BACKGROUND: Placental site nodules (PSNs) are benign tumor-like growths that develop from chorionic-type intermediate trophoblastic cells. Their clinical significance is unknown. This study aims to determine the risk factors associated with PSNs, with focus on possible reproductive impact.
METHODS: We performed a retrospective case series of all patients with a pathology diagnosis of PSN in a large urban hospital system from 2018 to 2022. We collected clinical variables such as pathology diagnosis/description, presenting symptoms, method of prior delivery, and prior history of infertility, pregnancy loss, and uterine instrumentation.
RESULTS: A total of 32 patients were included in this case series. The most common presenting symptom was abnormal uterine bleeding (40.6%, 13/32). Recurrent pregnancy loss (RPL) (15.6%, 5/32) and infertility (15.6%, 5/32) were common presenting symptoms as well. 62.5% (20/32) patients had a history of prior uterine instrumentation. Coexisting chronic endometritis was identified in 9.4% (3/32) of cases. Of the 5 RPL/infertility patients who underwent hysteroscopic resection of a PSN, 1 achieved a live birth.
CONCLUSIONS: PSNs may be associated with abnormal uterine bleeding, recurrent pregnancy loss, infertility, history of prior uterine instrumentation, and chronic endometritis. Although a rare diagnosis, the presence of a PSN should be considered in patients presenting for infertility or recurrent pregnancy loss workup.

OBJECTIVE: Vitamin D deficiency and variations in the vitamin D binding protein (VDBP) gene may play a role in the development of Polycystic ovary syndrome (PCOS). This study aims to investigate the association of the rs4588 polymorphism with PCOS in Iranian women, as well as its association with infertility and recurrent pregnancy loss (RPL) in these patients.
RESULTS: The analysis revealed statistically significant differences in the distributions of genotypes and alleles of the rs4588 polymorphism among the three groups (p < 0.0001). The AC genotype and A allele showed an association with an elevated risk of PCOS and infertility. In this study, no association was found between genotypes and alleles of the rs4588 polymorphism and the risk of RPL in women with PCOS. Subjects with the AA or AC genotype exhibited significantly higher levels of LDL compared to those with the CC genotype.

BACKGROUND: Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient.
METHODS: Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T > G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67 gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as \"pathogenic\". c.1415T > G (p.V472G) located in extra-cellular region, was classified as \"likely pathogenic\". Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband\'s prenatal phenotype.
CONCLUSIONS: The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67 and emphasizes the necessity of exome sequencing in RPL condition.

Background  A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023. Results  This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively. Patterns with recurrent normal karyotypes, alternating normal and abnormal karyotypes, and recurrent abnormal karyotypes were detected in 74 (33%), 71 (32%), and 80 (35%) of consecutive miscarriages, respectively. Repeat aneuploidies of monosomy X and trisomy 16, triploidy, and tetraploidy were detected in nine women. Conclusions  A comparable spectrum of cytogenomic abnormalities was noted in the SA and CA groups of RPL. A skewed likelihood of 2/3 for recurrent normal and abnormal karyotypes and 1/3 for alternating normal and abnormal karyotypes in consecutive miscarriages was observed. Routine cytogenetic analysis should be performed for consecutive miscarriages. Further genomic sequencing to search for detrimental and embryonic lethal variants causing miscarriages and pathogenic variants inducing aneuploidies and polyploidies should be considered for RPL with recurrent normal and abnormal karyotypes.

Recurrent pregnancy loss, premature birth, and associated complications exhibit a multifactorial etiology and persist as substantial challenges during pregnancy, despite the notable advancements in the medical field. Among several factors, cervical insufficiency or incompetence emerges as a prominent causal factor, characterized by painless softening and shortening of the cervix associated with absent contractions. The implementation of emergency cerclage represents a pivotal intervention in mitigating preterm birth among individuals with advanced cervical insufficiency. By extending gestational age, this procedure increases the likelihood of neonatal survival without elevating the risk of chorioamnionitis or preterm rupture of the membranes. In this study, an antenatal woman presented with advanced changes in the cervix along with intravaginal bulging amniotic membranes at 18 weeks and underwent a rescue cervical cerclage, resulting in a successful pregnancy.

In this report, we describe a 28-year-old woman, with unicornuate uterus and multiple mid-trimester losses, with two failed Mc Donald\'s cerclage. She presented to us as a case of recurrent pregnancy losses with history suggestive of cervical incompetence and on detailed investigation was found to be ANA and anti-cardiolipin antibody positive and Rh negative. We performed an interval laparoscopic cervical cerclage for her and were able to successfully deliver her at 35 + 3 weeks with a healthy baby by caesarean section after previous five pregnancy losses and two failed Mc Donald\'s cerclage. Cervical cerclage can be used as an effective method of preventing abortions in unicornuate uterus pregnancy, while laparoscopic cerclage would be a better choice for patients with cervical incompetence with previous failed Mc Donald\'s cerclage. The possibility of uterine rupture for these high-risk patients should be kept in mind and decision to deliver at appropriate period of gestation so as to avoid uterine rupture and prematurity should be taken.

UNASSIGNED: Unexplained recurrent pregnancy loss (RPL) accounts for >50% of the patients with RPL. Insulin resistance (IR) is a potential cause of unexplained RPL.
UNASSIGNED: To evaluate the relationship between insulin resistance (IR) and unexplained RPL among Saudi women.
UNASSIGNED: This is a single-center, case-control study conducted at a tertiary hospital in the Eastern Province of Saudi Arabia. The study group comprised Saudi women with unexplained RPL, while the control group had Saudi women with at least one live birth and no RPL. Blood samples were taken to determine the fasting glucose (FG) and fasting insulin (FI) levels. Women with diabetes mellitus and polycystic ovarian syndrome were excluded. A homeostatic model assessment of insulin resistance index (HOMA-IR) value ≥3 was considered as IR.
UNASSIGNED: The study and control groups comprised 43 and 56 women, respectively. Between the groups, there was a significant difference in the mean age (case: 37.9 ± 5.4 years; control: 32.2 ± 5.9 years; P < 0.0001) and the mean BMI (case: 31.5 ± 6.0; control: 26.1 ± 2.8; P < 0.0001). FG level was slightly higher in the control group (90.9 mg/dL vs 88.7 mg/dL; P = 0.068). FI level was significantly higher in the study group (16.33 μU/mL vs. 6.17 μU/mL; P < 0.0001). HOMA-IR of ≥3 was significantly more common in the study group (n = 22; 51.2%) than the control group (4; 7.1%) (P < 0.0001). After adjusting for age and BMI, IR ≥3 was found to be independently associated with unexplained RPL (aOR: 13.2; 95% CI: 3.77-46.36).
UNASSIGNED: This study showed that Saudi women with unexplained RPL had significantly higher levels of fasting insulin and insulin resistance than those without a history of RPL. Therefore, it is recommended to assess IR in women with RPL.

Recurrent pregnancy loss (RPL) can be a devastating experience for individuals trying to have children. Various potential causes contribute to the multifactorial pathogenesis of RPL, including chromosomal anomalies, endocrine conditions, autoimmunity, thrombophilias, and infectious agents. Antinuclear antibodies (ANAs) offer an unspecific clue to the underlying autoimmune pathogenic etiology of RPL. This case details a 40-year-old female with a history of RPL, fibromyalgia, and ANA positivity, who spontaneously developed lupus anticoagulant antibodies during her second trimester of pregnancy. Although the recommended American Society of Reproductive Medicine (ASRM) diagnostic criteria for initiating a thrombophilia evaluation was not formally met, the patient\'s maintenance of low-molecular-weight heparin (LMWH) throughout her pregnancy may have contributed to the success of the pregnancy. When treating a patient with RPL, consideration of the comprehensive clinical picture should precede the need to strictly adhere to published criteria for using non-proven clinical interventions. A risk-benefit analysis ought to be considered when offering patients additional medications that may come with some risks but could significantly improve the chances of a successful clinical outcome, such as live birth. We aim to provide evidence to promote greater flexibility in guidelines so that a patient\'s unique autoimmune etiologies of RPL are not overlooked.

OBJECTIVE: To investigate whether women with unexplained recurrent pregnancy loss have impaired arterial vascular health compared with controls, and to evaluate whether this is modifiable by exercise.
METHODS: Experimental case-control pilot study.
METHODS: University medical centre in the Netherlands.
METHODS: Twelve women with unexplained recurrent pregnancy loss, 11 nulliparous women and 19 primiparous women with a history of uncomplicated pregnancies.
METHODS: In all three groups we measured baseline characteristics, metabolic components and arterial vascular health, and repeated this in women with unexplained recurrent pregnancy loss after 1 month of protocolled and supervised cycle training.
METHODS: Differences in arterial vascular health between women with unexplained recurrent pregnancy loss and controls, and the effect of exercise on arterial vascular health in women with unexplained recurrent pregnancy loss.
RESULTS: Women with unexplained recurrent pregnancy loss have a significantly increased carotid intima media thickness in comparison with both controls (both P < 0.01), a significantly decreased brachial endothelial dependent flow-mediated vasodilation in comparison with both controls (nulliparous: P < 0.01; primiparous: P = 0.05) and a significantly decreased femoral endothelial dependent flow-mediated vasodilation in comparison with primiparous women (P = 0.01). The endothelium independent glyceryl trinitrate response was similar in all groups. With 1 month of exercise, the carotid intima media thickness decreased significantly by 7% (P = 0.05) and the femoral FMD increased significantly by 10% (P = 0.01) in women with unexplained recurrent pregnancy loss.
CONCLUSIONS: Women with unexplained recurrent pregnancy loss have an impaired vascular health in comparison with controls. This impaired arterial vascular health can be improved by exercise.

UNASSIGNED: To investigate the relationship of serum homocysteine, folic acid, and vitamin-B12 levels with recurrent pregnancy loss (RPL).
UNASSIGNED: A case-control study was conducted in the Department of Gynecology and Obstetrics, Dr. Ruth Pfau Civil Hospital, Karachi from July 2021 to June 2022. Total 124 participants were recruited from gynecology outpatient department after taking informed consent. The participants included 62 non-pregnant females with two or more consecutive unexplained RPLs and 62 healthy women having at least two successful deliveries without any pregnancy loss. Serum folic acid and vitamin-B12 levels were measured by chemiluminescent method and serum homocysteine was measured by enzyme-linked immunosorbent assay (ELISA). Comparison of quantitative variables with RPL cases and control was done by Mann-Whitney U-test (for non-normally distributed data) and independent sample t-test (for normally distributed data), while Pearson\'s chi-square test was used for the association of qualitative variables with RPL cases and control. Correlation of homocysteine with vitamin-B12 and folic acid was assessed in RPL cases.
UNASSIGNED: The median age of the study population was 27 (IQR 25-32) years. The median body mass index (BMI) was 26.25 (IQR 22-29) kg/m2. Cases had significantly lower serum folic acid (p-value=0.022), while vitamin-B12 was decreased in cases as compared to controls (p-value=0.295). Mean concentration of serum homocysteine was higher in RPL cases as compared to controls (p-value=0.094). There was significant association of serum vitamin B12 (p-value=0.001) and folic acid levels (p-value=0.004) with RPL. The homocysteine was not significantly correlated with vitamin-B12 (r=0.124, p=0.338) and folic acid (r=0.067, p=0.606) in the RPL group.
UNASSIGNED: Reduced level of serum folic acid and vitamin B12 was significantly associated with RPL cases, while homocysteine was marginally raised however the difference was not significant. Folic acid and vitamin B12 supplementation before next pregnancy in RPL patients is likely to be beneficial in improving pregnancy outcomes.