Sporadic Pregnancy Research Articles

An Ayurvedic approach on Bad Obstetric History w.s.r. to Putarghani Yonivyapad: A Case Study

Introduction: Spontaneous pregnancy loss can be physically and emotionally taxing for couples, especially when faced with recurrent losses. Recurrent pregnancy loss (RPL), also referred to as recurrent miscarriage or habitual abortion, is historically defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period. Based on the incidence of sporadic pregnancy loss, the incidence of recurrent pregnancy loss should be approximately 1 in 300 pregnancies. In Ayurveda Putraghni Yonivyapad is described where repeated abortions or the early neonatal deaths are explained which are due to Artava Dosha, Rakta Dosha, Raktastrava and Raktakshaya. When we came across with descriptions given by different Acharyas we come to know that these all points came under the Bad Obstetric History described in modern science. As we all know that Ayurveda is a science of life. Methods: In the present case study, a 34 years old women patient consulted to the OPD with the complaints of recurrent pregnancy loss in first trimester [5 Abortions]. Her hematological and sonographic reports were normal. Diagnosis was unexplained. She was supposed to be treated with Ayurvedic Shodhan and Shaman therapy. Result: Only Ayurvedic protocol were used during the course of the treatment. After this, patient conceived after 3 months of treatment, and no evidence of abortion was found. She delivered a healthy baby. Discussion: The present study shows the role of Ayurveda in bringing a positive result in the management of Putraghni Yonivayapad.

Cytogenetic studies in reproductive function disorders: a retrospective analysis

Aim. Fertility disorders are one of the most common problems of reproductive medicine. Chromosomal abnormalities play a crucial role in reproductive failure. The main purpose of our study was to determine the types and frequency of chromosomal aberrations in couples with history of infertility. Methods. Karyotyping was performed in 652 couples with reproductive failure between 2004 and 2022, including 203 couples with primary infertility (PI), 240 couples with recurrent pregnancy loss (RPL) and 209 – with sporadic pregnancy loss (SPL). Results. Numerical and structural karyotype abnormalities were detected in 37 (2.84 %) of 1304 individuals with infertility, most frequently in group with PI – 3.4 % and RPL – 3.3 %. Chromosomal abnormalities were detected in 3.1 % woman and 2.6 % men. The most common cytogenetic abnormalities (26 cases of 37; 2 %) are translocations, reciprocal – 18 cases (1.4 %) and Robertsonian – 8 cases (0.6 %). Numerical and structural gonosomal abnormalities were detected in 9 individuals (0.7 %), supernumerary marker chromosome – in 2 (0.14 %). Conclusions. Karyotype abnormalities are most common in individuals with PI and RPL and a occur with the same frequency among women and men. Numerical gonosomal abnormalities were detected only as mosaic form.

P-546 The structure of genome variations at CNV level differs in recurrent and sporadic pregnancy loss

Abstract 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 < 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

Preliminary report of intraovarian injections of autologous platelet-rich plasma (PRP) in extremely poor prognosis patients with only oocyte donation as alternative: a prospective cohort study.

STUDY QUESTIONDoes intraovarian injection of platelet-rich plasma (PRP) change ovarian function in patients with extremely low functional ovarian reserve (LFOR) who, otherwise, would likely only have a chance of pregnancy through third-party oocyte donation?SUMMARY ANSWERNo clinically significant effects of PRP treatment on ovarian function were observed over 1 year of follow-up.WHAT IS KNOWN ALREADYSeveral investigators have reported improved responses to ovulation induction after treatment with PRP. However, previous published reports have involved, at most, only small case series. Whether PRP actually improves ovarian performance is, therefore, still unknown. PRP is nevertheless widely offered as an ‘established’ fertility treatment, often under the term ‘ovarian rejuvenation’.STUDY DESIGN, SIZE, DURATIONWe are reporting a prospective cohort study of 80 consecutive patients at ages 28–54 with LFOR, defined by anti-Müllerian hormone <1.1 ng/ml, FSH >12 mIU/ml or at least one prior IVF cycle with ≤3 oocytes within 1 year. The women were followed for 1 year after an intraovarian PRP procedure.PARTICIPANTS/MATERIALS, SETTING, METHODSPRP (1.5 ml) was injected into the cortex of ovaries with an average of 12 injections per ovary. Study participants were followed every 3 days for 2 weeks after PRP treatment with estradiol and FSH measurements and vaginal ultrasound to observe follicle growth and thereafter followed weekly. Beginning 1 month after their PRP treatment, participants underwent one or more cycles of ovarian stimulation for IVF. Outcome measures were endocrine response, and numbers of oocytes and embryos produced in response to a maximal gonadotropin stimulation before and after PRP treatment.MAIN RESULTS AND THE ROLE OF CHANCEIn this study, women failed to demonstrate statistically significant outcome benefits from intraovarian PRP. However, two 40-year-old very poor-prognosis patients, with prior failed IVF cycles that never reached embryo transfer at other centers, achieved pregnancy, resulting in an ongoing pregnancy rate of 4.7% among patients who, following PRP, produced at least one oocyte (n = 42).LIMITATIONS, REASONS FOR CAUTIONAs an observational study of patients who performed poorly in past ovarian stimulation cycles, the improvement may be accounted for by regression to the mean. Similar considerations may also explain the occurrence of the two pregnancies.WIDER IMPLICATIONS OF THE FINDINGSThis study demonstrates that, even in extremely poor prognosis patients due to LFOR, sporadic pregnancies are possible. The study, however, does not allow for the conclusion that those pregnancies were the consequence of PRP treatments. A case series, indeed, does not allow for such conclusions, even if results are more suggestive than here. This registered study, therefore, must be viewed as a preliminary report, with further data expected from this study but also from two other prospectively randomized ongoing registered studies with more controlled patient selection.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by intramural funds from The Center for Human Reproduction and the not-for-profit research Foundation for Reproductive Medicine, both in New York, NY, USA. N.G. and D.H.B. are listed as co-inventors on several US patents. Some of these patents relate to pre-supplementation of hypo-androgenic infertile women with androgens, such as dehydroepiandrosterone and testosterone and, therefore, at least peripherally relate to the subject of this manuscript. They, as well as D.F.A., have also received research support, travel funds and speaker honoraria from several pharmaceutical and medical device companies, though none related to the here presented subject and manuscript. N.G. is a shareholder in Fertility Nutraceuticals and he and D.H.B. receive royalty payments from Fertility Nutraceuticals LLC. E.M. has no conflicts of interest to declare.TRIAL REGISTRATION NUMBERNCT04275700

Recurrent pregnancy loss: fewer chromosomal abnormalities in products of conception? a meta-analysis.

To compare the prevalence of chromosomal abnormalities detected in products of conception (POCs) between recurrent pregnancy loss and sporadic pregnancy loss. A systematic search was performed in the PubMed and Embase databases from inception to December 31, 2020. Relevant studies analysing the association between the number of pregnancy losses and the incidence of chromosomal abnormalities were included. Independent data extraction was conducted and study quality was assessed. Meta-analyses were carried out to calculate odds ratios by using fixed- or random-effects models according to statistical homogeneity. A total of 8320 POCs in 19 studies were identified for the meta-analyses. The incidence of chromosomal abnormalities in sporadic pregnancy loss was significantly higher than that in recurrent pregnancy loss. In subgroup analyses, the following studies reported a high incidence of abnormal outcomes of sporadic pregnancy loss: studies with ≥ 300 samples, studies published before 2014, studies conducted in European and American countries, and studies with analyses using conventional karyotype techniques. Moreover, the incidence of chromosomal abnormalities in women with two pregnancy losses was significantly higher than that in women with three or more pregnancy losses. However, there was no difference in the distribution of abnormal types between sporadic and recurrent pregnancy loss or between two and three or more pregnancy losses. The prevalence of chromosomal abnormalities detected in POCs was lower in recurrent pregnancy loss than in sporadic pregnancy loss, and decreased with an increasing number of pregnancy losses.

P–381 Deciphering the genetic cause of recurrent and sporadic pregnancy loss

Abstract Study question To investigate the prevalence and effect of (mosaic) de novo genomic aberrations in recurrent pregnancy loss (RPL) and sporadic abortion (SA). Summary answer Prevalence of maternal uniparental disomies (UPDs) was high in both cohorts. While chromosomal UPDs were found in both cohorts, genome wide UPDs were RPL specific. What is known already Spontaneous abortion occurs in 10–15% of clinically recognized pregnancies and recurrent pregnancy loss in 1–3%. SA and RPL are associated with reduced quality of life. Multiple factors contribute to SA and RPL, such as uterine malformations and parental/fetal chromosomal abnormalities. However, in ∼60% of SA and RPL the cause remains unknown. UPD is defined as the presence of two homologues chromosomes originating from a single parent. This phenomenon can lead to imprinting disorders that are characterised by clinical features affecting growth, development and metabolism in liveborn offspring. However, it could also be responsible for pregnancy loss. Study design, size, duration We recruited 32 families with pregnancy loss (n = 16 RPL cohort, n = 16 SA cohort) with no known genetic predispositions and normal karyotyping results in both parents and the fetus. Average maternal age was 28.68 years (SD = 5.43), paternal age 30.3 years (SD = 5.53), and the gestational age at pregnancy loss was 8.65 weeks (SD = 2.47). The average number of miscarriages in the RPL group was 3.57 (SD = 0.84). We profiled the genomic landscape of both cohorts using SNP typing. Participants/materials, setting, methods We isolated DNA from blood of both parents and the placental tissues from the miscarried products of conception. The placenta tissues were sampled from two distinct extraembryonic and embryonic germ layers, the extraembryonic mesoderm and the chorionic villi cytotrophoblast. Subsequently, we performed SNP-genotyping using Illumina’s Global-Screening Array–24 v2.0 BeadChips and applied haplarithmisis to delineate allelic architecture of fetal tissues of both cohorts. This allowed us to detect large de novo copy-number and -neutral (&amp;gt;10kb) changes. Main results and the role of chance In this pilot study, we have analyzed 132 DNA samples (n = 32 families), of which 16 families were in the RPL cohort and 16 in the SA cohort. Within the RPL cohort, we found: one family with mosaic genome wide hexaploidy both in the extraembryonic mesoderm and chorionic villi, one family with a non-mosaic genome wide hetero UPD of the chorionic villi tissue, one family with a mosaic UPD of chromosome 14 in both tissues and tetraploidy exclusively in the chorionic villi, one family with a mosaic UPD of chromosome 16 in both tissues, one family with a mosaic UPD of chromosome 6 in both tissues, and another family with a mosaic UPD of chromosome 5 in the extraembryonic mesoderm. Within the SA group, one family showed a UPD of chromosome 7 and another family showed a segmental UPD of chromosome 5 in both tissues. Strikingly, all the UPDs found in this study were maternal in origin. Limitations, reasons for caution The main limitation of this study is the resolution of detecting copy-neutral and copy-number variations, which is an inherent limiting factor of SNP-array technology. In addition, in the sample in which we observed non-mosaic genome wide UPD, maternal contamination is likely that can be investigated by other technologies. Wider implications of the findings: Multiple genome wide UPDs are found in the RPL group but none in the SA group, indicating an association between genome wide mosaic UPD and RPL. These findings could lead to a better understanding of causative factors for SA and RPL and the need for a SNP-based non-invasive prenatal testing. Trial registration number Not applicable

Chromosomal Aneuploidy Associated With Clinical Characteristics of Pregnancy Loss.

ObjectiveEmbryonic aneuploidy is found in about half of sporadic pregnancy losses and the associations between the chromosomal aneuploidy and clinical characteristics of pregnancy loss remain unclear. The aims of this study were to evaluate the associations between chromosomal aneuploidy of products of conception (POC) and clinical features of pregnancy loss.MethodsWe conducted a retrospective cohort study including 1,102 women experienced singleton pregnancy loss and underwent chromosomal microarray analysis (CMA) detection of POC in our hospital. The results of molecular karyotypes and clinical features including maternal age, history of pregnancy loss, gestational age, vaginal bleeding and ultrasonographic findings were extracted from the medical records. χ2 test was used to compare categorical data between groups.Results631 (57.26%) POC specimens were detected to be chromosomal aneuploidy. Aneuploid rates were significantly higher in women >35 years (P < 0.001) and pregnancy loss <11 gestational weeks (P = 0.044), but the rates of sex chromosome abnormalities and triploid were significantly higher in women ≤35 years (P < 0.001, P = 0.002) and the rates of viable autosomal trisomy and sex chromosome abnormalities were significantly high in those women with pregnancy loss ≥11 weeks (P < 0.001, P < 0.001). Aneuploid rate was overall similar between the sporadic and the recurrent pregnancy loss (RPL) (P = 0.404), but the rate of sex chromosome abnormalities was higher in women with sporadic pregnancy loss (P = 0.03). Aneuploid rates were higher in subjects with yolk sac or embryo than in those without (P < 0.001 and P = 0.001).ConclusionAdvanced maternal age is mainly associated with autosomal trisomy, while sex chromosome abnormalities and triploid might be more likely to occur in younger women. Aneuploidy rates might be no association with previous pregnancy loss except for sex chromosome abnormalities. Pregnancy loss without yolk sac or embryo might be less related to embryonic aneuploidy, and other factors should be emphasized.

Роль хромосомных аберраций эмбриона в генезе привычного и спорадического невынашивания беременности

Objective. To compare the frequency and nature of embryo/fetus chromosomal abnormalities (CA) in sporadic and recurrent pregnancy loss. Patients and methods. A retrospective cohort study that included 1000 patients with pregnancy loss at 6–12 weeks of gestation. The first group consisted of 681 patients who had their first sporadic miscarriage. The second group consisted of 319 patients who previously had a miscarriage. Chromosomal microarray analysis (CMA) of abortive material was performed. Results. In the first group, various chromosomal abnormalities in the embryo/fetus were detected in 378 (55.5%) samples, in the second group – in 203 (63.5%). The incidence of CA in patients with a history of miscarriage was higher than in sporadic miscarriage, the differences were statistically reliable (p = 0.015). No significant differences were found in the structure of CA. Autosomal trisomies and numerical abnormalities of sex chromosomes were most frequently detected. Conclusion. Chromosomal abnormalities in the embryo are a significant cause of miscarriage, both sporadic and recurrent. Genetic analysis of abortive material is an important component of the examination for choosing further management tactics for patients. CMA is an effective research method when conducting genetic analysis of conception products. Key words: pregnancy loss, preconception planning, recurrent miscarriage, chromosomal abnormalities, chromosomal microarray analysis

Sporadic pregnancy loss and recurrent miscarriage

Progesterone is essential for the maintenance of pregnancy, and progesterone deficiency is associated with miscarriage. The subject of whether progesterone supplementation in early pregnancy can prevent miscarriage has been a long-standing research question and has been investigated and debated in the medical literature for over 70 years. During this time, several different progestogens have been synthesised and tested for the prevention of miscarriage. In this article described the prior evidence alongside the latest research using micronized natural progesterone as well as synthetic progestogens, which were used to treat both recurrent and threatened miscarriage. The totality of evidence indicates that women with a past history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone. The clinical implications of the findings are discussed.

Sporadic pregnancy loss and recurrent miscarriage.

Progesterone is essential for the maintenance of pregnancy, and progesterone deficiency is associated with miscarriage. The subject of whether progesterone supplementation in early pregnancy can prevent miscarriage has been a long-standing research question and has been investigated and debated in the medical literature for over 70 years. During this time, several different progestogens have been synthesised and tested for the prevention of miscarriage. In this chapter, we describe the prior evidence alongside the latest research using micronized natural progesterone as well as synthetic progestogens, which were used to treat both recurrent and threatened miscarriage. The totality of evidence indicates that women with a past history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone. The clinical implications of the findings are discussed.

DNMT1 and DNMT3A Gene Polymorphisms and Early Pregnancy Loss

DNA methyltransferase DNMT3A and DMNT1 are required for de novo and maintenance methyltransferase activities that catalyze the establishment of methylation patterns during embryogenesis and gametogenesis. Inactivation of their genes may cause embryonic lethality. We conducted a case-control study to explore the association between DNMT3A rs7590760, DNMT1 rs2228611, and DNMT1 rs8101626 polymorphisms and early pregnancy loss susceptibility in Russian women. 100 women with early pregnancy loss (EPL) were involved and divided into two subgroups consisting of 50 women: sporadic pregnancy loss (SPL) and recurrent pregnancy loss (RPL). The control group included 56 women with full term pregnancies. Genotyping was performed using PCR-RFLP methods. GG genotype and allele G of DNMT1 rs2228611 were significantly associated with EPL and RPL, and GG genotype of DNMT1rs8101626 with EPL, SPL and RPL. Our findings have shown that women carrying GG genotype of DNMT1 rs2228611 had a higher risk of EPL and RPL (OR = 3.0, 95% CI: 1.44–6.23; OR = 3.94, 95% CI: 1.92–8.09 respectively) as well as that carrying GG genotype of DNMT1 rs8101626 are at higher risk of EPL and RPL (OR = 2.64, 95% CI: 1.2– 5.76). Conclusion: our results suggest that DNMT1 rs2228611 and DNMT1 rs8101626 gene polymorphisms are associated with early pregnancy loss and can be a genetic risk factor for recurrent pregnancy loss.

The Association of SYCP3 T657C Polymorphism with Early Pregnancy Loss in Russian Women

Background. Aneuploidy is a consequence of the chromosome nondisjunction. Majority of aneuploid embryos die in utero between the 6th and 10th week, resulting in early pregnancy loss of approximately 15% of all clinically recognized pregnancies. SYCP3 plays an important role in pairing and recombination of homologous chromosomes in meiosis I, and it has been shown that the lack of this gene leads to sterility in male and subfertility in female mice due to chromosome nondisjunction. So SYCP3 is a candidate gene to evaluate the hypothesis of fetal aneuploidy arisen from meiosis gene mutations as a cause for human early pregnancy loss. Methods. In our study, the SYCP3 T657C polymorphism in 100 Russian women with early pregnancy loss (EPL) that were classified into 2 subgroups: with sporadic pregnancy loss (SPL, n=50) and recurrent pregnancy loss (RPL, n=50), as well as 56 normal fertile women (control), was examined to determine whether there is an association between the polymorphism and early pregnancy loss in Russian population. Genomic DNA was extracted from peripheral blood samples using the standard procedure of a commercially available kit. Genotyping of SYCP3 gene was determined by allele-specific polymerase chain reaction method. Data were analyzed using SPSS statistical software version 22. The chi-square test and Fisher’s exact test were used to compare genotype and allele frequencies between analyzed groups. The odds ratio (OR) and 95% confidence intervals (CI) were used for risk estimation. Results. Frequency of the heterozygous genotype (CT) was significantly higher in the group of women with early pregnancy loss as well as in women with sporadic pregnancy loss (p&lt;0.05). In women with RPL, we found that the frequency of this genotype tended to increase but could not make a significant difference when compared with the control group. Conclusion. Our findings postulate that the T657C polymorphism of the SYCP3 gene is possibly associated with a sporadic early pregnancy loss. Актуальность. Анеуплоидия возникает вследствие нарушения расхождения хромосом, и большинство анеуплоидных эмбрионов погибают до 10 недели гестации, что приводит к потере на ранних сроках приблизительно 15% клинически диагностированных беременностей. Белок SYCP3 играет важную роль в конъюгации и рекомбинации гомологичных хромосом в первом мейотическом делении. Было показано, что отсутствие гена данного белка у мышей приводит к стерильности самцов и снижению фертильности самок вследствие нарушения расхождения хромосом. В этой связи SYCP3 можно рассматривать в качестве кандидатного гена для оценки гипотезы о фетальной анеуплоидии, возникающей в результате мутаций генов, продукты которых участвуют в мейозе, и ведущей к ранним репродуктивным потерям. Методы. В представленной работе был исследован полиморфизм Т657С гена SYCP3 у 100 женщин русской национальности с ранними репродуктивными потерями, подразделенных на две подгруппы: со спорадической потерей беременности (n=50) и привычным невынашиванием (n=50), а также у 56 фертильных женщин (контроль). Целью работы явилось изучение наличия ассоциации между данным полиморфизмом и ранними репродуктивными потерями в русской популяции. Геномная ДНК была выделена из периферической крови, генотипирование выполнялось с использованием аллель-специфической полимеразной цепной реакции. Для сравнения частот генов и генотипов в изучаемых группах применялись критерий Хи-квадрат и точный тест Фишера, для определения которых использовалось программное обеспечение SPSS Statistics, версия 22. Оно также было использовано для расчета отношения шансов (OR) и 95% доверительного интервала. Результаты. Частота гетерозиготного генотипа СТ была достоверно выше в группе женщин с ранними репродуктивными потерями и, в частности, в подгруппе со спорадической потерей беременности (р&lt;0,05). Несмотря на тенденцию к увеличению частоты данного генотипа у женщин с привычным невынашиванием, статистически значимых отличий от контроля обнаружено не было. Заключение. Полученные результаты позволяют предполагать наличие ассоциации между полиморфизмом Т657С гена SYCP3 и спорадической потерей беременности на ранних сроках.

Association of DNMT3B and DNMN3L Gene Polymorphisms with Early Pregnancy Loss.

A total of 100 women with early pregnancy loss were recruited and further classified into two subgroups: sporadic pregnancy loss and recurrent pregnancy loss; each subgroup consisted of 50 women. The control group included 56 women with normal pregnancies. Genotyping was performed by PCR with restriction fragment length polymorphism analysis. A statistically significant increase in the frequencies of TT genotype and T allele for DNMT3B rs2424913 polymorphism was found in the total patient group and in both patient subgroups in comparison with the control. Moreover, homozygous TT genotype was associated with increased risk of early pregnancy loss (both sporadic and recurrent). DNMT3B rs2424913 gene polymorphism in women can be used a marker of predisposition to early pregnancy loss and recurrent pregnancy loss.

Epigenetic status of imprinted genes in placenta during recurrent pregnancy loss

An analysis of differential methylation of 47 imprinted genes in placenta tissues of spontaneous abortions at the first trimester of pregnancy from women with recurrent pregnancy loss or with one sporadic abortion was performed using the DNA-microarray approach. We showed that epimutations of the imprinted genes were registered significantly more often in abortions from women with recurrent miscarriage in contrast to the embryos from women with sporadic pregnancy loss with frequency of 6.2 and 3.7% per locus, respectively (p < 0.01). The predominant type of epimutation appeared to be a postzygotic hypomethylation of the imprinted genes on chromosomes of maternal origin, which was observed in the examined samples in 5.1 and 2.89% of cases, respectively. Replicative study of the methylation status of seven imprinted genes (DLK1, PEG10, PLAGL1, KCNQ1OT1, PEG3, GRB10, and PEG1/MEST) in the enlarged embryo samples supported the results of microarray analysis in respect to both epimutation frequency and predominance of somatic hypomethylation of maternal alleles. It was also demonstrated that pregnancy loss was associated with multilocus methylation defects of imprinted genes, the frequency of which was also significantly increased in the placental tissues of spontaneous abortions in women with recurrent miscarriage.

Immunogenetic contributions to recurrent pregnancy loss

While sporadic pregnancy loss is common, occurring in 15% of pregnancies, recurrent pregnancy loss (RPL) impacts approximately 5% of couples. Though multiple causes are known (including structural, hormonal, infectious, autoimmune, and thrombophilic causes), after evaluation, roughly half of all cases remain unexplained. The idiopathic RPL cases pose a challenging therapeutic dilemma in addition to incurring much physical and emotional morbidity. Immunogenetic causes have been postulated to contribute to these cases of RPL. Natural Killer cell, T cell expression pattern changes in the endometrium have both been shown in patients with RPL. Human leukocyte antigen (HLA) and cytokine allelic variations have also been studied as etiologies for RPL. Some of the results have been promising, however the studies are small and have not yet put forth outcomes that would change our current diagnosis and management of RPL. Larger database studies are needed with stricter control criteria before reasonable conclusions can be drawn.

Comparative Cytogenetic Analysis of Spontaneous Abortions in Recurrent and Sporadic Pregnancy Losses

Background: The majority of miscarriages are sporadic; however, 1-5% of couples experience recurrent pregnancy loss (RPL). Approximately 50-60% of miscarriages result from chromosomal abnormalities. Currently, there are conflicting reports regarding the rates of chromosomal abnormalities between recurrent and sporadic pregnancy losses. Methods: A retrospective comparative cytogenetic analysis of 442 RPL and 466 sporadic abortions (SA) was performed. Maternal age and medical background were evaluated, and chromosomal abnormality rates were compared between groups. Results: The frequency of embryos with abnormal karyotypes was significantly higher in SA compared to RPL (56.7 and 46.6%, respectively), and abortions from women under 30 years of age were the main contributor to this difference. An age-dependent increase in the abnormal karyotype rate was observed in two groups of women - those with SA [53.0 and 70.1% for younger and older (≥35-year-old) mothers, respectively] and those with idiopathic RPL without any concomitant reproductive pathology (46.5 and 78.4% for younger and older mothers) - but not in the group of women with RPL associated with concomitant reproductive pathology. The incidence of recurrent abnormal karyotypes in subsequent miscarriages was significantly higher than random probability (odds ratio = 22.75). Conclusion: Our findings highlight the variability in the risk of aneuploidy in recurrent abortion.

Clinical significance of chromosome karyotyping of couple in women with pregnancy loss

Objective To evaluate the correlation between parental chromosomal abnormalities and pregnancy loss.Methods Clinical data were collected from 260 couples who experienced pregnancy loss in the outpatient of our hospital.Chromosomes from cultured peripheral blood lymphocytes were analyzed using conventional cytogenetic analysis.Results Parental chromosomal abnormality was detected in 48 cases (18.5％),which were structural abnormality (28 cases,58.3％),chromosome polymorphism (18 cases,37.5％)and numeric abnormality (2 cases,4.2％).Most of the structural abnormalities were balanced chromosomal translocations (71.4％,20/28).There was no significant difference in positive rate of chromosomal abnormality between sporadic and recurrent pregnancy loss (P ＞ 0.05).Conclusion Pregnancy loss can be caused by chromosomal abnormalities in couples,most of which are balanced translocations.It is very necessary for the clinicians to provide chromosome examination for the couples who experienced pregnancy loss in order to obtain a better pregnancy outcome. Key words: Pregnancy loss; Balanced translocation; Chromosomal abnormality

154: The role of circulating alpha-1 antitrypsin in recurrent pregnancy loss

in recurrent pregnancy loss Tamar Madar, Eli C Lewis, Galit Shahaf, Guy Twina, Joel Baron, Shimrit Yaniv Salem, Moshe Mazor, Arnon Wiznitzer, Gershon Holcberg, Eyal Sheiner Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Meitar, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Clinical Biochemistry, Faculty of Health Sciences, Beer-Sheva, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Beer-Sheva, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Beer-Sheva, IL, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Beer-Sheva, Israel OBJECTIVE: Alpha-1 antitrypsin (AAT) inhibits a wide variety of proteases and possesses anti-inflammatory, immune modifying and tissue-protective properties. AAT levels rise 4 to 6-fold during acute phase responses, as well as during pregnancy. Low AAT levels and activity were previously linked with several pregnancy complications. Various causes have been attributed to recurrent miscarriages, including immunologic and inflammatory factors. Therefore, the purpose of the present prospective study was to examine whether low plasma concentration and activity of AAT might correlate with recurrent pregnancy loss. STUDY DESIGN: We conducted a prospective case control study that included patients with recurrent pregnancy loss (two or more consecutive miscarriages; n 18), patients with sporadic pregnancy loss (n 16) and individuals undergoing elective termination of normal pregnancy per social considerations (n 13). Blood samples were drawn before performing dilatation and curettage and immediately transferred in cold to the analysis lab. AAT activity and concentration were determined in maternal serum samples by standard ELISA and enzymatic assays. Analyses were performed in duplicates and repeated twice for each sample in separate sessions. RESULTS: Patients with recurrent pregnancy loss as well as patients with sporadic miscarriages depicted AAT levels that were significantly lower than the control group of normal pregnancies; the levels in recurrent miscarriage was 2.39 0.33 -fold lower than the control group (1.344 0.09222 vs. 3.224 0.4498 mg/ml; p 0.001), and sporadic miscarriage was 2.05 0.28 -fold lower than the control group (1.569 0.1415 vs. 3.224 0.4498 mg/ml; p 0.001, figure). Although a consistent trend could be observed regarding circulating AAT anti-proteolytic activity between the groups, statistical significance was not attained. CONCLUSION: Alpha-1 antitrypsin concentrations are significantly lower in patients with sporadic and recurrent miscarriages compared to normal pregnancies. Accordingly, AAT may play an important role in the pathogenesis of spontaneous pregnancy loss.

Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss

Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss

Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss

We hypothesized that the thrombophilic G1691A factor V Leiden (FVL) gene mutation was a common, significant, and treatable cause of sporadic and recurrent pregnancy loss (RPL). We compared the frequency of the FVL mutation in 141 women with >or=1 pregnancy and 1 sporadic pregnancy loss (308 live births, 141 pregnancy losses), 44 women with >or=1 pregnancy and >or=3 pregnancy losses (105 live births, 180 pregnancy losses), and 638 women with >or=1 live birth pregnancy and 0 pregnancy loss (1553 live births). Outpatient Clinical Research Center. A total of 823 caucasian women with consecutive measures of the FVL mutation. We used polymerase chain reaction techniques to characterize the thrombophilic FVL G1691A gene mutation. Of the 638 controls, 47 (7.4%) had FVL heterozygosity versus 16 heterozygous and 2 homozygous FVL cases (18/141, 12.8%) in 141 women with 1 sporadic pregnancy loss versus 9/44 RPL cases (20.5%, 8 heterozygous and 1 homozygous FVL). The FVL frequency in cases with 1 sporadic pregnancy loss (18/141, 12.8%) did not differ from RPL cases (9/44, 20.45%). After unexplained sporadic pregnancy loss, as well as after RPL, to provide the option to prospectively optimize subsequent live birth outcomes with low-molecular-weight heparin thromboprophylaxis, we suggest that measurements be done of the FVL mutation, a treatable etiology for sporadic pregnancy loss as well as for RPL.