example of post-oocyte retrieval infections.

Can we monitor post-oocyte retrieval infections in the French national health data system to complement the French ART vigilance system? Medico-administrative databases provide a more comprehensive view of post-oocyte retrieval infections and can be used to detect abnormal increases in frequency and outlier ART centers as a complementary tool to the ART vigilance system. The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has set up a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. The study population was identified from the comprehensive French national hospital discharge database. It included women under 46 years of age undergoing an oocyte retrieval in 2019, classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF) , fertility preservation (FP), and oocyte donation (OD) . The study population included 52 098 women who had undergone 65 948 oocyte retrievals in 2019. Hospital stays and delivery of antibiotics within 31 days after oocyte retrieval were analyzed. Women and infections were characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay, type of antibiotherapy, etc.). Multivariate analysis was performed to determine the relation between the occurrence of infection and women's characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot and a box plot were used to compare the infection rate per center with the national average and to detect outliers. Infections in the month following the oocyte retrieval represented 6.9% of the procedures in 2019 (n = 4522). Of these infections, 112 were hospitalized (0.2% of oocyte retrievals), and 4410 were non-hospitalized (6.7% of oocyte retrievals). The hospitalized infections were essentially gynecological infections (40.9%) and urinary tract infections (23.5%). In 87.9% of non-hospitalized infections, a single antibiotic therapy was prescribed. Mixed-effect model analysis showed that the risk of infection was significantly higher in women under 30 years of age, in the FP population, in supplementary universal health coverage (CMU-C) beneficiaries, and women with endometriosis. Funnel plot and box plot analysis showed that three ART centers have an infection rate significantly higher than the national average. In the three centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Another limitation of this study is that we cannot confirm an attributable relation between the infection and the ART procedure, even if the delay of 31 days after oocyte retrieval is consistent with the occurrence of a post-retrieval complication. In addition, antibiotics may be prescribed as a 'precautionary' measure in certain situations (women with a susceptibility to infection, complicated procedures), or as antibiotic prophylaxis for embryo transfer. Despite the limits in identifying post-ART infections in medico-administrative databases, this approach is a promising way to complement the ART vigilance reporting system. This concept developed for infections will also be generalized to other complications with regular feedback to professionals. No specific funding was sought for the study. The study was supported by the Agence de la biomédecine, France. The authors declare that they have no conflict of interest. N/A.

Frozen autologous and donor oocytes are associated with differences in clinical and neonatal outcomes compared with fresh oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System Analysis

Frozen autologous and donor oocytes are associated with differences in clinical and neonatal outcomes compared with fresh oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System Analysis

Higher live birth rates are associated with a normal body mass index in preimplantation genetic testing for aneuploidy frozen embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study

To determine whether body mass index (BMI) was associated with live birth in patients undergoing transfer of frozen-thawed preimplantation genetic testing for aneuploidy (PGT-A) embryos. Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. All autologous and donor recipient PGT-A-tested cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to2017. Body mass index. The primary outcome measure was the live birth rate, and the secondary outcome measures were the clinical pregnancy and biochemical pregnancy rates. Multivariable generalized additive mixed models and log-binomial models were used to model the relationship between BMI and outcome measures. A total of 77,018 PGT-A cycles from 55,888 patients were analyzed. Of these cycles, 70,752 were autologous, and 6,266 were donor recipient. In autologous cycles, a statistically significant and clear nonlinear relationship was observed between the BMI and live birth rates, with the highest birth rates observed for the BMI range of 23-24.99 kg/m2. When using 23-24.99 kg/m2 as the referent, other BMI ranges demonstrated a lower probability of live birth and clinical pregnancy that continued to decrease as the BMI moved further from the reference value. Patients with a BMI of <18.5 kg/m2 had a 11% lower probability of live birth, whereas those with a BMI of ≥40 kg/m2 had a 27% lower probability than the referent. A normal-weight BMI range of 23-24.99 kg/m2 was associated with the highest probability of clinical pregnancy and live birth after a frozen-thawed PGT-A-tested blastocyst transfer in both autologous and donor recipient cycles. A BMI outside the range of 23-24.99 kg/m2 is likely associated with a malfunction in the implantation process, which is presumed to be related to a uterine factor and not an oocyte factor, as both autologous and donor recipient cycle outcomes were associated similarly with the BMI of the intended parent.

Impact of endometrial compaction on reproductive outcomes after cryotransfer of euploid embryos in a modified natural cycle: protocol for a prospective cohort study.

Embryo implantation is a complex and poorly understood process. Most studies to date have focused on the analysis of the endometrium at the end of the estrogenic phase, while the available data on its importance after secretory transformation are limited and inconsistent. Current evidence does not allow for a conclusive interpretation of the changes observed in the pre-implantation endometrium, whether in the natural or replacement cycle, and their relevance in the development of a pregnancy or the implications for clinical practice. Multicenter prospective observational cohort study. Based on our sample size calculation, the study group will consist of 206 women (exposed or "compaction" group: 103 women with a decrease of ≥ 5% in endometrial thickness between the estrogenic phase and the day of embryo transfer; non-exposed "non-compaction" group: 103 women with similar or greater endometrial thickness between these time points). The main objective of this study is to compare the ongoing pregnancy rates in natural cycles for euploid embryo transfer in patients who present endometrial compaction at the time of transfer versus those who with a stable or greater endometrial thickness with respect to the estrogenic phase. The estimated duration of the study is 30 months. Inclusion criteria are: 18 to 50 years of age, with primary or secondary infertility, subjected to endometrial preparation in a modified natural cycle for transfer of a genetically euploid blastocyst, from their own oocyte or oocyte donation, with a normal uterine cavity. Exclusion criteria are: uterine or endometrial disease (e.g., multiple myomatosis, severe adenomyosis, Asherman syndrome, refractory endometrium), conditions that prevent correct ultrasound assessment (tilted uterus), or a history of recurrent implantation failure or repeated miscarriages. The findings from this study will provide valuable insights into the potential influence of the "endometrial compaction" phenomenon on reproductive outcomes during natural cycle endometrial preparation. By examining this aspect, we aim to contribute to a better understanding of the factors that may impact successful outcomes in fertility treatments.

Obstetric and Neonatal Outcomes After Transferring More Than One Embryo in Patients With Preimplantation Genetic Testing.

To compare obstetric and neonatal outcomes after single embryo transfer (SET) compared with multiple embryo transfer (MET) from frozen-thawed transfer cycles of embryos that underwent preimplantation genetic testing for aneuploidies (PGT-A). We conducted a retrospective cohort study from the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) national database. Clinical and demographic data were obtained from the SART CORS database for all autologous and donor egg frozen-thawed transfer cycles of embryos that underwent PGT-A between 2014 and 2016, after excluding cycles that used frozen oocytes, fresh embryo transfer, and transfers of embryos from more than one stimulation cycle. Multivariable linear and log-binomial regression models were used to estimate the relative and absolute difference in live-birth rate, multiple pregnancy rate, gestational age at delivery, and birth weight between SET compared with MET. In total, 15,638 autologous egg transfer cycles and 944 donor egg transfer cycles were analyzed. Although the live-birth rate was higher with MET compared with SET in the autologous oocyte cycles (64.7% vs 53.2%, relative risk [RR] 1.24, 95% CI, 1.20-1.28), the multiple pregnancy rate was markedly greater (46.2% vs 1.4%, RR 32.56, 95% CI, 26.55-39.92). Donor oocyte cycles showed similar trends with an increased live-birth rate (62.0% vs 49.7%, RR 1.26, 95% CI, 1.11-1.46) and multiple pregnancy rate (54.0% vs 0.8%) seen with MET compared with SET. Preterm delivery rates and rates of low birth weight were significantly higher in MET compared with SET in both autologous and donor oocyte cycles and were also higher in the subanalysis of singleton deliveries that resulted from MET compared with SET. Despite some improvement in live-birth rate, nearly half of the pregnancies that resulted from MET of embryos that underwent PGT-A were multiples. Compared with SET, MET is associated with significantly higher rates of neonatal morbidity, including preterm delivery and low birth weight. The transfer of more than one embryo that underwent PGT-A should continue to be strongly discouraged, and patients should be counseled on the significant potential for adverse outcomes.

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).

Impact de la parité des donneuses sur les résultats du don d’ovocytes

ObjectivesSince 2015, in France, men and women who have never procreated are allowed to donate their gametes. This has led to an increase in the number of female oocyte donors, whereas there are many couples waiting for gametes that have a long waiting time. The aim of this study is to compare the results of donation with oocytes from nulliparous and non-nulliparous donors. MethodsMonocentric retrospective observational study (Lille University Hospital) between January 1st, 2016 and December 31st, 2019. Phenotypic characteristics and clinical and biological outcomes of oocytes donations were compared according to donor parity (nulliparous versus primiparous or multiparous). ResultsOne hundred and eighty-five donors (66 nulliparous and 119 non-nulliparous) were included in the study, allowing 284 ICSI cycles to be performed in recipient couples. On average, 11.5 oocytes were obtained per donation cycle, of which 7.8 were mature. In total, 4.6 mature oocytes were obtained per attempt and per recipient couple. Nulliparous donors are younger than non-nulliparous ones. An early pregnancy was obtained in 55.6% of the nulliparous donors and in 50.8% of the non-nulliparous donors (P=0.55). A progressive pregnancy was obtained in 49.2% of the nulliparous women and in 42.1% of the non-nulliparous women (P=0.36). There was therefore no difference in terms of early pregnancy and ongoing pregnancy whether the donation came from a nulliparous or non-nulliparous woman. ConclusionDonor parity does not seem to have an impact on the success of oocyte donation attempts.

Obstetrical and neonatal outcomes after single and double gamete donation

Introduction: An increasing number of women and couples need oocyte donation to help achieve pregnancy. Several studies have found a correlation between the use of oocyte donation and adverse obstetrical outcomes such as gestational hypertension and preeclampsia. A possible additive risk in using double donation (oocyte and sperm donation) compared to the use solely of oocyte donation has been suggested but only sparsely investigated. The aim of this study is to investigate the differences in obstetric and neonatal outcomes after double donation compared to oocyte donation.Methods: This is a retrospective cohort study of 197 women, who achieved pregnancy after oocyte donation between 2015 and 2022. The primary outcomes investigated were gestational hypertension and preeclampsia. Secondary outcomes were early pregnancy loss, HELLP (Hemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, fetal growth restriction, and gestational diabetes mellitus.Results: No significant differences between the use of oocyte and double donation were observed, when looking at the risk of developing gestational hypertension (AOR = 1.02, 95%CI = [0.33;3.15], P = 0.97) or preeclampsia (AOR = 2.4, 95%CI = [0.68;8.41], P = 0.17). We observed no significant differences between the two groups regarding any of the secondary outcomes.Conclusion: This study did not find an increased risk of obstetrical or neonatal complications such as preeclampsia, gestational diabetes mellitus, or fetal growth restriction after double donation compared to oocyte donation.

Conventional ovarian stimulation vs. delayed single dose corifollitropin alfa ovarian stimulation in oocyte donors: a prospective randomized study. Tail trial.

The present study compares two protocols for ovarian controlled stimulation in terms of number of cumulus-oocyte complexes and metaphase II oocytes. We employed a single injection of 150mcg of corifollitropin alfa after a 7-day oral contraceptive pill-free interval for TAIL group and a conventional administration of corifollitropin alfa after a 5-day OCP-free interval with additional rFSH from 8th of ovarian controlled stimulation. Prospective, randomized, comparative, non-inferiority, opened and controlled trial carried out in 180 oocyte donors 31 were excluded, 81 were randomized to the control group and 68 to the TAIL group. No differences were found in the number of follicles larger than 14 and 17 mm at triggering day. However, a lower number of cumulus-oocyte complexes and metaphase II oocytes were obtained in TAIL group compared to the control group, expressed as median (interquartile range): 10.5 (5.5-19) vs. 14 [11-21] and 9 (4-13) vs. 12 (9-17) respectively. Additionally, the incidence of failed retrieval or metaphase II oocytes = 0 was higher in TAIL group 7(10.3%) vs. 1(1.2%) p = 0.024. The use of a single injection of corifollitropin alfa after a 7-day oral contraceptive pill-free interval in oocyte donors resulted in a lower number of cumulus-oocyte complexes and metaphase II oocytes. No additional rFSH was administered in this group. Clinical Trial Registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-001343-44/results.

No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception? There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study. Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions. This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia). From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders. In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer. This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables. Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation. The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare. N/A.

ART in Europe, 2019: results generated from European registries by ESHRE†.

What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2019 as compared to previous years? The 23rd ESHRE report highlights the rising ART treatment cycles and children born, alongside a decline in twin deliveries owing to decreasing multiple embryo transfers; fresh IVF or ICSI cycles exhibited higher delivery rates, whereas frozen embryo transfers (FET) showed higher pregnancy rates (PRs), and reported IUI cycles decreased while maintaining stable outcomes. ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF-Monitoring (EIM) Consortium since 1997 and reported in a total of 22 manuscripts published in Human Reproduction and Human Reproduction Open. Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year. The data on treatment cycles performed between 1 January and 31 December 2019 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons in one of the 44 countries that are members of the EIM Consortium. Overall, 1487 clinics offering ART services in 40 countries reported, for the second time, a total of more than 1 million (1077813) treatment cycles, including 160782 with IVF, 427980 with ICSI, 335744 with FET, 64089 with preimplantation genetic testing (PGT), 82373 with egg donation (ED), 546 with IVM of oocytes, and 6299 cycles with frozen oocyte replacement (FOR). A total of 1169 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 147711) or donor semen (IUI-D; n = 51651) in 33 and 24 countries, respectively. Eighteen countries reported 24139 interventions in pre- and post-pubertal patients for FP, including oocyte, ovarian tissue, semen, and testicular tissue banking. In 21 countries (21 in 2018) in which all ART clinics reported to the registry 476760 treatment cycles were registered for a total population of approximately 300 million inhabitants, allowing the best estimate of a mean of 1581 cycles performed per million inhabitants (range: 437-3621). Among the reporting countries, for IVF the clinical PRs per aspiration slightly decreased while they remained similar per transfer compared to 2018 (21.8% and 34.6% versus 25.5% and 34.1%, respectively). In ICSI, the corresponding PRs showed similar trends compared to 2018 (20.2% and 33.5%, versus 22.5% and 32.1%) When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.5% (28.8% in 2018) and 26.2% (27.3% in 2018) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was at 35.1% (versus 33.4% in 2018), and with embryos originating from donated eggs at 43.0% (41.8% in 2018). After ED, the PR per fresh embryo transfer was 50.5% (49.6% in 2018) and per FOR 44.8% (44.9% in 2018). In IVF and ICSI together, the trend toward the transfer of fewer embryos continues with the transfer of 1, 2, 3, and ≥4 embryos in 55.4%, 39.9%, 2.6%, and 0.2% of all treatments, respectively (corresponding to 50.7%, 45.1%, 3.9%, and 0.3% in 2018). This resulted in a reduced proportion of twin delivery rates (DRs) of 11.9% (12.4% in 2018) and a similar triplet DR of 0.3%. Treatments with FET in 2019 resulted in twin and triplet DR of 8.9% and 0.1%, respectively (versus 9.4% and 0.1% in 2018). After IUI, the DRs remained similar at 8.7% after IUI-H (8.8% in 2018) and at 12.1% after IUI-D (12.6% in 2018). Twin and triplet DRs after IUI-H were 8.7% and 0.4% (in 2018: 8.4% and 0.3%) and 6.2% and 0.2% after IUI-D (in 2018: 6.4% and 0.2%), respectively. Eighteen countries (16 in 2018) provided data on FP in a total number of 24139 interventions (20994 in 2018). Cryopreservation of ejaculated sperm (n = 11592 versus n = 10503 in 2018) and cryopreservation of oocytes (n = 10784 versus n = 9123 in 2018) were most frequently reported. Caution with the interpretation of results should remain as data collection systems and completeness of reporting vary among European countries. Some countries were unable to deliver data about the number of initiated cycles and/or deliveries. The 23rd ESHRE data collection on ART, IUI, and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Although it is the largest data collection on MAR in Europe, further efforts toward optimization of both the collection and the reporting, from the perspective of improving surveillance and vigilance in the field of reproductive medicine, are awaited. The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

Conditional reciprocity in invertebrates is robust to disturbances

AbstractReciprocity, one of the evolutionary explanations for cooperation, evolves between individuals when helping is conditional upon receiving help in return (“A helps B because B helped A before”). Often tested in controlled laboratory conditions, its robustness to external disturbances has rarely been evaluated. Here, we investigated whether reciprocity is robust when disturbances occur in between the donation by one individual and its return by a partner. As model system, we used a simultaneously hermaphroditic polychaete worm (Ophryotrocha diadema), where partners in isolated dyads engage in iterated exchanges of eggs for sperm (eggs are a costly donation relatively to sperm). If a partner donates eggs and the other fertilizes them, the latter is likely to donate eggs a couple of days later. (Eggs and larvae are then cared by the parents which sit at the nest and only leave it for foraging.) We removed the eggs from the nests daily or weekly and found that reciprocity decisions were not substantially altered; focal worms were more likely to lay if the partner laid before. We also found that, irrespective of treatment, worms exchanged comparable number of eggs, and were stimulated to lay significantly sooner if the partners laid a second clutch before they reciprocated. These results show that reciprocity is robust to disturbances which may happen in the 2 days’ time gap between egg donation and egg reciprocation.

Perinatal outcomes in 6640 singleton pregnancies after donor oocyte IVF across three continents over 7years.

Are trends in singleton donor oocyte IVF perinatal outcomes consistent over time among four international ethnically diverse infertility centers? This retrospective cohort consisted of an infertility network of four international IVF centers across three continents. Singleton live births resulting from fresh and frozen donor oocyte embryo transfers from January 1, 2012 to December 31, 2018 were included. The main outcome measures were birth weight (BW), preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA) and gestational age (GA) at delivery. The entire cohort (n = 6640) consisted of 4753 fresh and 1887 frozen donor oocyte embryo transfers. Maternal age, parity, body mass index, neonatal sex and GA at delivery were similar for fresh and frozen donor oocyte embryo transfers in the entire cohort and within each infertility center. All four centers had a trend of decreased BW and rates of PTB before 32weeks annually, although significance was not reached. Three of the four centers had annual increased trends of PTB before 37weeks and LGA newborns, although significance was not reached. BWs for the entire cohort for fresh and frozen donor embryo transfers were 3166g ± 601g and 3137g ± 626g, respectively. Similar trends in perinatal outcomes were present across four international infertility centers over 7years. The overall perinatal trends in donor oocyte IVF may be applicable to centers worldwide, but further studies in more geographic regions are needed.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

Providers’ attitudes towards payment to egg donors: an international survey

The research question ‘How do fertility professionals worldwide perceive the issue of payment for egg donation and does this view change under different circumstances?’ was addressed. A worldwide online survey was conducted between January and March 2023, focusing on the views of fertility providers concerning egg donor payments. From the 3,790 IVF-Worldwide.com members invited, 532 (14%) from 88 countries responded. The majority of participants, primarily from Europe (38.9%) and Asia (20.1%), were fertility specialists, embryologists, and fertility nurses. Most (60.3%) favoured regulated donor compensation, with only 13% advocating for unrestricted amounts. Compensation opposition (22.4%) was often rooted in concerns about donors’ best interests. When considering egg donation from low-resource to high-resource countries, 38.5% were opposed. When asked about compensating women who underwent elective, non-medical egg freezing should they choose to donate their unused oocytes, most responders supported it to some degree, with only 28.4% opposing any compensation. The survey revealed that a significant majority of fertility professionals worldwide are supportive of some form of compensation for egg donors. However, perspectives diverge depending on the specific scenario and the country of practice.

Inflammatory placental lesions are specifically observed in healthy oocyte donation pregnancies with extreme fetal-maternal incompatibility

IntroductionOocyte donation (OD) pregnancy is a risk factor for pre-eclampsia (PE). Due to a higher extent of fetal-maternal human leukocyte antigens (HLA) mismatching in OD pregnancies compared to naturally conceived (NC) and in vitro fertilization (IVF) pregnancies, the immune response in OD placentas is probably divergent and affects clinical outcomes. We hypothesized that placental pathology varies among diverse pregnancy conditions and is related to fetal-maternal HLA incompatibility. MethodsPlacental lesions were scored in four patient groups: OD-PE (n = 16), OD-healthy (n = 37), NC-PE (n = 45), and IVF-healthy (n = 17). All combinations were genotyped for HLA-A, -B, -C, -DR, and -DQ to calculate fetal-maternal HLA mismatches. Placentas showing chronic deciduitis with plasma cells were immunofluorescently stained with CD138 and the anti-inflammatory cytokine interleukin-10 (IL-10). ResultsThe distribution and severity of placental lesions varied among groups. The OD-healthy group had the highest inflammation score and greatest extent of chronic deciduitis with plasma cells (p < 0.05). However, the majority of CD138+ plasma cells (90%) in OD-healthy group expressed IL-10, in contrast to the OD-PE group (58%). The OD-healthy group was separated into semi-allogeneic (≤5 HLA mismatches) and fully allogeneic (>5 mismatches) subgroups. The elevated inflammatory pathology score and chronic deciduitis with plasma cells were found more often in the HLA-class-I fully allogeneic OD-healthy group than the IVF-healthy group (p < 0.05). DiscussionPlacental inflammatory lesions are most often present in uncomplicated OD pregnancies. Immune cells that infiltrate these lesions might play an immunosuppressive role to protect OD pregnancies from complications when facing a higher extent of fetal-maternal HLA mismatching.

Recentering Labor in the Egg Donation Bioeconomy: Egg Donors’ (Re)productive Work and Subjectification in Spain

ABSTRACT In 2019, Spanish fertility clinics reached a historical record of ova extractions. A total of 14,521 surgeries were performed to serve the growing egg demand internationally. Here I show how bringing a cycle to completion is not an easy task for egg donors. Selecting a clinic, understanding their own biocapital in the industry and how to invest it, fitting the cycle into their lives, and managing pain and emotions become crucial parts of their work. I argue that these activities constitute a vast amount of labor that, although essential for the generation of value in reproductive bioeconomies, remains invisible and undertheorized.

Changes in the immunophenotype of endometrium during implantation window receptivity formation in healthy fertile women

IntroductionEndometrial receptivity is largely determined by the immunophenotype of endometrium, especially uterine NK-cells (uNK). Immune component is directly involved in the formation of favourable microenvironment for the blastocyst implantation and placenta formation, but the way it changes during the maturation of endometrial tissue in healthy fertile women is still underexplored. MethodsThe endometrium was collected from 47 healthy oocyte donors after controlled ovarian stimulation: 23 women on the day of oocytes retrieval (OR) and 24 women on the term of implantation window (IW). The OR group was analysed, published previously and used as a comparison group to show the dynamic of changes.Isolated endometrial lymphocytes and peripheral blood samples were stained with monoclonal antibodies and analysed according to the three-color flow cytometry protocol. ResultsThe proportion of NK-cells (CD3−CD56+) in endometrium grew significantly in the implantation window compared to the oocytes retrieval day. NK-cells acquired a more differentiated phenotype from the day of OR until IW: the expression of CD8 and CD158a significantly increased, while the expression of HLA-DR significantly decreased. Significant correlations between peripheral blood and endometrial NK-cells were found in CD8 expression during OR and IW, CD335(p46)neg and CD335(p46)++ subsets during IW term. DiscussionImmunophenotype of receptive endometrium forms due to the accumulation of uNK-cells, which actively proliferate, become mature, differentiative, and ready to meet the embryo.Endometrial immunophenotype is peculiar and specific but not autonomic and isolated.Differentiation (CD8 on NK-cells), and activity (p46 on NK-cells) of peripheral blood lymphocytes is reflected in endometrial lymphocytes profile, and therefore the research of peripheral blood immunophenotype is relevant.

Differential sperm histone retention in normozoospermic ejaculates of infertile men negatively affects sperm functional competence and embryo quality.

The unique epigenetic architecture that sperm cells acquire during spermiogenesis by retaining <15% of either canonical or variant histone proteins in their genome is essential for normal embryogenesis. Whilst heterogeneous levels of retained histones are found in morphologically normal spermatozoa, their effect on reproductive outcomes is not fully understood. Processed spermatozoa (n=62) were tested for DNA integrity by sperm chromatin dispersion assay, and retained histones were extracted and subjected to dot-blot analysis. The impact of retained histone modifications in normozoospermic patients on sperm functional characteristics, embryo quality, metabolic signature in embryo spent culture medium and pregnancy outcome was studied. Dot-blot analysis showed heterogeneous levels of retained histones in the genome of normozoospermic ejaculates. Post-wash sperm yield was affected by an increase in H3K27Me3 and H4K20Me3 levels in the sperm chromatin (p<0.05). Also, spermatozoa with higher histone H3 retention had increased DNA damage (p<0.05). Spermatozoa from these cohorts, when injected into donor oocytes, correlated to a significant decrease in the fertilisation rate with an increase in sperm histone H3 (p<0.05) and H3K27Me3 (p<0.01). An increase in histone H3 negatively affected embryo quality (p<0.01) and clinical pregnancy outcome post-embryo transfer (p<0.05). On the other hand, spent culture medium metabolites assessed by high-resolution (800MHz) nuclear magnetic resonance showed an increased intensity of the amino acid methionine in the non-pregnant group than in the pregnant group (p<0.05) and a negative correlation with sperm histone H3 in the pregnant group (p<0.05). Histone retention in spermatozoa can be one of the factors behind the development of idiopathic male infertility. Such spermatozoa may influence embryonic behaviour and thereby affect the success rate of assisted reproductive technology procedures. These results, although descriptive in nature, warrant further research to address the underlying mechanisms behind these clinically important observations.