Association of Tumor Necrosis Factor-\u03b1 -308G>A, -238G>A and -376G>A polymorphisms with recurrent pregnancy loss risk in the Greek population

Recurrent pregnancy loss is a common issue in Obstetrics&Gynaecology practice. Thyroid autoimmunity has been associated with pregnancy loss. Thyroid peroxidase antibodies (TPO-Ab) is the most common antithyroid autoantibodies observed in women with recurrent pregnancy loss history. Although the precise mechanisms of the TPO-Ab's role in recurrent pregnancy loss are not fully understood. The study was aimed to assess the relationship of Anti-TPO antibody with recurrent pregnancy loss. This cross-sectional comparative study was conducted in the Department of Obstetrics and Gynecology at Mymensingh Medical College Hospital, Bangladesh, during the period from March 2023 to August 2024. A total of 100 euthyroid women with or without history of recurrent pregnancy loss were included in the study based on inclusion and exclusion criteria. They were divided into two groups, 50 patients with history of recurrent pregnancy loss (RPL) group and 50 patients without history of recurrent pregnancy loss group as (Non RPL). The serum Anti-TPO antibody level was compared between RPL group and non-RPL group. The Statistical Package for Social Science (SPSS) v.23.0 was used for statistical analysis. In this study, maximum patients belonged to age group 21-30 years in both groups, the mean age was found 28.9±5.8 years in RPL group and 27.5±4.9 years in non-RPL group. There were no significant differences regarding age, occupational status, educational status, monthly income and BMI between two groups. In RPL group, majority 41(82.0%) had no children and in non-RPL group all patients had one or more children, that was significant between two groups (p<0.05). Positive anti-TPO antibody (≥100 u/ml) was significantly higher in RPL group than non-RPL group (68.0% vs. 8.0%), odds ratio of 24.43 with 95% CI (7.49-79.68). Thus, it can be concluded that positive anti-TPO antibody was significantly higher in patients with recurrent pregnancy loss than without history of pregnancy loss. Screening of anti-thyroid peroxidase antibody is may be considered in recurrent pregnancy loss cases.

Association between low basal serum total testosterone levels and the risk of recurrent pregnancy loss in women with infertility.

Study question Whether oxidative/nitrative stress biomarkers increased the risk of recurrent pregnancy loss (RPL)? Summary answer Patients with higher oxidative/nitrative stress biomarkers of 8-NO2Gua and HNE-MA had an increased risk of recurrent pregnancy loss compared with controls. What is known already In reproductive medicine, recurrent pregnancy loss (RPL) is a major problem including the most unknown and lack of evidence-based diagnostics and therapies. Certain oxidative stress markers play an important role in the progress of some diseases. In one study, subsequent increases in 8-OHdG levels in the RPL group indicated extensive DNA damage and the lipid peroxidation products dramatically increased before an abortion occurred. Large unknowns of other indicators of oxidative stress, such as markers of lipid peroxidation (8-isoPF 2α, HNE-MA, and MDA), and DNA damage (8-NO2Gua), are studied for their impacts on RPL. Study design, size, duration We used an established case-control study, the Taiwan Recurrent Pregnancy Loss and Environmental Study (TRIPLES), which included 514 reproductive age (20-50) women (including 397 cases and 117 controls) from obstetric clinics at National Cheng Kung University Hospital in southern Taiwan from 2013 to 2022. Participants/materials, setting, methods The physicians diagnosed two or more consecutive miscarriages before 20 weeks of pregnancy as RPL cases. They excluded uterine anomalies, maternal diseases, chromosomal abnormalities, polycystic ovarian syndrome (PCOS), premature ovarian failure, and endometriosis. As a control group, we included married women, who delivered at least one child without artificial reproduction, underwent laparotomy for other clinical reasons, and did not suffer from the above-mentioned gynecological diseases. Main results and the role of chance Recurrent pregnancy loss (RPL) groups were older (mean=35.13) and had more time to prepare for pregnancy (mean=10.66 months). Their marital status mainly was married, their household income exceeded around 33,000 USD, and they consumed coffee habits. The median oxidative/nitrative stress biomarkers of 8-NO2Gua and HNE-MA in the case group were significantly higher than those in the control group (6.15 and 30.12 vs. 3.77 and 21.54 ug/L, p&amp;lt;0.001), indicating that the oxidative stress biomarkers of 8-NO2Gua and HNE-MA could be an essential effect factor in RPL. By categorizing the data by tertile of oxidative/nitrative stress biomarkers, we found that the RPL risk was 3.19 times higher in the third tertile of log 8-NO2Gua than in the first tertile (OR: 3.19, 95% CI: 1.66–6.10) and that the RPL risk in log HNE-MA was higher in the third tertile (OR: 2.05, 95% CI: 1.12–3.74). After adjustment for age, time to pregnancy (months), and coffee drinking habits, the RPL risk in the third tertile of log 8-NO2Gua was 2.01 times significantly higher than that in the first tertile (AOR: 2.01, 95% CI: 1.00–4.04). Limitations, reasons for caution Limitation of a case-control study. The oxidative stress biomarkers 8-NO2Gua and HNE-MA were significantly higher in the RPL groups, however, the causes of oxidative stress (like multiple environmental exposures, etc.) remain more studies to elucidate. Wider implications of the findings We provided evidence for oxidative/nitrative stress biomarkers in RPL patients, which implies the reduction of oxidative/nitrative stress may improve the progress of RPL. As important information for preventive medicine, more studies are needed to understand the adverse outcome pathway of oxidative/nitrative stress in RPL. Trial registration number MOST 109-2314-B-400 −022 -MY3 and EM-112-PP-11

This case-control study investigates whether miR-27a rs895819 A>G polymorphism is associated with an increased risk of recurrent pregnancy loss (RPL) in Caucasian Greek women. This study included 93 women with at least two unexplained miscarriages before the 24th week of gestation (RPL group) and 107 women with no pregnancy loss history (control group). The miR-27a rs895819 A>G polymorphism was detected using PCR amplification, followed by DraIII-HF restriction enzyme digestion. The GG genotype was linked to a significantly higher risk of RPL (p-value = 0.00005), whereas the AA genotype was associated with a significantly lower risk (p-value = 0.00036). The AG genotype appeared more frequently in women with RPL (49.5% vs. 44.9% in controls), but the difference was not statistically significant (p-value = 0.5139). To our knowledge, this is the first study demonstrating that the miR-27a A>G polymorphism was significantly associated with a higher risk of recurrent miscarriage in Caucasian women. These findings provide evidence that the GG genotype may serve as a potential genetic marker for identifying women at higher risk of recurrent miscarriage, offering valuable insights for genetic counseling and reproductive medicine.

The present case-control study investigates whether TP53 Arg72Pro variant (rs1042522) serves as a risk factor for recurrent pregnancy loss (RPL) in Greek women. The study group consisted of 100 patients with at least two miscarriages of unexplained etiology, before the 24thweek of gestation. The control group included 106 women with no pregnancy loss history. DNA was extracted and genotyped using specific primers for PCR amplification of the Arg72 and Pro72 alleles. Sanger sequencing was used for the discrimination between heterozygotes and homozygotes for Arg72Pro variant. This is the first study demonstrating the statistically significant higher frequency of TP53 Arg72Pro variant in Greek RPL women compared to controls (38% vs. 6.6%; OR=8.6682, 95% CI: 3.6446-20.6160; p<0.0001). GC genotype (Arg/Pro) and CC genotype (Pro/Pro) were statistically more common in RPL patients than in controls (16% vs. 1.9%; p=0.0027, and 22 vs. 4.7%; p=0.0008, respectively). C allele frequency was statistically significant higher in RPL group than in controls (30.0 vs. 5.7%; p<0.0001). According to the inheritance mode analysis, the model that best fit the data was the dominant model (OR=8.67, 95% CI=3.64-20.62; p<0.0001). The is the first study disclosing strong evidence that TP53 rs1042522 is significantly associated with a higher risk for recurrent pregnancy loss in Greek women following a dominant model, thus, serving as a genetic marker for identifying women at increased risk of recurrent miscarriages.

Study question Whether the CNV load differs in fetal tissues of miscarriages from families with recurrent and sporadic pregnancy loss? Summary answer In RPL group duplications are more common than deletions, de novo variants than inherited ones. Pathogenic CNVs (dup16p11.2, del22q13, dupXq28) were found in both groups. What is known already Data on CNVs in tissues of miscarriages can be found in more than 24 articles. Altogether 7732 samples were analyzed by aCGH and NGS; 988 CNVs of uncertain clinical significance were found in 636 samples (8.2%). The origin was determined for 130 variants: 85 maternal (65.4%), 34 paternal (26.2%), 11 de novo (8.4%) CNVs. No aberration unambiguously associated with miscarriage was found so far. Comparative analysis of CNVs in family trios with recurrent and sporadic miscarriage may help to characterize structural genome variations associated with embryo lethality both from embryo and parental side. Study design, size, duration Identification of structural genome variations (SGV) at the CNV level was performed by aCGH-analysis for family trios: mother, father and fetal. Characteristics of SGV associated with embryo lethality included such parameters as CNV type (deletion/duplication) and its origin. It was assumed that the structure of genomic variability may differ in recurrent pregnancy loss (RPL) and sporadic pregnancy loss (SPL) both in embryonic tissues and in parents. Participants/materials, setting, methods Eleven family trios (7 RPL and 4 SPL) were included in the research. Standard G-banding was performed for all abortion samples to exclude aneuploidy. STR-haplotyping for the SRY gene was used to exclude maternal cell contamination. Finally all samples were analyzed for CNVs using SurePrint G3 Human CGH+SNP 4 × 180K microarrays (Agilent Technologies). Average gestation age was 7.9 weeks. Average maternal and paternal age was 30.8 and 30.5 years, respectively. Main results and the role of chance In seven and four embryos from RPL and SPL groups 110 and 60 CNVs were identified, respectively. In RPL, there was a tendency towards an increase in the frequency of duplications over deletions (72:38) in comparison to SPL (36:24) (p = 0.5). Duplications prevailed over deletions in five of seven embryos from RPL group; while there were two cases of each combination in SPL. One can suggest that some SPL cases can move into RPL group over time. De novo variants prevailed over inherited in the RPL group (76:43) and inherited prevailed in the SPL (32:28) (p &amp;lt; 0.05). This result allows to suggest that in cases with RPL there may be some common genetic/epigenetic factor predisposing to CNV generation either in primordial germ cells or during early blastomere cleavage. Among the inherited variants in the RPL group there were 24 maternal and 8 paternal CNVs, while in the SPL – 18 and 14 (p = 0.1). In both groups pathogenic CNVs associated with syndromes characterized by neurodevelopmental disorders (NDD) in children were found (del22q13, dupXq28 – in RPL group, dup16p11.2 – two cases in SPL). Presumably, such aberrations may explain a high risk of NDD in a child of a woman with RPL/SPL (PMID:30058166, PMID:33580539). Limitations, reasons for caution No one CNV unambiguously associated with pregnancy loss has been described so far. Possibly, total structural genome variations level should be considered as pathogenic factor for embryo development. There is no adequate algorithm of clinical significance CNV interpretation for the embryonic period. Wider implications of the findings Prenatal or preimplantation genetic testing should be considered if one of the parents is a carrier of CNV associated with microdeletion/microduplication syndrome. This study was supported by the Russian Science Foundation № 21-65-00017, https://rscf.ru/project/21-65-00017/. Trial registration number Russian Science Foundation № 21-65-00017

Interleukin-1 gene cluster variants and recurrent pregnancy loss among North Indian women: retrospective study and meta-analysis

Study question How the reproductive-aged women with recurrent pregnancy loss (RPL) through exposure to emerging contaminants such as per- and polyfluoroalkyl substances (PFAS) has not been evaluated Summary answer This is the first comprehensive investigation exploring the relationship between various lifestyle exposure characteristics of PFAS and the occurrence of RPL in the Taiwanese women. What is known already Recurrent Pregnancy Loss (RPL) refers to a clinically diagnosed medical condition in the women with a history of two or more consecutive miscarriages characterized by the termination of pregnancy before 20 weeks of gestation. Although the exact mechanism underlying RPL occurrence still needs to be evaluated, previous studies have suggested various associated mechanisms including the interactions between immunological, environmental, and genetic responses leading to RPL complications. Environmental exposure to endocrine-disrupting chemicals (EDCs) such as PFAS has been known to cause adverse pregnancy outcomes in women. However, their association with RPL occurrence based on the exposure characteristics in Taiwanese remains unclear. Study design, size, duration The study constituted a case-control design from an established Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES) cohort (August 2013 – October 2023) in Taiwan (N = 446) comprised of clinically diagnosed female (aged 20-50 years) RPL patients (n = 342) and health controls (n = 104) during their obstetric consultation. Urine samples were collected from participants to quantify PFAS and exposure characteristics including demographic information and lifestyle habits were collected using a retrospective questionnaire. Participants/materials, setting, methods Urine samples collected from participants (N = 446) were used to quantify 21 PFAS and their metabolites using the LC-MS/MS platform following stringent quality control procedures. Exposure characteristics of participants comprising their demographic information, lifestyle, and dietary habits acquired through questionnaires were used to compare their associations between RPL and control group. Descriptive statistics, group-wise comparison, and multivariate regression models were employed to evaluate the relationship between various exposure characteristics of PFAS and RPL occurrence among Taiwanese. Main results and the role of chance Participants in the RPL group had a significantly higher (p = 0.025) mean age (years), 34.8±4.42 vs. control 33.9±4.79. BMI (Kg/m2) also varied significantly (p = 0.036) between RPL 22.8(3.51) vs. control 23.3±3.16. About 59% of women in RPL group underwent treatment for infertility compared to the control group (25%), (p &amp;lt; 0.001). Among various lifestyle factors, the response (yes/no) against passive smoking status and personal care products (PCPs) usage varied significantly between the RPL (p = 0.026), vs. control (p = 0.026) respectively. Among the dietary habits, high consumption of unpeeled fruits (p = 0.004), melons (p = 0.002), dried tofu (p = 0.037), and nuts (p = 0.001) varied significantly in RPL vs. control. A significant association between median (P25,P75) PFDA levels (ng/mL) [0.31(0.21,0.39)] was observed for individuals with coffee drinking while levels of PFBA and 3-PFOS were significantly associated with packed hot food consumption in cartons [0.11(0.05,0.17)] and [0.93(ND,2.20)] respectively. Levels of PFBS and PFHxS were significantly associated with the use of PCPs [0.28(0.12,0.43)] and [1.89(0.94,2.66)] respectively. While body wash usage was significantly associated with PFBA [0.12(0.05,0.17)], PFHpA [0.16(0.06,0.25)], and PFNA [0.65(0.52,0.75)]. PFDoDA, 4-PFOS and 6-PFOS levels were in a significant relationship with use of lotion [0.18(0.06,0.31)], [0.29(ND,1.93)], and [0.44(ND,1.89)] respectively and cosmetic usage was significantly associated with high PFHpA [0.14(0.06,0.24) and PFHxS [1.55(0.85,2.39)]. Limitations, reasons for caution The study’s case-control design limits establishing causal relationships between various exposure characteristics, PFAS exposure, and RPL occurrence in Taiwanese women. Relying on the single-spot urine may infer bias in the result’s interpretation. Further, the concurrent effects of various other unknown EDCs and their effects on RPL should not be ignored. Wider implications of the findings Findings from the study emphasize the need for more comprehensive investigations involving multiple tests and large sample sizes to elucidate the results. The results also highlight the need for developing public health strategies to minimize PFAS exposure among reproductive-aged women along with the potential implications in policies for chemical regulations. Trial registration number No

C677T polymorphism of the methylenetetrahydrofolate reductase ( MTHFR) gene was a risk factor for recurrent pregnancy loss (RPL), but few studies have confirmed a possible role of MTHFR A1298C polymorphism in RPL risk. This study was carried out to determine the influence of the MTHFR gene polymorphisms in RPL Syrian women. A case-control study was performed on 2 groups (106 healthy and 100 RPL women). The frequency of the MTHFR gene polymorphisms was determined by polymerase chain reaction based on restriction fragment length gene polymorphism. In the RPL group, the genotype frequencies of MTHFR C677T were CC (41%), CT (41%), and TT (18%), and in the control group, the frequencies were CC (62.2%), CT (36.7%), and TT (1%). Statistical analysis showed a homozygous TT genotype and T allele were significantly different in the RPL group ( P = .000003 and P = .000019, respectively). The genotype frequencies of MTHFR A1298C were AA (53%), AC (44%), and CC (8%) in the RPL group, whereas in the control group, these were AA (61.3%), AC (37.8%), and CC (1%). A significant difference in the CC genotype and C allelic frequencies in the RPL women was observed ( P = .014 and P = .064, respectively). The patients having compound heterozygous (677 CT/1298AC) were associated with an estimated 4.86-fold increase in risk of pregnancy loss compared to individuals with a wild type ( P = .012). Our findings indicate that RPL women with homozygous genotype for (C677T and A1298C) either alone or compound heterozygous genotypes have a high risk of pregnancy loss in Syrian women.

The purpose of this prospective case–control study is to investigate the correlation of the miR-143 gene rs353292 polymorphism in Caucasian women with recurrent pregnancy loss (RPL) compared to a matched control group with at least one live birth and without pregnancy losses. In total, 110 women with recurrent pregnancy losses and 95 control women were recruited. Peripheral blood was collected from all women, and the isolation of DNA was performed with Monarch Genomic DNA Purification. Polymerase chain reaction was applied to amplify the DNA sequence of the miR-143 gene promoter, carrying the polymorphism rs353292. The incidence of genotype CC in the RPL group was statistically significantly higher than in control group (p < 0.0001). Allele C (CT + CC) in the control group was found in 47.36%, and in the RPL group was found in 68.17% (p = 0.006). SNP rs353292 T>C was associated with increased risk of recurrent pregnancy loss. The calculated odds ratio for CT + CC vs. TT and for CC vs. TT were significant higher (p = 0.0028 and p < 0.0001, respectively). The study results suggest that the rs353292 polymorphism is associated with a statistically significant increase in RPL prevalence. The present study provides additional evidence in favor of a shared pathophysiological mechanism that contributes to both RPLs, potentially through inflammatory processes and epithelial–mesenchymal transition dysregulation.

Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)? PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups. PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40-50% and 5-25% in patients with RPL, respectively. A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35-36, 37-38, 39-40 or 41-42years) were selected for PGT-A groups. All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted. There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16-13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28-10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02-0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03-0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients. The sample size was too small to find any significant advantage for improving the live birth rate and reducing the clinical miscarriage rate per patient. Further study is necessary. A large portion of pregnancy losses in the RPL group might be due to aneuploidy, since PGT-A reduced the overall incidence of pregnancy loss in these patients. Although PGT-A did not improve the live birth rate per patient, it did have the advantage of reducing the number of embryo transfers required to achieve a similar number live births compared with those not undergoing PGT-A. This study was supported by the Japan Society of Obstetrics and Gynecology and grants from the Japanese Ministry of Education, Science, and Technology. There are no conflicts of interest to declare. N/A.

Objective: To investigate the plasma levels of interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-17, IL-35 and suppressor of cytokine signaling 3 (SOCS3) in the women with history of idiopathic recurrent pregnancy loss (RPL) and in the fertile controls.Methods: This study was conducted with 60 idiopathic RPL cases and 40 age-matched fertile controls. Mid-follicular plasma levels of IL-17, IFN-gamma, TNF-alpha, TGF-beta, IL-6, IL-4, IL-10, SOCS3 and IL-35 were assayed by an enzyme linked immunosorbent assay.Results: The mean age of RPL and control cases were 31.6 ± 0.6 and 32.1 ± 0.7 years, respectively. While plasma IL-35 and SOCS3 levels of RPL group were significantly lower than that of the control group; IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, IL-17 and TGF-beta levels of RPL group were significantly higher than that of the control group. The comparison of cytokine ratios between RPL and control groups indicated significantly high TNF-alpha/IL-10, TNF-alpha/IL-4, IFN-gamma/IL-10, IFN-gamma/IL-6 and IFN-gamma/IL-4 ratios in the RPL group. IL-35/IL-17 ratio was significantly low in the RPL group compared to that in the control group. Overstimulation of TNF-alpha presented moderate influence on recurrent miscarriage risk.Conclusion: Decreased SOCS3 and IL-35 plasma levels and increased Th1/Th2 cytokine ratios in RPL cases pointed out the supression of anti-inflammatory process and this supression might play an important role in the pathogenesis of idiopathic RPL.

Oxidative/nitrosative stress increased the risk of recurrent pregnancy loss–Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES)

Antinuclear Antibody Positivity As a Risk Factor for Recurrent Pregnancy Loss: A Meta-Analysis

Since the first study was published reporting the candidate association between the prolactin receptor gene intron C/T polymorphism (rs37389) and recurrent miscarriage, no replication study has been performed. In this study, we investigated the role of the prolactin receptor gene C/T polymorphism in 311 Korean women with recurrent pregnancy loss and 314 controls. Genotyping for prolactin receptor gene intron C/T polymorphism was performed using a TaqMan assay. The significance of difference in the genotype distribution was assessed using a chi-square test, and continuous variables were compared using a Student’s t-test. The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent pregnancy loss group did not differ from that in the control group (CC/CT/TT rates were 49.8%/41.5%/8.7% and 52.5%/37.6%/9.9% for the recurrent pregnancy loss patient and control groups, respectively, p = .587). When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages or patients without prior live birth, there were also no differences in the genotype distribution between these subgroups and controls. In conclusion, the findings of the current study suggest that the prolactin receptor gene intron C/T polymorphism is not a major determinant of the development of recurrent pregnancy loss.Impact statementWhat is already known: Many studies have investigated whether there is a genetic component for the risk of recurrent pregnancy loss. Recently, one study investigated whether genetic polymorphisms involved in the regulation of the hypothalamic-pituitary-ovarian axis would be associated with recurrent miscarriage. Among 35 polymorphisms in 20 candidate genes, genotype distribution with regard to the prolactin receptor gene intron C/T polymorphism (rs37389) differed between the recurrent miscarriage and the control groups. Since this study reporting the candidate association between the prolactin receptor gene and recurrent miscarriage, no replication study has been performed.What the results of this study add: The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent miscarriage group did not differ from that in the control group.What the implications are of these findings: Our study may be useful in that it is the first replication study since the initial report of the association of prolactin receptor gene polymorphism with recurrent miscarriage. Although no association was found, the potential role of prolactin in pregnancy loss needs to be further investigated because prolactin and its receptor have been postulated to play an important role in the maintenance of normal pregnancy.