Research ArticleClinical Studies
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Pregnancy Outcomes Following In Vitro Fertilization: A Multicenter Comparative Analysis Between Donor-oocyte Recipients and Self-oocyte Patients in Greece

STEFANOS FLINDRIS, CHALITSIOS V. CHRISTOS, MICHAIL KALINDERIS, ALEXANDROS TRAIANOS, APOSTOLOS SIDIROPOULOS, ELIF EMPLIOUK, KONSTANTINOS PANTAZIS, KONSTANTINOS CHRISTOPOULOS, ELENI-MARKELA CHALKIA-PRAPA, KONSTANTINOS FLINDRIS, EFFROSYNI STYLIARA, FOTINI CHOULIARA, GEORGIOS MPOURAZANIS, PANAGIOTIS TSIRKAS, MARKOZANNES GEORGE, MINAS PASCHOPOULOS, GEORGIOS MICHOS, APOSTOLOS ATHANASIADIS, APOSTOLOS MAMOPOULOS and EVANGELOS PAPANIKOLAOU
In Vivo January 2026, 40 (1) 452-464; DOI: https://doi.org/10.21873/invivo.14209

Abstract

Background/Aim: Delayed childbearing has increased the reliance on in vitro fertilization (IVF) with donor oocytes for women of advanced maternal age often facing more obstetric complications compared to younger women using self-oocytes. This study evaluated and contrasted key obstetric and perinatal parameters between these two groups.

Patients and Methods: In this retrospective multicenter study, completed IVF embryo transfer cycles were analyzed. Clinical data including clinical pregnancy, miscarriage, ectopic pregnancy rates, and major pregnancy complications were collected. Obstetric outcomes (e.g., mode of delivery, preterm birth, and neonatal parameters such as birth weight, Apgar scores, and NICU admissions) were compared between the donor-oocyte recipients (DOR-IVF) and self-oocyte (SO-IVF) groups. Statistical analysis comprised chi-square tests, t-tests, and multivariable logistic and linear regressions to adjust for potential confounders.

Results: The DOR-IVF group demonstrated a clinical pregnancy rate of 44.8% (196 cases) with an 8.8% miscarriage rate, while the SO-IVF group reported 242 clinical pregnancies with an 8.1% miscarriage rate. Overall, nine ectopic pregnancies (2%) were noted, with statistically significant differences in ectopic and miscarriage rates between the groups (p=0.008 and p=0.025, respectively). Although the mean gestational age was similar and NICU admissions did not differ significantly (p=0.125), the DOR-IVF group exhibited a higher incidence of pregnancy complications (p=0.009). Multivariable logistic regression identified DOR-IVF as an independent predictor for pregnancy complications (adjusted odds ratio 2.38; 95% confidence interval=1.53-3.70). Additionally, subgroup analyses revealed that 1-minute Apgar scores were positively associated with DOR-IVF status (p=0.048) and birth weight was inversely related to the number of babies transferred (p=0.006).

Conclusion: DOR-IVF patients experience significantly increased risk in obstetric complications compared to younger women using SO-IVF, although neonatal outcomes remain largely similar.

Keywords:

Introduction

Oocyte donation is a well-established and increasingly utilized method of treating infertility worldwide (1). It offers a viable reproductive solution for women with diminished ovarian reserve, premature ovarian insufficiency, genetic disorders, advanced maternal age, or those who have undergone surgical menopause (2).

Pregnancy after 35 years (advanced maternal age) has become increasingly common (3). This trend is largely driven by social factors such as the prioritization of career development (4). Since the first successful birth from donor oocyte in 1984, several reproductive possibilities are available for women who previously had limited options for conception (5). In 2015, over 21,000 in vitro fertilization (IVF) cycles were reported, with the numbers continuing to rise exponentially (6, 7). Broader availability, improved accessibility, and financial support from national healthcare systems, have contributed to the growing acceptance of oocyte donation as a mainstream fertility treatment (8).

Women undergoing oocyte donation are often of advanced age and may have coexisting medical conditions that delay their decision to pursue pregnancy. Advanced maternal age is associated with a higher risk of adverse maternal and neonatal outcomes (4, 9). Masoudian et al. reported that pregnancy-induced hypertension and preeclampsia occur in 16-40% of pregnancies conceived through donor oocyte IVFs (10). One proposed mechanism underlying this risk involves immunological maladaptation. Specifically, the genetic dissimilarity between the donor oocyte and the recipient may provoke an immune response, creating an inflammatory environment that impairs placental development and predisposes to preeclampsia (6, 11). Although the precise biological mechanisms remain poorly understood, some studies suggest that the elevated risk of complications may be primarily driven by the maternal age of recipients (12, 13), whereas others implicate the immunologic novelty of the allogeneic fetus itself as a key contributor (14). Accordingly, it remains challenging to disentangle the respective roles of oocyte donation and advanced maternal age in these adverse outcomes (4, 14).

In this study, we aimed to evaluate and compare obstetric and perinatal outcomes, between pregnancies conceived through donor-oocyte and those conceived with self-oocytes. The results will provide clinically relevant insights for women considering oocyte donation as part of their fertility treatment.

Patients and Methods

Study setting and ethics. This multi-center, cross-sectional, comparative study was carried out at the 3rd Department of Obstetrics and Gynecology, Medical school, Aristotle University of Thessaloniki, Greece. Additional data were collected from the Department of Gynecology, Medical School, University of Ioannina, Greece and the private Assisted Reproduction Unit “Assisting Nature” in Thermi, Thessaloniki, Greece. The study retrospectively evaluated completed IVF-embryo transfer (IVF-ET) treatment cycles over a six-year period (January 2019-December 2024). IVF cycles were conducted by distinct clinical and embryology teams at each center, all adhering to standard IVF protocols.

All participants had consented to allow the use of anonymized data from their cases files for research and educational purposes at the time of enrollment for IVF treatment. The study was approved by the ethics and research committee of the Aristotle University of Thessaloniki (285/24-7-2025).

IVF process. At the time of the study, the protocol for IVF treatment followed standard ovarian stimulation protocols. All patients received oral contraceptive pills (OCPs) for 3-4 weeks prior to treatment initiation to synchronize their menstrual cycle. Subsequently, two standard stimulation methods, either the long agonist or antagonist protocol, were prescribed three to four weeks before the treatment cycle. In the long agonist protocol, downregulation was achieved using a subcutaneous daily dose of 0.2 mg Arvekap (Sanofi, Reading, Berkshire, UK), administered during the luteal phase (days 17-21) of the pretreatment cycle. Upon the onset of menstruation, the dose of Arvekap was reduced to 0.1 mg daily and continued until the day of ovulation induction. Ovarian stimulation commenced on day 3 of the menstrual cycle and continued for 10 to 14 days. Patients received either highly purified human menopausal gonadotropin (hMG) or recombinant follicle-stimulating hormone (FSH), at individualized daily doses ranging from 150 to 375 IU, adjusted according to the follicular response. Serial transvaginal ultrasonographic monitoring began on stimulation on days 5-6 and was repeated at regular intervals to assess follicle number, follicle size, and endometrial thickness. When at least three follicles reached a diameter of 17 mm or more, ovulation was triggered with 5,000-10,000 IU of human chorionic gonadotropin (hCG). Oocyte retrieval was scheduled 36 h following the HGG administration.

In the antagonist protocol, ovarian stimulation began on day 3 of the menstrual cycle using either hMG or recombinant FSH, at a daily dose of 150-375 IU for 10 to 14 days. When follicles reached 14 mm in diameter, typically on day 6 or 7 of stimulation, a daily subcutaneous dose of 0,25 mg of the GnRH antagonist (Cetrotide) was initiated to prevent any premature luteinizing hormone surge. Antagonist administration continued until the day of triggering. Final oocyte maturation was triggered with either intramuscular hCG or 0.2 mg of subcutaneous Arvekap when two or more follicles reached a size of ≥18 mm. Oocytes were retrieved by transvaginal needle aspiration under ultrasound guidance and immediately transferred to the laboratory for screening, selection, and fertilization using either conventional in vitro fertilization or intracytoplasmic sperm injection.

In recipients of donor oocytes recipients (DOR), endometrial preparation was initiated with oral estrogen (white pills of Cyclacur) starting on the first day of the menstrual cycle. The dose was titrated between 8 and 12 mg daily, depending on the endometrial thickness and sonographic appearance. Luteal support commenced on the day of the oocyte retrieval with vaginal progesterone 8% (Vasclor), administrated twice daily via the transvaginal route. Embryo transfer was performed on the third or fifth day following oocyte retrieval. The number of embryo(s) transferred was individualized based on the quality of embryo, typically involving the transfer of two or three embryos, and not exceeding four. The luteal phase support was continued with progesterone, and a pregnancy test was carried out 14 days after ET. Clinical pregnancy was defined as the presence of an intrauterine gestational sac using transvaginal ultrasound 28 days after ET (9, 15). Importantly, Tsakiridis et al. reported that employing corifollitropin alpha in combination with a GnRH agonist trigger constitutes a safe, effective, and well-tolerated stimulation protocol for oocyte donors (16).

Data collection. All medical records of patients who conceived through assisted reproductive technology during the study period were retrieved for analysis. Comprehensive collection and renewal of the data about pregnancy and delivery outcomes for all IVF patients were regularly updated in the databases of the tertiary hospital’s departments of Obstetrics and Gynecology as well as the Assisting Nature clinic, through a combination of pregnancy surveillance, reports from attending obstetricians, and direct communication with the pregnant participants.

Definitions. Comparative analysis of obstetric parameters encompassed outcomes such as, ectopic pregnancy, miscarriage, preeclampsia, hypothyroidism in pregnancy, breech lie, non-reassuring/pathologic Non-Stress Test (NST), pathologic doppler of umbilical artery pulsatility index (PI), gestational diabetes mellitus (GDM), antepartum hemorrhage, preterm delivery, fetal growth next restriction (FGR), intrahepatic cholestasis of pregnancy (ICP), cervical insufficiency/cervical cerclage, umbilical cord prolapse, placenta previa/placenta abruption, mode of delivery, thrombophilia, anemia, endocrine disorder, and postpartum complications (cesarean hysterectomy, venous thromboembolism and eclampsia).

Neonatal outcomes, including birth weight, Apgar scores and admission to a neonatal intensive care unit (NICU), were also compared between the two groups. Maternal and perinatal outcomes were classified according to the presence or absence of severe or debilitating intrapartum or postpartum complications, such as cesarean hysterectomy, maternal mortality, perinatal outcome or admission to a special care baby unit or early neonatal death.

Pregnancy was defined by an elevation in serum beta-hCG levels detected 16 days after embryo-transfer and subsequently confirmed by transvaginal ultrasound demonstrating a gestational sac at six weeks along with positive heart rate. Estrogen administration was gradually reduced and discontinued upon confirmation of fetal heart rate, whereas progesterone administration persisted until the 10th to 12th week of gestation.

Miscarriage was defined as the occurrence of vaginal bleeding, fetal expulsion, or absence of fetal cardiac activity before 20 weeks of gestation. Preeclampsia was diagnosed based on the presence of blood pressure readings ≥140/90 mmHg accompanied by proteinuria after 20 weeks of gestation. GDM referred to carbohydrate intolerance first diagnosed during pregnancy. Preterm delivery was defined as birth occurring before 37 completed weeks of gestation. FGR was classified as birth weight below the 10th percentile for the corresponding gestational age.

Statistical analysis. The analyses focus on comparisons between the SO-IVF and the DOR-IVF group. Aside from comparisons between the two IVF groups and given the well-documented higher risk of complications in multiple gestations, outcomes between singleton and twin pregnancies irrespectively from the IVF donors or self-oocytes group were also compared. Another subgroup analysis was performed to examine the associations between various pregnancy complications appearing in DOR-IVF group versus the SO-IVF group.

Descriptive statistics are reported as frequencies and percentages for categorical variables, and as means with standard deviations for continuous variables. Categorical variables were compared using the Chi-square test, whereas comparisons of continuous variables were performed using t-tests. Multivariable regression analyses were performed to determine significant independent predictors associated with pregnancy complications as well as adverse maternal and NICU admission between the two IVF groups. Continuous outcomes were evaluated using multivariable linear regression analyses. Dichotomous outcomes were analyzed using multivariable logistic regression. The logistic models were adjusted for parity and number of babies, whereas linear models were further adjusted for pregnancy complications. Statistical significance was considered at a p<0.05. The analyses were performed using STATA 18 (STATACorp. LLC, College Station, TX, USA).

Results

Descriptive statistics and IVF group comparisons. A total of 1,029 IVF treatment cycles were completed. The clinical pregnancy rate (CPR) was 42.6%, the miscarriage rate was 12.3%, and there were nine ectopic pregnancies (2%) (Table I). In total, 308 singleton and 130 twin deliveries were recorded. Of the 438 clinical pregnancies, 196 (44.8%) occurred in the DOR-IVF group and 242 (55.2%) in the SO-IVF group. In the DOR-IVF group, 23 miscarriages (8.8%) were reported, compared with 27 miscarriages (8.1%) in the SO-IVF group. Rates of ectopic pregnancy and miscarriage differed significantly between groups (p=0.008 and p=0.025, respectively).

View this table:
Table I.

Characteristics for the total sample and in vitro fertilization groups.

The overall mean maternal age was 41.8 years, with a higher mean in the DOR-IVF group (47.2 years) compared to the SO-IVF group (37.4 years) (p<0.001) (Table I). Nulliparous women comprised 84.0% of the sample, while primiparous and multiparous women accounted for 14.2% and 1.8%, respectively. The most frequently observed pregnancy complications included gestational diabetes (24.9%), hypertensive disorders (preeclampsia 9.8%; gestational hypertension 8.7%), FGR (12.6%), and hypothyroidism (11.2%). The overall rate of pregnancy complication differed significantly between the two group (p=0.009).

The mean gestational age at delivery was similar between groups (35.2 weeks for DOR-IVF vs. 35.1 weeks for SO-IVF; p=0.547). There was no significant difference in NICU admission rates (28.6.2% vs. 29.8%; p=0.125); with the majority of neonates (70.8%) not requiring NICU care. Early neonatal death did not occur in either group. Maternal adverse outcomes were rare (1.1%) and did not differ significantly between groups.

Cesarean section was the preferred mode of delivery in both groups, whether elective or emergent (Figure 1). Normal delivery was higher at the SO-IVF with a rate of 56.8% compared to 43.4% of the DOR-IVF group. Elective cesarean section occurred more frequently (57.6%) in the SO-IVF group, while the remaining 42.4% were in the DOR-IVF group. Similarly, operative delivery using vacuum device was utilized more in the self-group with a rate of 75% compared to 25% in DOR-IVF group. However, the emergency cesarean section rate was higher in the do DOR-IVF nor group at 56.8%, compared to 43.2% in the DOR-IVF group. This indicates a higher incidence of pregnancy complications in the DOR-IVF group, necessitating urgent measures to ensure fetal delivery.

Figure 1.
Figure 1.

Mode of delivery between the donor oocytes recipients- in vitro fertilization (IVF) and self oocytes-(SO)-IVF groups.

Comparison between singleton and twin births. The purpose of this analysis was to compare maternal and neonatal outcomes between singleton and twin pregnancies irrespectively from the DOR-IVF or SO-IVF group. Given the well-documented higher risk of complications in multiple gestations, we aimed to evaluate differences in key obstetric and neonatal parameters, including pregnancy complications, gestational age at birth, birth weight, and the need for neonatal intensive care. By analyzing these factors, we sought to provide insights into the perinatal challenges associated with twin pregnancies and their implications in clinical management.

Among the study population, pregnancy complications were significantly more frequent in singleton pregnancies compared to twin pregnancies (64.2% vs. 52.3%, p<0.001). Gestational age at birth was significantly lower in twin pregnancies, with a mean of 34.2 weeks compared to 35.8 weeks in singleton pregnancies (p=0.014). Similarly, birth weight was significantly lower in twins (2.1 kg vs. 2.3 kg, p=0.042). Admission to the Special Care Baby Unit (SCBU) was more common in twin pregnancies, occurring in 40.7% of cases compared to 23.7% in singleton pregnancies (p<0.001). These findings appear in Table II.

View this table:
Table II.

Comparison of pregnancy complications, gestational age at delivery, neonatal birth weight, and Neonatal Intensive Care Unit (NICU) admission between singleton and twin pregnancies.

Regression analyses. Multivariable regression analyses were performed to determine significant independent predictors associated with pregnancy complications as well as adverse maternal and NICU admission between two groups and are shown in Table III. An association between pregnancy complications and DOR-IVF was found, with an adjusted odds ratio (aOR) of 2.38 [95% confidence interval (CI)=1.53-3.70, p<0.0001). Neither parity nor the number of embryos were associated with pregnancy complications. Adverse maternal outcomes, although not statistically significant (aOR=4.83, 95%CI=0.54-42.9, p=0.158), indicated a potential trend towards higher risk in the DOR-IVF group. Parity showed a borderline association with adverse maternal outcomes (aOR=1.60, 95%CI=0.92-2.76, p=0.094), while the number of babies was not associated. NICU admissions did not demonstrate an association with DOR-IVF neonates (aOR=1.01, 95%CI=0.64-1.59, p=0.965), though parity again showed a near-significant trend (aOR=1.60, 95%CI=0.92-2.77, p=0.093). The number of babies was not significantly associated with NICU admissions. These findings are shown in Table III.

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Table III.

Association with pregnancy, adverse maternal complications as well as Neonatal Intensive Care Unit (NICU) admission between donor oocytes recipients- in vitro fertilization (IVF) and self oocytes (SO)-IVF groups.

The multivariable linear regression analysis indicates that donors’ cases are associated with an increased 1-minute Apgar score. No significant associations were identified between the 5-minute Apgar score and donor status or any other evaluated variables. In terms of birth weight, a significant inverse relationship was found with the number of babies, suggesting that a higher number of babies is associated with a lower birth weight in DOR-IVF group compared to the SO-IVF group. No other factors showed significant associations with birth weight. These findings are presented in Table IV and provide valuable insights into the factors that significantly correlate with Apgar scores and birth weight, highlighting differences between DOR-IVF and SO-IVF.

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Table IV.

Associations with Apgar scores and birthweight between donor oocytes recipients- in vitro fertilization (IVF) and self oocytes (SO)-IVF groups.

Multivariable logistic regression analysis was also performed to examine the associations between various pregnancy complications in the DOR-IVF group versus the SO-IVF group. The analysis revealed significant associations regarding overall pregnancy complications (OR=2.41, p<0.001) and non-reassuring/pathologic NST (OR=2.43, p=0.039), indicating these complications are more likely in the DOR-IVF group compared to the SO-IVF group (Table V). There were trends towards significance for anemia (OR=4.57, p=0.071) and cervical insufficiency/cerclage (OR=2.68, p=0.064), suggesting a potential but not statistically confirmed higher likelihood in the SO-IVF group. No significant associations were found for several factors, including FGR, gestational diabetes, pathologic umbilical artery (UA) Doppler, hypothyroidism, thrombophilia, hypertension, breech lie, preeclampsia, cholestasis, placenta previa/abruption, and umbilical cord prolapse. These results suggest that while some complications are significantly more prevalent in the DOR-IVF group, many others do not show a significant difference between DOR-IVF and SO-IVF.

View this table:
Table V.

Associations with pregnancy complications between donor oocytes recipients- in vitro fertilization (IVF) and self oocytes (SO)-IVF groups.

Discussion

Our study provides a comprehensive multicenter retrospective analysis of IVF outcomes in women of advanced maternal age by comparing DOR-IVF cycles with SO-IVF cycles. Our findings corroborate and extend those reported by previous investigators. In our sample, the DOR-IVF group had a significantly higher mean maternal age of 47.2 years compared with 37.4 years in the SO-IVF group (p<0.001), which places these patients in a very high-risk category as in similar studies (17). Despite the advanced maternal age, the DOR-IVF cycles achieved a clinical pregnancy rate (CPR) of 41.6%, which is well within the range of 33%-55% reported by other authors (15, 18). This finding underscores the advantage of using donor oocytes derived from younger, highly fertile women to overcome the ovarian aging process.

Moreover, our data on maternal complications further reinforce the association between advanced maternal age and adverse outcomes. In the DOR-IVF group, we observed a gestational diabetes rate of 24.9%, hypertensive disorders, including preeclampsia (9.8%), pregnancy-induced hypertension (8.7%) and FGR rate of 12.6%. This result is consistent with the observations of Krieg et al., who reported rates of pregnancy-induced hypertension and preeclampsia ranging from 16% to 40% in donor oocyte pregnancies (10, 18). Furthermore, many studies demonstrated high incidence of gestational diabetes and FGR in DOR-IVF group (9, 18-20). The overall pregnancy complications were significantly higher in the DOR-IVF group compared to the SO-IVF group (p=0.009). These results mirror those of Saccone et al.’s meta-analysis, which included over 31 million women and demonstrated that women aged ≥40 years have a 2.16-fold increased risk of stillbirth (95% CI=1.86-2.51) and sharply rising maternal mortality risks (with relative risks of 3.18, 11.60, and 42.76 for women over 40, 45, and 50 years, respectively) (21). Furthermore, our early pregnancy outcomes characterized by a slightly higher miscarriage rate (8.8% in DOR-IVF vs. 8.1% in SO-IVF) and a statistically significant difference in ectopic pregnancy rates (p=0.008) suggest that the combination of advanced maternal age and the donor oocyte process may subtly affect early gestational viability (18, 22, 23).

Notably, our study also delved into the mode of delivery and neonatal outcomes. The DOR-IVF group exhibited a higher incidence of emergency cesarean sections (56.8% vs. 43.2% in the SO-IVF group), while normal vaginal deliveries were more common in the SO-IVF group (56.8% vs. 43.4% in the donor group) which is reported also in other studies (22, 24, 25). Elective cesarean rates and the utilization of operative vacuum extraction also differed significantly between the groups, suggesting that the higher emergency intervention rate in DOR-IVF may be a direct reflection of increased obstetric complications in this older population aligning with the results of other reports (15, 24). These findings imply that older women undergoing DOR-IVF are more likely to receive elective cesarean deliveries, a practice that is supported also by the systematic review by Sugai et al. (2023) and Stoorgard et al. showed that although overall cesarean delivery rates are markedly higher in women aged ≥45 years, emergency cesarean delivery is unexpectedly less frequent, whereas maternal and antenatal complications are increased (26). Such a trend may reflect a clinical preference for pre-labor cesarean delivery in this high-risk group, possibly due to prior uterine scars, increased placental abnormalities, the anticipation of labor dystocia or women’s preference to ensure the safety of a precious gestation (27-29).

Interestingly, neonatal outcomes in our study were encouraging, showing that the mean gestational age at delivery was comparable between the groups (35.2 weeks for DOR-IVF versus 35.1 weeks for SO-IVF, p=0.547), and NICU admission rates did not differ significantly (p=0.125), indicating that while maternal risks are elevated, neonatal outcomes may be more resilient or subject to other modifying factors, as also reported by Montori et al. (30). This finding contrasts with several studies that have reported an increased risk of premature and preterm birth following DOR-IVF treatment (1, 24, 30-32). The multivariable linear regression analysis indicated that DOR-IVF cases were associated with a higher 1-minute Apgar score, but no significant differences were noted in the 5-minute Apgar scores which aligns with results of Ratiu et al., who, however, reported more antenatal complications in the DOR-IVF group (33). Additionally, we found an inverse relationship between birth weight and the number of fetuses in the DOR-IVF group, highlighting the adverse impact of multiple gestations a factor that emerged as an independent predictor of adverse pregnancy and delivery outcomes in our multivariable analyses and that of Malchau et al. (34).

Multivariable regression analyses provided further insight into the independent association of donor oocyte use. In our logistic regression model, being in the DOR-IVF group was associated with an aOR of 2.38 (95%CI=1.53-3.70; p<0.001) for overall pregnancy complications, independent of other confounders. Although adverse maternal outcomes (including events such as pulmonary thromboembolism, eclampsia, and massive obstetric hemorrhage) were low overall (1.1%) and did not reach statistical significance between groups (aOR=4.83; 95%CI=0.54-42.9; p=0.158), a trend towards increased risk in the DOR-IVF group was evident. Additionally, our subgroup analysis revealed that non-reassuring or pathologic NST findings were significantly associated with the donor group (OR=2.43, p=0.039), and there were trends toward higher odds for conditions like anemia (OR=4.57, p=0.071) and cervical insufficiency/cerclage (OR=2.68, p=0.064). These findings underscore that advanced maternal age, as reflected by the donor oocyte population, remains a strong predictor of adverse pregnancy outcomes, which are also associated with high complications rate in other studies (6, 18, 22, 35, 36).

Secondary outcomes in our study, including rates of GDM, placenta previa, placental abruption, and postpartum hemorrhage (PPH), are consistent with those reported in other studies (13, 20, 33). Although we did not directly assess outcomes such as stillbirth or maternal mortality, the pattern of increased hypertensive, metabolic, and placental complications in the DOR-IVF group aligns with broader epidemiological trends. Vandekerckhove et al. demonstrated that the risk of maternal-fetal complications increases steadily with age and is particularly high after 35 years, indicating the need for closer monitoring (37). However, Fredriksen et al. found no increased risk of stillbirth or congenital malformations in the DOR-IVF group (8).

An important aspect of our analysis was the subgroup evaluation of singleton versus multiple gestations. Our data show that in singleton pregnancies, delivery outcomes between DOR-IVF and SO-IVF groups are relatively comparable. However, in multiple gestations, where the risks of complications such as preterm birth and low birth weight are inherently higher, the adverse outcomes were significantly accentuated in the DOR-IVF group. We observed an inverse relationship between birth weight and the number of fetuses in the donor group, which supports previous findings that multiple gestations are a major independent predictor of adverse perinatal outcomes (21, 30).

Biological mechanisms likely underlying these findings include age-related increases in insulin resistance and heightened inflammatory responses, all of which predispose to GDM and hypertensive disorders (27, 38). In addition, uterine aging with diminished myometrial contractility, reduced oxytocin receptor density, and increased vascular stiffness may contribute to labor dystocia and a greater reliance on cesarean delivery (4, 11, 26, 30). In donor oocyte pregnancies, potential immunologic challenges arising from the allogenic embryo may further increase these risks, although the literature suggests that these immunologic factors are intertwined with the effects of advanced maternal age and multiple gestations rather than acting independently (18).

Clinically, these integrated findings underscore the need for tailored preconception counseling and rigorous antenatal care in this growing high-risk population. As more women delay childbearing and increasingly utilize DOR-IVF, it becomes imperative to address both the benefits and inherent risks associated with advanced maternal age (33, 39). Strategies to mitigate risk such as single embryo transfer (SET) or multifetal pregnancy reduction (MFPR) are particularly important, given our observation that multiple gestations significantly amplify the likelihood of adverse outcomes (15, 40). Moreover, individualized management plans that incorporate close monitoring for metabolic and hypertensive complications, along with judicious planning of the mode of delivery, are essential to optimize both maternal and neonatal outcomes.

Despite the strengths of our study, including a comprehensive evaluation of both maternal and neonatal outcomes and the use of rigorous statistical methodologies, certain limitations must be acknowledged. The retrospective design and reliance on data from public referral hospitals may introduce selection bias, limiting the generalizability of our findings to broader populations. Residual confounding from unmeasured sociodemographic or lifestyle factors (such as dietary habits and physical activity) cannot be ruled out. Moreover, while our analysis robustly demonstrates the association between advanced maternal age and adverse outcomes, it remains challenging to fully separate the effects of donor oocyte use from the intrinsic risks associated with aging.

In conclusion, our extensive analysis integrates our findings with those of previous investigators and provides robust evidence that although donor oocyte IVF offers a viable and effective pathway to pregnancy for women of advanced maternal age, it is accompanied by an elevated risk of adverse outcomes. These risks manifested in higher rates of elective cesarean delivery, increased hypertensive and metabolic complications, and a greater likelihood of adverse neonatal outcomes in multiple gestations are multifactorial in origin. As the demographic trend toward delayed childbearing continues, it is crucial for both clinicians and patients to be aware of these risks and to implement strategies aimed at mitigating them, thereby improving outcomes for this growing high-risk population. Future prospective studies are warranted to further elucidate the biological mechanisms and to develop interventions aimed at mitigating the risks associated with advanced maternal age in both natural and assisted reproductive settings.

Footnotes

  • Authors’ Contributions

    Conceptualization: SF, AA, EP and AM; Data Curation: All Authors; Formal Analysis: CVC, GM, SF, and KC; Funding Acquisition; Investigation: SF, CC, GM, MP, KC, MK, KP, AT, GMp, PT, and AS; Methodology: CC, GM, SF and KC; Project Administration: SF, EP, AA, AM, CVC, KC and GM; Resources Software: CVC, GM and KC; Supervision: AA, AM and EP; Validation: All Authors; Visualization: CVC, GM, SF, KF and KC; Writing – Original Draft Preparation: SF and CVC; Writing – Review & Editing: CVC, GM, KC, EP, AM, GM and AA.

  • Conflicts of Interest

    The Authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

  • Funding

    None.

  • Artificial Intelligence (AI) Disclosure

    No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.

  • Received October 15, 2025.
  • Revision received November 1, 2025.
  • Accepted November 13, 2025.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

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Pregnancy Outcomes Following In Vitro Fertilization: A Multicenter Comparative Analysis Between Donor-oocyte Recipients and Self-oocyte Patients in Greece
STEFANOS FLINDRIS, CHALITSIOS V. CHRISTOS, MICHAIL KALINDERIS, ALEXANDROS TRAIANOS, APOSTOLOS SIDIROPOULOS, ELIF EMPLIOUK, KONSTANTINOS PANTAZIS, KONSTANTINOS CHRISTOPOULOS, ELENI-MARKELA CHALKIA-PRAPA, KONSTANTINOS FLINDRIS, EFFROSYNI STYLIARA, FOTINI CHOULIARA, GEORGIOS MPOURAZANIS, PANAGIOTIS TSIRKAS, MARKOZANNES GEORGE, MINAS PASCHOPOULOS, GEORGIOS MICHOS, APOSTOLOS ATHANASIADIS, APOSTOLOS MAMOPOULOS, EVANGELOS PAPANIKOLAOU
In Vivo Jan 2026, 40 (1) 452-464; DOI: 10.21873/invivo.14209
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