Live Birth Delivery Research Articles

Disease progression in relation to pre-onset parity among women with rheumatoid arthritis

ObjectiveRheumatoid arthritis (RA) often ameliorates during pregnancy and flares postpartum, but the relationship of pregnancy and childbirth to RA prognosis is unclear. We examined RA severity for association with parity prior to RA onset and asked whether time from birth (latency) and/or the mother's HLA genotype influenced results. MethodsA cohort study was conducted of 222 women previously identified in a prospective study of newly diagnosed RA, who returned for follow-up evaluation a median of 8 years later. Stratified analyses using Mantel-Haenszel methods were conducted to evaluate 5 RA severity measures based on hand and wrist radiographs, physical exams, and Health Assessment Questionnaires for association with parity. ResultsOverall, we observed little evidence of altered risk of progression to severe RA in relation to pre-onset parity, adjusting for RA onset age and time to follow-up. Stratifying parous women who had only live births by latency (<15 years/15+ years) showed no difference in risk of severe RA compared to nulligravid women. Live birth deliveries were significantly protective for women with 0 but not for those with 1 or 2 copies of the RA risk-associated HLA-DRB1 shared epitope sequence for erosion score (RR 0.26 95% CI 0.09–0.89) and joint count (RR 0.28 95% CI 0.09–0.87). ConclusionWe observed little evidence of difference in severe RA by pre-onset parity overall. However, among women not predisposed to RA by possessing the risk-associated HLA genotype, parous women who had only live births had lower risk of progression to severe RA as measured by erosion score and joint count.

Postpartum mental health service utilization in women with Human Immunodeficiency Virus (HIV): a population-based study

ABSTRACTWomen with HIV have higher rates of psychiatric disorders than HIV-negative women, yet little is known about their postpartum mental health and associated service use. The purpose of this study was to characterize HIV-positive women’s use of ambulatory and acute mental health services in the first year postpartum, relative to HIV-negative women. Using health administrative data, we identified 861,365 women who had a live birth delivery from April 1, 2002 to March 31, 2012 in Ontario, Canada, of whom 530 were identified to be HIV-positive. We described their use of mental health services, including outpatient mental health visits, psychiatric emergency department (ED) visits and hospitalizations using adjusted odds ratios (aORs) and 95% confidence intervals (CIs). HIV-positive women were more likely to access outpatient mental health services (31.5% vs. 21.0%, aOR, 1.26; 95% CI, 1.03–1.55), but more likely to remain engaged in psychiatrist services only (15.6% vs. 6.5%, aOR, 2.35; 95% CI, 1.41–3.72). They were also more likely to require a psychiatric ED visit or hospitalization (3.3% vs. 1.1%, aOR, 2.74; 95% CI, 1.72–4.12). Our findings highlight the importance of considering postpartum mental health as part of comprehensive reproductive health care for women with HIV.

Assisted Reproductive Technology Surveillance - United States, 2016.

Problem/condition Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery ( Period covered 2016. Description of system In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). Results In 2016, a total of 197,706 ART procedures (range: 162 in Wyoming to 24,030 in California) with the intent to transfer at least one embryo were performed in 463 U.S. fertility clinics and reported to CDC. These procedures resulted in 65,964 live-birth deliveries (range: 57 in Puerto Rico to 8,638 in California) and 76,892 infants born (range: 74 in Alaska to 9,885 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART use rate, was 3,075. ART use rates exceeded the national rate in 14 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Utah, and Virginia). ART use exceeded 1.5 times the national rate in nine states, including three (Illinois, Massachusetts, and New Jersey) that also had comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four oocyte retrievals). Nationally, among ART transfer procedures for patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age (1.5 among women aged 37 years). Among women aged Interpretation Multiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. For women aged 1.5 times the national average. Although other factors might influence ART use, insurance coverage for infertility treatments accounts for some of the difference in per capita ART use observed among states because most states do not mandate any coverage for ART treatment. Public health action Twins account for almost all of ART-conceived multiple births born in multiple deliveries. Reducing the number of embryos transferred and increasing use of eSET, when clinically appropriate, could help reduce multiple births and related adverse health consequences for both mothers and infants. Because multiple-birth infants are at increased risk for numerous adverse sequelae that cannot be ascertained from the data collected through NASS alone, long-term follow-up of ART infants through integration of existing maternal and infant health surveillance systems and registries with data available from NASS might be useful for monitoring adverse outcomes.

SUN-445 A Brazilian Multicentric Study Evaluating Pregnancies Induced by Cabergoline in Patients Harboring Prolactinomas

BACKGROUND: Prolactinoma is the most common pituitary tumor and a frequent cause of infertility. Treatment with dopamine agonists (DA) usually reverse hyperprolactinemia and hypogonadism, subsequently allowing pregnancy. Cabergoline (CAB) presents a higher affinity to dopamine receptor type 2, better tolerance and more effectiveness than bromocriptine (BCR). Nevertheless, due to the larger experience and its shorter half-life, comparing to CAB, BRC is still the drug of choice to induce pregnancy. Although studies did not show higher rates of maternal and fetal complications in CAB induced-pregnancies, an increase in published data is needed to confimr the drug safety. OBJECTIVE: To evaluate maternal-fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large Brazilian cohort. PATIENTS AND METHODS: A Brazilian multicentric retrospective study assessed the outcomes regarding tumor expansion, abortion, preterm, low birth weight, congenital malformations and neuropsychological development of children from women with prolactinomas treated with CAB at the time of conception and/or during pregnancy. Breastfeeding safety and tumor remission after delivery were also reported. RESULTS: We included 194 women, median age of 31 (17-45) yrs, with prolactinomas, 46% microadenomas (MIC) and 54% macroadenomas (MAC), resulting in 233 pregnancies in which CAB was used. The drug was withdrawal after pregnancy confirmation in 89% of patients at a median gestation age of 6 (2-36) weeks. Symptoms secondary to tumor growth occurred in 22 cases, more frequently in MAC (23%) than MIC (7%) (p=0.005), being DA reintroduced in 21 patients. Neurosurgery was performed in six patients, five without tumor control with medical treatment. Abortion rate was 11%. From live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 3%. Impared neuropsychological development was reported in 7% of 145 children, one to 228 months of age. Twenty-two pregnancies are still ongoing. After one year of delivery, tumor imaging and prolactin reassessment showed remission in 22% of cases, unrelated to breastfeeding or tumor size. DISCUSSION: Due to its longer half-lime, as compared to BRC, CAB use in pregnancy is stiil a matter of concern. Our findings are in agreement with previous studies evaluating maternal and fetal outcomes in pregnancies induced by CAB. In our cohort and in the majority of cases in those studies, CAB was usually withdrawal after pregnancy confirmation. Additionally, tumor remission rate was similar to literature data. CONCLUSIONS: Our multicentric study, including 233 pregnancies, significantly increased the number of reported cases, reassuring CAB safety for pregnancy, induction in women harboring prolactinomas.

Factors influencing the clinical outcome of preimplantation genetic testing for polycystic kidney disease.

What are the factors influencing the success rate for couples undergoing preimplantation genetic testing (PGT) for polycystic kidney disease (PKD)? In our study cohort, the live birth delivery rate is significantly associated with female age while the male infertility accompanying autosomal dominant PKD (ADPKD) does not substantially affect the clinical outcome. While women with ADPKD have no specific fertility problems, male ADPKD patients may present with reproductive system abnormalities and infertility. This retrospective cohort study involves 91 PGT cycles for PKD for 43 couples (33 couples for PKD1, 2 couples for PKD2 and 8 couples for autosomal recessive PKD (ARPKD)) from January 2005 until December 2016 with follow-up of transfers until end of 2017. Sixteen single-cell clinical tests for PKD based on multiplex PCR of short tandem repeat markers, with or without a specific mutation were developed and applied for diagnosis of 584 Day 3 cleavage stage embryos. In 18 couples, the male partner was affected with ADPKD (=Group A) and 12 of them had a documented infertility status. Group A underwent 52 cycles to oocyte retrieval. For 18 other couples, the female partner was affected with ADPKD (=Group B) and four male partners from this group had a documented history of infertility. This group underwent 31 cycles to OR. Genetic analysis resulted in 545 embryos (93.3%) with a diagnosis, of which 215 (36.8%) were genetically transferable. Transfer of 74 embryos in 53 fresh cycles and of 34 cryopreserved embryos in 33 frozen-warmed embryo transfer cycles resulted in a live birth delivery rate of 38.4% per transfer with 31 singleton live births, two twin live births and one ongoing pregnancy. The observed cumulative delivery rate was 57.8% per couple after five treatment cycles. Thirty cryopreserved embryos still remain available for transfer. The clinical pregnancy rate per transfer (fresh + frozen; 45.9% in group A versus 60.0% in group B, P < 0.05) and the live birth delivery rate per transfer (fresh + frozen; 27.0% in group A versus 42.9% in group B, P < 0.05) was significantly lower for couples with the male partner affected with ADPKD compared with couples with the female partner affected with ADPKD. However, a multivariate logistic regression analysis showed that only female age was associated with live birth delivery rate (odds ratio = 0.87; 95% CI: 0.77-0.99; P = 0.032). This study is based on retrospective data from a single centre with Day 3 one-cell and two-cell biopsy. Further analysis of a larger cohort of PKD patients undergoing PGT is required to determine the impact of male infertility associated with ADPKD on the cumulative results. Knowledge about factors affecting the clinical outcome after PGT can be a valuable tool for physicians to counsel PKD patients about their reproductive options. Males affected with ADPKD who suffer from infertility should be advised to seek treatment in time to improve their chances of conceiving a child. No funding was obtained. There are no competing interests to declare. Not applicable.

Glucose screening in pregnancy and future risk of cardiovascular disease in women: a retrospective, population-based cohort study

In studies to date, gestational diabetes has consistently been associated with an increased future risk of cardiovascular disease, irrespective of the antepartum screening protocol or diagnostic criteria by which gestational diabetes is diagnosed. We reasoned that the resultant heterogeneity in the severity of dysglycaemia in women with gestational diabetes suggests that the relationship between gestational glycaemia and subsequent cardiovascular disease probably extends into the non-diagnostic range. Thus, we hypothesised that glucose screening in pregnancy would identify future risk of cardiovascular disease in women who did not have gestational diabetes. We did a population-based cohort study using information from health-care administrative databases from the Ministry of Health and Long Term Care of Ontario (Canada). We identified all women in Ontario who had a 50 g oral glucose challenge test in pregnancy between 24 and 28 weeks gestation with a livebirth delivery between July 1, 2007, and Dec 31, 2015. Women who had a history of diabetes before pregnancy or had been previously hospitalised for cardiovascular disease were excluded. Women with a 1-h post-challenge plasma glucose concentration of 11·1 mmol/L or greater were considered to have gestational diabetes, as were women with a reading between 7·8 and 11·0 mmol/L inclusive for whom diabetes was recorded as a diagnosis on the delivery hospital record. The study population was divided into six groups based on the results of the glucose challenge test (≤4·8 mmol/L; 4·9-5·5 mmol/L; 5·6-6·2 mmol/L; 6·3-6·9 mmol/L; 7·0-7·9 mmol/L; and ≥8·0 mmol/L). The primary outcome was cardiovascular disease (a composite of hospitalisation for myocardial infarction, acute coronary syndrome, stroke, coronary artery bypass grafting, percutaneous coronary intervention, or carotid endarterectomy). All women were followed up from the index pregnancy until cardiovascular disease event, death, migration, or Sept 30, 2017, whichever came first. 259 164 women were identified as eligible for this study: 13 609 who had gestational diabetes, and 245 555 women without gestational diabetes. The women were followed up over a median 3·9 years (IQR 2·8-5·6) for the development of cardiovascular disease. Each 1 mmol/L increment in the glucose challenge test result was associated with a 13% higher risk of cardiovascular disease (after adjustment for age, ethnicity, income, and rurality, adjusted hazard ratio [HR] 1·13, 95% CI 1·04-1·22). This relationship persisted after excluding women with gestational diabetes (1·14, 1·01-1·28). In women without gestational diabetes, those with an abnormal glucose challenge test result (≥7·8 mmol/L) and those with a result between 7·2 and 7·7 mmol/L had an increased risk of cardiovascular disease (HR 1·94, 95% CI 1·29-2·92; and 1·65, 0·99-2·76, respectively), compared with those with a result of 7·1 mmol/L or less (overall p=0·003). The relationship between gestational glycaemia and subsequent risk of cardiovascular disease extends into the normoglycaemic range. Accordingly, glucose screening in pregnancy could identify future risk of cardiovascular disease in women who do not have gestational diabetes. None.

Prevalence of Pre-Pregnancy Diabetes, Obesity, and Hypertension in Canada.

Pre-existing diabetes mellitus (D), obesity (O), and chronic hypertension (H) can each alter the natural course of pregnancy, especially when they cluster together. Because the prevalence of various combinations of D, O, and H is unknown, the current study was undertaken. This population-based cross-sectional study included 506483 singleton and twin live birth and stillbirth deliveries in Ontario, occurring at ≥20 weeks gestation. All hospital births from 2012 to 2016 were identified in the Better Outcomes Registry and Network information system. The prevalence per 1000 births (95% confidence interval [CI]) of D, O, and H and their combinations were calculated. Prevalence estimates were stratified by twin and singleton gestations, maternal age, parity, and ethnicity (Canadian Task Force Classification II-2). During the study period, 5493 women (10.8 per 1000 births; 95% CI 10.6-11.1) had D, 90,177 (178.2; 95% CI 177.0-179.3) had O, and 5667 (11.2; 95% CI 10.9-11.5) had H. The prevalence per 1000 of DO was 4.8, DH 1.0, and OH 5.5, whereas 359 women (0.71 per 1000) had all three. D and H each linearly increased with rising maternal age, along with their combinations, and to some degree with higher parity. The combination of O and H was highest among women of Black ancestry (14.5 per 1000) and lowest among those of Asian ancestry (3.0 per 1000). D, O, and H are common conditions in pregnancy, both alone and in various combinations. These data can be used to assess the impact of each state on perinatal health.

Pregnancy course, infant outcomes, rehospitalization, and mortality among women with intellectual disability

BackgroundPregnant women with intellectual disability (ID) may have greater levels of comorbidity and decreased care access, social support, or ability to monitor their status and communicate needs, but few studies have examined their pregnancy course and outcome, and little is known about their longer-term maternal and infant health. ObjectiveWe compared pre-pregnancy characteristics, pregnancy outcomes, and rehospitalization <2 years after delivery among women with and without ID. MethodWe identified all women with ID and randomly selected a 10:1 comparison group of women without ID with singleton live birth deliveries in Washington State population-based linked birth-hospital discharge data 1987–2012. Multivariable regressions estimated adjusted odds ratios comparing pre-pregnancy characteristics. In cohort analyses, we estimated relative risks (RR) and 95% confidence intervals (CI) for outcomes. ResultsWomen with ID (N = 103) more often had gestational diabetes (RR 3.39, 95% CI 1.81–6.37), preeclampsia (RR 1.88, 95% CI 1.03–3.42), and inadequate prenatal care (RR 2.48, 95% CI 1.67–3.70). Their infants more often were small for gestational age (RR 1.78, 95% CI 1.10–2.89). Need for rehospitalization postpartum was not increased among women with ID or their infants. ConclusionReasons for increased preeclampsia and gestational diabetes among pregnant women with ID are unclear. Barriers to inadequate prenatal care are multifactorial and warrant further study, with consideration that wellness during pregnancy and other times involves social, familial and clinical support systems responsive to each woman's needs.

Can we predict the IVF/ICSI live birth rate?

Objectives:To find a pretreatment predictor for achieving a live birth. Assisted reproduction technology with IVF/ICSI is the ultimate chance for some couples to conceive a child. The expectations are high and it is important to give them a realistic perspective about the chances of achieving a live birth.Methods:A retrospective cohort study of all IVF/ICSI cycles performed in our center between 2012 and 2016. We considered only those cycles with a live birth delivery after 24 weeks, or cycles with no surplus embryos left. The following data was evaluated: AMH; AFC; age; BMI; previous diagnosis; type of treatment; number of previous deliveries; ethnicity, smoking status. Univariate and multivariate analysis were used to examine the association of live birth with baseline patient characteristics. We determined the odds-ratio for all the statistically significant variables (p<0.05), in a multivariate model. The results are presented according to the predictors founded.Results:739 cycles were evaluated: 9.1% were canceled; 10.2% did not have oocytes; 15.6% did not have D2 embryos; 31.4% achieved a live birth. The univariate analysis revealed statistically significant differences regarding AMH, AFC and women’s age between couples with and without a live birth (p<0.001), and the cause of infertility. We found no association with live births in other variables. These variables were categorized and used in a multivariate analysis.Conclusion:Age, AMH, AFC and cause, when sub-classified, are independently associated with the results of an IVF/ICSI treatment. These results enable couples to face real expectations in their particular scenario.

Regenerative therapy by endometrial mesenchymal stem cells in thin endometrium with repeated implantation failure. A novel strategy.

ObjectiveOur primary objective was to evaluate the endometrial changes before and after the transfer of endometrial mesenchymal stem cells (enMSCs) in a population of thinned endometrium women, with absence or hypo-responsiveness to estrogen and repeated implantation failure (RIF). The secondary objective was to evaluate the clinical outcomes of the intervention in terms of clinical pregnancy (CP), early abortions, ongoing pregnancy and live birth delivery rate (LBDR) per in vitro fertilization (IVF) cycle.MethodsA longitudinal and experimental study. The intervention was defined as "subendometrial inoculation of enMSCs," and the post-intervention changes were evaluated by the following variables: endometrial thickness (Eth), endometrial flow cytometry (enFC), endometrial histopathology (enHP) and endometrial immunohistochemistry (enIHQ). The variables were analyzed after the intervention (Post-treatment) regarding previous values (Pretreatment).ResultsEth values before and after treatment with enMSCs were 5.24±1.24 mm vs. 9.93±0.77 (p=0.000), respectively. Endometrial Flow Cytometry showed significant differences in favor of Normalized variables in the post-treatment assessment, associated with the pretreatment, LT/Li, LB/Li, NK/Li, CD8/CD3+ and CD4/CD8 (p≤0.015), respectively. Only two variables Li/PC and CD4/CD3 had NS (p=0.167 and 0.118). A similar analysis was performed on enHP with an HP increase post-treatment (p=0.007). The CP rate was 79.31% (23/29), a live birth delivery rate per embryo transfer was 45.45% (10/22) and ongoing pregnancy 7/29 (24.14%).ConclusionSubendometrial enMSCs inoculation produces a significant increase in endometrial thickness; normalize the enHP, enIHQ and enFC. As a result, IVF after treatment with enMSCs yields a higher rate of CP and LBDR.

Parental age and stillbirth: a population-based cohort of nearly 10 million California deliveries from 1991 to 2011

PurposeParental age at delivery in the United States has been rising. Advanced maternal and paternal ages have been associated with adverse pregnancy outcomes including stillbirth. However, these relationships come from studies that often do not present results for both mother and father concurrently. The purpose of this study was to estimate the risk of stillbirth for maternal and paternal age in the same cohort of deliveries. MethodsThis is a population-based cohort study of all live birth and stillbirth deliveries in California from 1991 to 2011. The individual associations between maternal and paternal ages and stillbirth were estimated with hazard ratios from Cox proportional hazard models. Age was modeled continuously with restricted cubic splines to account for nonlinear relationships. Mean parental age was used as the referent group. ResultsJ-shaped associations between maternal and paternal ages were observed in crude models where older mothers and fathers had the highest hazard ratios for stillbirth. In maternal models, after adjusting for maternal and paternal covariates, young maternal age no longer showed increased hazard ratio for stillbirth, whereas the association with older mothers remained. In adjusted paternal models, the relationship between young paternal age and stillbirth was unchanged while the hazard ratio for older fathers was slightly smaller. ConclusionsAfter adjusting for both parents’ age, education, race/ethnicity, along with parity, older mothers and fathers were independently associated with elevated hazard ratios for stillbirth.

Prevalence of Severe Maternal Morbidity and Factors Associated With Maternal Mortality in Ontario, Canada

Severe maternal morbidity is defined by potentially life-threatening conditions. The association between the number of severe maternal morbidity (SMM) indicators and maternal death is not known. To quantify the association between the number of SMM indicators and maternal mortality. This population-based cohort study used provincial databases for data on all live birth and stillbirth hospital deliveries among women in Ontario, Canada, from April 1, 2002, to February 18, 2017. Excluded from this cohort were those with invalid identification number, non-Ontario residency, maternal age younger than 10 years or older than 55 years or unknown, or gestational age fewer than 20 weeks or unknown as well as any out-of-hospital births, ectopic pregnancies, or spontaneous or induced abortions. Number of SMM indicators identified between 20 weeks' gestation and 42 days after the index delivery. Maternal death occurring from delivery to 42 days after the index delivery. Of the 1 953 943 total births among 1 211 396 women, 181 maternal deaths occurred within 42 days after birth, a rate of 9.3 per 100 000 births. Of the 181 women who died, 123 (68.0%) had at least 1 SMM indicator compared with 1.7% (33 152) of women who survived. Standardized differences suggested that women who died, compared with the women who lived, were older (mean [SD] age, 31.0 [6.2] years vs 30.1 [5.5] years; standardized difference, 0.15) and more likely to reside in a lower-income area (99 [54.7%] vs 832 231 [42.6%]; standardized difference, 0.24), be nulliparous (93 [51.4%] vs 880 386 [45.1%]; standardized difference, 0.13), and be of Afro-Caribbean origin (12 [6.6%] vs 64 948 [3.3%]; standardized difference, 0.15). The most frequent SMM indicators were intensive care unit admission (81 [44.8%]), invasive ventilation (77 [42.5%]), cardiac conditions (69 [38.1%]), complications of obstetric surgery or procedures (32 [17.7%]), and postpartum hemorrhage with blood transfusion (31 [17.1%]). The rate of maternal mortality increased exponentially with the number of SMM indicators: 0 indicators (3.0 per 100 000 births), 1 (71.7 per 100 000 births), 2 (385.9 per 100 000 births), 3 (1274.2 per 100 000 births), 4 (2236.8 per 100 000 births), 5 (4285.7 per 100 000 births), and 6 or more (9422.5 per 100 000 births). Adjusted relative risks for maternal death ranged from 20.1 (95% CI, 11.6-34.7) with 1 SMM indicator to 2192.0 (95% CI, 1287.0-3735.0) with 6 or more SMM indicators compared with 0 indicators. Maternal death may be associated with the number of SMM indicators and occur in certain identifiable groups of women; targeting preventable SMM indicators or limiting their progression may reduce the number of maternal deaths.

Basal Serum Anti-Müllerian Hormone Level as a Predictor of Clinical Outcomes in Freezing-all Embryo Transfer Program.

As a novel biomarker, there is inconsistent evidence regarding the association between anti-Müllerian hormone (AMH) and live birth rate in freezing-all embryo transfer cycles. We aim to assess the prognostic effect of baseline AMH on clinical outcomes, especially live birth rate in freezing-all embryo transfer cycles. A total of 828 non-polycystic ovary patients that underwent their first frozen-thawed embryo transfers in our center between January 2010 and January 2015 were recruited in this retrospective analysis. Patients were stratified into three groups based on their baseline AMH concentration: low AMH group (<1.4 ng/mL), middle AMH group (1.4-5.8 ng/mL) and high AMH group (>5.8 ng/mL). The results showed that low AMH level was associated with adverse clinical outcomes. The differences in implantation rate (21.9% vs. 43.2% vs. 58.8%, P<0.001), clinical pregnancy rate (32.0% vs. 55.2% vs. 65.7%, P<0.001), live birth delivery rate (21.8% vs. 43.6% vs. 52.7%, P<0.001) and miscarriage rate (31.8% vs. 17.5% vs. 15.4%, P=0.014) among the three groups were statistically significant. After adjusting confounders (i.e. age, baseline FSH level, AFC, endometrium thickness, endometrium preparation protocols, number of embryos transferred, etiologies of infertility), differences in live birth rate, clinical pregnancy rate and implantation rate between groups remained significant. The further age subgroup analysis demonstrated that low AMH concentration was significantly associated with poor outcomes both in young and advanced patients. The area under the curve for serum AMH, age, AFC and FSH were 0.635, 0.634, 0.615 and 0.543 respectively, for predicting live birth. In conclusion, baseline AMH was an independent prognostic factor of live birth rate of freezing-all embryo transfers, but its predictive value on live birth rate was of limited clinical value.

The impact of endometrial thickness (EMT) on the day of human chorionic gonadotropin (hCG) administration on pregnancy outcomes: a 5-year retrospective cohort analysis in Malaysia

BackgroundChances of pregnancy in relation to endometrial thickness (EMT) remain elusive albeit some literatures suggest poorer pregnancy outcomes below the threshold of 6-7 mm, notwithstanding others perceive detrimental effect at thicker EMT. We aim to examine the implication of EMT on pregnancy outcomes using a cut-off of 8 mm and further explore for any effect of ‘thick’ EMT in our patient population.MethodsThis was a retrospective cohort study performed for 162 women to assess the associations between EMT on the human chorionic ganadotropin (hCG) trigger day and pregnancy outcomes in infertile patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and autologous fresh embryo transfer (ET) in controlled ovarian stimulation (COS) cycles under an assisted reproductive technology (ART) shared-care programme between public and private institutions from January 2012 through December 2016.The associations between pregnancy outcomes [Total Pregnancy Rate (TPR), Biochemical Pregnancy Rate (BPR), Clinical Pregnancy Rate (CPR), Ongoing Pregnancy Rate (OPR)/ Live Birth Delivery Rate (LBDR), Miscarriage Rate (MR) and Implantation Rate (IR)] and EMT (< 8 or ≥ 8 mm) on the hCG trigger day were evaluated. Besides, the associations between pregnancies outcomes with EMT ≥ 14 mm and ≥ 8 to < 14 mm were further assessed.ResultsWe found that the ≥8 mm group had a higher TPR (55.4% vs 21.4%; p = 0.015) and CPR (52.0% vs 21.4%; p = 0.029). However, the BPR, MR, OPR/ LBDR and IR were not associated with the EMT (p > 0.05). All pregnancy outcomes were comparable for ≥14 mm and ≥ 8 to < 14 mm subgroups.ConclusionsOur findings suggest that EMT < 8 mm on hCG trigger day could adversely affect TPR and CPR in infertile patients undergoing IVF/ICSI-ET. Besides, we also disprove the notion of reduced chances of pregnancy with EMT ≥ 14 mm. The findings are based on completed cycles which each has demonstrated a triple-line endometrial pattern on the hCG trigger day with fresh autologous ET consisted of high-quality morphological gradings. However, our findings are still preliminary to suggest decision for ET transfer, cycle cancellation or adjunctive therapies. Further studies with larger sample size from this geographical region are required to verify the findings.

Is genetic fatherhood within reach for all azoospermic Klinefelter men?

BackgroundMultidisciplinary management of Klinefelter cases is now considered good clinical practice in order to ensure optimal quality of life. Reproductive performance of Klinefelter men is an important issue however literature in this domain is limited and prone to bias.Study designThis was a retrospective longitudinal cohort study performed at a tertiary referral University Centre for Reproductive Medicine and Genetics. One hundred thirty-eight non-mosaic azoospermic Klinefelter patients undergoing their first testicular biopsy (TESE) between 1994 and 2013, followed by intracytoplasmic sperm injection (ICSI) with fresh or frozen-thawed testicular sperm in the female partner, were followed-up longitudinally. The main outcome measure was cumulative live birth rate per Klinefelter patient embarking on TESE-ICSI.FindingsIn forty-eight men (48/138) sperm were successfully retrieved at the first TESE (34.8%). The mean age of the patients was 32.4 years. Younger age at first TESE was associated with a higher sperm retrieval rate (p<0.001). Overall 39 couples underwent 62 ICSI cycles and 13 frozen embryo transfer cycles resulting in in 20 pregnancies and 14 live birth deliveries (16 children). The mean age of the female partner was 28.1 years. The crude cumulative delivery rate after four ICSI cycles was 35.9%. Per intention-to-treat however, only 10.1% (14/138) of the Klinefelter men starting treatment succeeded in having their biologically own child(ren).ConclusionNon-mosaic Klinefelter patients with azoospermia seeking treatment by TESE-ICSI should be counseled that by intention-to-treat the chance of retrieving sperm is fair, however only a minority will eventually father genetically own children.

Perinatal and Peripartum Outcomes in Vanishing Twin Pregnancies Achieved by In Vitro Fertilization.

To compare perinatal and peripartum outcomes of vanishing twin gestations with singleton and dichorionic twin gestations in pregnancies conceived by in vitro fertilization. We conducted a retrospective cohort study of vanishing twin pregnancies after fresh and cryopreserved autologous in vitro fertilization cycles performed at our institution from 2007 to 2015. Singleton, dichorionic twin, and dichorionic twin pregnancies with spontaneous reduction to one by 14 weeks of gestation (vanishing twins) were included. Analysis was restricted to patients with a live birth delivery at our institution at or beyond 24 weeks of gestation. The primary outcomes were gestational age and birth weight at delivery; secondary outcomes included peripartum morbidities. A subanalysis further differentiated the vanishing twin pregnancies between those in which demise of the twin occurred before compared with after identification of fetal cardiac activity. Logistic regression models were used to estimate the adjusted odds ratio (OR) with a 95% CI of outcomes. There were 1,189 pregnancies that met inclusion criteria (798 singleton, 291 twin, and 100 vanishing twin). The mean gestational age at birth and birth weights were 38.6±2.3 weeks of gestation and 3,207±644 g in singleton pregnancies, 35.5±2.7 weeks of gestation and 2,539±610 g in twin pregnancies, and 38.5±1.8 weeks of gestation and 3,175±599 g in vanishing twin pregnancies. When compared with twins, those with a vanishing twin had lower odds of preterm delivery (OR 0.13, 95% CI 0.07-0.23; adjusted OR 0.12, 95% CI 0.07-0.22) and small-for-gestational-age birth weight (OR 0.24, 95% CI 0.13-0.45; adjusted OR 0.14, 95% CI 0.07-0.28). In pregnancies conceived by in vitro fertilization that progress to at least 24 weeks of gestation, vanishing twin and singleton pregnancies had similar perinatal and peripartum outcomes. Both were significantly better than twin pregnancies.

The impact of thyroid-stimulating hormone levels in euthyroid women on intrauterine insemination outcome

BackgroundThe aim of this study was to examine the effect of thyroid-stimulating hormone (TSH) levels on intrauterine insemination (IUI) outcomes among euthyroid women.MethodsA retrospective cohort study was conducted. A total of 302 women who started their first IUI cycle in our fertility center were included in this study. The patients were categorized into two groups based on their preconception TSH values: 0.38–2.49 mIU/Land 2.50–4.99 mIU/L. The clinical pregnancy rate was the main outcome parameter. As secondary parameters, we evaluated the differences in spontaneous abortion rate, live-birth delivery rate, and perinatal outcomes according to the preconception TSH threshold (< 2.5 and < 5.00 mIU/L).ResultsThere was no significant difference between the two groups with respect to clinical pregnancy, miscarriage, and live-birth rates with an odds ratio of 1.67 (95% CI: 0.79–3.53), 1.08 (95% CI: 0.09–13.1), and 1.79 (95% CI: 0.77–4.2), respectively. In addition, there were no significant differences in perinatal outcomes (gestation at delivery, birth weight, and neonatal intensive care unit–administration rate) between the two groups.ConclusionsOur findings indicate that among euthyroid patients, preconception TSH values in the high-normal range (between 2.5 and 4.9 mIU/L) do not have a negative effect on IUI outcomes.Trial registrationThis study is retrospectively registered by Ethical Review Board at Inonu University in 19th December 2017; Ethics approval no is 2017–27-20.

Assisted Reproductive Technology Surveillance - United States, 2015.

Problem/ConditionSince the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g) infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART procedures performed in 2014 and 2015) with outcomes for all infants born in the United States in 2015.Period Covered2015.Description of SystemIn 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102–493 [October 24, 1992]). Data are collected through the National ART Surveillance System, a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico).ResultsIn 2015, a total of 182,111 ART procedures (range: 135 in Alaska to 23,198 in California) with the intent to transfer at least one embryo were performed in 464 U.S. fertility clinics and reported to CDC. These procedures resulted in 59,334 live-birth deliveries (range: 55 in Wyoming to 7,802 in California) and 71,152 infants born (range: 68 in Wyoming to 9,176 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15–44 years), a proxy measure of the ART utilization rate, was 2,832. ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Virginia).Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.6 among women aged <35 years, 1.8 among women aged 35–37 years, and 2.3 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 34.7% (range: 11.3% in Puerto Rico to 88.1% in Delaware).In 2015, ART contributed to 1.7% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.5% in Massachusetts). ART also contributed to 17.0% of all multiple-birth infants, 16.8% of all twin infants, and 22.2% of all triplets and higher-order infants. The percentage of multiple-birth infants was higher among infants conceived with ART (35.3%) than among all infants born in the total birth population (3.4%). Approximately 34.0% of ART-conceived infants were twins and 1.0% were triplets and higher-order infants.Nationally, infants conceived with ART contributed to 5.1% of all low birthweight infants. Among ART-conceived infants, 25.5% had low birthweight, compared with 8.1% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (31.2%) than among all infants born in the total birth population (9.7%). Among singletons, the percentage of ART-conceived infants who had low birthweight was 8.7% compared with 6.4% among all infants born. The percentage of ART-conceived infants who were born preterm was 13.4% among singletons compared with 7.9% among all infants.InterpretationMultiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. For women aged <35 years, who are typically considered good candidates for eSET, the national average of 1.6 embryos was transferred per ART procedure. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four cycles of IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use exceeding 1.5 times the national rate. This type of mandated insurance coverage has been associated with greater use of ART and likely accounts for some of the difference in per capita ART use observed among states.Public Health ActionTwins account for the majority of ART-conceived multiple births. Reducing the number of embryos transferred and increasing use of eSET when clinically appropriate could help reduce multiple births and related adverse health consequences for both mothers and infants. State-based surveillance of ART might be useful for monitoring and evaluating maternal and infant health outcomes of ART in states with high ART use.

Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in women with antiphospholipid antibody syndrome: a meta-analysis of randomized controlled trials

Objective: This study was designed to evaluate the efficacy of aspirin or heparin or both in the treatment for recurrent spontaneous abortion (RSA) in women with antiphospholipid antibody syndrome (APS).Methods: Systematic searches for randomized clinical trials (RCTs) evaluating on live birth and preterm delivery, preeclampsia, intrauterine growth restriction, gestational diabetes, bleeding of RSA with APS patients receiving aspirin, and heparin therapy were carried out, from PubMed, EMBASE, ScienceDirect, and CNKI. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Relative risk (RR) and its 95% confidence interval were calculated.Results: Nineteen publications with randomized controlled trials were selected for this study, which included a total of 1251 pregnant patients with diagnosis of RSA with APS. With respect to live birth, it was remarkably improved in aspirin plus heparin or heparin alone group [RR =1.23, 95% CI (1.12–1.36), p < .0001; RR = 1.18, 95% CI (1.03–1.35), p = .02]; aspirin alone group, however, there was no statistically significant difference compare to placebo [RR = 0.97, 95% CI (0.80–1.16), p = .71]. Meanwhile, aspirin plus heparin therapy did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications including preterm birth, intrauterine growth retardation (IUGR), gestational diabetes, and minor bleeding. A beneficial therapeutic effect of heparin alone therapy was found on preventing preterm birth and low-dose aspirin plus heparin therapy was significant reduce the risk of preeclampsia.Conclusion: An improvement of pregnancy outcomes in women with RSA and APS can be achieved by treatment strategies combining low-dose aspirin plus heparin or heparin alone. Aspirin alone, by contrast, seemed inferior to other treatments in achieving more live birth.

The number of oocytes retrieved during IVF: a balance between efficacy and safety.

What is the relationship between the number of oocytes collected in fresh IVF treatments and the likelihood of cumulative delivery rate (fresh and frozen) per oocyte aspiration, severe ovarian hyperstimulation syndrome (OHSS) and thromboembolic events? Cumulative delivery rate per aspiration increases up to 20 oocytes retrieved and then evens out while the incidence of severe OHSS increases more rapidly from around 18 oocytes and thromboembolic events, although rare, occurs in particular if 15 or more oocytes are retrieved. Previous studies have shown that the number of oocytes retrieved for IVF is a positive predictor of live birth in fresh cycles. Few studies have investigated cumulative live birth rates and OHSS in relation to the number of aspirated oocytes. Retrospective population-based registry study including 39 387 women undergoing 77 956 fresh IVF cycles in the period 2007-2013 and 36 270 consecutive transfers of frozen/thawed embryos in the period 2007-2014. Data from The Swedish National Quality Registry of Assisted Reproduction (Q-IVF) including all IVF cycles with oocyte retrieval performed in public or private infertility clinics during the study period, was cross-linked to the National Patient Register regarding diagnostic codes (ICD 10) for severe (OHSS) and thromboembolic events. Oocyte donation cycles were excluded. Live birth delivery rate in fresh cycles increased up to 11 oocytes retrieved and then evened out, where the live birth rate was 30.3% for a 34-year-old woman. The cumulative delivery rate per aspiration, including fresh transfer and all subsequent transfers of frozen-thawed embryos (FET cycles) per oocyte retrieval, increased up to approximately 20 oocytes where it reached 45.8%. The adjusted odds ratio (AOR) for live birth by the number of oocytes was 1.064 (95% CI: 1.061; 1.067). The incidence of severe OHSS increased significantly by the number of oocytes, particularly if more than 18 oocytes were retrieved. The AOR for OHSS by the number of oocytes was 1.122 (95% CI: 1.08; 1.137). Thromboembolic events were rare, a total of 16 events in 14 patients were observed, and occurred in particular if 15 or more oocytes were retrieved. All FET cycles might not be included. Some embryos cryopreserved between 2010 and 2013 might still result in additional births until 2018. Furthermore the gonadotrophin dose was not included in the Q-IVF Registry in the study period, thus adjustment for dose was not possible. The results suggest a shift at approximately 18-20 oocytes where the cumulative delivery rate per aspiration levels off and, at the same time, the incidence of severe OHSS increases more rapidly. Thromboembolic events, although rare, should also be taken into consideration at stimulation regimes for IVF. Evaluating data taking both efficacy and the most serious safety aspects into account, is a new approach and of crucial importance both for patients undergoing IVF and their physicians. Financial support was received through an agreement relating to research and the education of doctors (ALFGBG-70 940) and grant from the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.