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BackgroundReproductive health in women with human immunodeficiency virus (HIV) (WWH) has improved in recent decades. We aimed to investigate incidences of childbirth, pregnancy, spontaneous abortion, and induced abortion among WWH in a nationwide, population-based, matched cohort study.MethodsWe included all WWH aged 20–40 years treated at an HIV healthcare center in Denmark from 1995 to 2021 and a matched comparison cohort of women from the general population (WGP). We calculated incidence rates per 1000 person-years and used Poisson regression to calculate adjusted incidence rate ratios (aIRRs) of childbirth, pregnancy, spontaneous abortion, and induced abortion stratified according to calendar periods (1995–2001, 2002–2008, and 2009–2021).ResultsWe included 1288 WWH and 12 880 WGP; 46% of WWH were of African origin, compared with 1% of WGP. Compared with WGP, WWH had a decreased incidence of childbirth (aIRR, 0.6 [95% confidence interval, .6–.7]), no difference in the incidence of pregnancy (0.9 [.8–1.0]) or spontaneous abortion (0.9 [.8–1.0]), but an increased incidence of induced abortion (1.9 [1.6–2.1]) from 1995 to 2021. The aIRRs for childbirth, pregnancy, and spontaneous abortion increased from 1995–2000 to 2009–2021, while the aIRR for induced abortion remained increased across all time periods for WWH.ConclusionsFrom 1995 to 2008, the incidences of childbirth, pregnancy, and spontaneous abortion were decreased among WWH compared with WGP. From 2009 to 2021, the incidence of childbirth, pregnancy, and spontaneous abortion no longer differed among WWH compared with WGP. The incidence of induced abortions remains increased compared with WGP.

BackgroundTwin pregnancies carry a higher risk of congenital and structural malformations, and pregnancy complications including miscarriage, stillbirth, and intrauterine fetal death, compared with singleton pregnancies. Carrying a fetus with severe malformations or abnormal karyotype places the remaining healthy fetus at an even higher risk of adverse outcome and pregnancy complications. Maternal medical conditions or complicated obstetrical history could, in combination with twin pregnancy, cause increased risks for both the woman and the fetuses. To our knowledge, no previous studies have evaluated and compared the outcomes of all dichorionic twin pregnancies and compared the results of reduced twins with those of nonreduced and primary singletons in a national cohort. These data are important for clinicians when counseling couples about fetal reduction and its implications.ObjectiveThis study aimed to describe and compare the risks of adverse pregnancy outcomes, including the risk of pregnancy loss, in a national cohort of all dichorionic twins—reduced, nonreduced, and primary singletons. In addition, we examined the implications of gestational age at fetal reduction on gestational age at delivery.Study DesignThis was a retrospective cohort study of all Danish dichorionic twin pregnancies, including pregnancies undergoing fetal reduction and a large proportion of randomly selected primary singleton pregnancies with due dates between January 2008 and December 2018. The primary outcome measures were adverse pregnancy outcomes (defined as miscarriage before 24 weeks, stillbirth from 24 weeks, or single intrauterine fetal death in nonreduced twin pregnancies), preterm delivery, and obstetrical pregnancy complications. Outcomes after fetal reduction were compared with those of nonreduced dichorionic twins and primary singletons.ResultsIn total, 9735 dichorionic twin pregnancies were included, of which 172 (1.8%) were reduced. In addition, 16,465 primary singletons were included. Fetal reductions were performed between 11 and 23 weeks by transabdominal needle-guided injection of potassium chloride, and outcome data were complete for all cases. Adverse pregnancy outcome was observed in 4.1% (95% confidence interval, 1.7%–8.2%) of reduced twin pregnancies, and 2.4% (95% confidence interval, 0.7%–6.1%) were delivered before 28 weeks, and 4.2% (95% confidence interval, 1.7%–8.5%) before 32 weeks. However, when fetal reduction was performed before 14 weeks, adverse pregnancy outcomes occurred in only 1.4% (95% confidence interval, 0.0%–7.4%), and delivery before 28 and 32 weeks diminished to 0% (95% confidence interval, 0.0%–5.0%) and 2.8% (95% confidence interval, 0.3%–9.7%), respectively. In contrast, 3.0% (95% confidence interval, 2.7%–3.4%) of nonreduced dichorionic twins had an adverse pregnancy outcome, and 1.9% (95% confidence interval, 1.7%–2.1%) were delivered before 28 weeks, and 7.3% (95% confidence interval, 6.9%–7.7%) before 32 weeks. Adverse pregnancy outcomes occurred in 0.9% (95% confidence interval, 0.7%–1.0%) of primary singletons, and 0.2% (95% confidence interval, 0.1%–0.3%) were delivered before 28 weeks, and 0.7% (95% confidence interval, 0.6%–0.9%) before 32 weeks. For reduced twins, after taking account of maternal factors and medical history, it was demonstrated that the later the fetal reduction was performed, the earlier the delivery occurred (PConclusionIn a national 11-year cohort including all dichorionic twin pregnancies, transabdominal fetal reduction by needle guide for fetal or maternal indication was shown to be safe, with good outcomes for the remaining co-twin. Results were best when the procedure was performed before 14 weeks. BackgroundTwin pregnancies carry a higher risk of congenital and structural malformations, and pregnancy complications including miscarriage, stillbirth, and intrauterine fetal death, compared with singleton pregnancies. Carrying a fetus with severe malformations or abnormal karyotype places the remaining healthy fetus at an even higher risk of adverse outcome and pregnancy complications. Maternal medical conditions or complicated obstetrical history could, in combination with twin pregnancy, cause increased risks for both the woman and the fetuses. To our knowledge, no previous studies have evaluated and compared the outcomes of all dichorionic twin pregnancies and compared the results of reduced twins with those of nonreduced and primary singletons in a national cohort. These data are important for clinicians when counseling couples about fetal reduction and its implications.ObjectiveThis study aimed to describe and compare the risks of adverse pregnancy outcomes, including the risk of pregnancy loss, in a national cohort of all dichorionic twins—reduced, nonreduced, and primary singletons. In addition, we examined the implications of gestational age at fetal reduction on gestational age at delivery.Study DesignThis was a retrospective cohort study of all Danish dichorionic twin pregnancies, including pregnancies undergoing fetal reduction and a large proportion of randomly selected primary singleton pregnancies with due dates between January 2008 and December 2018. The primary outcome measures were adverse pregnancy outcomes (defined as miscarriage before 24 weeks, stillbirth from 24 weeks, or single intrauterine fetal death in nonreduced twin pregnancies), preterm delivery, and obstetrical pregnancy complications. Outcomes after fetal reduction were compared with those of nonreduced dichorionic twins and primary singletons.ResultsIn total, 9735 dichorionic twin pregnancies were included, of which 172 (1.8%) were reduced. In addition, 16,465 primary singletons were included. Fetal reductions were performed between 11 and 23 weeks by transabdominal needle-guided injection of potassium chloride, and outcome data were complete for all cases. Adverse pregnancy outcome was observed in 4.1% (95% confidence interval, 1.7%–8.2%) of reduced twin pregnancies, and 2.4% (95% confidence interval, 0.7%–6.1%) were delivered before 28 weeks, and 4.2% (95% confidence interval, 1.7%–8.5%) before 32 weeks. However, when fetal reduction was performed before 14 weeks, adverse pregnancy outcomes occurred in only 1.4% (95% confidence interval, 0.0%–7.4%), and delivery before 28 and 32 weeks diminished to 0% (95% confidence interval, 0.0%–5.0%) and 2.8% (95% confidence interval, 0.3%–9.7%), respectively. In contrast, 3.0% (95% confidence interval, 2.7%–3.4%) of nonreduced dichorionic twins had an adverse pregnancy outcome, and 1.9% (95% confidence interval, 1.7%–2.1%) were delivered before 28 weeks, and 7.3% (95% confidence interval, 6.9%–7.7%) before 32 weeks. Adverse pregnancy outcomes occurred in 0.9% (95% confidence interval, 0.7%–1.0%) of primary singletons, and 0.2% (95% confidence interval, 0.1%–0.3%) were delivered before 28 weeks, and 0.7% (95% confidence interval, 0.6%–0.9%) before 32 weeks. For reduced twins, after taking account of maternal factors and medical history, it was demonstrated that the later the fetal reduction was performed, the earlier the delivery occurred (PConclusionIn a national 11-year cohort including all dichorionic twin pregnancies, transabdominal fetal reduction by needle guide for fetal or maternal indication was shown to be safe, with good outcomes for the remaining co-twin. Results were best when the procedure was performed before 14 weeks.

Introduction: SARS-CoV-2 infection during pregnancy may cause viral inflammation of the placenta, resulting in fetal demise even without fetal or newborn infection. The impact of timing of the infection and the mechanisms that cause fetal morbidity and mortality are not well understood.Material and methods: To describe placental pathology from women with confirmed SARS-CoV-2 infection during pregnancy, a SARS-CoV-2 immunohistochemistry-positive placenta and late miscarriage, stillbirth, neonatal death, or medically indicated birth due to fetal distress.Results: The triad of trophoblastic necrosis, inflammatory intervillous infiltrates, and increased perivillous fibrinoid deposition was present in all 17 placentas; the pregnancies resulted in eight stillbirths, two late miscarriages (19 and 21 weeks' gestation), and seven liveborn children, two of which died shortly after delivery. The severity of maternal COVID-19 was not reflected by the extent of the placental lesions. In only one case, SARS-CoV-2 was detected in lung tissue samples from the fetus. The majority events (miscarriage, stillbirth, fetal distress resulting in indicated birth, or livebirth, but neonatal death) happened shortly after maternal SARS-CoV-2 infection was diagnosed. Seven of eight sequenced cases were infected with the Delta (B.1.617.2) virus strain.Conclusion: We consolidate findings from previous case series describing extensive SARS-CoV-2 placentitis and placental insufficiency leading to fetal hypoxia. We found sparse evidence to support the notion that SARS-CoV-2 virus had infected the fetus or newborn. Introduction: SARS-CoV-2 infection during pregnancy may cause viral inflammation of the placenta, resulting in fetal demise even without fetal or newborn infection. The impact of timing of the infection and the mechanisms that cause fetal morbidity and mortality are not well understood.Material and methods: To describe placental pathology from women with confirmed SARS-CoV-2 infection during pregnancy, a SARS-CoV-2 immunohistochemistry-positive placenta and late miscarriage, stillbirth, neonatal death, or medically indicated birth due to fetal distress.Results: The triad of trophoblastic necrosis, inflammatory intervillous infiltrates, and increased perivillous fibrinoid deposition was present in all 17 placentas; the pregnancies resulted in eight stillbirths, two late miscarriages (19 and 21 weeks' gestation), and seven liveborn children, two of which died shortly after delivery. The severity of maternal COVID-19 was not reflected by the extent of the placental lesions. In only one case, SARS-CoV-2 was detected in lung tissue samples from the fetus. The majority events (miscarriage, stillbirth, fetal distress resulting in indicated birth, or livebirth, but neonatal death) happened shortly after maternal SARS-CoV-2 infection was diagnosed. Seven of eight sequenced cases were infected with the Delta (B.1.617.2) virus strain.Conclusion: We consolidate findings from previous case series describing extensive SARS-CoV-2 placentitis and placental insufficiency leading to fetal hypoxia. We found sparse evidence to support the notion that SARS-CoV-2 virus had infected the fetus or newborn.

STUDY QUESTION Is idiopathic reduced ovarian reserve in young women, quantified as low response to ovarian stimulation in ART, associated with a concomitant loss of oocyte quality as determined by risk of pregnancy loss and chance of clinical pregnancy and live birth? SUMMARY ANSWER Young women with idiopathic accelerated loss of follicles exhibit a similar risk of pregnancy loss as young women with normal ovarian reserve. WHAT IS KNOWN ALREADY Normal ovarian ageing is described as a concomitant decline in oocyte quantity and quality with increasing age. Conflicting results exist with regard to whether a similar decline in oocyte quality also follows an accelerated loss of follicles in young women. STUDY DESIGN, SIZE, DURATION This national register-based, historical cohort study included treatment cycles from young women (≤37 years) after ART treatment in Danish public or private fertility clinics during the period 1995–2014. The women were divided into two groups dependent on their ovarian reserve status: early ovarian ageing (EOA) group and normal ovarian ageing (NOA) group. There were 2734 eligible cycles in the EOA group and 22 573 in the NOA group. Of those, 1874 (n = 1213 women) and 19 526 (n = 8814 women) cycles with embryo transfer were included for analyses in the EOA and NOA group, respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS EOA was defined as ≤5 oocytes harvested in both the first and second cycle stimulated with FSH. The NOA group should have had at least two FSH-stimulated cycles with ≥8 oocytes harvested in either the first or the second cycle. Cases with known causes influencing the ovarian reserve (endometriosis, ovarian surgery, polycystic ovary syndrome, chemotherapy, etc.) were excluded. The oocyte quality was evaluated by the primary outcome defined as the overall risk of pregnancy loss (gestational age (GA) ≤22 weeks) following a positive hCG and further stratified into: non-visualized pregnancy loss, early miscarriage (GA ≤ 12 weeks) and late miscarriage (GA > 12 weeks). Secondary outcomes were chance of clinical pregnancy and live birth per embryo transfer. Cox regression models were used to assess the risk of pregnancy loss. Time-to-event was measured from the day of embryo transfer from the second cycle and subsequent cycles. Logistic regression models were used to assess the chance of clinical pregnancy and live birth. MAIN RESULTS AND THE ROLE OF CHANCE The overall risk of pregnancy loss for the EOA group was comparable with the NOA group (adjusted hazard ratio: 1.04, 95% CI: 0.86; 1.26). Stratifying by pregnancy loss types showed comparable risks in the EOA and NOA group. The odds of achieving a clinical pregnancy or live birth per embryo transfer was lower in the EOA group compared to the NOA group (adjusted odds ratio: 0.77 (0.67; 0.88) and 0.78 (0.67; 0.90), respectively). LIMITATIONS, REASONS FOR CAUTION Only women with at least two ART cycles were included. We had no information on the total doses of gonadotropin administered in each cycle. WIDER IMPLICATIONS OF THE FINDINGS The present findings may indicate that mechanism(s) other than aneuploidy may explain the asynchrony between the normal-for-age risk of miscarriage and the reduced chance of implantation found in our patients with EOA. The results of this study could be valuable when counselling young patients with low ovarian reserve. STUDY FUNDING/COMPETING INTERESTS(S) The study was funded by the Health Research Fund of Central Denmark Region. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Funding: COPS is a sub-study of EAVE II, which is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government DG Health and Social Care and the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation. COPS has received additional funding from Tommy’s charity. SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). KB is funded by a Wellcome Senior Research Fellowship (220283/Z/20/Z). Data on the safety of COVID-19 vaccines in early pregnancy are limited. We conducted a national, population-based, matched cohort study assessing associations between COVID-19 vaccination and miscarriage prior to 20 weeks gestation and, separately, ectopic pregnancy. We identified women in Scotland vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Matched, unvaccinated women from the pre-pandemic and, separately, pandemic periods were used as controls. Here we show no association between vaccination and miscarriage (adjusted Odds Ratio [aOR], pre-pandemic controls = 1.02, 95% Confidence Interval [CI] = 0.96–1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92–1.38). We undertook additional analyses examining confirmed SARS-CoV-2 infection as the exposure and similarly found no association with miscarriage or ectopic pregnancy. Our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19. Publisher PDF

Background: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy that significantly affects perinatal outcomes. Objective: The aim of this study was to determine the prevalence of GDM and its relation with the incidence of stillbirth, preterm birth, macrosomia, abortion and cesarean section (C-section) delivery in pregnant women. Methods: This cross-sectional study was conducted on 3675 pregnant women in 11 provinces across Iran. Cluster sampling was used to select samples from mothers covered by health plans in 11 provinces of Iran. Prevalence of adverse pregnancy outcomes, including preterm delivery, type of delivery, macrosomic preterm birth, miscarriage, stillbirth, infant death, and birth weight were measured, using family record and face-to-face interviews. Data were analyzed by logistic regression, using STATA14.2 software. Results: About four percent of Iranian pregnant women had GDM during pregnancy. Prevalence of C-section was significantly higher in diabetic women than in the non-diabetic ones (53.19 vs 46.81, respectively, P < 0.001). Abortion in diabetic mothers was more than twice that of the non-diabetic mothers (P < 0.001). In the adjusted logistic regression model, the odds of stillbirth in mothers with GDM were 1.8 (95% CI: 1.11, 2.91, P = 0.018) times higher than that of the non-diabetics. The odds of macrosomia in diabetic women was about 7 times higher than the non-diabetic women (95% CI: 2.81, 17.14, P < 0.001). The odds of GDM had an increasing trend according to the BMI (p < 0.001). The risk of GDM were significantly lower, according to the daily physical activity (PA) (p < 0.001). Conclusion: The GDM prevalence has a decreasing trend in Iran. It increases the adverse pregnancy outcomes such as stillbirth, neonatal deaths, macrosomia, preterm birth, abortion and C-section delivery. As, some of these consequences like macrosomia are not treatable, thus early prevention is very crucial.

Pregnancy loss has multifactorial causes, and the maternal risk factors are the most investigated. Therefore, this review investigates the current literature regarding the effect of paternal health on pregnancy loss. This review is conducted according to the PRISMA guidelines. The electronic databases PubMed and Medline were the primary sources of information. The online tool covidence.org was used for the screening process. The Newcastle–Ottawa Scale was used for assessment of risk of bias across the non-RCT (Randomized Controlled Trials) included studies. Six cohort studies and one randomised clinical trial were included for assessment in this review. Especially three large retrospective studies reported that circulatory paternal health issue, increasing metabolic syndrome diagnoses and paternal age was significantly associated with a higher risk of pregnancy loss. Lower pregnancy loss was also found in couples with diabetes in the man compared to couples without diabetes. One study suggests a connection between varicocelectomy and improved sperm DNA fragmentation and lower abortion rate. This review confirms that paternal age, somatic health and particularly health regarding cardiovascular and metabolic disease are associated positively with risks of pregnancy loss. However, further research may lead to evidence, which are more conclusive.

BACKGROUND: In subfertile couples, couples who have tried to conceive for at least one year, intrauterine insemination (IUI) with ovarian hyperstimulation (OH) is one of the treatment modalities that can be offered. When IUI is performed a second IUI in the same cycle might add to the chances of conceiving. In a previous update of this review in 2010 it was shown that double IUI increases pregnancy rates when compared to single IUI. Since 2010, different clinical trials have been published with differing conclusions about whether double IUI increases pregnancy rates compared to single IUI. OBJECTIVES: To determine the effectiveness and safety of double intrauterine insemination (IUI) compared to single IUI in stimulated cycles for subfertile couples. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase and CINAHL in July 2020 and LILACS, Google scholar and Epistemonikos in February 2021, together with reference checking and contact with study authors and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled, parallel trials of double versus single IUIs in stimulated cycles in subfertile couples. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: We identified in nine studies involving subfertile women. The evidence was of low quality; the main limitations were unclear risk of bias, inconsistent results for some outcomes and imprecision, due to small trials with imprecise results. We are uncertain whether double IUI improves live birth rate compared to single IUI (odds ratio (OR) 1.15, 95% confidence interval (CI) 0.71 to 1.88; I2 = 29%; studies = 3, participants = 468; low quality evidence). The evidence suggests that if the chance of live birth following single IUI is 16%, the chance of live birth following double IUI would be between 12% and 27%. Performing a sensitivity analysis restricted to only randomised controlled trials (RCTs) with low risk of selection bias showed similar results. We are uncertain whether double IUI reduces miscarriage rate compared to single IUI (OR 1.78, 95% CI 0.98 to 3.24; I2 = 0%; studies = 6, participants = 2363; low quality evidence). The evidence suggests that chance of miscarriage following single IUI is 1.5% and the chance following double IUI would be between 1.5% and 5%. The reported clinical pregnancy rate per woman randomised may increase with double IUI group (OR 1.51, 95% CI 1.23 to 1.86; I2 = 34%; studies = 9, participants = 2716; low quality evidence). This result should be interpreted with caution due to the low quality of the evidence and the moderate inconsistency. The evidence suggests that the chance of a pregnancy following single IUI is 14% and the chance following double IUI would be between 16% and 23%. We are uncertain whether double IUI affects multiple pregnancy rate compared to single IUI (OR 2.04, 95% CI 0.91 to 4.56; I2 = 8%; studies = 5; participants = 2203; low quality evidence). The evidence suggests that chance of multiple pregnancy following single IUI is 0.7% and the chance following double IUI would be between 0.85% and 3.7%. We are uncertain whether double IUI has an effect on ectopic pregnancy rate compared to single IUI (OR 1.22, 95% CI 0.35 to 4.28; I2 = 0%; studies = 4, participants = 1048; low quality evidence). The evidence suggests that the chance of an ectopic pregnancy following single IUI is 0.8% and the chance following double IUI would be between 0.3% and 3.2%. AUTHORS' CONCLUSIONS: Our main analysis, of which the evidence is low quality, shows that we are uncertain if double IUI improves live birth and reduces miscarriage compared to single IUI. Our sensitivity analysis restricted to studies of low risk of selection bias for both outcomes is consistent with the main analysis. Clinical pregnancy rate may increase in the double IUI group, but this should be interpreted with caution due to the low quality evidence. We are uncertain whether double IUI has an effect on multiple pregnancy rate and ectopic pregnancy rate compared to single IUI.

ObjectiveTo compare the ongoing pregnancy rate between a freeze-all strategy and a fresh transfer strategy in assisted reproductive technology treatment.DesignMulticentre, randomised controlled superiority trial.SettingOutpatient fertility clinics at eight public hospitals in Denmark, Sweden, and Spain.Participants460 women aged 18-39 years with regular menstrual cycles starting their first, second, or third treatment cycle of in vitro fertilisation or intracytoplasmic sperm injection.InterventionsWomen were randomised at baseline on cycle day 2 or 3 to one of two treatment groups: the freeze-all group (elective freezing of all embryos) who received gonadotropin releasing hormone agonist triggering and single frozen-thawed blastocyst transfer in a subsequent modified natural cycle; or the fresh transfer group who received human chorionic gonadotropin triggering and single blastocyst transfer in the fresh cycle. Women in the fresh transfer group with more than 18 follicles larger than 11 mm on the day of triggering had elective freezing of all embryos and postponement of transfer as a safety measure.Main outcome measuresThe primary outcome was the ongoing pregnancy rate defined as a detectable fetal heart beat after eight weeks of gestation. Secondary outcomes were live birth rate, positive human chorionic gonadotropin rate, time to pregnancy, and pregnancy related, obstetric, and neonatal complications. The primary analysis was performed according to the intention-to-treat principle.ResultsOngoing pregnancy rate did not differ significantly between the freeze-all and fresh transfer groups (27.8% (62/223) v 29.6% (68/230); risk ratio 0.98, 95% confidence interval 0.87 to 1.10, P=0.76). Additionally, no significant difference was found in the live birth rate (27.4% (61/223) for the freeze-all group and 28.7% (66/230) for the fresh transfer group; risk ratio 0.98, 95% confidence interval 0.87 to 1.10, P=0.83). No significant differences between groups were observed for positive human chorionic gonadotropin rate or pregnancy loss, and none of the women had severe ovarian hyperstimulation syndrome; only one hospital admission related to this condition occurred in the fresh transfer group. The risks of pregnancy related, obstetric, and neonatal complications did not differ between the two groups except for a higher mean birth weight after frozen blastocyst transfer and an increased risk of prematurity after fresh blastocyst transfer. Time to pregnancy was longer in the freeze-all group.ConclusionsIn women with regular menstrual cycles, a freeze-all strategy with gonadotropin releasing hormone agonist triggering for final oocyte maturation did not result in higher ongoing pregnancy and live birth rates than a fresh transfer strategy. The findings warrant caution in the indiscriminate application of a freeze-all strategy when no apparent risk of ovarian hyperstimulation syndrome is present.Trial registrationClinicaltrials.gov NCT02746562.

BackgroundThe probability of a pregnancy, live birth, stillbirth and abortion has never been assessed in women with neurofibromatosis 1 (NF1) in a large population-based study.MethodsWe included 1006 women (15–49 years) registered with NF1 in the Danish National Patient Registry or followed in two national Centers for Rare Diseases and 10 020 women from the Danish population. Information on pregnancy outcomes was ascertained from health registries. Cumulative incidence, mean cumulative count, hazard ratios (HRs) and proportion ratios (PRs) with 95% CIs were calculated.ResultsThe cumulative incidence of a first pregnancy at age 50 years was slightly lower in women with NF1 (74%; 95% CI 70 to 77) than in population comparisons (78%; 95% CI 77 to 79). When all pregnancies were included, two pregnancies were expected per woman at age of 50 years, irrespective of a NF1 diagnosis. The hazard of a pregnancy did not differ between women with NF1 (HR 1.03; 95% CI 0.95 to 1.11) and the comparisons after adjustment for somatic and psychiatric disease. The proportion of pregnancies that resulted in a live birth was 63% (783/1252) among women NF1 and 68% (8432/12 465) among the comparisons, yielding a PR of 0.95 (95% CI 0.90 to 1.00). The proportions of stillbirths (PR 2.83; 95% CI 1.63 to 4.93) and spontaneous abortions (PR 1.40; 95% CI 1.09 to 1.79) were increased in women with NF1.ConclusionsA similar hazard for pregnancy was observed for women with NF1 and population comparisons after adjustment for potential medical consequences of NF1. However, women with NF1 experienced more spontaneous abortions and stillbirths.

STUDY QUESTION: What is the risk of venous thromboembolism (VTE) in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF?SUMMARY ANSWER: The VTE risk is low in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF.WHAT IS KNOWN ALREADY: There is an excess VTE risk during first trimester in complete IVF pregnancies leading to delivery. It is unknown whether this excess VTE risk also is present in IVF pregnancies terminated by early pregnancy loss (implantation failure, missed abortion, or spontaneous or induced abortion before 10 completed gestational weeks).STUDY DESIGN, SIZE, DURATION: A nationwide registry-based cohort study including all Danish IVF pregnancies registered in the Danish IVF Register between 1995 and 2005. Women who underwent frozen embryo replacement or oocyte donation were not included.PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all 24 931 IVF treatments leading to pregnancy among 19 260 women. We identified 16 701 complete IVF pregnancies, 7567 IVF pregnancies with early pregnancy loss, and 663 IVF pregnancies terminated by late abortion (≥gestational weeks 10). We followed women for 12 weeks after termination of pregnancy and calculated the absolute risk of VTE during follow-up with 95% CI. As a relative risk estimate, we calculated the risk ratio for VTE following IVF pregnancies with early loss compared to the VTE risk following complete IVF pregnancies.MAIN RESULTS AND THE ROLE OF CHANCE: During the 12 weeks of follow-up, only one case of VTE occurred in the group of early pregnancy loss, none in the late abortion group, and 13 VTE cases occurred in complete IVF pregnancies. The VTE risk per 10 000 pregnancies was 1.3 [0.03-7.4] for IVF pregnancies with early loss and 7.8 [4.1-13.3] for complete pregnancies; the corresponding risk ratio was 0.17 [0.02-1.3]. Thus, we found a low absolute VTE risk in the 12 weeks following early pregnancy loss in IVF pregnancies. The relative VTE risk was low in comparison to the VTE risk in early gestation reported for complete IVF pregnancies and for Danish background pregnancies.LIMITATIONS, REASONS FOR CAUTION: Despite the use of complete nationwide data, only a few VTE events were available for the statistical analyses thereby limiting the precision of our estimates. We included both inpatient and outpatient VTE hospital diagnoses, but we cannot rule out the occurrence of VTE cases not diagnosed at hospital and hence not registered in the National Patient Registry. No information was available on the use of prophylactic low molecular weight heparin: access to such might have helped to explain our findings, but would not have changed our conclusions.WIDER IMPLICATIONS OF THE FINDINGS: The results of the present study do not indicate a need for prophylactic anticoagulant therapy in women suffering early IVF pregnancy loss without other risk factors.STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There are no conflicts of interest to declare.

Millions of doses of HPV vaccine have been administered globally. Inadvertent administration of HPV vaccine during pregnancy occurs given that the main recipients of the vaccine are fertile young women, who might be unaware of their pregnancy at the time of their vaccination. To investigate the subject of HPV vaccine and pregnancy , the databases of PubMed and Embase were searched to find the relevant literature published in English within the last 10 y. Most of the evidence pertaining to fetal adverse events following HPV vaccination relates to spontaneous miscarriage. None of the relevant studies found any significantly increased rate of spontaneous abortion in the overall analyses. There was no indication of other HPV vaccine-associated adverse events in pregnancy or immediately post-conception.

Objectives To display and discuss the reasons and consequences of length and time-dependent bias. They might occur in presence of a time-dependent study entry or a time-dependent exposure which might change from unexposed to exposed. Study Design and Setting Recalling the popular study of Oscar nominees and using a real-data example from hospital epidemiology, we give innovative and easy-to-understand graphical presentations of how these biases corrupt the analyses via distorted time-at-risk. Cumulative hazard plots and Cox proportional hazards models were used. We are building bridges to medical disciplines such as critical care medicine, hepatology, pharmaco-epidemiology, transplantation medicine, neurology, gynecology and cardiology. Results In presence of time-dependent bias, the hazard ratio (comparing exposed with unexposed) is artificially underestimated. The length bias leads to an artificial underestimation of the overall hazard. When both biases coexist it can lead to different directions of biased hazard ratios. Conclusion Since length and time-dependent bias might occur in several medical disciplines, we conclude that understanding and awareness are the best prevention of survival bias.

OBJECTIVE: Brucellosis is a zoonosis with high morbidity in humans. This disease has gained interest recently due to its re-emergence and potential for weaponization. Pregnant women with this disease can develop severe complications. Its association with adverse obstetric outcomes is not clearly understood. The objective of this study was to describe the obstetric outcomes of brucellosis in pregnancy. METHODS: Cases of pregnant women with active brucellosis seen at the Hospital Nacional Cayetano Heredia from 1970 to 2012 were reviewed. Diagnostic criteria were a positive agglutination test and/or positive blood/bone marrow culture. Presentation and outcomes data were collected. The Chi-square test was used for nominal variables. A p-value of

PURPOSE: Heart rates in embryos (6-8 weeks' gestation) have rarely been studied. We attempted to identify embryonic heart rates at 4 stages during 6-8 weeks' gestation and to relate our findings to fetal outcome at the end of the first trimester. We also tried to determine the lower limit of the heart rate associated with a favorable outcome for each group. METHODS: We prospectively studied 2,164 singleton pregnancies between 1992 and 1995. Gestational age was calculated from the known date of the beginning of the last menstrual period and was confirmed by sonographic measurement of the crown-rump length. M-mode sonography was used to calculate the embryonic heart rate as the mean of at least 3 waves in beats/minute. RESULTS: Mean embryonic heart rates (+/-standard deviation) were 111+/-14 beats/min for group 1 (42-45 days), 125+/-15 beats/min for group 2 (46-49 days), 145+/-14 beats/min for group 3 (50-52 days), and 157+/-13 beats/min for group 4 (53-56 days). Statistically significant differences (p < 0.01) in the mean heart rates were seen between all groups. A heart rate between 116 and 125 beats/min was associated with the fewest losses in groups 1 (10.8% losses) and 2 (8.6%). In groups 3 and 4, a heart rate of 146 beats/min or more was associated with the fewest losses (5.5% and 3.3%, respectively). A highly significant (p < 0.01) linear decrease was seen in fetal losses with increasing gestational age. Embryos with heart rates below 85 beats/ min during 6-8 weeks' gestation did not survive. CONCLUSIONS: The heart rate during 6-8 weeks' gestation is associated with fetal outcome at the end of the first trimester and identifies those embryos that are in jeopardy. J Clin Ultrasound