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

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.

Reproductive outcomes of oocyte donation in patients with uterine Müllerian anomalies.

OBJECTIVE: To evaluate live-birth rates per embryo transfer in patients with uterine Müllerian anomalies (UMAs). Secondary objectives were to compare reproductive outcomes between the normal uterus group, the different UMA types, and UMA subgroups with and without required surgery. DESIGN: This retrospective study compared two cohorts, one with UMAs and other with normal uteri of our oocyte donation program at 12 Instituto Valenciano De Infertilidad/Reproductive Medicine Associates University affiliated clinics from January 2000 to 2020. The oocyte donation reduces confounding because of differences in embryo quality. The primary outcome was the live-birth rate per embryo transfer. Secondary outcomes included the rates of implantation, clinical pregnancy, miscarriage, and ongoing pregnancy. We calculated odds ratios with 95% confidence intervals. PATIENTS: Infertile women undergoing oocyte donation with UMAs. INTERVENTION: None. MAIN OUTCOME MEASURES: The rates of implantation, clinical pregnancy, miscarriage, ongoing pregnancy, and live birth. RESULTS: We analyzed 58,337 cycles of oocyte donation: 57,869 patients had no uterine malformation, and 468 women had UMAs. Compared with patients with normal uteri, patients with UMAs had lower rates of live births (36.67% [32.84-40.65] vs. 38.1% [95% confidence intervals {CI}: 37.82-38.42]) and ongoing pregnancy (39.74% [35.93-43.66] vs. 41.5% [41.24-41.83]). The miscarriage rate was higher in patients with UMAs (19.5% [16.55-22.85] vs. 16.6% [16.47-16.92]). Specifically, patients with a unicornuate uterus (n=29) had lower rates of implantation (24.07% [13.49-37.64] vs. 42.85% [95% CI: 42.6-43.09]), pregnancy (41.86% [27.01-57.87] vs. 59.51% [59.22-59.81]), ongoing pregnancy (16.67% [6.97-31.36] vs. 41.54% [41.24-41.83]), and live births (16.67% [6.97-31.36] vs. 38.12% [37.83-38.42]). In addition, patients with a partial septate uterus (n=91) had a higher miscarriage rate (26.50% [18.44-34.89] vs. 16.7% [16.47-16.92]). Compared with the normal uterus group, the live-birth rates were lower in the UMA without surgery group (33.09% [27.59-38.96] vs. 38.12% [37.83-38.42]). CONCLUSION: Among patients who received embryos derived from donated oocytes, live birth and ongoing pregnancy rates were lower in patients with UMAs compared with patients with normal uteri. A higher miscarriage rate was found in patients with UMAs. Patients with a unicornuate uterus had worse reproductive outcomes. Our results show that the uterus is less competent in patients with UMAs. TRIAL REGISTRATION: This study was registered at clinicaltrial.gov (NCT04571671).

Preeclampsia risk in oocyte donation versus double gamete donation pregnancies: A systematic review and meta-analysis.

The number of pregnancies achieved through gamete donation has escalated over the last decades. It has been hypothesized that double gamete donation pregnancies would have a higher risk of preeclampsia compared to single gamete donation pregnancies due to cumulative risk of preeclampsia in oocyte donation pregnancies and the separate risk associated with sperm donation. Therefore, a systematic review and meta-analysis was conducted to explore the association between double gamete donation pregnancies and the development of preeclampsia and gestational hypertension, comparing it with oocyte donation alone. A systematic search of five databases was conducted and meta-analysis was performed using a random-effects model. Of 795 screened articles, five met our selection criteria for a systematic review, and four were included in the meta-analysis.No statistically significant differences were found in the risk of preeclampsia between study subgroups (odds ratio [OR] 0.82; 95% confidence interval [95%CI] 0.29-2.36), even after subgroup analysis considering only high-quality studies (OR 1.30; 95%CI 0.61-2.76; I2 = 0%). Regarding gestational hypertension risk, neither the pooled analysis (OR 0.52; 95%CI 0.18-1.49; I2 = 84%) nor the high-quality studies subgroup analysis (OR 0.67; 95%CI 0.33-1.35; I2 = 0%) find any significant differences between oocyte donation or double gamete donation pregnancies. There appears to be little difference in gestational hypertension or preeclampsia risk between pregnancies resulting from double gamete donation and those from oocyte donation alone. Strict obstetrical surveillance should be considered standard of care for these women, in an attempt to perform early diagnosis and management of hypertensive disorders.

Development of hypertensive complications in oocyte donation pregnancy: protocol for a systematic review and individual participant data meta-analysis (DONOR IPD).

INTRODUCTION: The assisted reproductive technique of oocyte donation (OD) is comparable to in vitro fertilisation (IVF), with the distinction of using a donated oocyte and thus involving two women. Compared with IVF and naturally conceived (NC) pregnancies, OD pregnancies have a higher risk for pregnancy complications as pregnancy-induced hypertension (PIH) and pre-eclampsia (PE). Various covariates among women pregnant by OD, however, also contribute to an increased risk for developing hypertensive complications. Therefore, we will conduct the DONation of Oocytes in Reproduction individual participant data (DONOR IPD) meta-analysis to determine the risk for the development of hypertensive complications in OD pregnancy, in comparison to autologous oocyte pregnancy (non-donor IVF/intracytoplasmic sperm injection (ICSI) and NC pregnancy). The DONOR IPD meta-analysis will provide an opportunity to adjust for confounders and perform subgroup analyses. Furthermore, IPD will be used to externally validate a prediction model for the development of PE in OD pregnancy. METHODS AND ANALYSIS: A systematic literature search will be performed to search for studies that included women pregnant by OD, and documented on hypertensive complications in OD pregnancy. The authors from each study will be asked to collaborate and share IPD. Using the pseudoanonymised combined IPD, we will perform statistical analyses with one-stage and two-stage approaches, subgroup analyses and possibly time-to-event analyses to investigate the risk of developing hypertensive complications in OD pregnancy. Furthermore, we will formally assess a prediction model on its performance in an external validation with the use of IPD. ETHICS AND DISSEMINATION: Ethical approval and individual patient consent will not be required in most cases since this IPD meta-analysis will use existing pseudoanonymised data from cohort studies. Results will be disseminated through peer-reviewed journals and international conferences. PROSPERO REGISTRATION NUMBER: CRD42021267908.

Pre-eclampsia in pregnancies resulting from oocyte donation, natural conception or IVF: a systematic review and meta-analysis.

STUDY QUESTION: What is the prevalence of pre-eclampsia (PE) in pregnancies after oocyte donation (OD) compared to natural conception (NC) and to IVF with autologous oocytes (AO)? SUMMARY ANSWER: Overall the prevalence of PE after OD was 4-5 times higher than after NC and 2-3 times higher than after IVF with AO. WHAT IS KNOWN ALREADY: The indication for OD is expanding to lesbian women requesting shared lesbian motherhood. Previous reviews have shown that the risk of PE is higher in pregnancies after OD than after NC and after IVF with AO. Classification on the severity of PE is lacking as is the relationship with known risk factors such as maternal age and multiple gestations. Furthermore the actual prevalence of PE in pregnancies resulting from OD is not known. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis was conducted. A literature search was performed using the following databases: PubMed, EMBASE and CINAHL, OpenGrey and Greynet from January 1980 through July 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included retrospective and prospective cohort studies. The study population consisted of pregnancies after OD and NC or IVF and data had to be available about prevalence of PE. We compared the risk of (severe) PE in OD versus NC and IVF pregnancies, subgrouped by plurality and maternal age. We calculated individual and pooled odds ratios (OR) and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 27 studies comprising of 7089 OD pregnancies, 1 139 540 NC pregnancies and 72 742 IVF pregnancies were available for analysis. The risks of PE and severe PE was increased in OD pregnancies compared to NC pregnancies (pooled OR of all subgroups: 5.09, 95% CI: 4.29-6.04; I2 = 19% and OR: 7.42, 95% CI: 4.64-11.88; I2 = 49%, respectively). This suggests that compared to a PE risk of 2.9% with NC, the risk with OD was between 11.5% and 15.4%. Compared to a severe PE risk of 0.5% with NC, the risk with OD was between 2.3% and 5.6%. The pooled adjusted OR for PE was 3.24 (95% 2.74-3.83) for OD versus NC pregnancies. The risks of PE and severe PE were also increased in OD pregnancies compared to IVF pregnancies (pooled OR of all subgroups: 2.97, 95% CI: 2.49-3.53; I2 = 51% and OR: 2.97, 95% CI: 2.15-4.11; I2 = 0%, respectively). This suggests that compared to a PE risk of 5.9% with IVF, the risk with OD was between 13.5% and 18.0%. Compared to a severe PE risk of 3.3% with IVF, the risk with OD was between 6.8% and 12.2%. The pooled adjusted OR for PE was 2.67 (95% 2.28-3.13) for OD versus IVF. The pooled prevalence of PE in singleton pregnancies after OD was 10.7% (95% CI 6.6-15.5) compared to 2.0% (95% CI 1.0-3.1) after NC and 4.1% (95% CI 2.7-5.6) after IVF. The prevalence in multiple pregnancies was 27.8% (95% CI 23.6-32.2) after OD, 7.5% (95% CI 7.2-7.8) after NC and 9.7% (95% CI 6.2-13.9) after IVF. LIMITATIONS, REASONS FOR CAUTION: The precise definition of PE is still a matter of debate. The different criteria could have affected the prevalence estimate. WIDER IMPLICATIONS OF THE FINDINGS: Nearly one in six women will suffer PE after OD. Although it is uncertain whether these risks are consistent for lesbian couples undergoing shared motherhood, we feel that women who can conceive naturally could be advised to reconsider. In women with primary ovarian insufficiency, we feel that factors that may increase risk of PE ever further, such as double embryo transfer, should be avoided whenever possible. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests. REGISTRATION NUMBER: CRD42020166899.

Factors affecting live birth rates in donor oocytes from commercial egg banks vs. program egg donors: an analysis of 40,485 cycles from the Society for Assisted Reproductive Technology registry in 2016-2018.

OBJECTIVE: To examine the differences in live birth rates (LBRs), with single embryo transfer (SET), using oocytes from program generated egg donors vs. commercial egg bank donors and other factors affecting LBRs using donor oocytes. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 40,485 in vitro fertilization cycles using donor oocytes reported to the Society for Assisted Reproductive Technology registry in 2016-2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate and cumulative LBR for SET using donor oocytes. RESULT(S): Multivariate results from the first SET from 19,128 cycles, including 15,429 from program generated egg donors and 3,699 from commercial egg banks, showed, when controlling for all other variables, the following: the LBR in the first SET cycle using commercial egg banks was 53.3% compared with 55.4% using program recruited egg donors (odds ratio [OR], 0.92); a reduction in the LBR with increasing recipient age, ages 40-44 years (OR, 0.80), 45-49 years (OR, 0.77), and >49 years (OR, 0.65); a steady decline in the LBR with increases in recipient body mass index above normal; and a steady increase in the LBR in association with >16 oocytes retrieved. Double embryo transfer increased the LBR (SET, 52%, vs. double embryo transfer, 58%) but also significantly increased the multiple pregnancy LBR, with 43% twins and 0.9% triplets. Blastocyst transfer had a higher LBR than cleavage stage embryos (52.5% vs. 39.5%). Intracytoplasmic sperm injection vs. conventional insemination when using fresh oocytes from program donors had similar LBRs. CONCLUSION(S): When performing in vitro fertilization using donor oocytes with SET, the LBR is affected by oocyte source, recipient age, recipient body mass index, stage of embryo at transfer, and number of oocytes retrieved.

Characteristics of preeclampsia in donor cell gestations.

Pregnancies conceived through donor oocytes or sperm show increased risk for preeclampsia. We studied this issue in a preeclampsia case-control cohort (n = 2778), and found overrepresentation of donor cell gestations among women with preeclampsia (14/1627, 0.86%; OR 1.81; 95% CI: 1.07-3.08; P = 0.025) compared to the population data. Moreover, we observed excess of male births from donor cell pregnancies (male-to-female ratio 2.5 vs. 0.97; OR 2.57; 95% CI 1.02-6.36; P = 0.043). Maternal age (36.7 vs. 30.2; P < 0.0001) and preterm deliveries (64% vs. 38%; P = 0.046) distinguished donor cell gestations from other pregnancies with preeclampsia. These results support foreign fetal antigens as modulators of preeclampsia.

Lifting the veil of secrecy: maternal and neonatal outcome of oocyte donation pregnancies in Germany.

BACKGROUND: In Germany, performing fertility procedures involving oocyte donation is illegal, as stated by the Embryo Protection Law. Nonetheless, in our clinical routine we attend to a steadily rising number of pregnant women, who have sought oocyte donation abroad. Due to the legal circumstances many women opt to keep the origin of their pregnancy a secret. However, studies have shown, that oocyte donation is an independent risk factor for the development of pregnancy complications, such as preeclampsia. OBJECTIVE: The aim of this study is to evaluate maternal and neonatal outcomes of oocyte donation pregnancies in three large obstetric care units in Berlin, Germany. METHODS: We retrospectively analyzed all available medical data on oocyte donation pregnancies at Charité University hospital, Vivantes Hospital Friedrichshain, and Neukoelln in the German capital. RESULTS: We included 115 oocyte donation (OD) pregnancies in the present study. Our data are based on 62 singleton, 44 twin, 7 triplet, and 2 quadruplet oocyte donation pregnancies. According to our data, oocyte donation pregnancies are associated with a high risk of adverse maternal and fetal outcome, i.e., hypertension in pregnancy, preterm delivery, Cesarean section as mode of delivery, and increased peripartum hemorrhage. CONCLUSION: Although oocyte donation is prohibited by German law, many couples go abroad to seek reproductive measures using oocyte donation after former treatment options have failed. OD pregnancies are associated with a high risk of preeclampsia, C-section as mode of delivery, and peripartum hemorrhage. Detailed knowledge of the associated risks is of utmost importance to both the patient and the treating physician and midwife.

Oxidative Stress Induces Telomere Dysfunction and Shortening in Human Oocytes of Advanced Age Donors.

Research from the past decades provided strong evidence that in humans the pool of oocytes starts to decline already before the birth of a female individual, and from menarche to menopause the oocyte is exposed to different environmental stimuli. Since more and more women of the 21st century in developed countries wish to postpone the first pregnancy to their thirties, higher rates of miscarriage and chromosomal non-disjunction might occur. In oocytes of advanced maternal age, meaning above 35 years of age, characteristics such as chromosomal instabilities/abnormalities, spindle defects, decreased mitochondrial function and telomere shortening become more prevalent than in younger counterparts. Telomere attrition belongs to the so-called "hallmarks of aging" which are also relevant for the female germ-line cells. In oocytes, telomeres shorten with advancing maternal age due to the effects of reactive oxygen species and not upon replicative senescence, similar to how it is common in dividing cells.

Predictive value of cytoplasmic granulation patterns during in vitro fertilization in metaphase II oocytes: part II, donor oocyte cycles.

OBJECTIVE: To determine whether the ooplasm granulation patterns of donor oocytes, like those of oocytes from poor-prognosis patients, are predictive of in vitro fertilization (IVF) outcomes. DESIGN: Retrospective cohort study. SETTING: Academically affiliated private clinical infertility and research center. PATIENT(S): 770 fresh and 381 vitrified-thawed metaphase II oocytes from young donors (aged 21.0-34.6 years) used for IVF during 2017-2020. INTERVENTION(S): Determination of granulation patterns in every oocyte during intracytoplasmic sperm injection as fine, central, uneven, dispersed, and peripheral (thawed only). MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and live birth rates in fresh and thawed donor oocytes. Both overall and known-outcome analyses were performed for pregnancy and live birth. RESULT(S): In fresh donor oocytes, 2 pronuclei rates trended down from 96.1% to 90.2%, 88.9%, and 69.7% from fine to central, uneven, and dispersed granulations; overall pregnancy rates trended down from 50.4% to 29.0%, 17.7%, and 6.9%, as well as live birth rates (43.4%, 21.6%, 12.5%, and 6.4%), from fine to uneven, central, and dispersed granulations. Known pregnancy and known-live birth analyses showed similar findings. Thawed donor oocytes demonstrated similar trends in differences in fertilization, pregnancy, and live birth analyses with relatively worse outcomes. Peripheral granulation, unique to vitrification and thawing, always demonstrated the worst IVF outcomes. Moreover, granulation patterns were relatively disassociated from embryo morphological grades in fresh and largely disassociated in thawed donor oocytes. CONCLUSION(S): Predictive values of oocyte granulation patterns for fertilization, pregnancy, and live birth in IVF cycles are even more pronounced in young donors than results in older poor-prognosis patients, further supporting integration of oocyte granulation patterns into embryo selection.

Laser therapy for twin-twin transfusion syndrome in a dizygotic monochorionic twin pregnancy: A case report.

OBJECTIVE: A monochorionic dizygotic (MCDZ) twin is rare, especially when complicated with twin-twin transfusion syndrome (TTTS) and treated by laser therapy. CASE REPORT: A pregnancy achieved from oocyte donation and intracytoplasmic sperm injection resulted in two embryos transferred. A monochorionic diamniotic twin pregnancy was diagnosed by an early ultrasound; however, at 16 weeks of gestation, instead of the same sex, the ultrasound suspected there was sex discrepancy between the twins. TTTS with severe polyhydramnios occurred at 22 weeks, leading to a laser therapy, which was followed with a smooth post-operation course. Then the Cesarean section was performed at the gestational age of 29 weeks due to severe preeclampsia, giving birth to two live newborns: one female and one male baby both without neurological sequelae at the time of discharge. Blood chromosomes obtained at delivery and 65 days after delivery all revealed an XX and XY chimera from both babies. CONCLUSION: Laser therapy is also effective in MCDZ twin complicated with TTTS. Determination of chorionicity in early pregnancy could timely prompt us to watch out for complications unique to monochorionic twin pregnancy.

Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC). METHODS: We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups. RESULTS: Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60-1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20-1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00-6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58-1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33-1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively). CONCLUSIONS: Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.

Guidance regarding gamete and embryo donation.

This document provides the latest recommendations for the evaluation of potential sperm, oocyte, and embryo donors as well as their recipients, incorporating recent information about optimal screening and testing for sexually transmitted infections, genetic diseases, and psychological assessments. This revised document incorporates recent information from the US Centers for Disease Control and Prevention, US Food and Drug Administration, and American Association of Tissue Banks, which all programs offering gamete and embryo donation services must be thoroughly familiar with, and replaces the document titled "Recommendations for gamete and embryo donation: a committee opinion," last published in 2013.

Cardiometabolic and Thrombotic Risk Profile in Women Undergoing Oocyte Donation for Assisted Reproduction.

Background: The last two decades have seen a growing number of pregnancies in women who needed the donation of oocytes. With oocyte donation pregnancies, studies on obstetric outcomes among these women revealed an increased incidence of pre-eclampsia and pregnancy-induced hypertension. Furthermore, several studies have found a higher incidence of low birth weight, preterm birth, and delivery by cesarean section in oocyte donation rather than in women subjected to assisted reproduction techniques (ART) with autologous oocytes. Numerous studies have also shown a deep connection between cardiovascular and thrombotic risk factors and adverse pregnancy outcomes. In this setting, to strictly assess the preconceptional risk for women who undergo egg donation to achieve pregnancy, the aim of our study is to draw a detailed assessment of the vascular risk profile of patients with gamete donation ART indications through the evaluation of comorbidities and cardiometabolic and thrombophilic markers Materials and Methods: Patients undergoing ART with oocyte or sperm donation or double donation of gametes underwent a careful clinical assessment through a detailed personal and family anamnesis and they were evaluated for cardiometabolic and thrombophilic profile. Clinical and demographic characteristics, comorbidities, and biohumoral parameters were collected. The study was approved by the Regional Ethical Committee(Em 2018-017 CINECA 10189). Results: We evaluated 525 women. Around 73.1% were >40 years and 35% of them were older than 45 years. There was a high prevalence of dyslipidemias (58.1%), smoking habit (24.6%), a body mass index >25 in 28.6% of patients, a high abdominal circumference in 58.1% of cases, a prevalence of acquired thrombophilia in about 7% and hereditary of 19.2%. Around 39.2% of patients had total cholesterol >200 mg/dL, 19.5% had high-density lipoprotein <48 mg/dL and 43.6% had low-density lipoprotein >115 mg/dL, and 6.9% had triglyceride values >150 mg/dL. Conclusions: A careful assessment of the preconceptional status of patients undergoing ART programs with oocyte donation can be highly recommended.

Abnormal placental pathological findings and adverse clinical outcomes of oocyte donation.

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.

Decreased expression of ligands of placental immune checkpoint inhibitors in uncomplicated and preeclamptic oocyte donation pregnancies.

Oocyte donation (OD) pregnancies are characterized by a complete immunogenetic dissimilarity between mother and fetus, which requires enhanced immunoregulation compared to naturally conceived (NC) pregnancies. The trophoblast expresses co-inhibitory ligands crucial for regulation of the maternal T cell response. Therefore, we studied the role of placental immune checkpoint inhibitors for the establishment of fetal tolerance and their relation to the development of preeclampsia in OD compared to NC pregnancies. Placental tissue from uncomplicated OD (n = 21) and NC (n = 21) pregnancies, and OD (n = 9) and NC (n = 15) pregnancies complicated with preeclampsia were studied. Protein expression of co-inhibitory ligands PD-L1 and CD200 was double blind semi-quantitatively determined by immunohistochemistry. Messenger RNA expression of PD-L1, CD200 and indoleamine 2,3-dioxygenase (IDO) was determined using qPCR. Decreased PD-L1 and CD200 protein expression and increased IDO mRNA expression was observed in uncomplicated OD versus NC pregnancies (all p < 0.05). CD200 protein expression was positively correlated with PD-L1 expression in all groups, with the number of HLA total mismatches and with HLA class I mismatches in uncomplicated OD cases (all p < 0.05). Preeclamptic cases showed lower PD-L1 protein and CD200 protein and mRNA expression in OD compared to NC pregnancies (all p < 0.05). This study shows that signaling by co-inhibitory PD-L1 and CD200 and by immunosuppressive IDO is altered in the placenta of OD pregnancies, suggesting a contribution to the higher risk for preeclampsia. These insights provide future prospects in unraveling the immune paradox of oocyte pregnancy, which are applicable for better risk management and treatment of uncomplicated and preeclamptic pregnancies.

Is there a correlation between paternal age and aneuploidy rate? An analysis of 3,118 embryos derived from young egg donors.

OBJECTIVE: To investigate a possible correlation between chromosomal aberrations and paternal age, analyzing embryos derived from young oocyte donors, with available preimplantation genetic testing for aneuploidy results from day 5/6 trophectoderm biopsy obtained by next-generation sequencing for all 24 chromosomes. DESIGN: Retrospective cohort study. SETTING: Canadian fertility centre. PATIENT(S): A total of 3,118 embryos from 407 male patients, allocated into three paternal age groups: group A, ≤39 years (n = 203); group B, 40-49 years (n = 161); group C, ≥50 years (n = 43). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcomes were aneuploidy, euploidy, mosaicism, and blastocyst formation rates. Secondary endpoints were comparison of specific chromosome aneuploidy, segmental and complex (involving two chromosomes + mosaicism >50%) aneuploidy, and analysis of overall percentage of chromosomal gains and losses within each group. RESULT(S): The study included 437 in vitro fertilization (IVF) antagonist cycles using 302 oocyte donors in which preimplantation genetic testing for aneuploidy was performed. Overall, 70.04% of embryos were euploid, 13.9% were aneuploid, and 16.06% were mosaic. No significant differences among paternal age groups A, B, and C were found in euploidy rates (69.2%, 70.6%, 71.4%, respectively), aneuploidy rates (14.7%, 12.8%, 13.9%, respectively) or mosaicism rates (16.1%, 16.6%, 13.6%; respectively). The fertilization rate was lower in group C compared with group B (76.35% vs. 80.09%). No difference was found in blastocyst formation rate between the study groups (median 52% [interquartile range, 41%, 67%] vs. 53% [42%, 65%] vs. 52% [42%, 64%], respectively). A generalized linear mixed model regression analysis for embryo ploidy rates found older oocyte donor age to be independently associated with embryo aneuploidy (odds ratio = 1.041; 95% CI, 1.009-1.074). The rate of segmental aneuploidies was significantly higher in the older versus younger paternal age group (36.6% vs. 19.4%). CONCLUSION(S): No association was found between paternal age and aneuploidy rates in embryos derived from IVF cycles using young oocyte donors, after adjusting for donor, sperm, and IVF cycle characteristics. Advanced paternal age ≥ 50, compared with younger paternal ages, was associated with a lower fertilization rate and increased rate of segmental aberrations.

Comorbidities, risk factors and maternal/perinatal outcomes in oocyte donation pregnancies.

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.

Repetitive oocyte donation: a committee opinion.

Donors should be advised of the number of cycles/donations that a given oocyte donor may undergo. Although existing data cannot permit conclusive recommendations, concern for the issues of safety and well-being of oocyte donors warrants consideration. This document replaces the document of the same name, previously published in 2014.

Who's Afraid of the Big Bad (Germline Editing) Wolf?

Germline genome editing has garnered dire predictions about its societal effects, but experience with other reproductive technologies should caution us about making extravagant claims. Amniocentesis was predicted to result in increased stigmatization of people born with Down syndrome, but in fact people with these conditions have been increasingly integrated into schools and workplaces. Artificial insemination by donor was predicted to result in women choosing to "optimize" their children, but in fact most women eschewed the offerings of the so-called "genius sperm bank," and when choosing among donors, have tended to look for those who most resemble their husbands and partners. IVF was predicted to cause parents to view children as commodities, but no such change has been evidenced. Preimplantation genetic diagnosis was predicted to become widespread and used for an ever-increasing range of conditions, including those unrelated to serious disease or shortened life span, but this has not happened either. Critics of germline genome editing have argued that even if it were safe and effective, it would inevitably be abused by prospective parents who wish to improve upon what is already predicted to be a healthy outcome, and that this practice would become sufficiently widespread among those able to afford it that we would be creating a new genetic caste system. Before developing policy around such predictions, it is important to learn from the past.