Oocyte Donation Pregnancies Research Articles

Oocyte donation pregnancies with high fetal-maternal immunogenetic dissimilarity show alterations in the maternal peripheral immunoregulatory response

Oocyte donation (OD) pregnancies result in increased fetal-maternal immunogenetic dissimilarity due to paternal and donor-derived genes. Higher fetal-maternal HLA mismatches are correlated with preeclampsia. Therefore, this study explored the maternal immune response, focusing on regulatory T cells (Tregs), during low versus high allogeneic pregnancies, and healthy versus preeclamptic OD pregnancies. Ten healthy and five preeclamptic OD pregnancies were included. Maternal peripheral blood was collected at different stages of pregnancy. Fetal-maternal HLA mismatches were determined, and immunophenotyping of peripheral blood mononuclear cells was conducted using a 22-colour spectral flow cytometry panel. Cytokines and hormones were detected in maternal plasma using ELISA and Luminex assays. The findings show similarities, but also distinct differences between low and high allogeneic healthy OD pregnancies. Early high allogeneic OD pregnancy showed reduction in Tregs, and CD8+ T cells, alongside lower percentage of effector/memory Tregs expressing PD-1 and Helios. Additionally, high allogeneic OD pregnancies showed increased IL-6 and progesterone in the first trimester. These variations suggest a different mode of immune regulation in early high allogeneic OD pregnancies, possibly to maintain healthy pregnancy. Further comparative analyses revealed reduced CD45RO+CTLA-4+ Tregs and increased latent TGF-β1 and -β2 levels in early preeclamptic compared to healthy OD pregnancy. Late-stage preeclamptic OD pregnancies exhibited higher frequencies of CD45RO+TIGIT+ Tregs and higher levels of TNFα, indicating both a regulatory and pro-inflammatory environment. Overall, this study sheds light on the course of various immunoregulatory key players in OD pregnancy, and expands knowledge on maternal tolerance in this particular type of pregnancy.

Perinatal Outcomes of Singleton, Twin and Triplet Gestations after Oocyte Donation: A Retrospective, Population-Based Cohort Analysis.

Although high live birth rates are associated with oocyte donation (OD), these pregnancies are associated with increased obstetric and perinatal risks. This study evaluated maternal and neonatal risks after OD compared to in vitro fertilization (IVF) with autologous oocytes, and to spontaneous pregnancies (SPs), among singletons, twins and triplets. A retrospective, large, population-based cohort study was conducted based on electronic data from Maccabi Healthcare Services. A total of 469,134 pregnancies were grouped according to the mode of conception. The main outcome measures were preterm birth (PTB), small for gestational age (SGA) and pregnancy-induced hypertension (PIH). The data were analyzed separately for singletons, twins and triplets. The mean maternal age was older in the OD group compared with the IVF and SP groups (singletons: 39.7 ± 4.1 vs. 34.5 ± 4.8 and 31.7 ± 5.3 years; twins: 39 ± 4.6 vs. 32.6 ± 4.4 and 31.2 ± 5.1 years; and triplets: 35.6 ± 2.5 vs. 32 ± 3.9 and 29.7 ± 5 years). The mean gestational age was younger among the OD group compared to the SP group (singletons: 37.5 ± 3 vs. 39 ± 2 p = 0.001, and twins: 35 ± 3 vs. 36 ± 2.5 p = 0.001). Higher rates of PTB < 37, PTB < 34 and PTB < 28 weeks were found among OD singletons. Multivariable logistic regressions for PTB < 37 weeks and SGA in singletons demonstrated that OD and IVF are significant risk factors (OR = 4.1, 95%CI = 3.3-5.2; OR = 4.3, 95%CI = 4.1-4.6; OR = 1.9, 95%CI = 1.3-2.6; OR = 2.2, 95%CI = 2-2.4, respectively). Significantly higher rates of PIH were demonstrated among the OD vs. IVF and SP groups in singleton (4.3% vs. 1.7% and 0.7%) and in twin pregnancies (7.5% vs. 4.3% and 3.4%). OD pregnancies are at increased risk for PTB, SGA and PIH.

Hypertensive disorders and pregnancy outcomes in oocyte donation pregnancy in comparison with in vitro fertilization group

Hypertensive disorders and pregnancy outcomes in oocyte donation pregnancy in comparison with in vitro fertilization group

P-724 Long-term health outcomes of 19 years follow-up of mothers conceived after oocyte donation based on the registry of a large healthcare organization

Abstract Study question Short term outcomes of oocyte donation (OD) pregnancies are known. Yet, long term effect of OD pregnancies on mother’s health are lacking. Summary answer Comparing women after OD pregnancies to spontaneous pregnancies or nulliparous women, a higher risk of thyroid diseases was found (1.41, p &amp;lt; 0.0001 and 2.13, p &amp;lt; 0.0001, respectively) What is known already Short term outcomes of oocyte donation pregnancies show increased risk of placental disease and pregnancy-related hypertensive disorders. Study design, size, duration This retrospective cohort study, conducted from 2000 to 2018, utilized the computerized records of a major healthcare provider. It compared the demographic data and long-term health outcomes of mothers who had undergone OD pregnancies with three groups: In Vitro Fertilization using autologous oocytes, spontaneously pregnancies, and nulliparous women. Participants/materials, setting, methods The study tracked the onset of chronic diseases from the date of delivery to the diagnosis of any chronic disease. The risk of various diseases and mortality among these groups was assessed using a Cox proportional hazards model. This model adjusted for variables such as age at the index date, number of children, body mass index (BMI), and smoking habits. Statistical significance was determined using two-sided p-values, with a threshold of P &amp;lt; 0.05. Main results and the role of chance Regarding long-term outcomes, no difference was found between mothers after oocyte donation comparted to mothers after IVF (See table 1).. When comparing oocyte donation pregnancies to mothers after spontaneous conception, mothers after oocyte donation had less lower prevalence of rheumatology diseases (6% vs 8.9%) and more higher prevalence of thyroid diseases (21.9% vs. 17.6%). However, in cox regression, taking into account smoking, number of birth and mom’s age, we only found a higher risk of thyroid diseases (OD 1.41, p &amp;lt; 0.0001). Lastly, oocyte donation pregnancies compared to nulliparous had more thyroid diseases (21.9% vs. 6.7%, p &amp;lt; 0.001), also in cox regression (OD 2.13, p &amp;lt; 0.0001) Limitations, reasons for caution The temporal aspect of chronic disease diagnosis; a diagnosis made at a specific point does not preclude the presence of the disease at an earlier time. Also, the infrequency of some conditions within our study population could have reduced the statistical power to detect differences or associations. Wider implications of the findings The longer-term health outcome for women conceiving after OD is reassuring, and is very similar to that of IVF children and naturally conceived children, exempt for higher risk of thyroid disease. The main recommendation should be a yearly surveillance of thyroid function. Trial registration number 0046-18-BBL

P-751 Development of hypertensive complications in oocyte donation pregnancy: a systematic review and individual participant data meta-analysis (DONOR IPD)

Abstract Study question Is the risk for hypertensive complications, including pregnancy-induced hypertension and preeclampsia, increased in oocyte donation pregnancy compared to autologous oocyte pregnancies? Summary answer We found an approximate 2.5-fold increased risk for hypertensive complications in oocyte donation pregnancy compared to autologous oocyte pregnancy using individual participant data meta-analysis approaches. What is known already Oocyte donation (OD) is an established assisted reproductive technique involving an oocyte donor and recipient. Due to the expansion of indications and emerging trends, the number of OD treatments is rising. Previous meta-analyses highlight increased risks of hypertensive complications compared to naturally conceived (NC) and IVF/ICSI pregnancies, including pregnancy induced hypertension (PIH) and preeclampsia (PE). However, limitations exist due to study quality, lack of correction for confounders, and heterogeneity. Study design, size, duration We conducted 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. The DONOR IPD meta-analysis aims to address confounders, enhance statistical power, and provide robust evidence. Participants/materials, setting, methods A literature search was conducted using PubMed, EMBASE and Cochrane up to March 2023. We included observational studies that compared OD pregnancy beyond 20 weeks of gestation with autologous pregnancy, reporting on hypertensive pregnancy complications. Authors of eligible articles asked to share IPD. The DONOR IPD meta-analysis was executed using both a one- and two-stage approach, adjusted for confounders maternal age, parity and multiple gestation. Furthermore, sensitivity, meta-regression and subgroup analyses were performed. Main results and the role of chance IPD was sought for 58 cohorts, and eventually provided from sixteen cohorts with data of 2,747 OD, 4,699 autologous IVF/ICSI, and 33,323 NC pregnancies in total. The one- and two-stage approach comparing OD to autologous pregnancy resulted in adjusted ORs of respectively 2.62 (95% CI 2.22-3.10) and 2.65 (95% CI 2.08-3.39) for hypertensive complications in total, 2.15 (95% CI 1.73-2.68) and 1.49 (95% CI 0.80-2.80) for PIH, and 2.28 (95% CI 1.88-2.78) and 2.39 (95% CI 1.94-2.94) for PE. When the autologous group was split in NC and IVF/ICSI pregnancies, the higher risks in OD pregnancy for hypertensive complications, including PIH and PE, remained. However, compared to autologous pregnancies no significant increase in the risk for HELLP syndrome was observed in OD pregnancy. Limitations, reasons for caution The use of IPD still encounters certain limitations, such as IPD availability bias, and the dependency of methodological quality and heterogeneity of primary studies. To address these issues, we conducted additional sensitivity, meta-regression, and subgroup analyses. Wider implications of the findings Currently, none of the worldwide used guidelines indicate OD as a risk factor for hypertensive complications. As the DONOR IPD meta-analysis results in the best evidence based statement for international guidelines in obstetrics untill now, alertness of health care professionals must be increased towards the risk profile of these pregnancies. Trial registration number Financial support from the Leiden University Medical Center (the Netherlands) for an MD/PhD grant for K. van Bentem.

Hypertensive disorders and pregnancy outcomes in oocyte donation pregnancy in comparison with in vitro fertilization group

Hypertensive disorders and pregnancy outcomes in oocyte donation pregnancy in comparison with in vitro fertilization group

Development of the DONOR prediction model on the risk of hypertensive complications in oocyte donation pregnancy: study protocol for a multicentre cohort study in the Netherlands

IntroductionOocyte donation (OD) pregnancy is accompanied by a high incidence of hypertensive complications, with serious consequences for mother and child. Optimal care management, involving early recognition, optimisation of suitable treatment...

Fertility and pregnancy outcomes in women with Turner syndrome: A single centre experience.

Many women with Turner syndrome (TS) will consider fertility options and pregnancy. We wished to examine the fertility and pregnancy outcomes in women with TS undergoing oocyte donation (OD) treatment or spontaneous pregnancy in a large single-centre cohort. General population reference dataor data from those with idiopathic premature ovarian insufficiencywere used as comparators. A retrospective single-centre cross-sectional study. Seventy-four women with TS underwent OD treatment with a total of 105 pregnancies, and 31 women with TS had 71 spontaneous conceptions. Fertility outcomes included clinical pregnancy and live birth rate. Pregnancy outcomes included miscarriage rate, prevalence of hypertension, gestational diabetes, lower segment caesarean section (LSCS), small for gestational age (SGA), prematurity and vertical transmission of TS. In those with TS, OD pregnancies were associated with increased rates of LSCS and SGA compared to spontaneous pregnancies; LSCS (OR: 4.19, 95% CI: 1.6-10.8,p = .003) and SGA (OR: 2.92, 95% CI: 1.02-8.38,p = .04). There were no recorded cardiac events but 5 (17.2%) cases of vertical transmissions of TS in daughters were identified. OD in those with TS was associated with a lower live birth rate per cycle started (OR: 0.53, 95% CI: 0.34-0.84,p = .008) and a higher rate of miscarriage compared to women with POI (40% vs. 26.2%,p = .04). We show that pregnancy in women with TS, whether OD or spontaneously conceived, carries obstetric risks, and therefore, women with TS, considering pregnancy, should receive comprehensive pre-pregnancy counselling and optimal obstetric care.

Obstetric and maternal outcomes of IVF and oocyte donation pregnancies among women ages 40–45—a large cohort study

PurposeTo analyze the perinatal and maternal outcomes of women ranging in age from 40 to 45 years who gave birth after in vitro fertilization or oocyte donation, compared to spontaneous conception.MethodsThis retrospective cohort study used electronic data from a national healthcare service from 2000 through 2019. Three groups were compared: spontaneous pregnancy (SC), in vitro fertilization (IVF) utilizing autologous oocytes, and pregnancies resulting from oocyte donation (OD). The primary study outcomes were preterm labor (PTL) before 37 weeks of gestation, and infants classified as small for gestational age (SGA).ResultsThe cohort included 26,379 SC, 2237 IVF pregnancies, and 300 OD pregnancies for women ages 40–45 years at delivery. Women with OD or IVF had a higher incidence of PTL < 37 weeks compared to women with SC (19.7% vs. 18% vs. 6.9%, p = 0.001), PTL < 34 (7% vs. 4.5% vs. 1.4%, p = 0.001), PTL < 32 (3.7 vs. 2.1 vs. 0.6, p = 0.001). A multivariable logistic regression for PTL < 37 weeks demonstrated that age (OR = 1.18) and hypertensive diseases (OR = 3.4) were statistically significant factors. The OD group had a lower rate of SGA compared to SC (1% vs. 4.3%, p = 0.001), while the IVF group had a higher rate of SGA compared to SC (9.1% vs. 4.3%, p = 0.001). Hypertensive diseases in pregnancy were significantly higher among the OD group and the IVF group compared to SP pregnancies (3.3% vs. 1%, p = 0.002; 2.3% vs. 1%, p = 0.001, respectively).ConclusionsWomen ages 40–45 undergoing IVF or OD have a greater risk of PTL, possibly due to higher rates of hypertensive disorders of pregnancy.

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

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

Spatial composition of decidual immune cells in oocyte donation pregnancies in relation to fetal-maternal HLA incompatibility

Spatial composition of decidual immune cells in oocyte donation pregnancies in relation to fetal-maternal HLA incompatibility

Preeclamptic oocyte donation pregnancies show differences in peripheral T helper 1 and regulatory T cell cytokine profiles compared to uncomplicated oocyte donation pregnancies

Preeclamptic oocyte donation pregnancies show differences in peripheral T helper 1 and regulatory T cell cytokine profiles compared to uncomplicated oocyte donation pregnancies

16:00-16:10 Detection of microchimeric fetal cells in maternal peripheral blood during and after oocyte donation pregnancy

16:00-16:10 Detection of microchimeric fetal cells in maternal peripheral blood during and after oocyte donation pregnancy

P-778 Same mother-different Oocyte: Comparison of obstetric and perinatal outcomes between pregnancies achieved through oocyte donation versus those achieved through spontaneous conception for the same mother

Abstract Study question Is there a difference in obstetrical and perinatal outcomes between pregnancies achieved through oocyte donation versus those achieved through spontaneous conception for the same mother Summary answer OD pregnancies show higher incidences of preterm labor and pregnancy-induced hypertension, and lower incidences of small for gestational age, compared to spontaneous pregnancies What is known already Oocyte donation (OD) is an integral part of modern assisted reproductive care and has been used for over three decades. OD pregnancies have an increased rate of hypertension, cesarean section, and preterm labor. Yet most of these complications are attributed to the mothers going through OD, not to the biological effect of different oocyte sources (autologous Vs. donation). Study design, size, duration This study is a retrospective cohort study that utilizes electronic data from Maccabi Healthcare Services. This 2.5-million-patient integrated care organization represents 25% of the pregnant population in the country. The data used in this study were collected from 2000 through 2018. Participants/materials, setting, methods The study included mothers who experienced both a spontaneous conception (SP) pregnancy and later an oocyte donation (OD) pregnancy. The study compared obstetric and perinatal outcomes, including the incidence of preterm labor (PTL) and small for gestational age (SGA). Mother's obstetric outcomes such as pregnancy induced hypertension (PIH), gestational diabetes, malpresentation, and postpartum hemorrhage were also analyzed. A paired t-test was performed to compare each outcome for the same mother Main results and the role of chance The cohort included 194 mothers who had a first spontaneous pregnancy and a second pregnancy with oocyte donation. The mean age of the mother during her OD pregnancy was statistically older than the OD pregnancy (mean difference 2.2 years, p = 0.0028). No difference was found between pregnancies regarding the BMI (p = 0.216). A trend toward a higher prevalence of PIH was found in the OD pregnancy compared to the SP (mean difference 2.5, p = 0.058). No difference was found between pregnancies regarding gestational diabetes (p = 0.7), malpresentation (p = 1), retained placenta (p = 0.318), and Cesarean section (p = 0.565). Perinatal outcomes show a higher prevalence of premature labor before the 34th week and 32nd week in the OD pregnancies compared to SC pregnancies (mean difference 3.6, p = 0.034 and mean difference 3, p = 0.33 respectively). No difference was found between pregnancies regarding labor before the 37th week (p = 1). A statistically lower prevalence of SGA was found in the OD pregnancy compared to the SP (p = 0.0057). Limitations, reasons for caution Due to its retrospective character, some information is lacking. Information regarding indications leading to OD/AO are missing which might have elaborated our findings Wider implications of the findings OD pregnancies should be considered high-risk, primarily due to the increased risk of PTL and PIH. Adequate recommendations should be considered, including cervical length surveillance, frequent blood pressure measurements, and perhaps prophylactic low-dose aspirin to reduce the risk of preeclampsia. Trial registration number 0046-18-BBL

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

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

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

IntroductionThe 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...

Turner Syndrome and Fertility

Turner syndrome (TS) is tightly associated with hypergonadotropic hypogonadism and ovarian dysgenesis, typically resulting in infertility in the great majority of patients. Therefore females with TS are usually treated with female sex steroids from 11–12years of age until the normal age of natural menopause of around 53–54years of age. Infertility is rated among females with TS as a distressing concern and a detractor from a good quality of life. Options for motherhood for females with TS has expanded during recent years. Originally, only adoption was an option, unless of course for the small minority of TS females that still has ovarian function and are capable of achieving pregnancy through normal means. Oocyte donation has become the mainstream option in many countries and seems to work well, especially if patients have been treated with optimal estrogen and gestagen for a prolonged time before the intervention. It comes with an increased risk of cardiovascular complications and TS oocyte donation pregnancies are viewed as high risk pregnancies necessitating increased vigilance. Oocyte cryopreservation of own oocytes is also becoming an option in a select group of TS and has special challenges. Ovarian tissue cryopreservation is a promising new techniques that has been applied successfully in children with cancer. Currently, several trials are running around the world evaluating this techniques in TS. The genetics and genomics behind the ovarian dysgenesis seen in TS is not understood, but new studies have elucidated global changes in DNA methylation and RNA expression in blood from persons with TS and it is likely that similar changes are present in the ovaries. We still, however, need more thorough research to fully uncover the genetic background of ovarian failure in TS. Gene expression studies and methylation analysis from ovarian TS tissues still needs to be performed.

Reply: What is the true preeclampsia risk in oocyte donation pregnancies?-lack of deconfounding may lead to risk overestimation.

Reply: What is the true preeclampsia risk in oocyte donation pregnancies?-lack of deconfounding may lead to risk overestimation.

What is the true preeclampsia risk in oocyte donation pregnancies?-lack of deconfounding may lead to risk overestimation.

What is the true preeclampsia risk in oocyte donation pregnancies?-lack of deconfounding may lead to risk overestimation.

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

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)? 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. 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. 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. 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. 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. The precise definition of PE is still a matter of debate. The different criteria could have affected the prevalence estimate. 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. No funding or competing interests. CRD42020166899.