European Journal of Cardiovascular Medicine

Recurrent pregnancy loss (RPL) and perinatal deaths remain significant concerns in reproductive medicine, affecting approximately 1–2% of couples attempting conception (1). Miscarriage, defined as pregnancy loss before 20 weeks of gestation, and perinatal mortality, which includes fetal death after 28 weeks of gestation and neonatal death within the first week of life, contribute to both psychological distress and increased medical interventions (2,3). Various etiological factors, including genetic abnormalities, endocrine disorders, uterine anomalies, thrombophilic conditions, and immunological dysfunctions, have been implicated in these adverse pregnancy outcomes (4).

Advanced maternal age has been associated with a higher incidence of pregnancy loss due to increased chromosomal abnormalities, particularly aneuploidy (5). Additionally, metabolic conditions such as obesity and diabetes mellitus have been linked to impaired placental function and an elevated risk of fetal demise (6). The role of thrombophilic disorders, including antiphospholipid syndrome and factor V Leiden mutation, in recurrent pregnancy loss has been extensively studied, with evidence suggesting that anticoagulation therapy can improve live birth rates in affected women (7).

Optimizing reproductive performance in couples with a history of miscarriage and perinatal mortality requires a multidisciplinary approach, encompassing preconception counseling, targeted investigations, and individualized treatment plans (8). Recent advances in assisted reproductive technologies (ART), such as preimplantation genetic testing and endometrial receptivity assessment, have shown promise in enhancing pregnancy outcomes in high-risk couples (9). However, there is still a need for further research to establish standardized protocols for managing this vulnerable population.

This study aims to evaluate the reproductive performance of couples with previous miscarriages and perinatal deaths, identify associated risk factors, and assess the effectiveness of medical interventions in improving pregnancy outcomes. By understanding these variables, clinicians can develop evidence-based strategies to enhance maternal and fetal health, ultimately reducing the burden of pregnancy loss.

The study included 150 couples with a history of at least one miscarriage or perinatal loss. Couples were recruited from the outpatient gynecology and reproductive medicine clinics. Inclusion criteria comprised women aged 20–40 years with a history of recurrent pregnancy loss (≥2 consecutive miscarriages) or perinatal death (fetal demise after 28 weeks of gestation or neonatal death within the first week of life). Exclusion criteria included known chromosomal abnormalities in either partner, chronic maternal illnesses such as uncontrolled diabetes or hypertension, and structural uterine abnormalities requiring surgical intervention.

Data Collection

Detailed demographic and clinical histories were obtained, including maternal age, body mass index (BMI), obstetric history, lifestyle factors, and any prior medical conditions. Laboratory investigations included hormonal profiling (thyroid function tests, prolactin, and progesterone levels), genetic testing (karyotyping for both partners), thrombophilia screening (antiphospholipid antibodies, protein C and S, and factor V Leiden mutation), and infectious disease screening.

Ultrasound evaluations, including transvaginal sonography and Doppler studies, were performed to assess uterine morphology, endometrial thickness, and placental blood flow. Hysterosalpingography or saline infusion sonography was conducted when uterine anomalies were suspected. Sperm analysis, including DNA fragmentation assessment, was performed for male partners.

Intervention and Follow-Up

Couples received individualized treatment based on identified risk factors. Those with hormonal imbalances were managed with appropriate medications, such as levothyroxine for hypothyroidism and progesterone supplementation for luteal phase deficiency. Antithrombotic therapy (low-dose aspirin and low-molecular-weight heparin) was prescribed for patients with thrombophilic disorders. Lifestyle modifications, including dietary counseling, smoking cessation, and weight management, were advised.

Participants were followed for 12 months, with pregnancy outcomes recorded, including conception rates, live birth rates, miscarriage rates, gestational age at delivery, and neonatal outcomes. Follow-ups were conducted monthly during pregnancy and postpartum to monitor maternal and fetal health.

Statistical Analysis

Data were analyzed using SPSS software (version 26). Continuous variables were expressed as mean ± standard deviation (SD) and compared using the independent t-test. Categorical variables were presented as frequencies and percentages and analyzed using the chi-square test or Fisher’s exact test. Logistic regression analysis was employed to determine significant predictors of adverse pregnancy outcomes. A p-value <0.05 was considered statistically significant.

Demographic and Clinical Characteristics

A total of 150 couples were included in the study. The mean maternal age was 32.5 ± 4.2 years, while the mean paternal age was 35.8 ± 5.1 years. The mean BMI of female participants was 27.4 ± 3.6 kg/m². A history of recurrent pregnancy loss was present in 60% (n=90) of cases, while 40% (n=60) had experienced at least one perinatal death. Underlying medical conditions, such as hypothyroidism (15%), thrombophilia (12%), and polycystic ovary syndrome (10%), were identified in a subset of patients (Table 1).

Table 1: Baseline Characteristics of the Study Population

Pregnancy Outcomes

During the follow-up period, 120 (80%) of the couples achieved pregnancy. Of these, 78 (65%) had a live birth, while 30 (25%) experienced another miscarriage, and 12 (10%) had a stillbirth. Preterm delivery occurred in 20% of pregnancies, with an average gestational age at birth of 36.2 ± 2.5 weeks. Neonatal complications, including low birth weight (<2.5 kg) and neonatal intensive care unit (NICU) admissions, were reported in 18% of cases (Table 2).

Table 2: Pregnancy and Neonatal Outcomes

Risk Factors for Adverse Pregnancy Outcomes

Among the various factors assessed, advanced maternal age (>35 years) was significantly associated with an increased risk of miscarriage (p < 0.01). Obesity (BMI >30 kg/m²) and thrombophilic disorders were also significantly linked to adverse pregnancy outcomes (p < 0.05). Couples who underwent medical intervention, such as progesterone supplementation and anticoagulation therapy, had better pregnancy success rates compared to those who did not receive targeted treatment (p < 0.05) (Table 3).

Table 3: Risk Factors and Pregnancy Outcomes

The study demonstrated that couples with previous miscarriages and perinatal deaths have a higher risk of adverse pregnancy outcomes. However, targeted medical interventions significantly improved reproductive success. Advanced maternal age, obesity, and thrombophilia emerged as key predictors of poor pregnancy outcomes (Table 3). These findings highlight the need for early identification and personalized management strategies to enhance reproductive performance in this population.

The present study evaluated the reproductive performance of couples with a history of miscarriage and perinatal death, identifying key risk factors and assessing the impact of medical interventions. The findings indicate that advanced maternal age, obesity, and thrombophilic disorders significantly contribute to adverse pregnancy outcomes. Additionally, targeted medical interventions, including progesterone supplementation and anticoagulant therapy, improved reproductive success.

Recurrent pregnancy loss (RPL) is a multifactorial condition, with genetic, endocrine, immunological, and anatomical factors playing a role in its etiology (1). Previous studies have demonstrated that maternal age is a significant predictor of pregnancy loss, primarily due to an increased prevalence of chromosomal abnormalities in oocytes (2,3). In this study, women over 35 years had a significantly higher rate of miscarriage, consistent with prior research indicating a decline in oocyte quality and endometrial receptivity with age (4).

Obesity has been identified as a major contributor to pregnancy complications, including miscarriage, gestational diabetes, and hypertensive disorders (5). The present study found that a BMI >30 kg/m² was significantly associated with adverse pregnancy outcomes. This aligns with previous research highlighting obesity-related alterations in hormonal balance, insulin resistance, and inflammatory responses that negatively impact implantation and placentation (6,7).

Thrombophilic disorders, such as antiphospholipid syndrome and inherited thrombophilias, have been strongly linked to recurrent pregnancy loss (8). The findings of this study indicate a significant association between thrombophilia and pregnancy loss, supporting prior evidence that these conditions lead to placental insufficiency and fetal demise due to microvascular thrombosis (9). The use of low-dose aspirin and low-molecular-weight heparin in affected individuals improved live birth rates, which is consistent with existing literature on anticoagulation therapy in pregnancy (10).

In terms of perinatal outcomes, preterm birth and neonatal complications were prevalent in this study. A previous meta-analysis reported that women with a history of RPL are at an increased risk of preterm delivery, possibly due to underlying uterine abnormalities, placental dysfunction, or immune-mediated mechanisms (11). Furthermore, fetal growth restriction and low birth weight were common among neonates, reinforcing the importance of close antenatal monitoring in high-risk pregnancies (12).

The role of medical interventions in improving pregnancy outcomes was evident in this study. Progesterone supplementation significantly enhanced pregnancy success, which is in agreement with previous research demonstrating its role in maintaining endometrial stability and reducing the risk of miscarriage in women with luteal phase defects (13). Similarly, lifestyle modifications, including weight management and smoking cessation, contributed to better pregnancy outcomes, aligning with findings from public health studies emphasizing the importance of maternal health optimization (14,15).

Despite these findings, the study has certain limitations. The sample size was relatively small, and follow-up was limited to one year, which may not fully capture long-term reproductive trends. Additionally, the study was conducted at a single center, limiting the generalizability of the results. Future research should focus on larger, multicenter trials with extended follow-up periods to further validate these findings.

In conclusion, couples with previous miscarriages and perinatal deaths face a heightened risk of adverse pregnancy outcomes. Advanced maternal age, obesity, and thrombophilic disorders were identified as significant risk factors. However, targeted interventions, including progesterone supplementation, anticoagulation therapy, and lifestyle modifications, improved pregnancy success. These findings underscore the need for personalized preconception counseling and comprehensive antenatal care to enhance reproductive outcomes in this high-risk population.

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