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Study Question: What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?, Summary Answer: In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages., What Is Known Already: Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL., Study Design, Size, Duration: The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals., Participants/materials, Setting, Methods: Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth., Main Results and the Role of Chance: One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01)., Limitations, Reasons for Caution: Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered., Wider Implications of the Findings: Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system., Study Funding/competing Interest(s): The research received no specific funding, and the authors declare no competing interests., Trial Registration Number: clinicaltrial.gov NCT05557201., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Study Question: What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)?, Summary Answer: Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%., What Is Known Already: ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL., Study Design, Size, Duration: This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023., Participants/materials, Setting, Methods: Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria., Main Results and the Role of Chance: The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11-17%), 29 (7%; 95% CI: 5-9%), and 47 (11%; 95% CI: 8-14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3-7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2-5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2-6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3-6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19-27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3-7%)., Limitations, Reasons for Caution: The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems., Wider Implications of the Findings: The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies., Study Funding/competing Interest(s): No specific funding was used. The authors have no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Question: Is there a difference in the time interval between the first and second live births among individuals with and without recurrent pregnancy loss (RPL)?, Summary Answer: Primary RPL (two or more pregnancy losses before the first live birth) is associated with a shorter time interval between the first and second live births compared with individuals without RPL, but this association is reversed in patients with secondary RPL (RPL patients with no or one pregnancy loss before the first live birth)., What Is Known Already: There is limited information regarding the ability to have more than one child for patients with RPL. Previous studies have investigated the time to live birth and the live birth rate from the initial presentation to clinical providers. Most of the previous studies have included only patients treated at specialized RPL clinics and thus may be limited by selection bias, including patients with a more severe condition., Study Design, Size, Duration: We conducted a population-based retrospective cohort study of 184 241 participants who delivered in British Columbia, Canada, and had at least two recorded live births between 2000 and 2018. The aim was to study the differences in the time interval between the first and second live births and the prevalence of pregnancy complications in patients with and without RPL. Additionally, 198 319 individuals with their first live birth between 2000 and 2010 were studied to evaluate cumulative second live birth rates., Participants/materials, Setting, Methods: Among individuals with at least two recorded live births between 2000 and 2018, 12 321 patients with RPL and 171 920 participants without RPL were included. RPL was defined as at least two pregnancy losses before 20 weeks gestation. Patients with primary RPL had at least two pregnancy losses occurring before the first live birth, while patients with secondary RPL had no or one pregnancy loss before the first live birth. We compared the time interval from the first to second live birth in patients with primary RPL, those with secondary RPL, and participants without RPL using generalized additive models to allow for a non-linear relationship between maternal age and time interval between first and second live births. We also compared prevalence of pregnancy complications at the first and second live births between the groups using non-parametric Kruskal-Wallis H test and Fisher's exact test for continuous and categorical variables, respectively. We assessed the cumulative second live birth rates in patients with primary RPL and those without RPL, among participants who had their first live birth between 2000 and 2010. Cox proportional hazards model was used to estimate and compare hazard ratios between the two groups using a stratified modelling approach., Main Results and the Role of Chance: The adjusted time interval between the first and second live births was the longest in patients with secondary RPL, followed by individuals without RPL, and the shortest time interval was observed in patients with primary RPL: 4.34 years (95% CI: 4.09-4.58), 3.20 years (95% CI: 3.00-3.40), and 3.05 years (95% CI: 2.79-3.32). A higher frequency of pregnancy losses was associated with an increased time interval between the first and second live births. The prevalence of pregnancy complications at the first and second live births, including gestational diabetes, hypertensive disorder of pregnancy, preterm birth, and multiple gestations was significantly higher in patients with primary RPL compared with those without RPL. The cumulative second live birth rate was significantly lower in patients with primary RPL compared with individuals without RPL., Limitations, Reasons for Caution: This study may be limited by its retrospective nature. Although we adjusted for multiple potential confounders, there may be residual confounding due to a lack of information about pregnancy intentions and other factors, including unreported pregnancy losses., Wider Implications of the Findings: The results of this study provide information that will help clinicians in the counselling of RPL patients who desire a second child., Study Funding/competing Interest(s): This study was supported in part by a grant from the Canadian Institutes of Health Research (CIHR): Reference Number W11-179912. M.A.B. reports research grants from CIHR and Ferring Pharmaceutical. He is also on the advisory board for AbbVie, Pfizer, and Baxter. The other authors report no conflict of interest., Trial Registration Number: NCT04360564., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Question: 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)?, Summary Answer: PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups., What Is Known Already: 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., Study Design, Size, Duration: 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 41-42 years) were selected for PGT-A groups., Participants/materials, Setting, Methods: 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., Main Result and the Role of Chance: 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., Limitations, Reasons for Caution: 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., Wider Implication of the Findings: 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., Study Funding/competing Interest(s): 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., Trial Registration Number: N/A., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Study Question: Is a history of three or more miscarriages associated with adverse perinatal outcomes in a subsequent pregnancy?, Summary Answer: Recurrent miscarriage is associated with an increased risk of adverse perinatal outcomes, including preterm birth, very preterm birth and perinatal death, in a subsequent pregnancy., What Is Known Already: Published data are conflicting with some studies reporting an increase in adverse perinatal outcomes in association with prior recurrent miscarriage while others report little or no increase. Large-scale population-based studies have been lacking., Study Design, Size, Duration: We performed a retrospective cohort study of 30 053 women with a singleton pregnancy who booked for antenatal care and delivery between January 2008 and July 2011., Participants/materials, Setting, Methods: All women who attended a university affiliated hospital in Ireland had a detailed obstetric history taken, recording the outcome of all previous pregnancies. We compared the obstetric and perinatal outcomes of 2030 women (6.8%) who had a history of three or more miscarriages (recurrent miscarriage) with the outcomes of 28 023 women (93.2%) who did not. Logistic regression analyses were performed, adjusting for potential confounding factors., Main Results and the Role of Chance: Women with a history of recurrent miscarriage were more likely to be obese, to have undergone assisted conception, to have had a previous perinatal death, and to be delivered by scheduled Caesarean section. Recurrent miscarriage was associated with an increased incidence of preterm birth (<37 weeks gestation, 8.1 versus 5.5%, adjOR 1.54; 95% CI 1.29-1.84), very preterm birth (<32 weeks gestation, 2.2 versus 1.2%, adjOR 1.80; 95% CI 1.28-2.53), and perinatal death (1.2 versus 0.5%, adjOR 2.66; 95% CI 1.70-4.14). The results were similar for both primary and secondary recurrent miscarriage., Limitations, Reasons for Caution: This is a retrospective cohort study and while regression analyses adjusted for potential confounding factors, residual confounding may persist. The strict definition of recurrent miscarriage is three consecutive miscarriages and while each woman in the study group had three or more miscarriages, they were only confirmed to be consecutive in the primary RM group. The affected women have not been categorized according to aetiology of recurrent miscarriage and it may be that adverse outcomes differ according to aetiological subgroup., Wider Implications of the Findings: This study highlights the need for specialist obstetric care for women who have had three or more previous miscarriages, particularly in relation to the risk of preterm delivery., Study Funding/competing Interests: There was no specific funding obtained for this study and there are no conflict of interests., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Study Question: Is the prevalence of psychological stress and moderate/severe depression higher for women with recurrent pregnancy loss (RPL) than pregnancy planners trying to conceive naturally?, Summary Answer: Both psychological stress and major depression are significantly more common among women with RPL than in those trying to conceive naturally., What Is Known Already: RPL has a significant emotional impact on couples, especially the woman. Previous studies have shown inconclusive results., Study Design, Size, Duration: In this cross-sectional study, we compared the prevalence of stress and depression among 301 women with RPL and 1813 women attempting to conceive naturally. We defined RPL as three or more pregnancy losses before 12 weeks' gestation. RPL patients were enrolled from 2010 to 2013 and the comparison group from 2011 to 2014., Participants/materials, Setting, Methods: RPL patients completed an online questionnaire before their first consultation at the Danish RPL Unit. In addition, we included data from a comparison group of 1813 women who participated in the Soon Parents Study (www.SnartForældre.dk). The Major Depression Index (MDI) was used to assess symptoms of depression, and Cohen's Perceived Stress Scale (PSS) was used to measure stress. Relevant demographic data were also retrieved., Main Results and the Role of Chance: Of the RPL patients, 26 (8.6%) had a score on the MDI corresponding to moderate/severe depression, as did 40 (2.2%) of the women in Soon Parents Study (adjusted odds ratio (OR) 5.53 (95% confidence interval (CI): 2.09; 14.61)). A high stress level, defined as ≥19 on the PSS scale, was reported by 124 (41.2%) of the patients and 420 (23.2%) in the comparison group (adjusted OR 1.59 (95% CI 1.03; 2.44))., Limitations, Reasons for Caution: We used online questionnaires, and have no interview data. We were unaware if any of the women in the comparison group suffer from RPL., Wider Implications of the Findings: This study should entail a heightened awareness of mental distress among care providers for women with RPL., Study Funding/competing Interests: No specific funding was sought for this study. The Soon Parents Study is funded by National Institute of Child Health and Human Development (R01 HD060680-01A4). No authors have competing interests to declare., Trial Registration Number: N/A., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Unexplained recurrent miscarriage (RM) can be a challenging and frustrating condition for both patients and clinicians. For the former, there is no diagnosis available for consolation, while for the latter there is little evidence-based treatment to offer. However, the majority of these patients have an excellent prognosis without the need for any treatment. Epidemiological associations suggest that the reason for this is that the majority of women with unexplained RM are in fact healthy individuals, with no underlying pathology, who have suffered three miscarriages purely by chance. Nevertheless, a certain proportion of women with unexplained RM will continue to miscarry, and preliminary studies suggest the presence of pathology in some women of this group. As a result, two types of unexplained RM can be described: Type I unexplained RM, which occurs by chance in women who have no underlying pathology and has a good prognosis; and Type II unexplained RM, which occurs due to an underlying pathology that is currently not yet identified by routine clinical investigations and has a poorer prognosis. Distinguishing between Types I and II unexplained RM can be achieved by considering several factors: the age of the woman, the definition used for RM (i.e. whether biochemical pregnancy losses are considered as miscarriages), the number of previous miscarriages suffered and the karyotype of the products of conception, where available. A better understanding of the two types of unexplained RM could lead to more targeted referrals, investigations and treatments, which would improve cost-effectiveness and overall clinical care.

Background: The purpose of the study was to examine racial/ethnic differences in cervical insufficiency risk., Methods: We used the US 2005 Natality data file. Analysis was limited to singleton births. The prevalence of cervical insufficiency was examined by the maternal characteristic for each racial group. Unconditional logistic regression modeling was used to assess the association between race and cervical insufficiency while controlling for confounders., Results: Cervical insufficiency risk for Black women was more than twice that for their White counterparts [odds ratio (OR) (95% confidence interval (CI)) of 2.45 (2.22-2.71)]. Prior pregnancy termination showed a dose-response relationship with cervical insufficiency. Compared with women with no history of prior pregnancy termination, primiparous women who have had one pregnancy termination had an OR (95% CI) of 2.49 (2.23-2.77). The OR for two, three and four or more terminations were 4.66 (4.07-5.33), 8.07 (6.77-9.61) and 12.36 (10.19-15.00), respectively. Other predictors of cervical insufficiency included previous preterm birth, parity, marital status, renal disease, history of diabetes, polyhydramnios and anemia., Conclusions: There were significant racial/ethnic disparities with Black women having increased cervical insufficiency risk, independent of other studied factors. Prior pregnancy termination is also a major risk factor for cervical insufficiency. The White/Black disparity is evident in both primiparous and multiparous women.

Background: Recurrent fetal loss (RFL) is a prevalent problem affecting approximately 1% of all women of childbearing age. Many factors can lead to RFL; however, recent studies have indicated the important role of the maternal immune system in this process. The human leukocyte antigens (HLA), HLA-linked genes and regulatory factors play an important role in fetal loss and in fetal development. The current retrospective study was preformed to examine the HLA alleles shared between couples with RFL in Saudi Arabia, using a large cohort of women (having three or more RFL). Specific HLA alleles that could influence this condition, or the number of miscarriages experienced, were expected to be highlighted in this way., Methods: A total of 253 consecutive patients who visited the RFL clinic at the King AbdulAziz Medical City, National Guard Hospital in Riyadh were included in this study. They included 54 consanguineous couples, 132 non-consanguineous couples and another 67 couples shared only their tribal origin. Clinical examinations as well as laboratory investigations were carried out on each patient. Class I HLA, HLA-A, HLA-B and HLA-C, and Class II HLA, HLA-DR and HLA-DQ, were typed for each patient and their partner., Results: No relationship was seen between sharing of HLA alleles and the number of RFL experienced by the couples, among neither consanguineous nor non-consanguineous couples., Conclusions: Although the results of this study suggest that HLA sharing is not an indicative factor in RFL, definitive conclusions on this topic must be based on large case-control studies.

Background: Several studies have investigated plasma androgen levels in women with recurrent miscarriage (RM) with conflicting results on whether an association between hyperandrogenaemia and RM exists. However, none of these studies included sensitive androgen measurements using a large data set. We therefore investigated the free androgen index (FAI) in a large number of women with RM in order to ascertain whether hyperandrogenaemia is a predictor of subsequent pregnancy outcome., Methods: We studied 571 women who attended the Recurrent Miscarriage Clinic in Sheffield and presented with > or =3 consecutive miscarriages. Serum levels of total testosterone and sex hormone-binding globulin were measured in the early follicular phase and FAI was then deduced., Results: The prevalence of hyperandrogenaemia in RM was 11% and in a subsequent pregnancy, the miscarriage rate was significantly higher in the raised FAI group (miscarriage rates of 68% and 40% for FAI > 5 and FAI < or = 5 respectively, P = 0.002)., Conclusions: An elevated FAI appears to be a prognostic factor for a subsequent miscarriage in women with RM and is a more significant predictor of subsequent miscarriage than an advanced maternal age (> or =40 years) or a high number (> or =6) of previous miscarriages in this study.

Background: Recurrent miscarriage has been associated with antiphospholipid syndrome (APS) and other prothombotic conditions. We tested the hypothesis that women diagnosed as having APS as an aetiological factor for their miscarriages were at higher risk of thrombosis than those with idiopathic recurrent miscarriage., Methods: A retrospective case-control study was performed using validated questionnaires. A total of 141 women with recurrent miscarriage and APS alone were matched with 141 women with idiopathic recurrent miscarriage for age, number and type of pregnancy loss and number of years of follow-up. A subgroup of eight women included those who initially presented with recurrent miscarriage, thrombosis and APS., Results: The mean length of follow-up was 7.3 years and response rate 74%. The incidence of thrombosis was similar in the recurrent miscarriage and APS women (6/1000 women-years) and in the idiopathic recurrent miscarriage women (2/1000 women-years) (P = 0.18). All eight women who presented with recurrent miscarriage, APS and thrombosis reported further thrombotic events., Conclusions: Both idiopathic and APS-associated recurrent miscarriage were associated with a similar long-term risk of thrombosis.

Background: The carriage of a male fetus often initiates maternal immunological reactions against male-specific minor histocompatibility (HY) antigens, which, in theory, could result in subsequent recurrent miscarriage (RM)., Methods: Information about subsequent pregnancy outcome was procured among 182 women with RM after a birth (secondary RM) referred since 1986 using questionnaires, telephone interviews and registers., Results: Significantly more of the women had had a male first-born as compared with a female first-born (110 versus 72; P < 0.02). By January 2002, 58% of those who had a male first-born had given birth to a second live infant compared with 76% of those who previously had had a female first-born (P = 0.01). Women in the former group had a significantly lower chance of having a second child than those in the latter (adjusted hazard ratio 0.59; 95% confidence interval 0.41-0.86). The number of miscarriages after admission and the risk of secondary infertility were significantly greater in women with a male first-born than among those with a female first-born (P < 0.001 and P = 0.02; respectively)., Conclusions: A male first-born seems to be associated with a less favourable reproductive potential among women with secondary RM. Maternal immunization against HY antigens may be responsible for these findings.

Objective: The aim of this study was to assess pregnancy loss patterns in women with repeated miscarriage (RM), according to fetal chromosome karyotypes and aetiologies of RM., Methods: In this cohort study, 168 fetal chromosome karyotypes of miscarriages were investigated. The pregnancy loss patterns were compared between 75 miscarriages from RM women who had a history of two or more consecutive miscarriages and 93 miscarriages from control women whose previous pregnancies ended in live births without a history of RM. By serial ultrasonography, embryo loss (EL) was defined as miscarriage before fetal heat movement was identified and fetal loss (FL) as miscarriage after fetal heat movement was identified. The EL rate was calculated as EL/(EL+FL)., Results: The EL rate (66.7%) in miscarriages with normal karyotypes among RM women (n=42) was higher (P<0.05) than that (45.7%) in controls (n=46), while the EL rate (30.3%) in miscarriages with abnormal karyotypes among RM women (n=33) did not differ from that (25.5%) in the controls (n=47). The EL rate (71.4%) in miscarriages with normal karyotypes among unexplained RM women (n=21) was much higher (P<0.05) than that in the controls., Conclusions: By evaluating fetal karyotypes, we demonstrated for the first time that EL was predominant in miscarriages with normal karyotype among RM women.

Background: Some cases of recurrent miscarriage have a thrombotic basis. Thromboelastography is a rapid, reproducible test of whole-blood haemostasis., Methods: Thromboelastography was performed in 494 consecutive, non-pregnant women (median age 35 years; range 21-48) with a history of miscarriages at <12 weeks gestation (median 4; range 3-12) and 55 parous women (median age 33 years; range 20-41) with no history of pregnancy loss. The prospective outcome of untreated pregnancies amongst 108 women with recurrent miscarriage was studied., Results: The maximum clot amplitude (MA) (median 66.0 mm; range 48.0-76.0) was significantly higher and the rate of clot lysis (LY30) (median 2.5%; range 0.5-7.8) significantly lower amongst women with recurrent miscarriage compared with controls (MA 61.5 mm; range 50.0-67.0; P = 0.01; LY30 4.9%; range 2.9-9.7; P = 0.01). The pre-pregnancy MA was significantly higher amongst women who subsequently miscarried (median 66.0 mm; range 54.0-73.0) compared with those whose had a live birth (median 61.7 mm; 48.0-71.5; P < 0.01). A pre-pregnancy MA >or=64 mm has a sensitivity of 68% and specificity of 82% to predict miscarriage., Conclusions: Thromboelastography identifies a subgroup of women with recurrent miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a state are at increased risk of miscarriage in future untreated pregnancies.

Background: Unexplained miscarriage is speculated to be due to a Th1/Th2 cytokine imbalance at the feto-maternal interface and immunological functions are known to be under the influence of various psychological factors. Indeed, the psycho-neuro-immuno-endocrine network has been proposed to contribute to miscarriage. To assess whether psychological disorders might induce spontaneous abortion we carried out a prospective study to determine if any psychological parameter influenced risk in those patients with a history of recurrent miscarriages., Methods: A prospective study was carried out on 61 patients with a history of two consecutive first-trimester miscarriages. A battery of self-report questionnaires including Symptom Checklist-90 Revised and the NEO Five Factor Index and semi-structured interviews were conducted before a subsequent pregnancy. We investigated whether or not these parameters predicted subsequent miscarriages., Results: Ten (22.2%) of the 45 patients who conceived miscarried again. Baseline depressive symptoms influenced subsequent miscarriage (P = 0.004). This statistically significant effect remained when we corrected with Bonfferoni adjustment (P = 0.036)., Conclusions: A high depression scale is associated with a high miscarriage rate in those patients suffering recurrent miscarriage.

Background: In recurrent pregnancy loss, there is much debate about cause and association, as exact pathophysiological mechanisms have not been elucidated. The aim of this study was to assess whether recurrent pregnancy loss (RPL) patterns differ according to causal/associated conditions, suggesting differing disease processes., Methods: Following investigation, 427 women with RPL were classified into the following 'diagnostic' groups: idiopathic, oligomenorrhoea, antiphospholipid syndrome (APS) and 'possible' APS. A total of 323 subsequently conceived, and underwent serial ultrasonography in early pregnancy; of these, 87 (26.9%) miscarried, and the types of pregnancy loss for the four diagnostic groups were allocated to either embryo loss (fetal heart never seen) and fetal loss (fetal heart seen prior to pregnancy loss)., Results: Overall, there were 75 embryonic losses and 12 fetal losses. The fetal loss rates in each group were similar: idiopathic 5.1%, oligomenorrhoea 3.4%, 'possible' APS 4.9% and APS 4.8%., Conclusions: Serial ultrasound helps to discriminate type of pregnancy loss and demonstrates that embryo loss is more common than fetal loss. More importantly, pregnancy loss patterns do not seem to differ between diagnostic groups in a treated population. The fetal loss rate in each of the diagnostic groups is similar to that in other reported populations.

Background: Previous trials of intravenous immunoglobulin (IvIg) treatment of women with recurrent miscarriage (RM) have provided diverging results. This may be due to different inclusion criteria and suboptimal treatment protocols in some trials., Methods: According to a computer-generated list, 58 women with at least four unexplained miscarriages were randomly assigned to receive infusions of high doses of IvIg or placebo starting as soon as the pregnancy test was positive., Results: In the intention-to-treat analysis, a 45% live birth rate was found in both allocation groups. In patients with secondary RM, 50% in the treatment group and 23% in the placebo group had successful pregnancies (P = not significant). When data from the present and a previous placebo-controlled trial of the same treatment were combined, 15/26 (58%) of the patients with secondary RM in the treatment group versus 6/26 (24%) in the placebo group had successful outcomes (P < 0.02). Only 7% of the karyotyped abortuses were abnormal., Conclusions: IvIg may improve pregnancy outcome in patients with secondary RM. A new placebo-controlled trial focusing on this subgroup should be conducted to confirm the results.

The prevalence of polycystic ovaries (PCO) was established amongst 2199 consecutive women (median age 33 years; range 19-46) with a history of recurrent miscarriage (median 3; 3-14). A diagnosis of PCO was made if the ovarian volume was enlarged (>9 ml), there were >/=10 cysts of 2-8 mm in diameter in one plane and there was increased density of the stroma. In a cohort study, the prospective pregnancy outcome of 486 of the women scanned who were antiphospholipid antibody negative and who received no pharmacological treatment during their next pregnancy was studied. The prevalence of PCO was 40.7% (895/2199). The livebirth rate was similar amongst women with PCO (60.9%; 142/233) compared to that amongst women with normal ovarian morphology (58.5%; 148/253; not significant). Neither an elevated serum luteinizing hormone concentration (>10 IU/l) nor an elevated serum testosterone concentration (>3 nmol/l) was associated with an increased miscarriage rate. Polycystic ovarian morphology is not predictive of pregnancy loss amongst ovulatory women with recurrent miscarriage conceiving spontaneously. The search for a specific endocrine abnormality that can divide women with PCO into those with a good and those with a poorer prognosis for a future successful pregnancy continues.

The underlying causes and rationale for treatment of recurrent abortion are not entirely clear. The Euro-Team early pregnancy protocol was developed as a diagnostic work-up based on the evaluation of risk factors. Possibilities for therapy can be based only on the expectancy that elimination of some risk factors may improve the prognosis.