Effect of maternal high body mass index on outcome of pregnancy in women with recurrent miscarriages

The epidemic of obesity is spreading worldwide and subsequently, rate of obesity during pregnancy has also increased. Maternal overweight and obesity are widely associated with adverse pregnancy outcomes. Recurrent miscarriage is an important reproductive health issue, because it affects many couples. So the present study is planned to study the relationship between maternal obesity and pregnancy outcome in women with recurrent miscarriages. Observational Cross sectional study was conducted in a tertiary care hospital. 111 Postnatal women between 18 to 44 years of age with history of two or more miscarriages less than 20 weeks of gestation in previous pregnancy were included in the study. First trimester weight at the first visit (registration) was recorded, BMI was calculated & women were divided into obese and non obese groups. The outcome of present pregnancy was noted as Mode of delivery, Gestational diabetes mellitus, Pregnancy induced hypertension, Preterm delivery etc. Statistical tests were used to quantify the risk. Gestational diabetes (OR= 13.6) and pregnancy induced hypertension (OR=4.2) were significantly associated with obesity in women with recurrent miscarriages. [At 95% CI] The incidence of LSCS and preterm delivery was more in overweight and obese mothers, though not statistically significant. Maternal obesity significantly contributes to poor prognosis for the mother and the baby during delivery. Hence the women of this group should be regarded as ‘high risk’ and counselling and the risk assessment should be done during ANC visits.

Frequency of Anticardiolipin Antibodies in Women with Recurrent Fetal Loss

Aim: To find out the frequency of Anticardiolipin Antibodies in women with recurrent fetal loss Study design & duration: One year descriptive study Methods: Seventy five females were included in the study with ages ranging from 20-40 years with minimum two miscarriages. Diabetic females and females with history of bacterial or viral diseases were excluded from the study. Results: In this group the mean age was 27.60±3.29 years. Mean number of fetal losses was 2.95±1.45 whereas mean duration of marriage was 5.79±4.11 years. Conclusion: It is suggested that the patient with history of recurrent miscarriages must be screened for Anticardiolipin Antibodies to bring them out of psychological and physical trauma. Keywords: Anticardiolipin Antibodies (aCL), Recurrent fetal loss (RFL), aPTT

PCOS, Hashimoto's disease, celiac disease, endometriosis - genetically conditioned autoimmune disorder causing infertility?

Infertility is a social problem today. The causes of infertility can be both on the side of the woman and on the side of the man. One of the most common causes of infertility in women is polycystic ovary syndrome (PCOS). It has been proven that it often coexists with autoimmune thyroiditis (AIT), i.e. with Hashimoto's disease. In many patients with PCOS and AIT, endometriosis and celiac disease are also found. It seems that these disorders: PCOS, AIT, endometriosis and celiac disease may have a common autoimmune basis. More and more patients with infertility or recurrent miscarriages have autoimmune problems. Probably a genetic predisposition is necessary to reveal the disease.

Association of inherited thrombophilia gene polymorphism with sporadic and recurrent miscarriages

Aim. Despite numerous scientific studies of possible causes of miscarriage, their etiology remains unclear in approximately 50% of cases. Investigate the prevalence of thrombophilia associated gene polymorphism FGB 455G/A, FII 20210 G/A, FV 1691G/A, ITGA2 807C/T, PAI-1 5G/4G and MTHFR 677C/T in women with sporadic and recurrent miscarriages. Methods. Group I included 35 women with sporadic miscarriage (SM), group II consisted of 57 women with recurrent miscarriage (RM) and 55 women of control group. Genetic testing was performed by PCR-RFLP. Results. In group I of women with SM the 455GA genotype of the FGB gene was more common and its presence in the genotype increases the risk of SM by 4 times and the presence of the 455A allele by 2 times. The Leiden mutation increases the risk of SM by 5 times. In II group of women with RM, the frequency of the 455 AA genotype of the FGB gene was more prevalent and the risk of RM was increased 2.5 times. It is shown that the risk of RM increases 4 times in the presence of the Leiden mutation. The 4G allele of the PAI-1 5G/4G polymorphism leads to a 2-fold increase in the risk of RM, and the presence of the 677TT genotype of the MTHFR gene increases the risk of RM by 3 times. Conclusions. Genetic factors of inherited thrombophilia alleles 455A of the FGB gene, 1691A of the FV gene, 4G of the PAI-1 gene and 677T of the MTHFR gene are alleles of significant risk of reproductive losses both sporadic and, to a greater extent, recurrent. Keywords: sporadic miscarriage, recurrent.miscarriage, inherited thrombophilia, genetic polymorphism.

Spontaneous Miscarriage in Women Having More Than Three Miscarriages and Advanced Maternal Age

Background: Miscarriages are negative outcomes of a pregnancy. Their ratio increases in women with recurrent miscarriages. Objective: To identify the role of age and recurrent miscarriages in spontaneous abortions. Study Design: Comparative analytical study Place and Duration of Study: Department of Obstetrics & Gynecology, Mohtarma Benazir Bhutto Medical College Mir Pur, Azad Kashmir from 1st October 2020 to 31st March 2021. Methodology: One hundred and twenty pregnant women between the age group of 19-40 years. The clinical history of recurrent miscarriages and demography was noted. Results: The mean age was 29.85±4.71 years with 42% of previous miscarriage occurred in pregnant women at their first trimester. The highest number of recurrent miscarriages (>4) was noted in 36-40 years of age group. Conclusion: The rate spontaneous miscarriages increases with increasing age and recurrent history of miscarriages Key words: Spontaneous miscarriage, Advanced maternal age, Recurrent

P–383 Cytogenetic analysis of products of conception from miscarriages following natural conception and IVF pregnancy: a comparative study

Study question Do cytogenetic results from products of conception from miscarriages differ from patients conceiving by natural conception versus IVF? Summary answer: Cytogenetic results were similar, with no statistical difference from miscarriages following natural conception and assisted conception. What is known already Cytogenetic sampling of products of conception (POC) following recurrent miscarriages (RM) are recommended to rule out parental chromosomal rearrangements. The RCOG recommends cytogenetic testing in cases of recurrent miscarriages (3 consecutive miscarriages). However some units routinely request cytogenetic analysis following a single miscarriage following an IVF pregnancy. There is no evidence to support the routine sampling of POCs following assisted conception. Study design, size, duration: Retrospective cohort study of 117 cytogenetic samples, followed up by the outcome of parental karyotyping if applicable. Patients were categorised based on mode of conception into natural conception (NC) with recurrent miscarriages (≥3) or one miscarriage following IVF. Data collected between 2018–2020. Primary Outcome measure: Presence and type of cytogenetic abnormality; individual parental targeted G-band karyotyping result. Participants/materials, setting, methods: A total of 117 cytogenetic results were reviewed, of which 35 were unsuitable for analysis due to contamination (Total n = 79: NC = 60, IVF = 19). Main results and the role of chance: Cytogenetic analysis showed abnormal results in 59% of miscarriages following natural conception and 53% of miscarriages from IVF pregnancy (p = 0.46). Abnormal cytogenetic results were mainly sporadic. Trisomy 16 was the commonest abnormality in both groups. Others included Trisomy 15, 22, 21, 8, 13, 5, 9, 10, 14, 18, single X (Turner’s), all occurring in the same frequency in both groups. As expected 35 out of 45 abnormal cytogenetic results occurred with a maternal age greater than 35 years. One couple from the NC group were referred to a geneticist for a Trisomy 9 imbalance. All other parental karyotyping results were normal. Limitations, reasons for caution This study contains a small sample size, and would benefit from further data collection to account for a percentage of samples being inadequate for analysis. Wider implications of the findings: Cytogenetic results were similar from miscarriages following natural conception and assisted conception. IVF does not increase the risk of miscarriage from abnormal embryonic karyotype. Routine cytogenetic testing following one miscarriage in patients undergoing IVF is not cost effective. Trial registration number Not applicable

P–553 Women with molar pregnancies have a genetic susceptibility to aneuploid miscarriages

Study question What causes non-molar miscarriages in women with one hydatidiform mole (HM)? Summary answer We found a higher rate of aneuploidies in the non-molar miscarriages of women with HM than in those from women with sporadic or recurrent miscarriages. What is known already Women with hydatidiform moles have higher rates of miscarriages and women with recurrent miscarriages have higher rates of moles than women from the general population. Study design, size, duration We retrieved archived formalin-fixed paraffin embedded tissues from non-molar miscarriages of patients with one HM and analyzed them for the presence of aneuploidies using single nucleotide polymorphism (SNP)-microarray. We next determined the meiotic origin of the aneuploidies by genotyping the aneuploid non-molar miscarriages along with the parental genomes using microsatellite markers. Participants/materials, setting, methods All participants and some of their partners provided written consent to participate in our study, agreed to a blood draw for genotyping analysis, and agreed for us to retrieve their molar and non-molar tissues from various histopathology laboratories for research purposes. Main results and the role of chance We demonstrate for the first time that patients with an HM and miscarriages are at higher risk for aneuploid miscarriages [83.3%, 95% confidence interval (CI): 0.653–0.944] than women with sporadic (51.5%, 95% CI: 50.3–52.7%, p value = 0.0003828) or recurrent miscarriages (43.8%, 95% CI: 40.7–47.0%, p value = 0.00002). Genotyping the aneuploid miscarriages and the parental genomes demonstrated that most of the aneuploidies originated from errors in maternal meiosis I or II. Limitations, reasons for caution We were able to retrieve only 30 non-molar miscarriages from women with one HM for analysis. Expanding such analysis to a larger and independent cohort of miscarriages from such patients will be important to validate our observations. Wider implications of the findings: Our data suggest common genetic female germline defects predisposing to HM and aneuploid non-molar miscarriages in some patients. Trial registration number Not applicable