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Research Question: Can inadvertent pregnancies go unnoticed when initiating random-start ovarian stimulation (RSOS) despite monitoring?, Design: Case series at a university-based tertiary care fertility clinic., Results: Between June 2022 and December 2023, two cases of undetected early pregnancy at the onset of RSOS were identified, both leading to severe ovarian hyperstimulation syndrome (OHSS) with hospitalization., Conclusion: RSOS protocols add flexibility in fertility clinics when there is no intention of a fresh embryo transfer, but may be associated with insidious risk of OHSS. The authors advocate for comprehensive consultation and serial monitoring of human chorionic gonadotrophin during ovarian stimulation, while cautioning against over-reliance on baseline hormone concentrations when initiating RSOS. If the benefits of RSOS seem limited, healthcare providers should consider delaying ovarian stimulation to avert health, but also medicolegal and financial, complications., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: Does very advanced maternal age (VAMA; age ≥45 years) influence obstetric outcomes among women using donor oocytes in IVF?, Design: This retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 years and older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth and twin pregnancy rates, alongside perinatal outcomes such as Caesarean section rates, pre-eclampsia, gestational diabetes and birthweight., Results: The study included 1226 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women aged 50 years and older (54.2%) compared with those aged 45-46 years (58.0%), but these differences were not statistically significant (P = 0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant trend towards a decrease in live birth rate and birthweight with increasing maternal age. The study also found that single-embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates., Conclusions: IVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What is the attitude of Belgian women of reproductive age towards enucleated egg donation? Does the willingness of women to donate differ when they would donate enucleated or whole eggs?, Design: In 2022, an online survey was conducted among a representative sample of 1000 women in Belgium aged 18-50 years. The item on willingness to anonymously donate enucleated eggs was dichotomized into those willing to donate and those not willing to donate or uncertain., Results: No statistically significant difference was found between the willingness to donate enucleated eggs and whole eggs (whether anonymously or identifiably). Anonymity, however, affected the willingness to donate, with considerably fewer women willing to donate identifiably. The respondents were divided about their parental status if they were to donate enucleated eggs, with less than one-half (44%) not considering themselves to be a genetic mother. Women willing to donate enucleated eggs anonymously were less likely to view themselves as a genetic mother of the child compared with others. Fewer than one in five considered the technique unacceptable because the resulting child would carry genetic material of three persons., Conclusions: Women in the general population did not show a greater willingness to donate enucleated eggs than whole eggs. The fact that the respondents were strongly divided on whether or not they would consider themselves to be a genetic mother of the resulting child may explain this result. Other factors, such as the potential high risk for the child, may also have contributed to less willingness., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Modern medicine has revolutionized family planning. Remarkably, women 1 can carry to term embryos with whom they share no genetic connection, a feat made possible through egg donation and/or gestational surrogacy. Our reproductive systems evolved to accommodate embryos that are 50% related to the carrier, not 0% related. Here, we apply evolutionary theory to explain how and why pregnancy is riskier with an unrelated embryo. When a woman gestates an unrelated embryo, she is significantly more likely to develop preeclampsia and other diseases above and beyond the known risks associated with advanced maternal age, IVF, multiple gestation, and subfertility. Such "allogeneic pregnancies" are riskier even in fertile, healthy, commercial surrogates and when the egg is donated by a young, healthy donor. We propose that unrelated embryos present a special immune challenge to the gestational carrier, because they have fewer matching genes to the maternal body-therefore exacerbating symptoms of evolutionary maternal-fetal conflict. Indeed, maternal risks seem lower when the embryo is more related to the carrier, e.g., if a sister donates the egg. Finally, we discuss microchimerism in egg donation pregnancies, whereby wholly foreign cells pass from mother to embryo and vice-versa. We conclude with several medical proposals. First, egg donors and surrogates should be informed of the increased health risks they would face. In considerations of risk, these young, fertile women should not be compared to older, infertile women undergoing IVF; the proper comparison group is other young, fertile women. Second, contrary to some medical advice, perhaps genetically-related egg donors and surrogates should be preferred, all else equal. An immunological matching scheme, like what is used for organ transplants, could improve surrogate pregnancy outcomes. Third, more research is needed on microchimerism, sperm exposure, and the long-term impacts of allogeneic pregnancies on maternal and child health., (Copyright © 2024. Published by Elsevier B.V.)

Research Question: Is late follicular phase stimulation as efficient as early follicular phase stimulation in a gonadotrophin-releasing hormone (GnRH) antagonist protocol in oocyte donors in terms of the number of oocytes., Design: In this open label, phase 3, non-inferiority, randomized controlled trial using a two-arm design with a 1:1 allocation ratio, 84 oocyte donors were allocated to the early follicular start group (control group, n = 41) or the late follicular start group (study group, n = 43). In the control group, women followed a fixed GnRH antagonist protocol with recombinant FSH (r-FSH) 225 IU. In the study group, r-FSH 225 IU was initiated in the late follicular phase. The primary outcome was the number of oocytes. The secondary outcomes were the number of mature oocytes, consumption of gonadotrophins and GnRH antagonist, and cost of medication., Results: The number of oocytes did not differ between the control group and the study group (intent-to-treat analysis 15.5 ± 11.0 versus 14.0 ± 10.7, P = 0.52; per-protocol analysis 18.2 ± 9.7 versus 18.8 ± 7.8, P = 0.62). In addition, the number of mature oocytes did not differ between the groups (14.1 ± 8.1 versus 12.7 ± 8.5, P = 0.48). The duration of stimulation was shorter in the control group (10.0 ± 1.4 versus 10.9 ± 1.5 days, P = 0.01). The total amount of r-FSH used was lower in the control group (2240.7 ± 313.9 IU versus 2453.9 ± 330.1 IU, P = 0.008). A GnRH antagonist was used for approximately 6 days in the control group, while a GnRH antagonist was only prescribed for one woman in the study group (6.0 ± 1.4 days versus 0.13±0.7 days, P < 0.001). There was a significant difference in the cost of medication per cycle between the groups (1147.9 ± 182.8€ in control group versus 979.9 ± 129.0€ in study group, P < 0.001)., Conclusions: Late follicular phase stimulation is as efficient as early follicular phase stimulation in terms of the number of oocytes., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Although the potential advantages of clinical germline genome editing (GGE) over currently available methods are limited, the implementation of GGE in the clinic has been proposed and discussed. Ethical issues related to such an application have been extensively debated, meanwhile, seemingly less attention has been paid to ethical implications of studies which would have to be conducted in order to evaluate potential clinical uses of GGE.In this article, we first provide an overview of the debate on potential clinical uses of GGE. Then, we discuss questions and ethical issues related to the studies relevant to evaluation of potential clinical uses of GGE. In particular, we describe the problems related to the acceptable safety threshold, current technical hurdles in human GGE, the destruction of human embryos used in the experiments, involvement of egg donors, and genomic sequencing performed on the samples of the research participants.The technical and ethical problems related to studies on GGE should be acknowledged and carefully considered in the process of deciding to apply technology in such a way that will provide benefits and minimize harms.

Research Question: Does a progestin-primed ovarian stimulation (PPOS) protocol with dydrogesterone from cycle day 7 yield similar outcomes compared with a gonadotrophin-releasing hormone (GnRH) antagonist protocol in the same oocyte donors?, Design: This retrospective longitudinal study included 128 cycles from 64 oocyte donors. All oocyte donors had the same type of gonadotrophin and daily dose in both stimulation cycles. The primary outcome was the number of cumulus-oocyte complexes (COC) retrieved., Results: The number of COC retrieved (mean ± SD 19.7 ± 10.8 versus 19.2 ± 8.3; P = 0.5) and the number of metaphase II oocytes (15.5 ± 8.4 versus 16.2 ± 7.0; P = 0.19) were similar for the PPOS and GnRH antagonist protocols, respectively. The duration of stimulation (10.5 ± 1.5 days versus 10.8 ± 1.5 days; P = 0.14) and consumption of gonadotrophins (2271.9 ± 429.7 IU versus 2321.5 ± 403.4 IU; P = 0.2) were also comparable, without any cases of premature ovulation. Nevertheless, there was a significant difference in the total cost of medication per cycle: €898.3 ± 169.9 for the PPOS protocol versus €1196.4 ± 207.5 (P < 0.001) for the GnRH antagonist protocol., Conclusion: The number of oocytes retrieved and number of metaphase II oocytes were comparable in both stimulation protocols, with the advantage of significant cost reduction in favour of the PPOS protocol compared with the GnRH antagonist protocol. No cases of premature ovulation were observed, even when progestin was started later in the stimulation., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the preference of sperm donors with identity disclosure (ID) versus anonymous donors (AD) and to understand if this selection affects clinical outcomes in an Israeli population., Methods: This retrospective study included patients who chose imported sperm donation during 2017-2021. Of these, 526 used their own (autologous) oocytes and 43 patients used donated oocytes (DO). The primary endpoint was the type of chosen donor with ID versus AD. We examined the tendency toward ID according to demographic parameters and the theoretical impact of donor-type selection on reproductive outcome and compared patients who performed cycles with autologous oocytes with those using DO., Results: Single women had a significantly higher probability of choosing sperm donors with ID than heterosexual couples (55.6% vs. 33.3%, OR 2.5, CI 95% 1.52-4.11, P < 0.001). Although not significant, same-sex couples were more likely to choose sperm donors with ID than heterosexual couples (49.1% vs. 33.3%, OR 1.93, CI 95% 0.97-3.85, P = 0.06). Sperm donor samples, 2501 vials, were imported. It was performed 698 intra-uterine insemination and 812 in vitro fertilization cycles were performed, respectively, resulting in 283 pregnancies without differences between patients who chose sperm donors with ID versus AD sperm. No significant differences were observed regarding the option for sperm donors with ID between patients using DO (44.2%) and those using autologous oocytes (51.3%)., Conclusion: While ID is important for a certain section (mainly single) of recipients, it is far from the only dominant factor during donor selection. Sperm donation type does not impact clinical outcomes., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Research Question: What effect does direct-to-consumer genetic testing (DTCGT) have on information finding and sharing in relation to gamete donor conception?, Design: This study used in-depth qualitative interviews with parents through donor conception, donors, the relatives of donors and donor-conceived people who have used, or considered using, DTCGT. Interviews were conducted between September 2021 and February 2023. Sixty people defined themselves as having been affected by donor conception and DTCGT. Fifty-seven of these were resident in the UK at the time of interview. The final sample included 19 (spermatozoa, egg or embryo) donors, 25 donor-conceived people, 20 parents through donor conception and two relatives of donors. Five participants occupied more than one of these roles., Results: The rise of DTCGT is affecting how information about donor conception is managed: it shifts patterns of knowledge about donor conception; increases flexibility regarding the age of access to information about donor relatives; can lead to a growing role for non-professionals, including wider family members, in gatekeeping information about donor conception; accentuates the effect of donor conception for donors' and the relatives of donor-conceived people; and shapes, and is shaped, by the formal regulatory donor information management systems., Conclusion: Fertility professionals should inform people using, or considering, donor conception, or (potential) donors, about the different ways DTCGT can affect sharing information about donor conception. Support is needed for those affected by these changes., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A personal description and goodwill message is often the only form of communication a gamete recipient receives from the donor. However, the nature of the information gamete donors leave for recipients is not well understood. This Viewpoint article discusses a recent study published in this journal that makes a significant contribution to our understanding of this area of research and raises important questions for research going forward., (Copyright © 2023. Published by Elsevier Ltd.)

Research Question: Do live birth rates differ between recipients matched with donors using conventional ovarian stimulation compared with those using random-start protocols?, Design: Retrospective analysis of 891 ovarian stimulations in egg donors (January-December 2018) and clinical outcomes in matched recipients (n = 935). Donors commenced ovarian stimulation on day 1-3 of the menstrual cycle (n = 223) or in the mid/late-follicular (n = 388) or luteal phase (n = 280) under a conventional antagonist protocol. Live birth rate of matched recipients was the main outcome., Results: Duration of stimulation and total gonadotrophin dose were comparable between conventional versus random-start groups. The number of collected eggs were similar (17.6 ± 8.8 versus 17.2 ± 8.5, P = 0.6, respectively). Sub-group analysis showed that stimulation length (10.2 ± 1.8 versus 9.8 ± 1.7 versus 10.4 ± 1.7, P < 0.001) and gonadotrophin consumption (2041.5 ± 645.3 versus 2003.2 ± 647.3 versus 2158.2 ± 685.7 IU, P = 0.01) differed significantly between the conventional, mid/late follicular and luteal phase groups, respectively. In matched recipients receiving fresh oocytes and undergoing fresh embryo transfer, the biochemical pregnancy (63.8% and 63.3%; P = 0.9), clinical pregnancy (54.6% and 56.1%; P = 0.8) and live birth rates (47.7% and 46.6%; P = 0.7) per embryo-transfer were similar between conventional versus random groups. Similar results were obtained in recipients receiving vitrified eggs. Euploidy rate was also comparable., Conclusions: No notable variations were found in clinical outcomes using oocytes obtained from random-start protocols and those proceeding from conventional ovarian stimulation in oocyte donation treatments. Luteal-phase stimulation seems to require longer stimulation and higher FSH consumption. Random-start stimulation strategy does not impair the potential of the oocyte yield or clinical outcomes in oocyte donation cycles., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Oocyte cryopreservation has notably increased in recent times, to become an essential part of clinical infertility treatment. Since the 1980s, many improvements in oocyte cryopreservation (OC) have been adopted, including the great advance with the application of vitrification. The commonly used vitrification protocol applies different cryoprotectants (Ethylene glycol and/or DMSO and/or PROH and sucrose and/or Trehalose) and two different steps: firstly, exposure in equilibration solution for 5-15 min, followed by a vitrification solution for 60-90 s at room temperature. The warming method includes a first step for 1 min at 37 °C and 3 subsequent steps at room temperature to remove the cryoprotectant for a total of 9-12 min. In addition, biosafety is a critical aspect to mention, and it is related to devices used during the vitrification, mainly in terms of whether the biological vitrified material comes in direct contact with liquid nitrogen (open vitrification) or not (closed vitrification), where LN 2 may contain potentially contaminating viruses or pathogens. Furthermore, during early development major waves of epigenetic reprogramming take place. Recent literature suggests that epigenetic and transcriptomic profiles are sensitive to the stress induced by vitrification, including osmotic shock, temperature, rapid changes of pH and toxicity of cryoprotectants. It is, therefore, important to better understand the potential perturbations of epigenetic modifications that may be associated with the globally used vitrification methods. Therefore, we here discuss the benefits and efficiency of human oocyte vitrification; we also review the evidence surrounding oocyte cryopreservation-related epigenetic modifications and potential epigenetic dysregulations, together with long-term consequences for offspring health., Competing Interests: Declaration of competing interest The authors declare that do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2023. Published by Elsevier Inc.)

Research Question: What are the predictors of willingness to donate frozen oocytes among women of reproductive age in Australia?, Design: An online survey involving 303 women of reproductive age (18-49 years) in Australia who had not frozen their oocytes or planned to freeze their oocytes in the next 12 months. The survey assessed demographic variables, prototype willingness model variables (attitude, subjective norm, prototype similarity and prototype favourability) and additional variables (altruism, empathy and infertility awareness) as predictors of hypothetical scenarios of willingness to donate frozen oocytes. A multivariate repeated measures analysis of variance explored differences in willingness to donate frozen oocytes. Hierarchical multiple regression analysis examined predictors of donor willingness., Results: Women's willingness to donate their frozen oocytes was higher for donating to a friend or family member and to research compared with an egg bank or fertility clinic, or a couple advertising online for an egg donor (all P < 0.001). The prototype willingness model variables were significant predictors of willingness to donate showing slightly varied patterns across four scenarios. After accounting for demographics, regression models including prototype willingness model variables and additional variables accounted for 45-64% of variance in donor willingness., Conclusions: Frozen oocyte donation may be facilitated by improving attitudes towards donation and establishing positive images of donors. Professionals requiring frozen oocytes for research could focus on creating a sense of social approval for donating in this context. Encouraging frozen oocyte donation could increase access to oocytes for IVF treatment and aid in reducing the psychological burdens associated with involuntary childlessness., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Oocyte 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., Methods: Placental 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)., Results: The 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)., Discussion: Placental 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., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Research Question: What are mothers' disclosure intentions and practices from infancy to early childhood, and is perceived donor threat associated with disclosure in identity-release egg donation families when the children are aged 5 years?, Design: This longitudinal study included 73 heterosexual-couple families with infants born following IVF-egg donation at phase one, and 61 families with 5-year-old children at phase two. At both phases, mothers were interviewed about their disclosure intentions and practices. At phase two, mothers were interviewed about their feelings about future donor-child contact., Results: Most mothers (75.3%) intended to disclose their use of egg donation to their children at phase one; half had begun to do so when their children were aged 5. Most remaining mothers planned to tell, although a minority were uncertain or planned not to disclose. When the child was aged 5, four mothers had started telling them that they could access their donor's identifying information at age 18, and most (84%) intended to do so in the future. Most couples agreed on a disclosure strategy at phase two. Most mothers perceived at least some threat from future donor-child contact, but this was unrelated to their disclosure practices., Conclusions: Disclosure intentions in infancy are borne out in early childhood. Despite perceiving some threat from future donor-child contact, most mothers intended telling their child that they could access the donor's identifying information at age 18. Revisiting these families as the children grow older will be important to understand how the mothers' perceived donor threat may change over time, and how this is related to family processes., (Copyright © 2023. Published by Elsevier Ltd.)

Research Question: Does long-term storage of vitrified oocytes affect laboratory and reproductive outcomes after intracytoplasmic sperm injection?, Design: Retrospective cohort study including 41,783 vitrified-warmed oocytes from 5362 oocyte donation cycles between 2013 and 2021. Five categories of storage time were established to analyse its effect on clinical and reproductive outcomes (≤1 year [reference group], 1-2 years, 2-3 years, 3-4 years and >4 years)., Results: The mean number of warmed oocytes was 8.0 ± 2.5 oocytes. Oocyte storage time ranged from 3 days to 8.2 years (mean: 0.7 ± 0.9). Mean oocyte survival (90.2% ± 14.7% overall) did not significantly decrease with longer storage time after adjusting for confounders (88.9% for time >4 years, P = 0.963). A linear regression model did not show a significant effect of oocyte storage time on fertilization rate (about 70% in all time categories) (P > 0.05). Reproductive outcomes after the first embryo transfer were statistically comparable across storage times (P > 0.05 for all categories). Longer term oocyte storage (>4 years) did not affect the chances of clinical pregnancy (OR 0.700, 95% CI 0.423 to 1.158, P = 0.2214) or live birth (OR 0.716, 95% CI 0.425 to 1.208, P = 0.2670)., Conclusions: Oocyte survival, fertilization rate, pregnancy and live birth rates are not affected by the time spent by vitrified oocytes in vapour-phase nitrogen tanks., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What are the reproductive outcomes and the prognostic factors of live birth rates in patients with endometriosis referred to oocyte donation after multiple IVF failures?, Design: Observational cohort study including all women with endometriosis-related infertility and two or more failed IVF/intracytoplasmic sperm injection (ICSI) cycles referred to oocyte donation between January 2013 and June 2022. Endometriosis was diagnosed based on published imaging criteria, and was confirmed histologically in women who had a history of surgery for endometriosis. The main outcome measured was the cumulative live birth rate (CLBR). The characteristics of women who had a live birth were compared with those who did not using univariate and multivariate analysis to identify determinant factors of fertility outcome., Results: Fifty-seven patients underwent 90 oocyte donation cycles after 244 failed autologous IVF cycles. The mean ± SD age of the population was 36.8 ± 3.3 years, with a mean duration of infertility of 3.6 ± 2.2 years, and a mean number of autologous IVF/ICSI cycles of 4.4 ± 2.3 cycles per patient. Three patients (5.3%) had superficial peritoneal endometriosis, two patients (3.5%) had ovarian endometriomas, and 52 patients (91.2%) had deep infiltrating endometriosis, among which 30 patients (57.7%) had bowel lesions. Thirty patients (52.6%) had associated adenomyosis. Overall, CLBR per patient was 36/57 (63.2%). After multivariate analysis, only being nulligravida (P=0.002) remained an independent negative predictive factor of the live birth rate. Previous surgery did not impact reproductive outcomes., Conclusion: This study suggests that oocyte donation appears to be a viable option to optimize the live birth rate in women with endometriosis-related infertility and recurrent IVF failures., (Copyright © 2023. Published by Elsevier Ltd.)

Research Question: What was the utilization, effectiveness and safety of assisted reproductive technology (ART) in Latin America during 2020?, Design: Retrospective collection of multinational data on ART performed by 188 institutions in 16 countries., Results: Overall, 87,732 initiated cycles resulted in 12,778 deliveries and 14,582 births. The major contributors were Brazil (46.0%), Mexico (17.0%) and Argentina (16.8%). However, the highest utilization (cycles/million inhabitants) was Uruguay with 558, followed by Argentina with 490 and Panama with 425 cycles/million. Globally, women aged ≥40 years increased to 34% while women ≤34 dropped to 24.7%. After removing freeze-all cycles, the delivery rate per oocyte retrieval was 14.8% for intracytoplasmic sperm injection and 15.6% for IVF. Single-embryo transfer (SET) represented 38.3% of all fresh transfers, with delivery rate per transfer of 20.0%; this increased to 32.4% for elective SET (eSET) and 34.2% for blastocyst eSET, compared with blastocyst elective double embryo transfer (eDET) of 37.9%. However, multiple births increased from 1% in eSET to 30.5% in eDET. Perinatal mortality increased from 7.7‰ in singletons to 24.4‰ in twins and 64.0‰ in triplets. Frozen embryo transfer (FET) represented 66.6% of all transfers, with a delivery rate/transfer of 29.0%, significantly higher than 23.9% after fresh transfers at all ages (P < 0.0001). Preimplantation genetic testing, reported in 8920 cycles, significantly improved delivery rate and decreased miscarriage rates at all ages (P ≤ 0.041), including oocyte donation (P = 0.002). Endometriosis was diagnosed in 28.3% of cases. The delivery rate in 5779 women after removal of peritoneal endometriosis was significantly better than tubal and endocrine factors in women aged 35-39 (P = 0.0004) and women aged ≥40 (P = 0.0353)., Conclusions: Systematic collection and analysis of big data in a south-south cooperation model allow regional growth by implementing evidence-based reproductive decisions., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Many people hope that the unused and unwanted eggs frozen by women for self-use could be applied to reduce the shortage of donor eggs. However, several practical (additional screening and counselling) and ethical (informed consent and reimbursement) issues may dampen this hope. This paper also considers the question of whether elective egg freezers who want to donate their eggs should be reimbursed for the costs they have met for the IVF cycle and storage. It is argued that a partial reimbursement for the collection (hormonal stimulation and retrieval) is morally acceptable because it is limited to proven expenses (and does not violate the altruism rule) and because the recipients should contribute to the costs of a scheme from which they are benefiting. The storage fee should be paid by the egg freezer herself and no reward for effort, time and inconvenience should be given. This compromise benefits both donors and recipients., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What is the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in young oocyte donors in terms of ovarian response to stimulation, fertilization rate, embryo development and clinical outcomes in recipients?, Design: This retrospective, multicentre cohort study evaluated 115 oocyte donors who had undergone at least two ovarian stimulation protocols (before and after complete SARS-CoV-2 vaccination) between November 2021 and February 2022. Comparisons were made of the primary outcomes of days of stimulation, total dose of gonadotrophins and laboratory performance in ovarian stimulation in oocyte donors before and after vaccination. A total of 136 cycles in matched recipients were analysed as secondary outcomes and, from those, 110 women received a fresh single-embryo transfer, with analysis of biochemical β-human chorionic gonadotrophin concentrations and rates of clinical pregnancy with heartbeat., Results: Longer stimulation was required in the post-vaccination than pre-vaccination group (10.31 ± 1.5 versus 9.51 ± 1.5 days; P < 0.001) along with higher gonadotrophin consumption (2453.5 ± 740 versus 2235.5 ± 615 IU; P < 0.001) with a similar starting dose of gonadotrophins in both groups. More oocytes were retrieved in the post-vaccination group (16.62 ± 7.1 versus 15.38 ± 7.0; P = 0.02). However, the number of metaphase II (MII) oocytes was similar between groups (pre-vaccination 12.61 ± 5.9 versus post-vaccination 13.01 ± 6.6; P = 0.39) and the ratio of MII/retrieved oocytes favoured the pre-vaccination group (0.83 ± 0.1 versus 0.77 ± 0.2 post-vaccination; P = 0.019). In recipients with a similar number of provided oocytes, the fertilization rate, total number of obtained blastocysts, number of top-quality blastocysts, and rates of biochemical pregnancy and clinical pregnancy with heartbeat were not significantly different between groups., Conclusions: This study shows no adverse influence of mRNA SARS-CoV-2 vaccination on ovarian response in a young population., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Embryo donation (ED) involves the donation of surplus embryos post family formation to others in need. Commensurate with Australian and New Zealand legislation and policy, ED is practiced as an identity-release programme shaped by four paramount principles. These include: the need to consider the longitudinal health and well-being of donor-conceived children born from assisted reproductive technologies (ART); recognition that offspring should be made aware of and be able to access information about their genetic origins; awareness that the short and long-term health and psychological welfare of other stakeholders (i.e., recipients and donors) should be ensured; and finally, that all donations are altruistic. Whilst embedded in ART legislation or professional guidelines, how these principles are operationalized through counselling in both countries remains variable. In this paper, we draw upon Australian and New Zealand research, legislation and policy shaping the counselling milieu. We highlight some of the key clinical issues that counsellors need to explore with participants of an ED arrangement and the implications of these as they apply to dilemmas within counselling practice such as counsellor roles and responsibilities., Competing Interests: Declaration of competing interests None to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This review examined whether the absence of a genetic link with one or both parents in families using reproductive donation induced a different quality of parenting from that found in families with spontaneous conception or autologous assisted reproductive technology (AUT-ART), where the genetic mother carries the pregnancy and both parents have a genetic link with their children. MEDLINE, PsycINFO and PubMed were searched for English-language studies published from January 1993 to October 2021. A total of 45 studies were included in the systematic review, and 11 in the meta-analysis. The meta-analysis showed that in reproductive donation families, where there was no genetic link between parents and children, there were higher positive parental values (P = 0.007) and lower negative parental values (P = 0.007) than for parents and children in families that had spontaneously conceived. No statistically significant differences emerged when the reproductive donation families were compared with the AUT-ART families. The study showed that the quality of parenting was not conditioned by the presence or absence of a genetic link; instead, it was influenced by the processes underlying family building, such as the desire to have a child, the involvement of both parents in the childcare and the quality of disclosure., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What is the relationship between oocyte donor characteristics and their pain perception, their expectation and experience of pain, and the interaction between pain and overall satisfaction with the donation process?, Design: Institutional Review Board approved, retrospective survey of commercial, US oocyte donors was emailed to recent donors recruited through Donor Egg Bank USA before 2020., Results: Of the 503 opened emails, 246 individuals responded (48.9%). Most donors ranked their pain between minimal and moderate at all time points analysed. Altruistically motivated donors and parous donors were less likely to experience unexpected levels of pain. A high proportion (93.9%) of donors reported being informed of the risk of pain. Those who recalled being informed of the risk of pain were less likely to report higher levels of pain than expected. Although 94.2% of donors reported having an average to positive experience overall, 92.3% (12 out of 13 donors) in the group reporting a negative overall experience said they felt more pain than expected., Conclusions: Donors were well informed about the risk of pain. Altruistically motivated donors and parous donors were less likely to experience unexpected levels of pain. Report of unexpected levels of pain was highly related to low donor satisfaction., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Which factors influence the success rate of egg donation programmes with imported vitrified oocytes?, Design: Observational longitudinal cohort study of 431 oocyte donation cycles conducted between January 2015 and February 2019. A total of 398 couples underwent an IVF cycle with imported donated vitrified eggs. All consecutive oocyte donation cycles conducted at the Centre for Reproductive Medicine of the European Hospital in Rome, Italy, were included., Results: A univariable analysis was conducted. Among the demographic characteristics studied, body mass index (BMI) was significantly able to influence outcome. In 49% of unsuccessful cycles, men were overweight, compared with 39.4% in cycles with a positive beta-HCG test (P = 0.03). The relationship between female or donor BMI and treatment outcome, however, was not statistically significant. The day on which the embryo is transferred affects the outcome of the cycle: transferring on day 2 versus day 5 reduces the probability of clinical pregnancy. The relationship between male BMI classes and semen parameters was studied: obese men have a significantly lower sperm concentration than normal-weight men (P = 0.006 after Bonferroni correction). No statistically significant differences were found in semen volume (P = 0.722), sperm morphology (P = 0.100) and motility (P = 0.179) in obese men compared with normal weight men., Conclusion: In addition to the number of oocytes available after warming, male BMI, semen characteristics and blastocyst transfer are critical parameters able to influence the reproductive outcomes of egg donation programmes with imported vitrified oocytes., (Copyright © 2022. Published by Elsevier Ltd.)

Research Question: Is embryo cryopreservation a cause of high birth weight and large for gestational age (LGA) in singletons resulting from vitrified-warmed embryo transfer?, Design: Retrospective cohort study evaluating 670 oocyte recipients who underwent fresh (367 cycles) or vitrified-warmed embryo transfer (303 cycles) at Instituto Bernabeu between July 2017 and March 2019. All single blastocyst transfers carried out in an artificial cycle that resulted in a singleton live birth were included., Results: Maternal age (42.21 ± 4.45; 42.79 ± 3.83; P = 0.519), body mass index (23.34 ± 3.69; 23.80 ± 3.78; P = 0.075), gestational age (38.96 ± 1.97; 38.77 ± 2.15; P = 0.207), maternal smoking (10.8%; 13.0%; P = 0.475), gestational diabetes (4.9%; 4.3% P = 0.854), preeclampsia (2.7%; 5.6%; P = 0.074), hypertensive disorders (3.3%; 2.3%; P = 0.494), maternal parity (multiparous 18.5%; 14.5%; P = 0.177) and liveborn gender (female 44.5%; 48.8%; P = 0.276) were not significantly different between fresh or vitrified-warmed groups. Endometrial thickness was significantly higher in the fresh versus vitrified-warmed group (8.83 ± 1.73 versus 8.57 ± 1.59; P = 0.035, respectively). Oocyte donor height was similar between the fresh versus vitrified-warmed group (163.22 ± 5.88 versus 164.27 ± 6.66 cm; P = 0.057, respectively). Mean birth weight was not significantly different (3239.21 ± 550.43; 3224.56 ± 570.83; adjusted P = 0.058). No differences were observed in macrosomia (7.1%; 6.3%; adjusted OR 0.857, 95% CI 0.314 to 2.340, P = 0.764), LGA (6.0%; 6.7%; adjusted OR 0.450, 95% CI 0.176 to 1.149, P = 0.095), pre-term birth (10.9%; 9.0% adjusted P = 0.997), very pre-term birth (0.8%; 1.3%; adjusted P = 1.000), extremely pre-term birth (0%; 1.0%; adjusted P = 0.998); underweight (10.0%; 7.0%; adjusted P = 0.050); very low weight (0.6; 1.1%; adjusted P = 1.000) and small for gestational age (1.9%; 0.7%; adjusted P = 0.974) between fresh or vitrified-warmed groups., Conclusion: This study eliminates potential confounders that might influence fetal growth and demonstrates that embryo vitrification and warming procedures do not affect birth weight., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does embryo transfer day (day 5 versus day 3) affect cumulative live birth rates (CLBR), time to live birth (TLB) and cost per live birth (CPL) in recipients of donated oocytes?, Study Design: A single-centre RCT conducted between April 2017 and August 2018. Recipients of donated oocytes were randomized to cleavage-stage (day 3) or to blastocyst-stage (day 5) embryo transfer. Eligible recipients were aged 18-50 years and in their first or second synchronous cycle. Primary outcome was CLBR (12 months from first embryo transfer), and fresh and subsequent cryopreserved transfers were considered; TLB and CPL were also analysed., Results: Recipients (n = 134) were randomized to the day-3 group (n = 69) or to the day-5 group (n = 65). Day-5 transfer resulted in a 15.9% relative increase in CLBR and a significant shorter TLB compared with day-3 transfer. To reach a 50% CLBR, the day-3 group required 6 months more than the day-5 group (15.3 versus 8.9 months, respectively). The average CPL in the day-3 strategy cost 24% more than the day-5 strategy (€14817.10 versus €10959.20). Clinical pregnancy rate was 25% less in the day-3 group. The trial was prematurely stopped after poor initial results in the day-3 arm led to unplanned interim analysis., Conclusions: The transfer of blastocyst-stage embryos in recipients of donated oocytes is preferred as it leads to a higher clinical pregnancy rate, live birth rate, shorter time to pregnancy and lower costs to achieve live birth, compared with cleavage-stage embryo transfer., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does type of LH peak suppression (progesterone-primed ovarian stimulation [PPOS] versus gonadotrophin releasing hormone [GnRH] antagonist) affect oocyte competence, embryo development and live birth rates in recipients of vitrified donated oocytes?, Design: Retrospective cohort study conducted between 2016 and 2018, involving 187 recipient cycles of donated vitrified oocytes. Oocyte donors were stimulated under LH suppression with desogestrel for PPOS (DSG group) or ganirelix GnRH antagonist (ANT group). Recipients younger than 50 years received vitrified oocytes from DSG donation cycles (DSG-R) or ANT donation cycles (ANT-R)., Results: A mean of 10.07 ± 3.54 oocytes per recipient were warmed (survival rate of 80.7%), and 5.90 ± 2.89 were fertilized (fertilization rate 72.6%). Out of 187 recipients, 168 achieved embryo transfers. No significant differences were found in warming survival rates, fertilization rates and embryo development between DSG-R and ANT-R groups. Ninety-four clinical pregnancies and 81 live births were achieved. No statistically significant differences were found in clinical pregnancy rates (47.7% versus 52.5, P = 0.513) and live birth rates (39.5% versus 46.5%, P = 0.336) per recipient cycle between DSG-R and ANT-R, respectively. Multivariable logistic regression was applied to assess the effect of treating oocyte donors. Live birth rate adjusted for associated factors was not statistically different between vitrified oocytes from DSG or ANT (OR 0.74, 95% CI 0.37 to 1.47)., Conclusion: Reproductive outcomes of recipients of vitrified oocytes are not affected by donor PPOS treatment. PPOS is suitable for suppressing LH peak in elective fertility preservation and in freeze-all strategies., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does the oocyte donor's age affect live birth rate (LBR) in recipients?, Design: Retrospective study of 3766 oocyte recipient cycles carried out between January 2009 and December 2018. Cycles were categorized into groups according to donor's age: <20 years (4.7%); 20-25 years (41.1%); ≥26 years (54.2%). Chi-squared test was used to evaluate differences in LBR and analysis of variance was used to test differences in embryo quality, and fertilization and embryo development rates. A generalized linear mixed model was applied to estimate the odds for each end point., Results: LBR was 40.7%. When analysed according to donors' age, significant differences were found: 33.9% for the youngest group, 39.1% for the group aged 20-25 years, and 42.5% for donors aged ≥26 years (P = 0.022). When adjusting for confounding factors (recipient age, number of transferred embryos and day of embryo transfer), LBR was lower in the group aged <20 years (OR 0.70; CI 95% 0.50 to 0.99) and in the group aged 20-25 years (OR 0.85; CI 95% 0.74 to 0.98) compared with the group aged ≥26 years. No significant differences were observed in fertilization rates (74.2%, 76.1% and 77.5%) or embryo development rates (57.0%, 61.4% and 62.0%). The number of good-quality embryos transferred was significantly lower in the group aged <20 years (1.03 ± 0.71; 1.18 ± 0.69; 1.19 ± 0.67; P = 0.015)., Conclusions: LBR is significantly lower when donors are younger than 25 years and, especially, when they are younger than 20 years., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Is the efficacy of imported vitrified oocyte donation affected by the cryobank of origin?, Design: Longitudinal cohort study, including 249 completed oocyte warming cycles from 200 recipients (January 2016-July 2020). No severe male factor was included. Vitrified oocytes were provided by three Spanish cryobanks. Primary outcome was cumulative live birth delivery rate (CLBR) per completed oocyte warming cycle., Results: After warming 1535 oocytes, 1244 survived (81.0%) and 945 fertilized (76.0%); embryo utilization rate was 65.3%. The overall CLBR per completed cycle was 47.0% but was lower in cryobank 1 (31.2%) versus cryobank 2 (56.0%, P = 0.0010) and cryobank 3 (50.8%, P = 0.0241). Multivariate logistic regression analysis identified survival of four or more oocytes as the strongest predictor for delivery (P = 0.0282). Only 202 out of 249 oocyte warming cycles had four or more survived oocytes in a proportion that was significantly lower in cryobank 1 versus cryobank 2 (70.1% versus 89.0%, P = 0.0020); comparison with cryobank 3 (81.0%) was not significant. In the 202 oocyte warming cycles, CLBR in cryobank 1 (37.0%) was lower versus cryobank 2 (58.8%, P = 0.0115) and cryobank 3 (60.8%, P = 0.0019), suggesting a reduced viability in oocytes from cryobank 1 that survived warming., Conclusions: Differences were found in the efficacy of imported vitrified oocytes in relation to the cryobank of origin. Each centre needs to evaluate the results internally when starting a collaboration with an oocyte cryobank to establish the necessary measures to maximize treatment efficacy., (Copyright © 2021. Published by Elsevier Ltd.)

Research Question: In women at the advanced age of 43-45 years undergoing repeated IVF cycles with autologous oocytes, who has the highest chance for birth and who should be referred early to receive donor oocytes?, Design: A retrospective cohort study was conducted at a university hospital reproductive centre. The computerized database of 394 women aged 43-45 years undergoing 1528 non-donor IVF or intracytoplasmic sperm injection cycles between 2010 and 2019 was analysed. A decision tree was developed, enabling a comprehensive study of a set of clinical parameters and the expected outcomes., Results: The cumulative clinical pregnancy rate was 15.0% (59/394) and the cumulative live birth rate was 8.4% (33/394). The decision tree developed to predict women who should be offered egg donation included age, poor ovarian response to stimulation, the number of top-quality embryos, dominant follicles, previous pregnancy or live birth, fertilized oocytes and body mass index. The model showed that a good ovarian response in the first cycle was the best predictor for live birth (13.3% gave birth). However, among women with poor responses, 7.1% of those who were younger than 43.5 years gave birth, and none of the women who were older than 43.5 years did., Conclusions: Women over 43.5 years old with fewer than four oocytes collected in their first IVF cycle should be offered ovum donation, since their live birth rate in subsequent cycles is negligible., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Premature ovarian insufficiency (POI) is a rare pathology affecting 1-2% of under-40 year-old women, 1 in 1000 under-30 year-olds and 1 in 10,000 under-20 year-olds. There are multiple etiologies, which can be classified as primary (chromosomal, genetic, auto-immune) and secondary or iatrogenic (surgical, or secondary to chemotherapy and/or radiotherapy). Despite important progress in genetics, more than 60% of cases of primary POI still have no identifiable etiology; these cases are known as idiopathic POI. POI is defined by the association of 1 clinical and 1 biological criterion: primary or secondary amenorrhea or spaniomenorrhea of>4 months with onset before 40 year of age, and elevated follicle-stimulating hormone (FSH)>25IU/L on 2 assays at>4 weeks' interval. Estradiol level is low, and anti-Müllerian hormone (AMH) levels have usually collapsed. Initial etiological work-up comprises auto-immune assessment, karyotype, FMR1 premutation screening and gene-panel study. If all of these are normal, the patient and parents may be offered genome-wide analysis under the "France Génomique" project. The term ovarian insufficiency suggests that the dysfunction is not necessarily definitive. In some cases, ovarian function may fluctuate, and spontaneous pregnancy is possible in around 6% of cases. In confirmed POI, hormone replacement therapy is to be recommended at least up to the physiological menopause age of 51 years. Management in a rare diseases center may be proposed., (Copyright © 2021. Published by Elsevier Masson SAS.)

Introduction: Assisted reproductive technology including in vitro fertilization (IVF) and oocyte donation (OD) may increase risk for placenta-mediated diseases. Comprehensive analysis of histopathological placental lesions according to source of oocytes used in the IVF procedure - recipient derived (RD-IVF) vs oocyte donation (OD-IVF), has not been conducted in a population with a hypertensive disorder of pregnancy (HDP) and/or intrauterine growth restriction (IUGR)., Methods: A retrospective cohort study of archived placenta specimens from RD-IVF and OD-IVF pregnancies affected by HDP and/or IUGR was conducted with blinded histopathological placental examination. Three categories of lesions were differentiated and defined as main outcomes: maternal vascular malperfusion (MVM), chronic inflammation, and fetal vascular malperfusion (FVM). To determine the relationship between conception method and placental lesions, multivariable regressions were performed with maternal age, gestational age, HDP, birth and placental weight percentiles as model covariates., Results: 115 placentas were included 83 (72.2%) RD-IVF, 32 (27.8%) OD-IVF. Adjusted OR (aOR) for conception method was 5.05 (95%CI 0.58-43.90, p=0.142) for MVM, 1.87 (95%CI 0.68-5.15, p=0.228) for chronic inflammatory and 0.61 (95%CI 0.15-2.37, p=0.471) for FVM lesions. Multiple gestation demonstrated borderline association with MVM (aOR=0.24, 95%CI 0.04-1.51, p=0.129) and total pathology score (aRR=0.79, 95%CI 0.62-1.01, p=0.058). Subgroup analysis suggested greater odds of villitis of unknown etiology (VUE) for OD-IVF (aOR=2.98, 95%CI 1.12-7.93, p=0.029)., Discussion: Source of oocyte derivation demonstrated no evidence of association with main outcomes in cases of HDP and/or IUGR. Subgroup analysis demonstrated increased rates of inflammatory lesions for OD-IVF. Multiple gestation may be associated with decreased MVM and total lesions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: A growing literature suggests that minority races, particularly Black women, have a lower probability of live birth and higher risk of perinatal complications after autologous assisted reproductive technology. However, questions still remain as to whether these racial disparities have arisen because of associations between race and oocyte/embryo quality, the uterine environment, or a combination of the two. Oocyte donation assisted reproductive technology represents a unique approach to examine this question., Objective: This study aimed to evaluate the associations between the race of female oocyte donors and recipients and live birth rates following vitrified donor oocyte assisted reproductive technologies., Study Design: This was a retrospective study conducted at a single, private fertility clinic that included 327 oocyte donors and 899 recipients who underwent 1601 embryo transfer cycles (2008-2015). Self-reported race of the donor and recipient were abstracted from medical records. Live birth was defined as the delivery of at least 1 live-born neonate. We used multivariable cluster weighted generalized estimating equations with binomial distribution and log link function to estimate the adjusted risk ratios of live birth, adjusting for donor age and body mass index, recipient age and body mass index, tubal and uterine factor infertility, and year of oocyte retrieval., Results: The racial profile of our donors and recipients were similar: 73% white, 13% Black, 4% Hispanic, 8% Asian, and 2% other. Women who received oocytes from Hispanic donors had a significantly higher probability of live birth (adjusted risk ratio, 1.20; 95% confidence interval, 1.05-1.36) than women who received oocytes from white donors. Among Hispanic recipients, however, there was no significant difference in probability of live birth compared with white recipients (adjusted risk ratio, 1.07; 95% confidence interval, 0.90-1.26). Embryo transfer cycles using oocytes from Black donors (adjusted risk ratio, 0.86; 95% confidence interval, 0.72-1.03) and Black recipients (adjusted risk ratio, 0.84; 95% confidence interval, 0.71-0.99) had a lower probability of live birth than white donors and white recipients, respectively. There were no significant differences in the probability of live birth among Hispanic, Asian, and other race recipients compared with white recipients., Conclusion: Black female recipients had a lower probability of live birth following assisted reproductive technology, even when using vitrified oocytes from healthy donors. Female recipients who used vitrified oocytes from Hispanic donors had a higher probability of live birth regardless of their own race., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Research Question: Do donor spermatozoa improve IVF outcomes after first oocyte donation failure?, Design: Retrospective, multicentre study including couples undergoing oocyte donation cycles using autologous or donor spermatozoa after a failed first attempt. Male partners were further characterized as normozoospermic or oligoasthenoteratospermic, i.e. fewer than 5 million motile progressive spermatozoa in the ejaculate. The main outcomes measured were live birth rate (LBR) per embryo transfer, LBR per number of embryos transferred, and cumulative LBR (CLBR) considering oocytes consumed in the previous donation cycles., Results: Analysis comprised 6065 cycles of oocyte donation failure; among these, subgroup analyses by sperm quality comprised 4113 cycles with severe male factor and 1150 cycles with suboptimal/normal spermatozoa. Sperm replacement in the first cycle after failure increased LBR per embryo transfer (OR 2.21, 95% CI 1.7-2.8, P < 0.001) and per number of embryos transferred (OR 2.46, 95% CI 1.9-3.1, P < 0.001) for normospermic and oligoasthenoteratospermic men. Replacement by the third cycle after failure was less beneficial (LBR per embryo transfer: OR 1.35, 95% CI 0.9-2.1, P = 0.16; LBR per embryos transferred: OR 1.33, 95% CI 0.9-2.0, P = 0.186). Kaplan-Meier curves of CLBR per oocyte fertilized with autologous or donor spermatozoa were statistically different (P < 0.001) and demonstrate how each additional oocyte may affect success based on sperm source (donor/autologous)., Conclusions: Donor spermatozoa improved outcomes when used after an initial failed oocyte donation cycle. The CLBR curves can be used to determine the cumulative chances of live birth using either autologous or donor spermatozoa, providing guidance on when to replace spermatozoa., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: It has been established that radiotherapy can increase the risk of adverse pregnancy outcomes. However, there is currently no consensus on the effective sterilizing dose of adulthood uterine radiotherapy., Design: This is a case report of a 36-year-old women with three different cancer types who received repeated high-dose radiotherapy of 66 Gy and 50 Gy to the pelvis. The study used a dose-volume histogram, the most widely used tool to calculate the radiation distribution within a volume of interest in a patient during radiotherapy. It was determined that the current patient's uterus might have received the highest uterine radiation dosage for full-term live birth that has been reported in the current literature., Results: Due to iatrogenic ovarian failure, the woman was only able to use donor eggs. After preparation of the endometrium for 18 days, it had reached 8.7 mm in thickness with a triple-line appearance. Two cleavage-stage embryos were transferred, one of which implanted successfully. The course of the pregnancy was uneventful. Finally, the patient gave birth to a healthy baby via Caesarean section at 38 +5 weeks of gestation., Conclusions: The uterus may be more resistant to radiotherapy than previously understood. Uterine fertility preservation methods should be guided by the age of the patient receiving radiotherapy and the actual dose of radiation exposure of the uterus. Future studies should implement a dose-volume histogram to calculate the radiation exposure of the reproductive organs., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The use of oocyte donation (OD) has increased continuously over the last three decades, and it is now an indispensable part of assisted reproductive technology (ART). With OD, it has become possible to overcome the biological barrier of ovarian follicle pool depletion and the general age-related decline in fertility. This review contains a thorough appraisal of the safety of OD with an analysis of short-term pregnancy outcomes. Salient up-to-date evidence was evaluated, which revealed that in comparison with both IVF with autologous oocytes, and naturally conceived pregnancies, there is: (i) an increased risk of hypertensive disorders of pregnancy and preeclampsia; (ii) an increased risk of low birth weight and preterm birth and (iii) an increased risks of obstetric emergencies, following OD treatment. As a precaution, it is therefore highly encouraged to perform only single embryo transfer (SET) and to prescribe prophylactic low-dose aspirin during OD pregnancies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

A delay in childbearing to later in life has increased the number of women of advanced maternal age (AMA) opting for assisted reproduction. Women should be made aware that there are age-related changes to fertility, including a decline in oocyte reserve and quality, in addition to an increase in the number of oocyte chromosomal aberrations. Success rates of assisted reproductive technology (ART) cycles decrease with advanced maternal age. There are different fertility options for women of AMA, including fertility preservation (oocyte or embryo freezing), in vitro fertilisation (IVF treatment) with or without preimplantation genetic screening and oocyte or embryo donation. Detailed counselling needs to be offered to these women with regard to the risks, success rates, ethical and legal implications of these fertility treatment options. Women of AMA should be screened for underlying medical conditions that could have an impact on maternal and neonatal morbidity and mortality., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

We sought to assess chronic inflammatory responses in patients who achieved pregnancy by oocyte donation and non-oocyte donation-assisted reproductive technology and delivered at The Ottawa Hospital. Data describing maternal health, obstetrical outcomes, neonatal outcomes, and placental pathology were collected and analyzed from electronic medical records. An increased frequency of adverse obstetrical outcomes was observed. In the oocyte donation-assisted reproductive technology group, placental pathology data demonstrated increased frequency of fetal vascular malperfusion (p = 0.02) and placenta accreta (p < 0.001), representing a chronic inflammatory response. Placental pathology reflecting dysregulated immune processes and vasculopathy is associated with oocyte donation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Research Question: To evaluate pre-existing comorbidities, obstetric risk factors and adverse obstetric and neonatal outcomes in pregnancies conceived by oocyte donation, compared with naturally conceived pregnancies or by conventional IVF/intracytoplasmic sperm injection (IVF/ICSI)., Design: This retrospective single-centre contemporary cohort study reviewed data from singleton deliveries at the University Hospital of Careggi, Florence, from 2009 to 2017. Maternal and perinatal outcomes were analysed., Results: The study included 25,851 pregnancies and newborns: 276 (1.1%) children were conceived after oocyte donation, 925 (3.6%) after IVF/ICSI and 24,650 (95.4%) after natural conception. Women in the oocyte donation group were significantly older compared with IVF/ICSI and natural conception groups (P < 0.0001) and had a higher prevalence of chronic hypertension compared with the natural conception group (P = 0.0090). They were administered anticoagulant medications more frequently during pregnancy. The incidence of gestational hypertension was significantly higher than in natural conception (aOR 3.6) and IVF/ICSI pregnancies (aOR 2.7). The incidence of Caesarean section in oocyte donation pregnancies was higher than in natural conception and IVF/ICSI groups (aOR 3.4 and 2.3, respectively). An 11-fold increased risk of post-partum haemorrhage (PPH) was found in oocyte donation versus natural conception and an almost four-fold increased risk was found in oocyte donation versus IVF/ICSI; prematurity and low birthweight were more frequent after oocyte donation versus natural conception (aOR 2.4 and 1.8, respectively)., Conclusions: Patients undergoing oocyte donation represent a group with increased comorbidities and risk factors for adverse obstetric outcomes. Oocyte donation seems to be independently associated with gestational hypertension and PPH. Pregnancies after oocyte donation warrant clinical surveillance with proper screening and, possibly, preventive strategies., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: Oocyte donation (OD) is associated with an increased risk of pregnancy-induced hypertension, but the evidence of an association between OD and infant outcomes, including birth weight and gestational age, is conflicting. This study sought to determine the associations between oocyte donation and birth weight or gestational age compared with other forms of autologous oocyte assisted reproductive technology (ART)., Methods: Medline, Embase, and the CENTRAL Trials Registry of the Cochrane Collaboration were searched using a comprehensive search strategy. Studies of women over 24 weeks gestation compared infant outcomes among OD pregnancies versus other ART. Study quality was assessed, and a meta-analysis of mean birth weight and gestational age was conducted using a random effects model., Results: Nineteen studies were included. Four studies showed a significant association between OD and lower birth weights, and five studies found significant differences in gestational age between OD and autologous oocyte ART. The pooled difference in birth weight means between OD and autologous ART was -42 (-88, 4) . The pooled difference in gestational age was -0.4 weeks (-0.8, 0.0 weeks)., Conclusion: A high degree of interstudy heterogeneity exists, and the association between OD and infant outcomes remains unclear., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Research Question: The study aimed to evaluate the percentage of oocyte donors who regretted their donation at least 3 years later., Design: Between December 2018 and January 2019, this single-centre study sought to contact by telephone all women who had donated oocytes during the 6-year period from 2010 to 2015 at the Lille Centre for the study and storage of eggs and spermatozoa (CECOS)., Results: Among 118 women, 72 responded to the questionnaire by telephone and were included in the study. The response rate was 61%. No woman regretted having donated an oocyte, and 89% said that they would do it again in the same situation. The survey distinguished two types of donors: 'relational' (58%) and 'altruistic' (42%); some of their responses differed. Ninety per cent of the women had talked about the donation to family and friends. Among them, 74% felt supported by their family and friends, and 72% by their partner. The donation was something that 76% of the women sometimes thought about; 83% felt that this donation was something useful that they had accomplished. Finally, most donors felt that oocyte donation should remain unremunerated and anonymous., Conclusions: None of the donors we interviewed regretted their donation. In France, the current principles governing this donation appear satisfactory to oocyte donors., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Is minority race associated with worse oocyte donation outcomes?, Design: Retrospective analysis of 926 oocyte recipients who underwent a donor cycle with fresh embryo transfer at a single fertility centre between January 2009 and June 2015. Race was self-reported. To adjust for repeat donors within the sample, mixed models were used to analyse donor parameters and recipient outcomes. The recipient outcome models were adjusted for age, body mass index and primary infertility diagnosis., Results: The study consisted of 767 (82.8%) White, 41 (4.4%) Black, 63 (6.8%) Asian and 55 (5.9%) Hispanic women. Compared with White recipients, the adjusted odds ratio (aOR) for clinical pregnancy was 0.39 (95% confidence interval [CI] 0.19-0.79) for Black, 0.55 (95% CI 0.31-0.98) for Hispanic and 0.88 (95% CI 0.51-1.53) for Asian recipients. The aOR for live birth was 0.47 (95% CI 0.23-0.98) for Black, 0.58 (95% CI 0.32-1.06) for Hispanic and 0.62 (95% 0.35-1.09) for Asian recipients. A subgroup analysis restricted to cycles with racially concordant donors and recipients showed that the odds of clinical pregnancy and live birth were further reduced among Black recipients, with aOR of 0.28 (95% CI 0.09-0.81) and 0.30 (95% CI 0.09-0.98), respectively., Conclusions: Black and Hispanic oocyte donation recipients experience lower clinical pregnancy rates and Black recipients experience lower live birth rates compared with White recipients. Racially discordant donor oocyte cycles involving donors and recipients of different races present an opportunity to further investigate the cause of disparity., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Is live birth rate among recipients of donated oocytes different depending on mode of treatment for endogenous LH suppression administered to oocyte donors during ovarian stimulation?, Design: A retrospective cohort study of recipients of freshly donated oocytes from oocyte donors who underwent ovarian stimulation with gonadotrophins at a private, university-based infertility clinic between January 2017 and March 2018. For endogenous LH suppression, oocyte donors received daily injections of gonadotrophin releasing hormone antagonist ganirelix (GNR) or daily oral 75 µg desogestrel (DSG) until triggering with 0.2 mg of triptorelin. Three hundred recipient cycles of freshly donated oocytes were included: 154 from oocyte donor DSG cycles and 146 from oocyte donor GNR cycles., Results: Comparison of basal characteristics of oocyte donors showed no differences in mean age, anti-Müllerian hormone levels and body mass index between the oocyte donor DSG p and oocyte donor GNR groups, respectively. Similarly, no differences were observed among mean age of recipients and body mass index. Out of 300 fresh embryo transfers, 190 clinical pregnancies (63.3%) and 150 live births (50%) were achieved. Per embryo transfer clinical pregnancy rate was 66.2% in the DSG recipient group and 60.3% in the GNR recipient group (P = 0.338). Live birth rates were not significantly different between both groups (48.7% among DSG recipient group and 51.4% among GNR recipient group; P = 0.729)., Conclusions: Live birth rate among recipients of donated oocytes does not differ depending on the mode of treatment for endogenous LH suppression administered to the oocyte donors during ovarian stimulation. This information is reassuring and will be of interest to teams using these kinds of protocols, although further research is needed., (Copyright © 2020. Published by Elsevier Ltd.)