The Impact of Environmental PCB Exposure on IVF Outcomes: Exploring the Relationship between Specific Congeners and Abortion Rates in Women from Varying Pollution Zones.Affiliations

The Impact of Environmental PCB Exposure on IVF Outcomes: Exploring the Relationship between Specific Congeners and Abortion Rates in Women from Varying Pollution Zones.Affiliations | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Impact of Environmental PCB Exposure on IVF Outcomes: Exploring the Relationship between Specific Congeners and Abortion Rates in Women from Varying Pollution Zones.Affiliations Raimondo Salvatore, Gentile Raffaella, Angela Amoresano, Gentile MariaCira, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7227937/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Although the production of polychlorinated biphenyls (PCBs) ceased in 1977, human exposure persists. This may have adverse effects on reproductive health, including reduced fertility and increased abortion risk. However, human data remain largely inconclusive. This study investigates the potential association between blood concentrations of specific PCB congeners and abortion rates in women undergoing in vitro fertilization (IVF) cycles between 2017 and 2019. Participants lived in areas classified by different environmental impact: Group A (low environmental impact, LEI) and Group B (high environmental impact, HEI). Methods The study analyzed blood levels of estrogenic, anti-estrogenic, and other PCB congeners. Blood samples were collected from 60 participants during their IVF cycles. Joint statistical models were used to assess embryo implantation failure, abortion rates, and term pregnancies. Results PCBs 31, 44, 77, 110, 114, 118, 126, 153, 156, and 169 were significantly elevated in participants residing in HEI. PCB 169 had the highest concentration (229.62 ng/g), accounting for 94.8% of the total PCBs measured. No significant differences were observed between the two groups regarding oocyte pick-up rate, metaphase I and II oocyte ratio, fertilization rate, or pregnancy rate. Although embryo implantation rates were similar, the abortion rate was more than five times higher in Group B. The probability of live birth was 72.7% in Group A and 33.3% in Group B. Conclusions The significant elevation of PCB congeners in Group B, coupled with the observed increase in abortion rates within this group, suggests a potential link between exposure to these specific PCB congeners and a higher risk of abortion in women undergoing IVF. Further research is warranted to explore this association and elucidate the underlying biological mechanisms. PCBs in vitro fertilization (IVF) abortion high pollution low pollution Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Background An increasing recognition within the scientific and medical communities highlights the profound influence of environmental pollution on human reproductive health [ 1 , 2 ]. A growing body of evidence suggests that exposure to pollutants can adversely impact fertility, manifesting in a variety of detrimental effects. These consequences are observed in both males and females, indicating that reproductive vulnerability to environmental contaminants is not gender-specific [ 3 – 8 ]. Polychlorinated biphenyls (PCBs) are a group of synthetic chemicals that were extensively used in various industrial applications until their production ceased in 1977. These compounds were widely used as insulating fluids in electrical equipment, flame retardants in plastics, and electronics manufacturing (Agency for Toxic Substances and Disease Registry) [ 9 ]. Despite the cessation of PCB production, concerns about their potential health effects persist, owing to their environmental persistence, lipophilic nature, ability to bioaccumulate in food chains, and long biological half-life, which ranges from 1 to 10 years depending on the specific congener [ 10 – 12 ]. Ongoing exposure to PCBs remains a significant public health concern, as these chemicals are classified as endocrine-disrupting compounds (EDCs), which have the potential to interfere with normal endocrine system functioning and may result in adverse health outcomes [ 13 ]. Although PCB exposure has been linked to various reproductive health effects in women, findings from both experimental and epidemiological studies remain inconsistent [ 13 ]. Due to their widespread environmental distribution and persistence, PCB concentrations are detectable in the general population. A study conducted in the United States between 2003 and 2004, in which blood samples were collected from 1,800 individuals aged 12 years and above, found that 31 out of 35 PCB congeners were present in 60% of the samples, while 21 congeners were detected in 95% of the samples (14 Patterson et al., 2009). Primary exposure to PCBs occurs through the consumption of contaminated food, such as fish from contaminated waters and meat or dairy products from animals exposed to PCBs through contaminated feed or storage facilities [ 15 – 16 ]. Additional exposure can occur through environmental and occupational sources [ 17 – 24 ]. PCB congeners have been found in several tissues of the female reproductive system, suggesting that exposure occurs even in sensitive areas during prenatal development. They have been found at varying concentrations in human follicular fluid [ 26 – 28 ], ovarian tissue [ 29 – 30 ], placenta, uterine muscle, and amniotic fluid [ 31 – 33 ], as well as in embryos and fetuses [ 34 – 36 ]. This evidence indicates the transfer of PCBs from mother to fetus via the placenta, leading to prenatal exposure, followed by postnatal exposure through breastfeeding [ 37 , 38 ]. PCBs have been associated with a range of toxic effects on human health, including reproductive impairments [ 9 , 39 ]. Elevated blood PCB levels in women have been linked to disruptions in the menstrual cycle, such as shorter cycles and metrorrhagia [ 40 – 42 ], as well as decreased fertility, potentially due to endocrine disruption affecting oocytes and prolonging the time to conception [ 43 – 47 ]. Furthermore, exposure to PCBs has been associated with an increased risk of early abortion [ 45 , 48 – 50 ]. Several studies have also suggested a potential link between PCB exposure and conditions such as uterine fibroids [ 51 ], polycystic ovary syndrome [ 52 ], and endometriosis [ 53 ]. Additionally, research has examined the effects of PCB exposure on neonatal Apgar scores [ 54 ], birth weight [ 55 , 56 ], preterm birth [ 57 , 58 ], birth defects [ 59 , 60 ], gestational diabetes [ 61 – 63 ], and hypertensive disorders of pregnancy [ 64 , 65 ], though the results have been inconsistent. Given the increasing concern surrounding PCBs as endocrine disruptors, there is a pressing need for long-term studies to clarify their reproductive effects. However, the existing data on these matters remains limited and inconclusive [ 36 ]. Our study aims to examine the relationship between blood concentrations of PCB congeners, particularly those most commonly linked to toxicity, and the occurrence of early abortion in women undergoing in vitro fertilization (IVF) treatments. This population represents a unique model for studying early pregnancy losses, which often go undetected in the general population. Methods Ethical statements This study, conducted within the framework of the EcoFoodFertility project, adhered to the World Medical Association's Declaration of Helsinki. All experimental protocols received ethical approval from the Ethics Committee of ASL Campania Sud-Salerno, Italy (Committee Code 43/2015/06). Informed consent was obtained from all participants in accordance with the ethical principles of human experimentation. This study also followed the 1975 Declaration of Helsinki, as revised in 2000. Study areas and recruitment Sixty couples were enrolled between February 2017 and December 2019 as part of the EcoFoodFertility project [66], a multidisciplinary study that compares lifestyle and dietary habits to exposure to toxic substances released into the environment and contaminated foods. Of these sixty couples, twenty-nine (Group A) are from a low environmental impact area (LEI), an area in the Campania region (Southern Italy). This area includes Cilento, Vallo di Diano, and Alburni National Park. The economy of this area is primarily based on small and medium-scale agriculture, with no reported illegal dumping of toxic waste (blue circle in Figure 1) [67]. The remaining thirty-one couples (Group B) are from a high environmental impact area (HEI) in the same region. This area, designated as such by ARPAC through Legislative Decree 136/2013-l, was formally recognized on February 6, 2014, [67], known as the "Terra dei Fuochi" (Land of Fires) due to the multiple pollution sources (illegal disposal of urban, toxic and industrial waste, illegal dumps, vehicle traffic, intensive agriculture) [68-74] (Figure 1). The "Terra dei Fuochi" in Campania, Italy, is a recognized HEI, primarily due to extensive illegal dumping of toxic waste, as documented by the Regional Environmental Protection Agency of Campania. These illegal landfills, consisting of civil, industrial, and hospital waste, are frequently set on fire, resulting in significant contamination of agricultural land and aquifers. As a result, this pollution has been linked to an increased incidence of chronic degenerative diseases in the region [71,72,74,75]. Blood samples were collected from two groups of healthy female participants: Group A (n=29) residing in LEI, and Group B (n=31), residing in the "Terra dei Fuochi". Samples were obtained at participating assisted reproductive technology (ART) centers during IVF cycles. Anamnestic and clinical data on recurrent abortion risk factors [76-78] were collected using a standardized participation form. This helped create a comprehensive database. Participants provided self-reported data on medical and lifestyle conditions, and alcohol, tobacco, and drug use. All participants were free of chronic diseases and had resided in their respective areas for at least five years. They had no occupational exposure to risk factors and reported no drug use in the 12 months before sample collection. Anamnestic and clinical study of couples Group A Female Participants: all participants underwent an IVF cycle and completed a form detailing lifestyle, dietary habits, menarche, parity (nulliparous/multiparous), and history of spontaneous or voluntary abortions. Body mass index, waist circumference, waist-to-hip ratio, and Ferriman-Gallwey hirsutism scores were calculated for each participant. Inclusion criteria were normal menstruation (cycle length 28-30 days with regular rhythm, quantity, and duration) and no oral contraceptive use in the two years preceding blood sample collection. Blood samples were collected on the day of oocyte retrieval. Serum Anti-Müllerian hormone (AMH) levels were assessed before the IVF cycle. A summary of participant characteristics is provided in Tables 1 and 2. Table 1. Characteristics of female participants in Group A. References Group A (LEI) n=29 Age (years old) 32.9 + 0.8 Smoke 6 (20.69%) Alcohol 8 (27.58%) Drugs NO Menarche 10 12 Nulliparous 24 (82.76%) Multiparous 5 (17.24%) Previous abortion 2 (6.89%) BMI score 21 - 28 Waist circumference (cm) 69 - 87 Waist-to-hip ratio 1 Ferriman-Gallwey (score 1) 24 (82.76%) Ferriman-Gallwey (score 2) 5 (17.24%) FSH (mIU/ml) 3.48 + 0.27 AMH (ng/ml) 3.21 + 0.36 E2 (pg/ml) 34.83 + 3.15 Normo-ovulatory 21 (72.41%) Table 2. Occupations of female participants in Group A. Job Group A (LEI) n=29 Clothes shop assistant 5 (17.24%) Supermarket saleswoman 5 (17.24%) Agricultural labourer (not in greenhouses) 6 (20.71%) Teacher 3 (10.34%) Secretary in a professional studio 1 (3.44%) Housewife 6 (20.69%) Freelancer 3 (10.34%) Group B Female participants : all participants underwent an IVF cycle and completed a form detailing their lifestyle, dietary habits, menarche, parity (nulliparous/multiparous), and history of spontaneous/induced abortions. Body mass index, waist circumference, waist-to-hip ratio, and Ferriman-Gallwey hirsutism score were calculated. Inclusion criteria were normal menstruation with a cycle length of 27 to 31 days, regular rhythm, flow, and duration, and no oral contraceptive use within two years before blood sample collection. Blood samples were obtained on the day of oocyte retrieval. Serum anti-Müllerian hormone levels were measured before the IVF cycle. Table 3 provides a summary of the collected data, while Table 4 shows the occupations of the female partners in Group B. Table 3. Characteristics of the female participants in Group B. References Group B (HEI) n=31 Age (years old) 34.1 + 0.6 Smoke 12 (38.70%) Alcohol 7 (22.58%) Drugs NO Menarche 9 14 Nulliparous 28 (90.32%) Multiparous 3 (9.68%) Previous abortion 12 (38.70%) BMI score 21 - 38 Waist circumference (cm) 66 - 110 Waist-to-hip ratio 1 Ferriman-Gallwey (score 1) 12 (38.70%) Ferriman-Gallwey (score 2) 17 (54.83) Ferriman-Gallwey (score 3) 2 (6.45%) FSH (mIU/ml) 7.74 + 0.38 AMH ng/ml 2.22 + 0.27 E2 (pg/ml) 58.60 + 5.18 Normo-ovulatory 15 (48.38%) Table 4. Occupations of female partners in Group B. Job Group B (HEI) n=31 Clothes shop assistant 3 (9.68%) Supermarket saleswoman 7 (22.60%) Agricultural labourer (not in greenhouses) 1 (3.22%) Teacher 5 (16.12%) Secretary in a professional studio 5 (16.12%) Housewife 2 (6.45%) Freelancer 8 (25.80%) Serum collection and analysis of PCB congeners Before oocyte retrieval, blood samples were collected in glass tubes for subsequent analysis. The analysis focused on PCB congeners with reported associations with gynecological pathologies. These included estrogenic congeners (PCBs 31, 44, 52, 101, and 153), anti-estrogenic congeners (PCBs 77, 105, 110, 114, 126, 156, and 169), and other congeners (PCBs 28, 118, 138, and 180). The classification of PCB congeners is provided in Table 5. Table 5. PCB Congener List and Classification PCB Congener Chemical Name Estrogenic/Anti-estrogenic PCB 28 2,4,4'-Trichlorobiphenyl Other PCB 31 2,4′,5-Trichlorobiphenyl Estrogenic PCB 44 2,2′,3,5′-Tetrachlorobiphenyl Estrogenic PCB 52 2,2',5,5'-Tetrachlorobiphenyl Estrogenic PCB 77 3,3′,4,4′-Tetrachlorobiphenyl Anti-estrogenic PCB 101 2,2',4,5,5'-Pentachlorobiphenyl Estrogenic PCB 105 2,3,3',4,4'-Pentachlorobiphenyl Anti-estrogenic PCB 110 2,3,3',4',6-Pentachlorobiphenyl Anti-estrogenic PCB 114 2,3,4,4',5-Pentachlorobiphenyl Anti-estrogenic PCB 118 2,3',4,4',5-Pentachlorobiphenyl Other PCB 126 3,4,5,3',4'-Pentachlorobiphenyl Anti-estrogenic PCB 138 2,2',3,4,4',5'-Hexachlorobiphenyl Other PCB 153 2,2',4,4',5,5'-Hexachlorobiphenyl Estrogenic PCB 156 2,3,3',4,4',5-Hexachlorobiphenyl Anti-estrogenic PCB 169 2,3,3,4,4',5,5'-Heptachlorobiphenyl Anti-estrogenic PCB 180 2,2',3,4,4',5,5'-Heptachlorobiphenyl Other Serum and semen samples were analyzed for PCB congeners using mass spectrometry at the Department of Chemical Sciences, University of Naples Federico II, Italy. Reagents and Standards High-performance liquid chromatography-grade acetonitrile, hexane, and cyclohexane were used. Water was purified using a Milli-Q system. PCB congeners (IUPAC numbers 28, 31, 52, 77, 101, 105, 110, 114, 118, 126, 138, 153, 156, 169, and 180, in isooctane, all at 100 µg/mL) were obtained from Accustandard. Acetonitrile was purchased from Romil, and formic acid was obtained from Millinckrodt Baker. Sample Preparation Stock standard solutions of PCB congeners were prepared in cyclohexane at a concentration of 1 µg/mL. Sample aliquots (200 µL) were added to 10 mL of deionized water in a centrifuge tube. After a 30-minute incubation, 10 mL of acetonitrile was added, and the mixture was vortexed for 3 minutes. Samples were centrifuged at 5,000 rpm for 5 minutes. The supernatants were dried under nitrogen, and the residue was dissolved in 1 mL of cyclohexane and filtered through a 0.22-µm polytetrafluoroethylene. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis was performed using an Agilent 7890A GC system equipped with an Agilent 7693 autosampler and an Agilent 7000C Triple Quadrupole MS detector. Separation was performed using an Agilent HP-5 MS UI column (30 m × 0.25 mm, 0.25 μm film thickness). The oven temperature program was as follows: initial temperature of 60°C held for 1 minute, ramped to 120°C at 40°C/min, and then ramped to 275°C at 5°C/min. Helium was used as the carrier gas at a flow rate of 1.0 mL/min. The injection port temperature was maintained at 280°C, and 1.0 μL of sample was injected in splitless mode. The MS conditions were as follows: electron ionization source with an ionization voltage of 70 eV, ion source temperature of 280°C, quadrupole temperatures (Q1 and Q2) of 150°C, and interface temperature of 280°C. A solvent delay of 10.0 minutes was applied. Data acquisition and qualitative analysis were performed using Agilent MassHunter Data Acquisition Software (Ver. B.04.00) and MassHunter Workstation Software for Qualitative Analysis (Ver. B.03.01), respectively. Two transitions were monitored for each compound, and the collision energies were optimized for analysis. Quantification was performed using external calibration curves constructed from six standard mixtures at known concentrations for each compound class. Three replicates were analyzed for each calibration point, with coefficient variations below 10%. Analyte concentrations were determined by interpolating the measured peak areas against the corresponding calibration curves. The limit of detection and limit of quantification for each analyte in both serum and semen were 0.001 ng/mL and 0.003 ng/mL, respectively. A value equal to half the LOQ (0.0005 ng/mL) was assigned to congeners detected in at least 30% of the samples. Following Cocco et al., PCB congeners were categorized into functional groups: immunotoxic (PCBs 138, 153, and 180), low-chlorinated with pseudo-estrogenic activity (PCBs 28, 52, and 153), highly-chlorinated with anti-estrogenic activity (PCBs 170, 180, and 194), and phenobarbital-inducing (PCBs 101, 153, 180, and 194). Given the shared aryl hydrocarbon receptor-mediated mechanism of action between certain PCBs and polychlorinated dibenzo-p-dioxins, total dioxin-like PCB concentration was calculated as the sum of PCBs 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189. To assess potential opposing endocrine effects on spermatogenesis, we also calculated the ratio of pseudo-estrogenic to anti-estrogenic PCBs. Total serum PCB concentration was determined by summing all measured congeners. Statistical analysis Statistical analysis was performed on the entire dataset (n=60) for each geographic area, as well as for the combined population. The Shapiro-Wilk Test was used to test the normality of data distribution. The Mann-Whitney U Test was used to compare differences between LEI and HEI groups. The chi-square test or Fisher’s exact test was used to assess the abortion rate and pregnancy rate between groups. Analyses were conducted using GraphPad Prism 10 (GraphPad Software, Inc., La Jolla, CA, USA). Data are expressed as mean ± standard error of the mean (SEM). Results In Group A (n=29), 213 oocytes were retrieved, of which 20 (9.39%) were in metaphase I and 190 (90.05%) in metaphase II. The fertilization rate was 93.9%, with 189 embryos reaching the 8-cell stage. All participants underwent three embryo transfers. Unused embryos were either cryopreserved or left to naturally degenerate. Serum βHCG was measured 14 days post-transfer to assess pregnancy. Eleven participants achieved βHCG levels above 400 mIU/mL, indicative of successful implantation. Of these, 8 pregnancies resulted in live births, while one ended in abortion at 11 weeks. The mean maternal age in Group A was 32.9 years. All participants were Caucasian, and 20.68% were smokers. One participant (3.4%) had a prior full-term live birth. The primary infertility diagnoses were: unexplained (56.8%), male factor (17%), tubal factor (5.6%), polycystic ovary syndrome (10.3%), and ovulatory dysfunction (10.3%) (Table 9). In Group B (n=31), 217 oocytes were retrieved, with 18 (8.73%) in metaphase I and 199 (91.7%) in metaphase II. The fertilization rate was 92.6%, with 192 embryos developing to the 8-cell stage. All participants received three embryo transfers, and surplus embryos were either cryopreserved or underwent natural involution. Serum βHCG levels were measured 14 days post-embryo transfer to confirm successful implantation. Nine participants had βHCG levels exceeding 400 mIU/mL, a threshold indicative of successful implantation. Of these, six pregnancies resulted in abortion between 10- and 13-week gestation, while 3 resulted in live births. The mean maternal age was 34.1 years. All participants were Caucasian, and 38.7% reported smoking. Three participants (9.7%) had previously delivered a full-term infant. The most frequent infertility diagnoses were: unexplained (38.7%), male factor (25.7%), tubal factor (8.6%), polycystic ovary syndrome (16.1%), ovulatory dysfunction (6.4%), and dysormonosis (2.9%) (Table 8). Serum PCB concentrations were expressed both on a wet weight basis (ng/g serum) and lipid-adjusted (ng/g lipid). Table 8. Comparison of IVF Outcomes Between Groups A and B females. Group A (LEI) n=29 Group B (HEI) n=31 P value References 213 217 - Collected oocytes 20 (9.39%) 18 (8.73%) - MI oocytes 190 (90.5%) 199 (91.7%) - MII oocytes 200 (93.9%) 217 (92.06%) - Fertilisation 192 (91.42%) 201 (92.62%) - No. of embryos (8 cells) 23 out of 29 30 out of 31 - transfer 11 9 - HCG > 400 mIU/ml 38% 29% - Pregnancy rate 1 6 - Abortions 3.44% 19.35% - Abortion rate 8 (27.58%) 3 (9.68%) - Live births 2.51 ± 0.25 2.78 ± 0.27 NS PCB 28 0.77 ± 0.14 1.64 ± 0.26 P<0.01 PCB 31 0.03 ± 0.02 0.27 ± 0.12 P<0.05 PCB 44 0.003 ± 0.003 0.09 ± 0.04 NS PCB 52 0.75 ± 0.07 1.70 ± 0.22 P<0.001 PCB 77 0.18 ± 0.08 0.14 ± 0.06 NS PCB 101 0.27 ± 0.10 0.32 ± 0.09 NS PCB 105 0.24 ± 0.09 0.57 ± 0.10 P<0.05 PCB 110 0.03 ± 0.03 0.15 ± 0.06 P<0.05 PCB 114 0.34 ± 0.08 1.64 ± 0.23 P<0.001 PCB 118 0.38 ± 0.09 1.15 ± 0.18 P<0.001 PCB 126 0.07 ± 0.04 0.25 ± 0.09 NS PCB 138 0.07 ± 0.04 0.69 ± 0.18 P<0.001 PCB 153 0.07 ± 0.04 0.34 ± 0.10 P<0.01 PCB 156 160.1 ± 6.38 171.7 ± 6.36 P<0.01 PCB 169 0.004 ± 0.002 0.11 ± 0.02 NS PCB 180 NS: not significant. Serum PCB concentrations were expressed both on a wet weight basis (ng/g serum) and lipid-adjusted (ng/g lipid). Among PCBs with estrogenic activity, PCBs 31, 44, and 153 showed statistically higher concentrations in HEI females compared to LEI females (p<0.01, p<0.5, p<0.001, respectively). No significant difference was observed between the two groups for PCB 52 and PCB 101 (Figure 2). Among PCBs with antiestrogenic activity, PCB 77 and PCB 126 showed statistically higher concentration in the group of HEI females compared to the group of LEI females (p<0.001). PCB 169 showed a statistically significantly higher concentration in HEI females compared to LEI females (p<0.01); it was also the PCB with the highest concentration, reaching a peak of 229.72 ng/g and comprising 94.8% of the total PCB concentration. The concentration of PCB 110, 114, and 156 was also statistically higher in HEI females compared to LEI females (p<0.05). No statistically significant difference emerged between the two groups for PCB 105 (Figure 3). PCBs 118 and 180 showed statistically significantly higher concentrations in HEI females compared to LEI females (p<0.001). No significant difference emerged between the groups for PCBs 28 and 138 (Figure 4). Although the values of FSH, AMH, and Estradiol (E2) were within the normal range, significant differences were observed between the two groups. FSH levels in HEI females were significantly higher than those in LEI females (p<0.001). AMH levels in HEI females were significantly lower than those in LEI females (p<0.05). E2 levels in HEI females were significantly higher than those in LEI females (p<0.001) (Figure 5). Through the Ferriman-Gallwey score, which assesses and quantifies hirsutism, it was found that HEI females had significantly higher Ferriman-Gallwey scores than LEI females (p<0.001) (Figure 6). The medical history of normo-ovulation in HEI females, although not statistically significant, was slightly lower than in LEI females (p=0.057). While the other medical conditions (such as polycystic ovary syndrome, endometriosis, and oligomenorrhea) were overlapping (Figure 7). The relationship between the number of births and abortions differed between the two groups. The proportion of females with a history of previous abortions tended to be higher in HEI females compared to LEI females (p=0.052) (Figure 8A). Additionally, the number of females who underwent abortions following IVF was significantly higher in the HEI group compared to LEI females (p<0.05) (Figure 8B). Summing the total number of HEI females who experienced abortions, both before and after IVF, was also significantly higher than the LEI group (p<0.001). The total number of LEI females who underwent abortion was 3 (10.34%), while 13 (44.82%) have given birth. The total number of HEI females who underwent abortion was 18 (58.06%), while 6 (19.35%) have given birth (Figure 8C). Discussion Exposure to environmental contaminants has been shown to affect nearly every dimension of reproductive health, extending from conception and fertility to pregnancy outcomes, as well as the developmental trajectories of children and adolescents, and even long-term adult health. Recent investigations conducted within the framework of the EcoFoodFertility project [66] have provided compelling molecular-level evidence of how environmental pollutants disrupt reproductive functions. These substances interfere with multiple stages of the reproductive process in both men and women. Specifically, they have been found to alter hormone production, compromise the quality of gametes, and impair embryonic development. Such disruptions contribute to reduced fertility and an increased prevalence of reproductive disorders [79-85]. Our findings indicate an association between serum concentrations of specific PCB congeners (31, 44, 77, 110, 114, 118, 126, 153, 156, and 169) and adverse IVF outcomes. Although no significant differences were observed between the groups in terms of oocyte retrieval rate, metaphase I and II oocyte ratios, fertilization rates, or overall pregnancy rates, a significant disparity was found in pregnancy outcomes. Specifically, the abortion rate in Group B was more than five times higher than that of Group A. This resulted in a live birth rate of 72.7% in Group A compared to 33.3% in Group B, suggesting a potential link between exposure to the aforementioned PCBs and an increased risk of pregnancy loss. Limited research has investigated the association between PCB exposure and abortion [26,86]. Our study examines the relationship between pregnancy loss and serum concentrations of PCBs in two populations residing in geographically distinct areas with different environmental impacts. Many studies report an association between PCB exposure and increased TTP (time to pregnancy) [87]. A reduced fecundability odds ratio (FOR) is reported in women with high blood concentrations of PCBs [88]. In a study involving 81 women followed for 444 menstrual cycles, a diversity of interference of estrogenic and anti-estrogenic PCB congeners on TTP emerged [43]. Other studies conducted on a population of fishermen investigated the effects of PCB congeners detected in contaminated fish in relation to TTP, with conflicting results. [89-94]. Limitations on the presumed role of PCB congeners on reproductive health lie in the fact that it is not possible to ascertain an abortion rate because the studies conducted are based on TTP or on women who have a clinical pregnancy or on full-term live births. Our analysis of the relationship between PCB congeners and abortion seems to be innovative as we begin with a pregnancy rate, following IVF, followed by abortions, and confirmed term pregnancies. Early studies on this relationship were limited to small samples or indirect exposure assessments (the dietary pathway). Some reported no association [95-99], but the growing interest in this issue has intensified the studies and the lack of association between serum PCBs and risk of spontaneous abortion is reported in a study on 1,344 pregnancies in Michigan women [49], other works led to opposite conclusions [48,100,101], while a European study involving 1,710 women reported an association between PCB-153 and increased risk of fetal loss (spontaneous abortion or stillbirth) [50]. Other epidemiological studies have reported associations between PCB exposure and changes in the menstrual cycle [102-106] and endometriosis [107-110]. Animal studies have shown that PCBs cause reduced oocyte maturation [111], increased embryo degeneration, decreased embryo cell proliferation, blastocyst formation and development, and increased rates of in vitro fertilisation failure [112-120]. Furthermore, a study on the relationship between PCB congeners (77, 118, 153, and 180) and several factors affecting female fertility raises further doubts [121]. In our study, we also found significant changes in the concentrations of some hormones. FSH levels were higher in females exposed to a HEI. FSH has important roles in ovulation and follicular growth. Alteration levels of this hormone are associated with ovarian dysfunction and early or delayed puberty [122]. AMH levels were statistically lower in HEI females. This indicates a decreased ovarian reserve and an increased susceptibility to menopause [123]. Some studies report that high FSH levels and low AMH levels are found more in women who abort [124]. Some of the PCBs found at higher concentrations in HEI females than in LEI females had estrogenic activity. Further evidence of this activity is that E2 levels were also statistically higher in HEI females. This hormone has important roles in the menstrual cycle and ovulation, so it can lead to important hormonal imbalances [125]. Some authors report how high E2 levels are associated with increased abortions [126]. Our study monitored the participants' reproductive cycle before, during, and at the end with detailed and accurate information, and IFV cycles gave statistically valid information to detect the probable association between blood concentrations of PCB congeners, failed implantation, chemical pregnancies, and spontaneous abortions. Although we have set up a strict control and survey protocol, our study also has limitations, as with almost all epidemiological studies on environmental impact, there may be confounders or co-exposures that could interfere with the observed associations. Our study was conducted on women undergoing IVF, permanently living in areas with a different environmental impact, and our data showed a higher exposure of women in Group B than in Group A to certain PCB congeners. It is not possible to determine whether the participants in Group B are more sensitive to PCB exposure or whether some women are more sensitive to PCB exposure than others, although PCB exposure may influence a couple's fertility to the point where IVF treatment becomes necessary. In our study, no significant differences were observed between the two groups (A and B) in terms of oocyte quality, fertilisation rate, and embryo quality, although animal studies suggest that these parameters may be influenced by PCB exposure. In conclusion, we found that the increased blood concentrations of PCB 31, 44, 77, 110, 114, 118, 126, 153, 156, 169 found in Group B are associated with a higher probability of abortion among women undergoing IVF. It is possible that the inconsistent results between PCB exposure and reproductive outcomes are due to the different congeners of polyhalogenated organic compounds, unknown confounding factors, and exposure times. Although PCBs are no longer produced, exposure to these compounds remains widespread due to their long biological half-life, accumulation in the food chain, and the structurally similar compounds that continue to be produced. Therefore, the study of these old chemicals is still relevant and important. The relationship between PCBs and recurrent abortion certainly needs to be further investigated with greater numbers and a wider selection of participants. Conclusions This study contributes to the growing body of evidence suggesting that environmental contaminants, particularly PCBs, may adversely affect reproductive outcomes in women undergoing IVF. Although no significant differences were found between groups in terms of oocyte quality, fertilization rate, or initial pregnancy rate, women residing in areas with HEI (Group B) exhibited significantly elevated blood concentrations of several PCB congeners, which correlated with a markedly higher rate of spontaneous abortion and a substantially lower live birth rate compared to women from LEI (Group A). Our findings highlight a potential association between specific PCB congeners—namely PCB 31, 44, 77, 110, 114, 118, 126, 153, 156, and 169—and increased risk of pregnancy loss. In particular, PCB 169 accounted for the vast majority of total PCB concentration, raising concerns about its possible role in reproductive failure. The study also observed significant endocrine alterations in the high-exposure group, including elevated FSH and E2 levels and decreased AMH levels, all of which are markers of impaired ovarian function and increased abortion risk. This investigation is notable for its prospective design, detailed monitoring of the IVF process, and its consideration of pregnancy outcomes beyond clinical pregnancy rates, including implantation failure and spontaneous abortion. By focusing on a clearly defined and medically supervised population, the study provides valuable insights into the potential reproductive toxicity of persistent organic pollutants in humans. Nevertheless, several limitations must be acknowledged. As with most epidemiological studies, potential confounding variables and co-exposures cannot be entirely ruled out. Furthermore, it remains unclear whether the observed associations are due to inherent sensitivity among certain individuals or are broadly generalizable across populations. Despite the cessation of PCB production decades ago, ongoing environmental exposure due to bioaccumulation and environmental persistence underscores the continued relevance of research in this field. The results of this study underscore the importance of further large-scale, multidisciplinary investigations to confirm these findings, better understand the underlying biological mechanisms, and inform public health strategies aimed at reducing exposure to harmful environmental pollutants. In summary, our findings suggest that elevated exposure to specific PCB congeners is associated with adverse reproductive outcomes, particularly increased rates of abortion, in women undergoing IVF. This relationship warrants deeper investigation, given its implications for reproductive medicine, environmental health, and policy-making. Declarations Ethics approval and consent to participate All experimental protocols received ethical approval from the Ethics Committee of ASL Campania Sud-Salerno, Italy (Committee Code 43/2015/06). Informed consent was obtained from all participants in accordance with the ethical principles of human experimentation. This study also followed the 1975 Declaration of Helsinki, as revised in 2000. Consent for publication “not applicable’ Funding No funding Availability of data and materials “not applicable” Author Contribution S.R. and L.M have made substantial contributions to the conception, S.R., L.M., G.R. design of the work; S.R.,G.R., G.MC, G.A., G.T., R.L, the acquisition, analysis, R.S., L.M., A.M.,C.ML., . G.L. M.P.,R.B., M.T., V.C.. F.C. interpretation of data; S.R... 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Hum Reprod 2008;23(1):193–200. Anger DL, Foster WG. The link between environmental toxicant exposure and endometriosis. Front Biosci 2008;13:1578–1593. Heilier JF, Donnez J, Lison D. Organochlorines and endometriosis: a mini-review. Chemosphere 2008;71(2):203–210. Porpora MG, Ingelido AM, di Domenico A, Ferro A, Crobu M, Pallante D, et al.,. Increased levels of polychlorobiphenyls in Italian women with endometriosis. Chemosphere 2006; 63(8):1361–1367. Porpora MG, Medda E, Abballe A, Bolli S, De Angelis I, di Domenico A, et al.,. Endometriosis and organochlorinated environmental pollutants: a case–control study on Italian women of reproductive age. Environ Health Perspect 2009;117:1070–1075. Schisterman EF, Whitcomb Pocar P, Brevini TA, Antonini S, Gandolfi F. Cellular and molecular mechanisms mediating the effect of polychlorinated biphenyls on oocyte in vitro maturation. Reprod Toxicol 2006;22(2):242–249. Kholkute SD, Rodriguez J, Dukelow WR. Reproductive toxicity of Aroclor-1254: effects on oocyte, spermatozoa, in vitro fertilization, and embryo development in the mouse. Reprod Toxicol 1994a;8(6):487–493. Kholkute SD, Rodriguez J, Dukelow WR.. The effects of polybrominated biphenyls and perchlorinated terphenyls on in vitro fertilization in the mouse. Arch Environ Contam Toxicol 1994b;26(2):208–211. Kholkute SD, Dukelow WR. 1997. Effects of polychlorinated biphenyl (PCB) mixtures on in vitro fertilization in the mouse. Bull Environ Contam Toxicol 59(4):531–536. Lindenau A, Fischer B. Embryotoxicity of polychlorinated biphenyls (PCBS) for preimplantation embryos. Reprod Toxicol1996;10(3):227–230. Krogenaes AK, Nafstad I, Skare JU, Farstad W, Hafne AL. In vitro reproductive toxicity of polychlorinated biphenyl congeners 153 and 126. Reprod Toxicol 1998;12(6):575–580. Kuchenhoff A, Eckard R, Buff K, Fischer B. 1999. Stage-specific effects of defined mixtures of polychlorinated biphenyls on in vitro development of rabbit preimplantation embryos. Mol Reprod Dev 1999;54(2):126–134. Pocar P, Perazzoli F, Luciano AM, Gandolfi F. In vitro reproductive toxicity of polychlorinated biphenyls: effects on oocyte maturation and developmental competence in cattle. Mol Reprod Dev 2001;58(4):411–416. Campagna C, Sirard MA, Ayotte P, Bailey JL. Impaired maturation, fertilization, and embryonic development of porcine oocytes following exposure to an environmentally relevant organochlorine mixture. Biol Reprod 2001;65(2):554–560. Campagna C, Guillemette C, Paradis R, Sirard MA, Ayotte P, Bailey JL. An environmentally relevant organochlorine mixture impairs sperm function and embryo development in the porcine model. Biol Reprod 2002;67(1):80–87. Neblett MF, Curtis SW, Gerkowicz SA, et al., Examining Reproductive Health Outcomes in Females Exposed to Polychlorinated Biphenyl and Polybrominated Biphenyl. Sci Rep 2020;10:3314. Orlowski M, Sarao MS. Physiology, Follicle Stimulating Hormone. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535442/] Kruszyńska A, Słowińska-Srzednicka J. Anti-Müllerian hormone (AMH) as a good predictor of time of menopause. Prz Menopauzalny. 2017 Jun;16(2):47-50. doi: 10.5114/pm.2017.68591. Epub 2017 Jun 30. PMID: 28721129; PMCID: PMC5509971 Li, F., Niu, A., Feng, X. et al., The threshold effect of factors associated with spontaneous abortion in human-assisted reproductive technology. Sci Rep 11, 11368 (2021). https://doi.org/10.1038/s41598-021-90970-5 Reed BG, Carr BR. The Normal Menstrual Cycle and the Control of Ovulation. [Updated 2018 Aug 5]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279054/ Neal G Mahutte ∙ Antoni J Duleba ∙ Hugh S Taylor ∙ Aydin Arici ∙ Ervin Jones ∙ Denny Sakkas. Elevated estradiol levels are associated with increased miscarriage rates in women undergoing IVF/ICSI, 2002. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7227937","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":500113796,"identity":"ab467577-9e81-4ed3-b575-0425629f9fc6","order_by":0,"name":"Raimondo Salvatore","email":"","orcid":"","institution":"Gentile Research Center, Gragnano","correspondingAuthor":false,"prefix":"","firstName":"Raimondo","middleName":"","lastName":"Salvatore","suffix":""},{"id":500113797,"identity":"5312005b-9ba0-4792-8a51-86bed26052f2","order_by":1,"name":"Gentile Raffaella","email":"","orcid":"","institution":"University of Naples Federico II","correspondingAuthor":false,"prefix":"","firstName":"Gentile","middleName":"","lastName":"Raffaella","suffix":""},{"id":500113798,"identity":"09171aac-f1d7-4246-b88e-1925f7559378","order_by":2,"name":"Angela Amoresano","email":"","orcid":"","institution":"University of Naples Federico II","correspondingAuthor":false,"prefix":"","firstName":"Angela","middleName":"","lastName":"Amoresano","suffix":""},{"id":500113799,"identity":"249db490-44c2-4e87-a996-f07b19720e40","order_by":3,"name":"Gentile MariaCira","email":"","orcid":"","institution":"University of Milano-Bicocca","correspondingAuthor":false,"prefix":"","firstName":"Gentile","middleName":"","lastName":"MariaCira","suffix":""},{"id":500113800,"identity":"76458117-4a19-4b4b-8860-a5e115af6dc7","order_by":4,"name":"Carolina Fontanarosa","email":"","orcid":"","institution":"University of Naples Federico II","correspondingAuthor":false,"prefix":"","firstName":"Carolina","middleName":"","lastName":"Fontanarosa","suffix":""},{"id":500113801,"identity":"e9c22f28-d348-4dcb-9c3d-07121631d359","order_by":5,"name":"Gentile Alberto","email":"","orcid":"","institution":"Gentile Research Center, Gragnano","correspondingAuthor":false,"prefix":"","firstName":"Gentile","middleName":"","lastName":"Alberto","suffix":""},{"id":500113802,"identity":"6c6f9d3d-1a04-4b4f-81f7-0889b69a06b5","order_by":6,"name":"Gentile Tommaso","email":"","orcid":"","institution":"Gentile Research Center, Gragnano","correspondingAuthor":false,"prefix":"","firstName":"Gentile","middleName":"","lastName":"Tommaso","suffix":""},{"id":500113803,"identity":"26d6e91c-9814-40f2-aee2-6ed71c6b1840","order_by":7,"name":"Lacatena Raffaele","email":"","orcid":"","institution":"University of Naples Federico II","correspondingAuthor":false,"prefix":"","firstName":"Lacatena","middleName":"","lastName":"Raffaele","suffix":""},{"id":500113804,"identity":"d32ef520-5c89-421e-b88c-6fd7fbd24fce","order_by":8,"name":"Chiusano Maria Luisa","email":"","orcid":"","institution":"University of Naples Federico II","correspondingAuthor":false,"prefix":"","firstName":"Chiusano","middleName":"Maria","lastName":"Luisa","suffix":""},{"id":500113805,"identity":"72a32aaa-04bf-472b-95c6-65da1f69a469","order_by":9,"name":"Renato Lombardi","email":"","orcid":"","institution":"Local Health Authority, ASL Foggia","correspondingAuthor":false,"prefix":"","firstName":"Renato","middleName":"","lastName":"Lombardi","suffix":""},{"id":500113806,"identity":"377fdcb3-b79b-4137-82e1-e6c23ea1a1b1","order_by":10,"name":"Fabio Castagna","email":"","orcid":"","institution":"University of Catanzaro Magna Graecia","correspondingAuthor":false,"prefix":"","firstName":"Fabio","middleName":"","lastName":"Castagna","suffix":""},{"id":500113807,"identity":"aa0e1f3f-6d2f-4300-aa58-8b6bbedfb64f","order_by":11,"name":"Roberto Bava","email":"","orcid":"","institution":"University of Catanzaro Magna Graecia","correspondingAuthor":false,"prefix":"","firstName":"Roberto","middleName":"","lastName":"Bava","suffix":""},{"id":500113808,"identity":"ce74fc83-84e2-4e06-a422-e3354fe55ae2","order_by":12,"name":"Stefano Ruga","email":"","orcid":"","institution":"University of Catanzaro Magna Graecia","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Ruga","suffix":""},{"id":500113809,"identity":"4a28348a-3614-4f58-ac31-0af7ba4001b3","order_by":13,"name":"Abagnale Gennaro Maria","email":"","orcid":"","institution":"Gentile Research Center, Gragnano","correspondingAuthor":false,"prefix":"","firstName":"Abagnale","middleName":"Gennaro","lastName":"Maria","suffix":""},{"id":500113812,"identity":"ed7e84ec-a541-414e-9e6a-37f0894b6e0c","order_by":14,"name":"Antonio Marfella","email":"","orcid":"","institution":"Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale","correspondingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Marfella","suffix":""},{"id":500113813,"identity":"577aac58-14da-41c9-987f-a0a9ad47a65f","order_by":15,"name":"Verona Corsetti","email":"","orcid":"","institution":"National Counsil Research, Institute of Translational Pharmacology","correspondingAuthor":false,"prefix":"","firstName":"Verona","middleName":"","lastName":"Corsetti","suffix":""},{"id":500113814,"identity":"38e0b02c-93e9-49a4-b729-ef6b5b6c7f52","order_by":16,"name":"Marco Ticonosco","email":"","orcid":"","institution":"University of Modena and Reggio Emilia","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Ticonosco","suffix":""},{"id":500113815,"identity":"8b5a19b8-01c7-451b-90fe-9c27ff4a28da","order_by":17,"name":"Marina Piscopo","email":"","orcid":"","institution":"University of Naples Federico II","correspondingAuthor":false,"prefix":"","firstName":"Marina","middleName":"","lastName":"Piscopo","suffix":""},{"id":500113816,"identity":"87392492-a596-44c0-b5ce-13b7cfe5b555","order_by":18,"name":"Giovanna Liguori","email":"","orcid":"","institution":"Local Health Authority, ASL Foggia","correspondingAuthor":false,"prefix":"","firstName":"Giovanna","middleName":"","lastName":"Liguori","suffix":""},{"id":500113817,"identity":"ac112dbf-42d8-4537-b265-1dfa941de47b","order_by":19,"name":"Luigi Montano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYBACPgbGBoYEGO8DELOxE9DCBtPCA8SMM0AizAS1QAFICzOIYCCoRSK5+cXDHJs8e/azBx/b/Nomz8fMwPjhYw4+LYltFonb0op5ePKSjXP7bhu2MTMwS87chl+LQeK2w4k9DDlm0rk9txmBWtiYeYnSwv/GTNqy57Y9MVqaH4C1SABtYfhxO5GwFp6HbQxAvyT23HhjbNjbcDu5jZmxGa9f+NnTH3/8uc0msb0/x/DBjz+3bee3Nx/88BGPFrDb4EzGNjDZgFc9EDB/QLD/EFI8CkbBKBgFIxEAAI9qTXHR4062AAAAAElFTkSuQmCC","orcid":"","institution":"Local Health Authority, ASL Salerno","correspondingAuthor":true,"prefix":"","firstName":"Luigi","middleName":"","lastName":"Montano","suffix":""}],"badges":[],"createdAt":"2025-07-27 18:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7227937/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7227937/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89397891,"identity":"7cb04ecf-9b5d-4b8b-af74-8b392c2231d1","added_by":"auto","created_at":"2025-08-19 13:50:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":608947,"visible":true,"origin":"","legend":"\u003cp\u003eThis figure highlights the areas of interest for this study.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/05446dc485506a414a2548c8.png"},{"id":89394422,"identity":"17b5042f-71da-4734-a177-a8aeae5b676a","added_by":"auto","created_at":"2025-08-19 13:34:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50723,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of estrogenic PCB levels in LEI and HEI females.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/3a1801ba6f83fe21220a0d87.png"},{"id":89394418,"identity":"293e9592-2f6f-41d1-ace4-b3e007c679d0","added_by":"auto","created_at":"2025-08-19 13:34:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":69722,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of antiestrogenic PCB levels in LEI and HEI females.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/f75290cb6b6a395c98d1412b.png"},{"id":89397890,"identity":"e4e4e459-9108-473c-8d5d-f5d86f8d8881","added_by":"auto","created_at":"2025-08-19 13:50:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":41580,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of other PCB levels in LEI and HEI females.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/a42c469429776f056661148f.png"},{"id":89396874,"identity":"3f6df95c-b6e7-43ab-a0f4-af07ae7df891","added_by":"auto","created_at":"2025-08-19 13:42:55","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":67056,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of hormone levels between LEI and HEI females. (A) FSH level, (B) AMH level, (C) E2 level.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/a1242621d30e211d7f58b759.png"},{"id":89394420,"identity":"61d7ae78-e561-4c9f-88e2-6271c61dc338","added_by":"auto","created_at":"2025-08-19 13:34:55","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":18929,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the Ferriman-Gallwey score between LEI and HEI females. Ferriman-Gallwey score: 1 = minimal hair growth, 2 = mild hair growth, 3 = moderate hair growth.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/6a47b9ee8e8fd477009f810a.png"},{"id":89394426,"identity":"61b2438a-eb1d-4537-aa97-40bf59cb5ffe","added_by":"auto","created_at":"2025-08-19 13:34:55","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":21446,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of medical history between LEI and HEI females.\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/f2b76f0a5fb09f4d953f51f3.png"},{"id":89399157,"identity":"1cf974a6-64e3-4c35-a12c-2d1a43633aef","added_by":"auto","created_at":"2025-08-19 13:58:55","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":57563,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the number of LEI and HEI females who aborted or gave birth. (A) Previous births and abortions. (B) Births and abortions after IVF. (C) Total abortions and births.\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/5346f4bbe4cd3b39476374d1.png"},{"id":106402720,"identity":"f34f8232-aeab-4a2e-b698-34756fb68d2c","added_by":"auto","created_at":"2026-04-08 09:12:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1841099,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7227937/v1/4ff02542-4083-41e7-b8f8-79664201aa1f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Impact of Environmental PCB Exposure on IVF Outcomes: Exploring the Relationship between Specific Congeners and Abortion Rates in Women from Varying Pollution Zones.Affiliations","fulltext":[{"header":"Background","content":"\u003cp\u003eAn increasing recognition within the scientific and medical communities highlights the profound influence of environmental pollution on human reproductive health [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. A growing body of evidence suggests that exposure to pollutants can adversely impact fertility, manifesting in a variety of detrimental effects. These consequences are observed in both males and females, indicating that reproductive vulnerability to environmental contaminants is not gender-specific [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePolychlorinated biphenyls (PCBs) are a group of synthetic chemicals that were extensively used in various industrial applications until their production ceased in 1977. These compounds were widely used as insulating fluids in electrical equipment, flame retardants in plastics, and electronics manufacturing (Agency for Toxic Substances and Disease Registry) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite the cessation of PCB production, concerns about their potential health effects persist, owing to their environmental persistence, lipophilic nature, ability to bioaccumulate in food chains, and long biological half-life, which ranges from 1 to 10 years depending on the specific congener [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Ongoing exposure to PCBs remains a significant public health concern, as these chemicals are classified as endocrine-disrupting compounds (EDCs), which have the potential to interfere with normal endocrine system functioning and may result in adverse health outcomes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough PCB exposure has been linked to various reproductive health effects in women, findings from both experimental and epidemiological studies remain inconsistent [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Due to their widespread environmental distribution and persistence, PCB concentrations are detectable in the general population. A study conducted in the United States between 2003 and 2004, in which blood samples were collected from 1,800 individuals aged 12 years and above, found that 31 out of 35 PCB congeners were present in 60% of the samples, while 21 congeners were detected in 95% of the samples (14 Patterson et al., 2009). Primary exposure to PCBs occurs through the consumption of contaminated food, such as fish from contaminated waters and meat or dairy products from animals exposed to PCBs through contaminated feed or storage facilities [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Additional exposure can occur through environmental and occupational sources [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22 CR23\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePCB congeners have been found in several tissues of the female reproductive system, suggesting that exposure occurs even in sensitive areas during prenatal development. They have been found at varying concentrations in human follicular fluid [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], ovarian tissue [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], placenta, uterine muscle, and amniotic fluid [\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], as well as in embryos and fetuses [\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. This evidence indicates the transfer of PCBs from mother to fetus via the placenta, leading to prenatal exposure, followed by postnatal exposure through breastfeeding [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePCBs have been associated with a range of toxic effects on human health, including reproductive impairments [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Elevated blood PCB levels in women have been linked to disruptions in the menstrual cycle, such as shorter cycles and metrorrhagia [\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], as well as decreased fertility, potentially due to endocrine disruption affecting oocytes and prolonging the time to conception [\u003cspan additionalcitationids=\"CR44 CR45 CR46\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Furthermore, exposure to PCBs has been associated with an increased risk of early abortion [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan additionalcitationids=\"CR49\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Several studies have also suggested a potential link between PCB exposure and conditions such as uterine fibroids [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e], polycystic ovary syndrome [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e], and endometriosis [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Additionally, research has examined the effects of PCB exposure on neonatal Apgar scores [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e], birth weight [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e], preterm birth [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e], birth defects [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e], gestational diabetes [\u003cspan additionalcitationids=\"CR62\" citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e], and hypertensive disorders of pregnancy [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e, \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e], though the results have been inconsistent. Given the increasing concern surrounding PCBs as endocrine disruptors, there is a pressing need for long-term studies to clarify their reproductive effects. However, the existing data on these matters remains limited and inconclusive [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur study aims to examine the relationship between blood concentrations of PCB congeners, particularly those most commonly linked to toxicity, and the occurrence of early abortion in women undergoing in vitro fertilization (IVF) treatments. This population represents a unique model for studying early pregnancy losses, which often go undetected in the general population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical statements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study, conducted within the framework of the EcoFoodFertility project, adhered to the World Medical Association\u0026apos;s Declaration of Helsinki. All experimental protocols received ethical approval from the Ethics Committee of ASL Campania Sud-Salerno, Italy (Committee Code 43/2015/06). Informed consent was obtained from all participants in accordance with the ethical principles of human experimentation. This study also followed the 1975 Declaration of Helsinki, as revised in 2000.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy areas and recruitment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSixty couples were enrolled between February 2017 and December 2019 as part of the EcoFoodFertility project [66], a multidisciplinary study that compares lifestyle and dietary habits to exposure to toxic substances released into the environment and contaminated foods.\u003c/p\u003e\n\u003cp\u003eOf these sixty couples, twenty-nine (Group A) are from a low environmental impact area (LEI), an area in the Campania region (Southern Italy). This area includes Cilento, Vallo di Diano, and Alburni National Park. The economy of this area is primarily based on small and medium-scale agriculture, with no reported illegal dumping of toxic waste (blue circle in Figure 1) [67].\u003c/p\u003e\n\u003cp\u003eThe remaining thirty-one couples (Group B) are from a high environmental impact area (HEI) in the same region. This area, designated as such by ARPAC through Legislative Decree 136/2013-l, was formally recognized on February 6, 2014, [67], known as the \u0026quot;Terra dei Fuochi\u0026quot; (Land of Fires) due to the multiple pollution sources (illegal disposal of urban, toxic and industrial waste, illegal dumps, vehicle traffic, intensive agriculture) [68-74] (Figure 1).\u003c/p\u003e\n\u003cp\u003eThe \u0026quot;Terra dei Fuochi\u0026quot; in Campania, Italy, is a recognized HEI, primarily due to extensive illegal dumping of toxic waste, as documented by the Regional Environmental Protection Agency of Campania. These illegal landfills, consisting of civil, industrial, and hospital waste, are frequently set on fire, resulting in significant contamination of agricultural land and aquifers. As a result, this pollution has been linked to an increased incidence of chronic degenerative diseases in the region [71,72,74,75].\u003c/p\u003e\n\u003cp\u003eBlood samples were collected from two groups of healthy female participants: Group A (n=29) residing in LEI, and Group B (n=31), residing in the \u0026quot;Terra dei Fuochi\u0026quot;. Samples were obtained at participating assisted reproductive technology (ART) centers during IVF cycles. Anamnestic and clinical data on recurrent abortion risk factors [76-78] were collected using a standardized participation form. This helped create a comprehensive database. Participants provided self-reported data on medical and lifestyle conditions, and alcohol, tobacco, and drug use. All participants were free of chronic diseases and had resided in their respective areas for at least five years. They had no occupational exposure to risk factors and reported no drug use in the 12 months before sample collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAnamnestic and clinical study of couples\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eGroup A\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eFemale Participants:\u003c/u\u003e\u003c/strong\u003e all participants underwent an IVF cycle and completed a form detailing lifestyle, dietary habits, menarche, parity (nulliparous/multiparous), and history of spontaneous or voluntary abortions. Body mass index, waist circumference, waist-to-hip ratio, and Ferriman-Gallwey hirsutism scores were calculated for each participant. Inclusion criteria were normal menstruation (cycle length 28-30 days with regular rhythm, quantity, and duration) and no oral contraceptive use in the two years preceding blood sample collection. Blood samples were collected on the day of oocyte retrieval. Serum Anti-M\u0026uuml;llerian hormone (AMH) levels were assessed before the IVF cycle. A summary of participant characteristics is provided in Tables 1 and 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Characteristics of female participants in Group A.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReferences\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A (LEI) n=29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eAge (years old)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e32.9 \u003cu\u003e+\u003c/u\u003e 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eSmoke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e6 (20.69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eAlcohol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e8 (27.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDrugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eMenarche\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e10 \u0026lt; years old \u0026gt; 12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eNulliparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e24 (82.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eMultiparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e5 (17.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ePrevious abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e2 (6.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eBMI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e21 - 28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eWaist circumference (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e69 - 87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eWaist-to-hip ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eFerriman-Gallwey (score 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e24 (82.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eFerriman-Gallwey (score 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e5 (17.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eFSH (mIU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e3.48 \u003cu\u003e+\u003c/u\u003e 0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eAMH (ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e3.21 \u003cu\u003e+\u003c/u\u003e 0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eE2 (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e34.83 \u003cu\u003e+\u003c/u\u003e 3.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eNormo-ovulatory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e21 (72.41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Occupations of female participants in Group A.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJob\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A (LEI) n=29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eClothes shop assistant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e5 (17.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eSupermarket saleswoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e5 (17.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eAgricultural labourer (not in greenhouses)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e6 (20.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eTeacher\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e3 (10.34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eSecretary in a professional studio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e1 (3.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eHousewife\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e6 (20.69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eFreelancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003e3 (10.34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eGroup B\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eFemale participants\u003c/u\u003e\u003c/em\u003e: all participants underwent an IVF cycle and completed a form detailing their lifestyle, dietary habits, menarche, parity (nulliparous/multiparous), and history of spontaneous/induced abortions. Body mass index, waist circumference, waist-to-hip ratio, and Ferriman-Gallwey hirsutism score were calculated. Inclusion criteria were normal menstruation with a cycle length of 27 to 31 days, regular rhythm, flow, and duration, and no oral contraceptive use within two years before blood sample collection. Blood samples were obtained on the day of oocyte retrieval. Serum anti-M\u0026uuml;llerian hormone levels were measured before the IVF cycle. Table 3 provides a summary of the collected data, while Table 4 shows the occupations of the female partners in Group B.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Characteristics of the female participants in Group B.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReferences\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B (HEI) n=31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eAge (years old)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e34.1 \u003cu\u003e+\u003c/u\u003e 0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eSmoke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e12 (38.70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eAlcohol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e7 (22.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eDrugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eMenarche\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e9 \u0026lt; years old \u0026gt; 14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eNulliparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e28 (90.32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eMultiparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e3 (9.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003ePrevious abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e12 (38.70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eBMI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e21 - 38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eWaist circumference (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e66 - 110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eWaist-to-hip ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eFerriman-Gallwey (score 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e12 (38.70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eFerriman-Gallwey (score 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e17 (54.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eFerriman-Gallwey (score 3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e2 (6.45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eFSH (mIU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e7.74 \u003cu\u003e+\u003c/u\u003e 0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eAMH ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e2.22 \u003cu\u003e+\u003c/u\u003e 0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eE2 (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e58.60 \u003cu\u003e+\u003c/u\u003e 5.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.7677%;\"\u003e\n \u003cp\u003eNormo-ovulatory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.2323%;\"\u003e\n \u003cp\u003e15 (48.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Occupations of female partners in Group B.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.9261%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJob\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.0739%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B (HEI) n=31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.9261%;\"\u003e\n \u003cp\u003eClothes shop assistant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.0739%;\"\u003e\n \u003cp\u003e3 (9.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.9261%;\"\u003e\n \u003cp\u003eSupermarket saleswoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.0739%;\"\u003e\n \u003cp\u003e7 (22.60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.9261%;\"\u003e\n \u003cp\u003eAgricultural labourer (not in greenhouses)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.0739%;\"\u003e\n \u003cp\u003e1 (3.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.9261%;\"\u003e\n \u003cp\u003eTeacher\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.0739%;\"\u003e\n \u003cp\u003e5 (16.12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.9261%;\"\u003e\n \u003cp\u003eSecretary in a professional studio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.0739%;\"\u003e\n \u003cp\u003e5 (16.12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.9261%;\"\u003e\n \u003cp\u003eHousewife\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.0739%;\"\u003e\n \u003cp\u003e2 (6.45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 54.9261%;\"\u003e\n \u003cp\u003eFreelancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.0739%;\"\u003e\n \u003cp\u003e8 (25.80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSerum collection and analysis of PCB congeners\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBefore oocyte retrieval, blood samples were collected in glass tubes for subsequent analysis. The analysis focused on PCB congeners with reported associations with gynecological pathologies. These included estrogenic congeners (PCBs 31, 44, 52, 101, and 153), anti-estrogenic congeners (PCBs 77, 105, 110, 114, 126, 156, and 169), and other congeners (PCBs 28, 118, 138, and 180). The classification of \u003cem\u003ePCB congeners is provided in Table 5.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTable 5.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ePCB Congener List and Classification\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB Congener\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003eChemical Name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eEstrogenic/Anti-estrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,4,4\u0026apos;-Trichlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,4\u0026prime;,5-Trichlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eEstrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,2\u0026prime;,3,5\u0026prime;-Tetrachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eEstrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,2\u0026apos;,5,5\u0026apos;-Tetrachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eEstrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e3,3\u0026prime;,4,4\u0026prime;-Tetrachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eAnti-estrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,2\u0026apos;,4,5,5\u0026apos;-Pentachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eEstrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,3,3\u0026apos;,4,4\u0026apos;-Pentachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eAnti-estrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,3,3\u0026apos;,4\u0026apos;,6-Pentachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eAnti-estrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,3,4,4\u0026apos;,5-Pentachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eAnti-estrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,3\u0026apos;,4,4\u0026apos;,5-Pentachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e3,4,5,3\u0026apos;,4\u0026apos;-Pentachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eAnti-estrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,2\u0026apos;,3,4,4\u0026apos;,5\u0026apos;-Hexachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,2\u0026apos;,4,4\u0026apos;,5,5\u0026apos;-Hexachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eEstrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,3,3\u0026apos;,4,4\u0026apos;,5-Hexachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eAnti-estrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,3,3,4,4\u0026apos;,5,5\u0026apos;-Heptachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eAnti-estrogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.632%;\"\u003e\n \u003cp\u003ePCB 180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43.8662%;\"\u003e\n \u003cp\u003e2,2\u0026apos;,3,4,4\u0026apos;,5,5\u0026apos;-Heptachlorobiphenyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.5019%;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSerum and semen samples were analyzed for PCB congeners using mass spectrometry at the Department of Chemical Sciences, University of Naples Federico II, Italy.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eReagents and Standards\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHigh-performance liquid chromatography-grade acetonitrile, hexane, and cyclohexane were used. Water was purified using a Milli-Q system. PCB congeners (IUPAC numbers 28, 31, 52, 77, 101, 105, 110, 114, 118, 126, 138, 153, 156, 169, and 180, in isooctane, all at 100 \u0026micro;g/mL) were obtained from Accustandard. Acetonitrile was purchased from Romil, and formic acid was obtained from Millinckrodt Baker.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eSample Preparation\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eStock standard solutions of PCB congeners were prepared in cyclohexane at a concentration of 1 \u0026micro;g/mL. Sample aliquots (200 \u0026micro;L) were added to 10 mL of deionized water in a centrifuge tube. After a 30-minute incubation, 10 mL of acetonitrile was added, and the mixture was vortexed for 3 minutes. Samples were centrifuged at 5,000 rpm for 5 minutes. The supernatants were dried under nitrogen, and the residue was dissolved in 1 mL of cyclohexane and filtered through a 0.22-\u0026micro;m polytetrafluoroethylene. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis was performed using an Agilent 7890A GC system equipped with an Agilent 7693 autosampler and an Agilent 7000C Triple Quadrupole MS detector. Separation was performed using an Agilent HP-5 MS UI column (30 m \u0026times; 0.25 mm, 0.25 \u0026mu;m film thickness). The oven temperature program was as follows: initial temperature of 60\u0026deg;C held for 1 minute, ramped to 120\u0026deg;C at 40\u0026deg;C/min, and then ramped to 275\u0026deg;C at 5\u0026deg;C/min. Helium was used as the carrier gas at a flow rate of 1.0 mL/min. The injection port temperature was maintained at 280\u0026deg;C, and 1.0 \u0026mu;L of sample was injected in splitless mode. The MS conditions were as follows: electron ionization source with an ionization voltage of 70 eV, ion source temperature of 280\u0026deg;C, quadrupole temperatures (Q1 and Q2) of 150\u0026deg;C, and interface temperature of 280\u0026deg;C. A solvent delay of 10.0 minutes was applied. Data acquisition and qualitative analysis were performed using Agilent MassHunter Data Acquisition Software (Ver. B.04.00) and MassHunter Workstation Software for Qualitative Analysis (Ver. B.03.01), respectively.\u003c/p\u003e\n\u003cp\u003eTwo transitions were monitored for each compound, and the collision energies were optimized for analysis. Quantification was performed using external calibration curves constructed from six standard mixtures at known concentrations for each compound class. Three replicates were analyzed for each calibration point, with coefficient variations below 10%. Analyte concentrations were determined by interpolating the measured peak areas against the corresponding calibration curves. The limit of detection and limit of quantification for each analyte in both serum and semen were 0.001 ng/mL and 0.003 ng/mL, respectively. A value equal to half the LOQ (0.0005 ng/mL) was assigned to congeners detected in at least 30% of the samples.\u003c/p\u003e\n\u003cp\u003eFollowing Cocco et al., PCB congeners were categorized into functional groups: immunotoxic (PCBs 138, 153, and 180), low-chlorinated with pseudo-estrogenic activity (PCBs 28, 52, and 153), highly-chlorinated with anti-estrogenic activity (PCBs 170, 180, and 194), and phenobarbital-inducing (PCBs 101, 153, 180, and 194). Given the shared aryl hydrocarbon receptor-mediated mechanism of action between certain PCBs and polychlorinated dibenzo-p-dioxins, total dioxin-like PCB concentration was calculated as the sum of PCBs 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189. To assess potential opposing endocrine effects on spermatogenesis, we also calculated the ratio of pseudo-estrogenic to anti-estrogenic PCBs. Total serum PCB concentration was determined by summing all measured congeners.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed on the entire dataset (n=60) for each geographic area, as well as for the combined population. The Shapiro-Wilk Test was used to test the normality of data distribution. The Mann-Whitney U Test was used to compare differences between LEI and HEI groups. The chi-square test or Fisher\u0026rsquo;s exact test was used to assess the abortion rate and pregnancy rate between groups. Analyses were conducted using GraphPad Prism 10 (GraphPad Software, Inc., La Jolla, CA, USA). Data are expressed as mean \u0026plusmn; standard error of the mean (SEM).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn Group A (n=29), 213 oocytes were retrieved, of which 20 (9.39%) were in metaphase I and 190 (90.05%) in metaphase II. The fertilization rate was 93.9%, with 189 embryos reaching the 8-cell stage. All participants underwent three embryo transfers. Unused embryos were either cryopreserved or left to naturally degenerate. Serum \u0026beta;HCG was measured 14 days post-transfer to assess pregnancy. Eleven participants achieved \u0026beta;HCG levels above 400 mIU/mL, indicative of successful implantation. Of these, 8 pregnancies resulted in live births, while one ended in abortion at 11 weeks. The mean maternal age in Group A was 32.9 years. All participants were Caucasian, and 20.68% were smokers. One participant (3.4%) had a prior full-term live birth. The primary infertility diagnoses were: unexplained (56.8%), male factor (17%), tubal factor (5.6%), polycystic ovary syndrome (10.3%), and ovulatory dysfunction (10.3%) (Table 9).\u003c/p\u003e\n\u003cp\u003eIn Group B (n=31), 217 oocytes were retrieved, with 18 (8.73%) in metaphase I and 199 (91.7%) in metaphase II. The fertilization rate was 92.6%, with 192 embryos developing to the 8-cell stage. All participants received three embryo transfers, and surplus embryos were either cryopreserved or underwent natural involution.\u003c/p\u003e\n\u003cp\u003eSerum \u0026beta;HCG levels were measured 14 days post-embryo transfer to confirm successful implantation. Nine participants had \u0026beta;HCG levels exceeding 400 mIU/mL, a threshold indicative of successful implantation. Of these, six pregnancies resulted in abortion between 10- and 13-week gestation, while 3 resulted in live births. The mean maternal age was 34.1 years. All participants were Caucasian, and 38.7% reported smoking. Three participants (9.7%) had previously delivered a full-term infant. The most frequent infertility diagnoses were: unexplained (38.7%), male factor (25.7%), tubal factor (8.6%), polycystic ovary syndrome (16.1%), ovulatory dysfunction (6.4%), and dysormonosis (2.9%) (Table 8).\u003c/p\u003e\n\u003cp\u003eSerum PCB concentrations were expressed both on a wet weight basis (ng/g serum) and lipid-adjusted (ng/g lipid).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 8. Comparison of IVF Outcomes Between Groups A and B females.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A (LEI) n=29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B (HEI) n=31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eReferences\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e217\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCollected oocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003cp\u003e(9.39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003cp\u003e(8.73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMI oocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e190\u003c/p\u003e\n \u003cp\u003e(90.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e199\u003c/p\u003e\n \u003cp\u003e(91.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMII oocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003cp\u003e(93.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e217\u003c/p\u003e\n \u003cp\u003e(92.06%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFertilisation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e192\u003c/p\u003e\n \u003cp\u003e(91.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e201\u003c/p\u003e\n \u003cp\u003e(92.62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNo. of embryos (8 cells)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 out of 29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30 out of 31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003etransfer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHCG \u0026gt; 400 mIU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePregnancy rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAbortions\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;3.44%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e19.35%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAbortion rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e(27.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e(9.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLive births\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.51 \u0026plusmn; 0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.78 \u0026plusmn; 0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.77 \u0026plusmn; 0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.64 \u0026plusmn; 0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.03 \u0026plusmn; 0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.27 \u0026plusmn; 0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.003 \u0026plusmn; 0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.09 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.75 \u0026plusmn; 0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.70 \u0026plusmn; 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.18 \u0026plusmn; 0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.14 \u0026plusmn; 0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 101\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.27 \u0026plusmn; 0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.32 \u0026plusmn; 0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 105\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.24 \u0026plusmn; 0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.57 \u0026plusmn; 0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.03 \u0026plusmn; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.15 \u0026plusmn; 0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.34 \u0026plusmn; 0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.64 \u0026plusmn; 0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 118\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.38 \u0026plusmn; 0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.15 \u0026plusmn; 0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.07 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.25 \u0026plusmn; 0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 138\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.07 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.69 \u0026plusmn; 0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.07 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.34 \u0026plusmn; 0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e160.1 \u0026plusmn; 6.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e171.7 \u0026plusmn; 6.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 169\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.004 \u0026plusmn; 0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.11 \u0026plusmn; 0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCB 180\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNS: not significant.\u003c/p\u003e\n\u003cp\u003eSerum PCB concentrations were expressed both on a wet weight basis (ng/g serum) and lipid-adjusted (ng/g lipid). Among PCBs with estrogenic activity, PCBs 31, 44, and 153 showed statistically higher concentrations in HEI females compared to LEI females (p\u0026lt;0.01, p\u0026lt;0.5, p\u0026lt;0.001, respectively). No significant difference was observed between the two groups for PCB 52 and PCB 101 (Figure 2).\u003c/p\u003e\n\u003cp\u003eAmong PCBs with antiestrogenic activity, PCB 77 and PCB 126 showed statistically higher concentration in the group of HEI females compared to the group of LEI females (p\u0026lt;0.001). PCB 169 showed a statistically significantly higher concentration in HEI females compared to LEI females (p\u0026lt;0.01); it was also the PCB with the highest concentration, reaching a peak of 229.72 ng/g and comprising 94.8% of the total PCB concentration. The concentration of PCB 110, 114, and 156 was also statistically higher in HEI females compared to LEI females (p\u0026lt;0.05). No statistically significant difference emerged between the two groups for PCB 105 (Figure 3).\u003c/p\u003e\n\u003cp\u003ePCBs 118 and 180 showed statistically significantly higher concentrations in HEI females compared to LEI females (p\u0026lt;0.001). No significant difference emerged between the groups for PCBs 28 and 138 (Figure 4).\u003c/p\u003e\n\u003cp\u003eAlthough the values of FSH, AMH, and Estradiol (E2) were within the normal range, significant differences were observed between the two groups. FSH levels in HEI females were significantly higher than those in LEI females (p\u0026lt;0.001). AMH levels in HEI females were significantly lower than those in LEI females (p\u0026lt;0.05). E2 levels in HEI females were significantly higher than those in LEI females (p\u0026lt;0.001) (Figure 5).\u003c/p\u003e\n\u003cp\u003eThrough the Ferriman-Gallwey score, which assesses and quantifies hirsutism, it was found that HEI females had significantly higher Ferriman-Gallwey scores than LEI females (p\u0026lt;0.001) (Figure 6).\u003c/p\u003e\n\u003cp\u003eThe medical history of normo-ovulation in HEI females, although not statistically significant, was slightly lower than in LEI females (p=0.057). While the other medical conditions (such as polycystic ovary syndrome, endometriosis, and oligomenorrhea) were overlapping (Figure 7).\u003c/p\u003e\n\u003cp\u003eThe relationship between the number of births and abortions differed between the two groups. The proportion of females with a history of previous abortions tended to be higher in HEI females compared to LEI females (p=0.052) (Figure 8A). Additionally, the number of females who underwent abortions following IVF was significantly higher in the HEI group compared to LEI females (p\u0026lt;0.05) (Figure 8B). Summing the total number of HEI females who experienced abortions, both before and after IVF, was also significantly higher than the LEI group (p\u0026lt;0.001). The total number of LEI females who underwent abortion was 3 (10.34%), while 13 (44.82%) have given birth. The total number of HEI females who underwent abortion was 18 (58.06%), while 6 (19.35%) have given birth (Figure 8C).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eExposure to environmental contaminants has been shown to affect nearly every dimension of reproductive health, extending from conception and fertility to pregnancy outcomes, as well as the developmental trajectories of children and adolescents, and even long-term adult health. Recent investigations conducted within the framework of the EcoFoodFertility project [66] have provided compelling molecular-level evidence of how environmental pollutants disrupt reproductive functions. These substances interfere with multiple stages of the reproductive process in both men and women. Specifically, they have been found to alter hormone production, compromise the quality of gametes, and impair embryonic development. Such disruptions contribute to reduced fertility and an increased prevalence of reproductive disorders [79-85].\u003c/p\u003e\n\u003cp\u003eOur findings indicate an association between serum concentrations of specific PCB congeners (31, 44, 77, 110, 114, 118, 126, 153, 156, and 169) and adverse IVF outcomes. Although no significant differences were observed between the groups in terms of oocyte retrieval rate, metaphase I and II oocyte ratios, fertilization rates, or overall pregnancy rates, a significant disparity was found in pregnancy outcomes. Specifically, the abortion rate in Group B was more than five times higher than that of Group A. This resulted in a live birth rate of 72.7% in Group A compared to 33.3% in Group B, suggesting a potential link between exposure to the aforementioned PCBs and an increased risk of pregnancy loss.\u003c/p\u003e\n\u003cp\u003eLimited research has investigated the association between PCB exposure and abortion [26,86]. Our study examines the relationship between pregnancy loss and serum concentrations of PCBs in two populations residing in geographically distinct areas with different environmental impacts.\u003c/p\u003e\n\u003cp\u003eMany studies report an association between PCB exposure and increased TTP (time to pregnancy) [87]. A reduced fecundability odds ratio (FOR) is reported in women with high blood concentrations of PCBs [88]. In a study involving 81 women followed for 444 menstrual cycles, a diversity of interference of estrogenic and anti-estrogenic PCB congeners on TTP emerged [43]. Other studies conducted on a population of fishermen investigated the effects of PCB congeners detected in contaminated fish in relation to TTP, with conflicting results. [89-94].\u003c/p\u003e\n\u003cp\u003eLimitations on the presumed role of PCB congeners on reproductive health lie in the fact that it is not possible to ascertain an abortion rate because the studies conducted are based on TTP or on women who have a clinical pregnancy or on full-term live births.\u003c/p\u003e\n\u003cp\u003eOur analysis of the relationship between PCB congeners and abortion seems to be innovative as we begin with a pregnancy rate, following IVF, followed by abortions, and confirmed term pregnancies.\u003c/p\u003e\n\u003cp\u003eEarly studies on this relationship were limited to small samples or indirect exposure assessments (the dietary pathway). Some reported no association [95-99], but the growing interest in this issue has intensified the studies and the lack of association between serum PCBs and risk of spontaneous abortion is reported in a study on 1,344 pregnancies in Michigan women [49], other works led to opposite conclusions [48,100,101], while a European study involving 1,710 women reported an association between PCB-153 and increased risk of fetal loss (spontaneous abortion or stillbirth) [50].\u003c/p\u003e\n\u003cp\u003eOther epidemiological studies have reported associations between PCB exposure and changes in the menstrual cycle [102-106] and endometriosis [107-110].\u003c/p\u003e\n\u003cp\u003eAnimal studies have shown that PCBs cause reduced oocyte maturation [111], increased embryo degeneration, decreased embryo cell proliferation, blastocyst formation and development, and increased rates of in vitro fertilisation failure [112-120]. Furthermore, a study on the relationship between PCB congeners (77, 118, 153, and 180) and several factors affecting female fertility raises further doubts [121].\u003c/p\u003e\n\u003cp\u003eIn our study, we also found significant changes in the concentrations of some hormones. FSH levels were higher in females exposed to a HEI. FSH has important roles in ovulation and follicular growth. Alteration levels of this hormone are associated with ovarian dysfunction and early or delayed puberty [122].\u003c/p\u003e\n\u003cp\u003eAMH levels were statistically lower in HEI females. This indicates a decreased ovarian reserve and an increased susceptibility to menopause [123].\u003c/p\u003e\n\u003cp\u003eSome studies report that high FSH levels and low AMH levels are found more in women who abort [124]. Some of the PCBs found at higher concentrations in HEI females than in LEI females had estrogenic activity. Further evidence of this activity is that E2 levels were also statistically higher in HEI females. This hormone has important roles in the menstrual cycle and ovulation, so it can lead to important hormonal imbalances [125]. Some authors report how high E2 levels are associated with increased abortions [126].\u003c/p\u003e\n\u003cp\u003eOur study monitored the participants\u0026apos; reproductive cycle before, during, and at the end with detailed and accurate information, and IFV cycles gave statistically valid information to detect the probable association between blood concentrations of PCB congeners, failed implantation, chemical pregnancies, and spontaneous abortions.\u003c/p\u003e\n\u003cp\u003eAlthough we have set up a strict control and survey protocol, our study also has limitations, as with almost all epidemiological studies on environmental impact, there may be confounders or co-exposures that could interfere with the observed associations.\u003c/p\u003e\n\u003cp\u003eOur study was conducted on women undergoing IVF, permanently living in areas with a different environmental impact, and our data showed a higher exposure of women in Group B than in Group A to certain PCB congeners.\u003c/p\u003e\n\u003cp\u003eIt is not possible to determine whether the participants in Group B are more sensitive to PCB exposure or whether some women are more sensitive to PCB exposure than others, although PCB exposure may influence a couple\u0026apos;s fertility to the point where IVF treatment becomes necessary.\u003c/p\u003e\n\u003cp\u003eIn our study, no significant differences were observed between the two groups (A and B) in terms of oocyte quality, fertilisation rate, and embryo quality, although animal studies suggest that these parameters may be influenced by PCB exposure.\u003c/p\u003e\n\u003cp\u003eIn conclusion, we found that the increased blood concentrations of PCB 31, 44, 77, 110, 114, 118, 126, 153, 156, 169 found in Group B are associated with a higher probability of abortion among women undergoing IVF. It is possible that the inconsistent results between PCB exposure and reproductive outcomes are due to the different congeners of polyhalogenated organic compounds, unknown confounding factors, and exposure times. Although PCBs are no longer produced, exposure to these compounds remains widespread due to their long biological half-life, accumulation in the food chain, and the structurally similar compounds that continue to be produced. Therefore, the study of these old chemicals is still relevant and important.\u003c/p\u003e\n\u003cp\u003eThe relationship between PCBs and recurrent abortion certainly needs to be further investigated with greater numbers and a wider selection of participants.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study contributes to the growing body of evidence suggesting that environmental contaminants, particularly PCBs, may adversely affect reproductive outcomes in women undergoing IVF. Although no significant differences were found between groups in terms of oocyte quality, fertilization rate, or initial pregnancy rate, women residing in areas with HEI (Group B) exhibited significantly elevated blood concentrations of several PCB congeners, which correlated with a markedly higher rate of spontaneous abortion and a substantially lower live birth rate compared to women from LEI (Group A).\u003c/p\u003e\n\u003cp\u003eOur findings highlight a potential association between specific PCB congeners\u0026mdash;namely PCB 31, 44, 77, 110, 114, 118, 126, 153, 156, and 169\u0026mdash;and increased risk of pregnancy loss. In particular, PCB 169 accounted for the vast majority of total PCB concentration, raising concerns about its possible role in reproductive failure. The study also observed significant endocrine alterations in the high-exposure group, including elevated FSH and E2 levels and decreased AMH levels, all of which are markers of impaired ovarian function and increased abortion risk.\u003c/p\u003e\n\u003cp\u003eThis investigation is notable for its prospective design, detailed monitoring of the IVF process, and its consideration of pregnancy outcomes beyond clinical pregnancy rates, including implantation failure and spontaneous abortion. By focusing on a clearly defined and medically supervised population, the study provides valuable insights into the potential reproductive toxicity of persistent organic pollutants in humans.\u003c/p\u003e\n\u003cp\u003eNevertheless, several limitations must be acknowledged. As with most epidemiological studies, potential confounding variables and co-exposures cannot be entirely ruled out. Furthermore, it remains unclear whether the observed associations are due to inherent sensitivity among certain individuals or are broadly generalizable across populations.\u003c/p\u003e\n\u003cp\u003eDespite the cessation of PCB production decades ago, ongoing environmental exposure due to bioaccumulation and environmental persistence underscores the continued relevance of research in this field. The results of this study underscore the importance of further large-scale, multidisciplinary investigations to confirm these findings, better understand the underlying biological mechanisms, and inform public health strategies aimed at reducing exposure to harmful environmental pollutants.\u003c/p\u003e\n\u003cp\u003eIn summary, our findings suggest that elevated exposure to specific PCB congeners is associated with adverse reproductive outcomes, particularly increased rates of abortion, in women undergoing IVF. This relationship warrants deeper investigation, given its implications for reproductive medicine, environmental health, and policy-making.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll experimental protocols received ethical approval from the Ethics Committee of ASL Campania Sud-Salerno, Italy (Committee Code 43/2015/06). Informed consent was obtained from all participants in accordance with the ethical principles of human experimentation. This study also followed the 1975 Declaration of Helsinki, as revised in 2000.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;not applicable\u0026rsquo;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo funding\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;not applicable\u0026rdquo;\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eS.R. and L.M have made substantial contributions to the conception, S.R., L.M., G.R. design of the work; S.R.,G.R., G.MC, G.A., G.T., R.L, the acquisition, analysis, R.S., L.M., A.M.,C.ML., . G.L. M.P.,R.B., M.T., V.C.. F.C. interpretation of data; S.R... C.ML, the creation of new software used in the work; S.R., L.M., G.L, have drafted the work or substantively revised it\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFerrero G, Festa R, Follia L, Lettieri G, Tarallo S, Notari T, Giarra A, Marinaro C, Pardini B, Marano A, Piaggeschi G, Di Battista C, Trifuoggi M, Piscopo M, Montano L, Naccarati A. Small noncoding RNAs and sperm nuclear basic proteins reflect the environmental impact on germ cells. Mol Med. 2024 Jan 20;30(1):12. doi: 10.1186/s10020-023-00776-6. \u003c/li\u003e\n\u003cli\u003eMontano L, Baldini GM, Piscopo M, Liguori G, Lombardi R, Ricciardi M, Esposito G, Pinto G, Fontanarosa C, Spinelli M, Palmieri I, Sofia D, Brogna C, Carati C, Esposito M, Gallo P, Amoresano A, Motta O. Polycyclic Aromatic Hydrocarbons (PAHs) in the Environment: Occupational Exposure, Health Risks and Fertility Implications. 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Scand J Work Environ Health 2002;28(2):124\u0026ndash;132.\u003c/li\u003e\n\u003cli\u003eAxmon A, Rylander L, Stromberg U, Jonsson B, Nilsson-Ehle P, Hagmar L. Polychlorinated biphenyls in serum and time to pregnancy. Environ Res 2004;96(2):186\u0026ndash;195.\u003c/li\u003e\n\u003cli\u003eAxmon A, Thulstrup AM, Rignell-Hydbom A, Pedersen HS, Zvyezday V, Ludwicki JK, et al.,. Time to pregnancy as a function of male and female serum concentrations of 2,2\u0026Aring;L4,4\u0026Aring;L5,5\u0026Aring;L-hexachlorobiphenyl (CB-153) and 1,1-dichloro- 2,2-bis (p-chlorophenyl)-ethylene (p,p\u0026Aring;L-DDE). Hum Reprod 2006;21(3):657\u0026ndash;665.\u003c/li\u003e\n\u003cli\u003eArakawa C, Yoshinaga J, Okamura K, Nakai K, Satoh H. 2006. Fish consumption and time to pregnancy in Japanese women. Int J Hyg Environ Health 2006;209(4):337\u0026ndash;344.\u003c/li\u003e\n\u003cli\u003eDar E, Kanarek MS, Anderson HA, Sonzogni WC. Fish consumption and reproductive outcomes in Green Bay, Wisconsin. Environ Res 1992;59(1):189\u0026ndash;201.\u003c/li\u003e\n\u003cli\u003eMendola P, Buck GM, Vena JE, Zielezny M, Sever LE. Consumption of PCB-contaminated sport fish and risk of spontaneous fetal death. Environ Health Perspect 1995;103:498\u0026ndash;502.\u003c/li\u003e\n\u003cli\u003eAxmon A, Rylander L, Stromberg U, Hagmar L. Miscarriages and stillbirths in women with a high intake of fish contaminated with persistent organochlorine compounds. Int Arch Occup Environ Health 2000a;73(3):204\u0026ndash;208.\u003c/li\u003e\n\u003cli\u003eSugiura-Ogasawara M, Ozaki Y, Sonta S, Makino T, Suzumori K. PCBs, hexachlorobenzene and DDE are not associated with recurrent miscarriage. Am J Reprod Immunol 2003;50(6):485\u0026ndash;489.\u003c/li\u003e\n\u003cli\u003eKhanjani N, Sim MR. Maternal contamination with PCBs and reproductive outcomes in an Australian population. J Expo Sci Environ Epidemiol 2007;17(2):191\u0026ndash;195.\u003c/li\u003e\n\u003cli\u003eBercovici B, Wassermann M, Cucos S, Ron M, Wassermann D, Pines A. Serum levels of polychlorinated biphenyls and some organochlorine insecticides in women with recent and former missed abortions. Environ Res 1983;30(1):169\u0026ndash;174.\u003c/li\u003e\n\u003cli\u003eTsukimori K, Tokunaga S, Shibata S, Uchi H, Nakayama D, Ishimaru T, et al.,. Long-term effects of polychlorinated biphenyls and dioxins on pregnancy outcomes in women affected by the Yusho incident. Environ Health Perspect 2008;116:626\u0026ndash;630.\u003c/li\u003e\n\u003cli\u003eYu ML, Guo YL, Hsu CC, Rogan WJ. Menstruation and reproduction in women with polychlorinated biphenyl (PCB) poisoning: long-term follow-up interviews of the women from the Taiwan Yucheng cohort. Int J Epidemiol 2000;29(4):672\u0026ndash;677.\u003c/li\u003e\n\u003cli\u003eCooper GS, Klebanoff MA, Promislow J, Brock JW, Longnecker MP. Polychlorinated biphenyls and menstrual cycle characteristics. Epidemiology 2005;16(2):191\u0026ndash;200.\u003c/li\u003e\n\u003cli\u003eChao HR, Wang SL, Lin LY, Lee WJ, Papke O. Placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in Taiwanese mothers in relation to menstrual cycle characteristics. Food Chem Toxicol 2007;45(2):259\u0026ndash;265.\u003c/li\u003e\n\u003cli\u003eToft G, Hagmar L, Giwercman A, Bonde JP. Epidemiological evidence on reproductive effects of persistent organochlorines in humans. Reprod Toxicol 2004;19(1):5\u0026ndash;26.\u003c/li\u003e\n\u003cli\u003eToft G, Axmon A, Lindh CH, Giwercman A, Bonde JP. Menstrual cycle characteristics in European and Inuit women exposed to persistent organochlorine pollutants. Hum Reprod 2008;23(1):193\u0026ndash;200.\u003c/li\u003e\n\u003cli\u003eAnger DL, Foster WG. The link between environmental toxicant exposure and endometriosis. Front Biosci 2008;13:1578\u0026ndash;1593.\u003c/li\u003e\n\u003cli\u003eHeilier JF, Donnez J, Lison D. Organochlorines and endometriosis: a mini-review. Chemosphere 2008;71(2):203\u0026ndash;210.\u003c/li\u003e\n\u003cli\u003ePorpora MG, Ingelido AM, di Domenico A, Ferro A, Crobu M, Pallante D, et al.,. Increased levels of polychlorobiphenyls in Italian women with endometriosis. Chemosphere 2006; 63(8):1361\u0026ndash;1367.\u003c/li\u003e\n\u003cli\u003ePorpora MG, Medda E, Abballe A, Bolli S, De Angelis I, di Domenico A, et al.,. Endometriosis and organochlorinated environmental pollutants: a case\u0026ndash;control study on Italian women of reproductive age. Environ Health Perspect 2009;117:1070\u0026ndash;1075. Schisterman EF, Whitcomb\u003c/li\u003e\n\u003cli\u003ePocar P, Brevini TA, Antonini S, Gandolfi F. Cellular and molecular mechanisms mediating the effect of polychlorinated biphenyls on oocyte in vitro maturation. Reprod Toxicol 2006;22(2):242\u0026ndash;249.\u003c/li\u003e\n\u003cli\u003eKholkute SD, Rodriguez J, Dukelow WR. Reproductive toxicity of Aroclor-1254: effects on oocyte, spermatozoa, in vitro fertilization, and embryo development in the mouse. Reprod Toxicol 1994a;8(6):487\u0026ndash;493.\u003c/li\u003e\n\u003cli\u003eKholkute SD, Rodriguez J, Dukelow WR.. The effects of polybrominated biphenyls and perchlorinated terphenyls on in vitro fertilization in the mouse. Arch Environ Contam Toxicol 1994b;26(2):208\u0026ndash;211.\u003c/li\u003e\n\u003cli\u003eKholkute SD, Dukelow WR. 1997. Effects of polychlorinated biphenyl (PCB) mixtures on in vitro fertilization in the mouse. Bull Environ Contam Toxicol 59(4):531\u0026ndash;536.\u003c/li\u003e\n\u003cli\u003eLindenau A, Fischer B. Embryotoxicity of polychlorinated biphenyls (PCBS) for preimplantation embryos. 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Prz Menopauzalny. 2017 Jun;16(2):47-50. doi: 10.5114/pm.2017.68591. Epub 2017 Jun 30. PMID: 28721129; PMCID: PMC5509971\u003c/li\u003e\n\u003cli\u003eLi, F., Niu, A., Feng, X. \u003cem\u003eet al.,\u003c/em\u003e The threshold effect of factors associated with spontaneous abortion in human-assisted reproductive technology. \u003cem\u003eSci Rep\u003c/em\u003e 11, 11368 (2021). https://doi.org/10.1038/s41598-021-90970-5\u003c/li\u003e\n\u003cli\u003eReed BG, Carr BR. The Normal Menstrual Cycle and the Control of Ovulation. [Updated 2018 Aug 5]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279054/\u003c/li\u003e\n\u003cli\u003eNeal G Mahutte ∙ Antoni J Duleba ∙ Hugh S Taylor ∙ Aydin Arici ∙ Ervin Jones ∙ Denny Sakkas. Elevated estradiol levels are associated with increased miscarriage rates in women undergoing IVF/ICSI, 2002.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"PCBs, in vitro fertilization (IVF), abortion, high pollution, low pollution","lastPublishedDoi":"10.21203/rs.3.rs-7227937/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7227937/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAlthough the production of polychlorinated biphenyls (PCBs) ceased in 1977, human exposure persists. This may have adverse effects on reproductive health, including reduced fertility and increased abortion risk. However, human data remain largely inconclusive. This study investigates the potential association between blood concentrations of specific PCB congeners and abortion rates in women undergoing in vitro fertilization (IVF) cycles between 2017 and 2019. Participants lived in areas classified by different environmental impact: Group A (low environmental impact, LEI) and Group B (high environmental impact, HEI).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe study analyzed blood levels of estrogenic, anti-estrogenic, and other PCB congeners. Blood samples were collected from 60 participants during their IVF cycles. Joint statistical models were used to assess embryo implantation failure, abortion rates, and term pregnancies.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003ePCBs 31, 44, 77, 110, 114, 118, 126, 153, 156, and 169 were significantly elevated in participants residing in HEI. PCB 169 had the highest concentration (229.62 ng/g), accounting for 94.8% of the total PCBs measured. No significant differences were observed between the two groups regarding oocyte pick-up rate, metaphase I and II oocyte ratio, fertilization rate, or pregnancy rate. Although embryo implantation rates were similar, the abortion rate was more than five times higher in Group B. The probability of live birth was 72.7% in Group A and 33.3% in Group B.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe significant elevation of PCB congeners in Group B, coupled with the observed increase in abortion rates within this group, suggests a potential link between exposure to these specific PCB congeners and a higher risk of abortion in women undergoing IVF. Further research is warranted to explore this association and elucidate the underlying biological mechanisms.\u003c/p\u003e","manuscriptTitle":"The Impact of Environmental PCB Exposure on IVF Outcomes: Exploring the Relationship between Specific Congeners and Abortion Rates in Women from Varying Pollution Zones.Affiliations","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-19 13:34:50","doi":"10.21203/rs.3.rs-7227937/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"703ae8f0-3016-4f15-9260-2fa31666aaa7","owner":[],"postedDate":"August 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-04T11:23:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-19 13:34:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7227937","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7227937","identity":"rs-7227937","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}